Table of contents

Advanced sensors for detection of gases and vapors are required for energy and environmental monitoring. For example, detection of refrigerant leaks from HVAC equipment specifically difluoromethane at low concentrations in air is required. When a refrigerant leak occurs from a HVAC system, there are several consequences, i) reduction in cooling efficiency and ii) higher greenhouse gas emissions to the atmosphere. Sensing refrigerant leaks requires sorbents with high affinity at low partial pressures. Having a highly effective sorbent sensitive to fluorocarbon refrigerant vapors provides a means to develop a sensing device for leak detection. In this regard, Pacific Northwest National Laboratory is exploring novel classes of materials including metal organic frameworks (MOFs), covalent organic frameworks and porous organic cages as a thin film on surface acoustic wave sensor for detection of refrigerant leaks. The structure and selectivity of these materials can be tailored by the selection of various organic bridging ligands used in the synthesis. Further these materials shown to have high surface area and shown to have high gas mobility higher than many other sorbent materials. These characteristics are highly favorable for development sorptive materials for sensing refrigerant molecules from air. Our work in this area suggest these materials reflect a range of sorbent properties from high uptake capacity (over 170 wt%) at high vapor pressures to very high sorption affinities at very low vapor pressures. I will discuss methods to use these materials as a thin film on surface acoustic wave sensor for detection of refrigerant molecules

Melanin is a natural pigment produced by melanocytes and has many physiological functions. Recent studies have suggested that melanin can behave like a free radical scavenging antioxidant. In biological systems, free radicals can damage a wide array of the essential components in the human body, such as cells/tissues, DNA, proteins, and lipids. Peroxynitrite (PON) has emerged as a combination of two free radicals and it can yield secondary free radicals per homolytic decomposition. PON is a biological oxidant that has been linked with oxidative damage and disruption of redox control systems. The short lifespan and fast reactivity of PON add more challenge to measure its concentration under physiologic conditions.

Carbon fiber electrodes (CFEs) have the advantage of providing a minimally invasive and a non-toxic platform when compared to other metal-based electrodes. In this research study, synthetic melanin-coated CFEs were prepared using electro-deposition of 5,6-dihydroxyindole monomer. Surface characterizations including scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were utilized to confirm the melanin deposition and to examine the morphological differences between the modified CFEs before and after exposure to PON. Cyclic voltammetry, differential pulse voltammetry, and amperometry were used to test the performance of CFEs modified with synthetic melanin in terms of detection and quantification of PON. Our preliminary findings have shown that synthetic melanin modified CFEs have greater sensitivity when compared to glassy carbon electrodes and other macro-electrodes. In addition, melanin-coated CFEs exhibit high selectivity when they tested for PON detection in the presence of biological interferents. The present results indicate the possibility of using melanin-coated CFEs as a sensitive and selective sensing platforms for peroxynitrite detection in the nanomolar range at physiologic conditions.

An enzymatic electrochemical biosensor for catechol detection based on silver nanowires (AgNWs), has been developed. The employment of AgNWs was essential to improve the electron transfer in comparison with that offered by an ITO substrate. AgNWs' electrocatalytic properties and high affinity with biomolecules make them desirable for constructing biosensors. Combining nanomaterials with enzymes reduces insulating effects, due to the high-efficient electrical activity from the active site of the enzyme to the electrode. Moreover, the employment of these proteins increases the specificity of the sensor.

Among the variety of processes available to synthesize AgNWs [1,2], polyol process has been selected, because of the simplicity and reliability it offers. The employed method consisted in a silver precursor (AgNO₃) reduction in presence of Ethylene glycol as a solvent and polyvynilpyrrolidone, which is a surfactant that facilitates the AgNWs dispersion. The developed biosensor results from the immobilization of tyrosinase (TYR) on the top of the AgNWs deposited by spin coating in a different concentration ratio. FTIR, UV-vis, DRX and AFM have confirmed the proposed structure and cyclic voltammetry has shown the amplification caused by the combination of the nanomaterial and the enzyme in the film denoting their excellent performance, sensitivity and reproducibility. Moreover it has been demonstrated that the concentration of AgNWs employed in the development of the biosensors is crucial in terms of reproducibility, in addition to being excellent electronic mediators.

Figure 1. Voltametric response of ITO-Tyr (red) and ITO-AgNWs-TYR (black) onto ITO surface to 10^-4M catechol in phosphate buffer 10^-2M.

[1] Xu, L. et al. Anal. Methods 7, 5649-5653 (2015), [2] Kumar-Krishnan, S. et al. RSC Adv. 6, 20102–20108 (2016)

Acknowledgments: Financial support by MINECO and FEDER (RTI2018-097990-B-100 and BES-2016-077825) and the Junta de Castilla y León-FEDER (VA-275P18) is gratefully acknowledged.

Figure 1

Oxygen concentration is one of the critical factors tightly controlled in each part of an organism to regulate the cells' role and function. Yet, changes in tissue oxygenation often occur in small focal areas with aging or as a result of an injury. Despite the serious health implications of focal hypoxia, no methodologies exist that can model oxygen supply system accordingly in animal models or in vitro models. Therefore, we designed a novel local hypoxia system as a sensing interface for in vitro cell culture. The oxygen removal efficiencies measured by Clark electrodes showed that O₂ concentration can be reduced from 20.9% / 140mmHg or 5% / 35mmHg and maintained at hypoxia (< 1.5% / 10mmHg) in 15 or 8 minutes respectively. The induced hypoxia stimulated localized time-dependent HIF-1α transcription factor nuclear accumulation at the region of interest on human neural progenitor cells. This is the first system capable of robustly generating normoxia and hypoxia side-by-side on the same culture dish for comparative study. The new culture system provides the opportunity to decipher the pathophysiology of hypoxia-related diseases including stroke, dementia and cardiovascular complications.

The detection, collection and/or conversion of biological-based molecules has applications to sensing, wearables, and biofuels. Flexible, wearable electronics for real-time detection of, for example, Neuropeptide Y in human sweat [1], or flagella protein in biofuels, enables deviation from bulky laboratory benchtop analyses such as ELISA. Challenges include required limits of detection, as biological materials can be present in small amounts (nM to pM concentrations) in complex high ionic strength environments[2], the need for a highly selective sensor interface that avoids non-specific binding, and a quick response to account for degradation of analytes.

This work will discuss the implementation of a mixed self-assembled monolayer (SAM) interface with highly selective bio-recognition elements (BREs) on gold disk electrodes, focusing on target application for aqueous sensing in biofuels, with room for expansion to sensing in other biological fluids. The SAM composition was systematically varied to assess functionality towards preventing fouling/non-specific binding and increase the selectivity of the interface for the analyte of interest. Briefly, mixed monolayer combinations included pseudo-zwitter surfaces to prevent fouling, blocking groups similarly employed in the literature[3] to help rectify BREs, and dithiobis(succinimidyl propionate) (DSP) cross-linking chemistry[4] to attach various BREs to the gold electrode. BREs include concanavilin A, streptavidin, nanobodies, and synthetic lectins. Streptavidin and it's interaction with biotin was chosen as a control, due to their known strong interaction. Electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV) were used to estimate changes in the resistance to charge transfer to redox mediators either immobilized or in solution. EIS is one of the most common modern techniques used in biosensing, but as a time-intensive measurement it can be undesirable for accurate sensing in analyte-degrading environments. Therefore, SWV was employed as a substitute which reduces times of measurements by an order of magnitude, and is shown to provide the same information as EIS. To corroborate these electrochemical effects with a definite surface coverage/binding event, ellipsometric experiments of functionalized electrodes are underway.

Our SAM interface produces nM level detection for yeast through the employment of gold immobilized charge transfer mediators and concanavalin A with selective binding to the yeast cell wall. Specifically, a decrease in charge transfer resistance (or increase in peak current as measured in SWV) occurs upon binding of yeast cells to concanavalin A. The streptavidin-biotin interaction also manipulated the charge transfer resistance similarly, confirming our method effectiveness. Nanobodies (binding fragment of antibodies) were also shown to have some success in detecting flagella protein with redox mediators in solution.

These proof-of-concept results demonstrate feasibility and indicate forward paths towards highly selective sensor electrodes with simultaneous anti-fouling properties that prevents non-specific binding. Ongoing efforts include modifying electronic device interfaces with SAMs for combined signaling and amplification, such as modification of gate electrodes in printable electrochemical transistors.

References:

[1] G. Cizza et al., "Elevated Neuroimmune Biomarkers in Sweat Patches and Plasma of Premenopausal Women with Major Depressive Disorder in Remission: The POWER Study," Biol. Psychiatry 64, 907–911 (2008); doi: 10.1016/j.biopsych.2008.05.035

[2] Z. Sonner et al., "The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications," Biomicrofluidics 9, 031301(2015); doi: 10.1063/1.4921039

[3] R. Levicky, T. M. Herne, M. J. Tarlov, and S. K. Satija, "Using Self-Assembly To Control the Structure of DNA Monolayers on Gold: A Neutron Reflectivity Study," J. Am. Chem. Soc. 120, 9787–9792 (1998); doi: 10.1021/ja981897r

[4] A. J. Lomant and G. Fairbanks, "Chemical probes of extended biological structures: Synthesis and properties of the cleavable protein cross-linking reagent [35S] dithiobis(succinimidyl propionate)," J. Mol. Biol. 104, 243–261, (1976); doi: 10.1016/0022-2836(76)90011-5

Figure 1

Introduction

Engineered nanoparticles (ENPs) have found widespread use in modern technology, medicine and daily life. Ag-NPs for example are used as antimicrobials in several medical and cosmetic products, whereas Au-NPs have attracted great interest in medical applications, such as drug delivery systems. However, ENPs can potentially cause adverse toxic effects due to their small size and high surface to volume ratio and their increased utilization in different medical and consumer products leads to an increased exposure to humans. While a range of state-of-the-art technologies, such as ICP-MS, is available for the detection of ENPs, they usually require thorough sample preparation, highly trained personnel and expensive equipment. [1]

To circumvent these limitations, the use of artificial recognition materials, as for instance molecularly imprinted polymers (MIPs), is a promising alternative. MIPs are synthesized via (radical) polymerization in the presence of template molecules. After template removal, cavities, which are complementary to the template in size, shape and chemical functionality, form in the material. These can rebind target molecules with high sensitivity and selectivity. [2] MIPs can be used as receptors for quartz-crystal microbalances (QCMs), which are mass-sensitive transducers that measure a change in mass via a change in resonant frequency of the oscillating quartz. [3]

In this work, we report on developing an easy-to-use and low-cost MIP-based QCM sensor for detection of ENPs in aqueous matrices.

Method

Stamps with immobilized metal-based NPs were used to imprint template material on PU layers. Particle distribution and shape of NPs, immobilized on PDMS stamps, were analyzed using atomic force microscopy (AFM). MIPs were prepared by pressing NP-stamps onto PU layers. After polymerization overnight, stamps were removed and remaining NPs were washed off the surface. MIPs were characterized via AFM and QCM. In case of QCM, we utilized an in-house dual-electrode system. In that case, one of the two electrode pairs served as reference and was coated with the non-imprinted polymer (NIP) to compensate for external effects, such as temperature changes.

Results and Discussion

Two different imprinting strategies were tested for fabrication of NP MIPs: bulk and surface imprinting. Bulk imprinting did not result in cavity formation on the polymer surface as examined via AFM. Consequently, we could not observe any significant differences of sensor signals between MIP and NIP during QCM measurements. In contrast to this, surface imprinting led to more favorable outcomes. NP-stamps were used for that purpose and characterized using AFM to verify the presence of NPs on stamp surfaces. As shown in Figure 1a, NPs are distributed evenly across the surface. Figure 1b displays an AFM image of the corresponding imprinted PU layer, which clearly reveals cavities on the polymer surface, matching the template in size and shape, thus confirming successful NP imprinting. In addition, an image of the reference, the non-imprinted polymer (NIP), is given for comparison, bearing no binding sites on the polymer surface (Figure 1c).

Frequency measurements of MIP and NIP coated QCMs resulted in reversible and concentration-dependent sensor responses with no cross-selectivity to larger NPs. Furthermore, frequency shifts of MIPs, caused upon injection of NP solution, were much higher than those of NIPs. Fist results on acrylate-based MIPs using self-initiating monomers seem promising. First QCM measurements revealed incorporation of NPs by MIPs, with a way higher sensor response compared to the NIP. However, there is still room for improvement regarding batch-to-batch reproducibility. Further characterization of these sensing materials is necessary and still ongoing.

Conclusion and Outlook

Imprinting of thin polymer-films using metal-based ENPs is a novel concept with considerable potential in the field of sensor technology. PU-based MIPs were prepared by surface imprinting and characterized using AFM, revealing corresponding NP cavities on the polymer surface and thus confirming successful imprinting of NPs. Moreover, frequency measurements of MIP coated QCMs led to sensor responses in a reversible and quantitative manner. In the near future, selectivity studies will be performed in order to assess binding responses as a function of NP size, stabilizer and core material. Moreover, surface morphology of MIPs will be further characterized using PeakForce QNM.

Overall, this work demonstrates the potential use of MIPs for analysis of NPs in complex matrices, such as food, cosmetic or medical products.

Acknowledgements

This work has been funded by the Austrian Science Fund FWF, project number I 3568-N28, which we gratefully acknowledge.

References

[1] A. M. Schrand, M. F. Rahman, S. M. Hussain, J. J. Schlager, D. A. Smith, A. F. Syed, Metal-based nanoparticles and their toxicity assessment, WIREs Nanomedicine Nanobiotechnology. 2 (5), 2010, 544-568. doi: 10.1002/wnan.103.

[2] P. A. Lieberzeit, J. Wackerlig, Molecularly imprinted polymer nanoparticles in chemical sensing – Synthesis, characteriaztion and application, Sensors and Actuators B. 207, 2015, 144-157. doi: 10.1016/j.snb.2014.09.094.

[3] R. P. Buck, E. Lindner, W. Kutner, G. Inzelt, Piezoelectric chemical sensors (IUPAC Technical Report), Pure and Applied Chemistry. 76 (6), 2004, 1139-1160. doi: 10.1351/pac200476061139.

Figure 1

Stimuli responsive release of biomolecules from surfaces such as gold and carbon is gaining importance for past couple of decades due to its application in biomedical field. Electrochemically induced release of biomolecules from the surfaces is one of such techniques. The simplicity of the electrochemical techniques brings-in a wide opportunity for loading and releasing biomolecules from the electrode surfaces. Here-in we report the loading and electrochemical release of His-tagged proteins from the electrode surfaces such as gold and graphite¹. Reversible chelation of His-tagged proteins on Ni-NTA surfaces is studied for decades. Competing ligands such as imidazole and EDTA are used for releasing the His-tagged proteins from the Ni-NTA surfaces. However, switching the metal to Cu(II) instead of Ni(II) brings an excellent opportunity for releasing the His-tagged proteins by the reduction of Cu(II). The affinity of Cu(I) towards complexation with NTA and His-tag is substantially lower than Cu(II) which facilitates the release of the protein. Cu-NTA crafted graphite and gold electrodes were used for the coordinative loading of His-tagged proteins and electrochemical reduction of metal ion for the release of the proteins from the surface. In this study a redox mediator coupled model peptide (ferrocene-hexahistidine) and a model recombinant protein (containing His-tag) "Protein A" were used as examples for loading and electrochemical release.

ǂ These authors equally contributed to the work

Reference:

1. Bellare, M.; Kadambar, V. K.; Bollella, P.; Gamella, M.; Katz, E. and Melman, A; Electrochemical release of His-tagged proteins by destruction of NTA-Cu(II)-protein complex; Electroanalysis2019, accepted manuscript.

Rapid diagnosis of infectious pathogens in patients can be performed by analyzing specific antibodies produced by the immune system. The ability to specifically capture these antibodies directly in the body fluids such as whole blood, is a huge advancement toward rapid point-of-care diagnostics. We introduce a highly selective strategy for antibody detection based on integrating an electrochemical DNA-based assay with peptide-antibody bioconjugate to specifically capture human antibodies on the surface of electrodeposited nanostructures. We have shown that one-pot detection of macromolecules such as antibodies can be done by sterically inhibiting the hybridization of complementary DNA strand carrying the antibody to the surface bound DNA strand. We also showed that using our electrodeposited nanostructured electrode, we can overcome the limitations of surface toward capturing of peptide recognition, but enhance the inhibition of macro-size molecules for the surface hybridization. Here, we introduce a peptide-assisted electrochemical assay implemented on nanostructured electrode that enables the capturing of real human antibodies directly in whole blood. We improved the linear range and limit of detection by applying the assay using a particular nanostructured platform with tunable roughness. We present the application of the proposed platform to detect HIV-1 human antibodies in real patient samples.

In the last decade, the rise of synthetic biology has driven the efforts to construct artificial allosteric protein switches in order to detected and quantify natural and artificial chemistries in vitro and in vivo. Typically, this involves construction of chimeric enzymes via insertion of a regulatory receptor domain into the biocatalytic reporter domain. Construction of such chimeric enzymes utilizes the recombinant DNA technology that is a core technology of protein engineering [1].

Herein, we report on the bioelectrocatalytic properties of pyrroloquinoline quinone-dependent glucose dehydrogenase fusion with calmodulin (PQQ-GDH-CaM). This protein is catalytically inactive in its ground form but can be activated by the addition of calmodulin binding peptide that induces its conformational transition and activation. The PQQ-GDH-CaM was immobilized onto highly porous gold (hPG) produced electrochemically [2] by using a bifunctional linker, namely 4-mercaptobenzoic acid further activated through 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide (EDC/NHS) coupling to covalent bind the PQQ-GDH-CaM chimeric enzyme [3].

At first, we characterized the switchable features of PQQ-GDH-CaM by simply exposing it to the activating peptide. Subsequently we devised an approach to use proteolytic activation of a caged-peptide to generate activating peptide for PQQ-GDH-CaM. Furthermore, the system was utilized to study different pathways for PQQ-GDH-CaM triggered activation according to different logic gates in order to realize multipurpose biosensors (e.g., glucose detection, peptide detection etc.) [4].

References

• Gamella, M., Guo, Z., Alexandrov, K., Katz, E. (2019). ChemElectroChem, 6(3), 638-645.

• Bollella, P., Hibino, Y., Kano, K., Gorton, L., Antiochia, R. (2018). Analytical chemistry, 90(20), 12131-12136.

• Koushanpour, A., Gamella, M., Guo, Z., Honarvarfard, E., Poghossian, A., Schöning, M. J., Alexandrov, K., Katz, E. (2017). The Journal of Physical Chemistry B, 121(51), 11465-11471.

• Bollella, P., Katz, E. (2019). International Journal of Unconventional Computing, 14(3-4), 181-198.

Humidity is a very important physical parameter that plays an imperative role in technology and human activity. Researchers are paying more attention to develop moisture-responsive materials with outstanding characteristics such as high sensitivity, wide humidity detection range, fast response and short recovery times to keep pace with the on-going development in technology. Abundant, bio-sourced and biodegradable organic materials, such as melanin, are needed to enable the development of eco-designed technologies that alleviate the environmental footprint of the electronics sector. Melanin is a ubiquitous biomacromolecule with diverse functions including hydration dependent electrical response [1], photoresponse [2], antioxidant [3] , metal chelation [4], and free radical scavenging [5]. Melanin originates from the oxidative polymerization of (5,6)-dihydroxindole (DHI) and (5,6)-dihydroxindole 2-carboxyl acid (DHICA) building blocks [6]. Natural melanin is expected to contain up to 70% of DHI in molecular ratio [7]. Due to the absence of the carboxyl group in the molecular structure, DHI-melanin features a ordered, conjugated structure thus expected to show better electrical conductivity with respect to DHICA-melanin [5]. Herein, we investigate DHI-melanin and DHI-DHICA melanin thin films (7:3 weight ratio), spin coated and polymerized on technologically relevant and potentially biodegradable substrates, as active layers for fast response moisture sensors.

References

[1] Wünsche J, Deng Y, Kumar P, Di Mauro E, Josberger E, Sayago J, Pezzella A, Soavi F, Cicoira F and Rolandi M 2015 Protonic and electronic transport in hydrated thin films of the pigment eumelanin Chem. Mater.27 436-42

[2] Mostert A B, Rienecker S B, Noble C, Hanson G R and Meredith P 2018 The photoreactive free radical in eumelanin Science advances4 eaaq1293

[3] Tu Y-g, Sun Y-z, Tian Y-g, Xie M-y and Chen J 2009 Physicochemical characterisation and antioxidant activity of melanin from the muscles of Taihe Black-bone silky fowl (Gallus gallus domesticus Brisson) Food Chem.114 1345-50

[4] Hong L and Simon J D 2007 Current understanding of the binding sites, capacity, affinity, and biological significance of metals in melanin. ACS Publications)

[5] Panzella L, Gentile G, D'Errico G, Della Vecchia N F, Errico M E, Napolitano A, Carfagna C and d'Ischia M 2013 Atypical structural and π‐electron features of a melanin polymer that lead to superior free‐radical‐scavenging properties Angew. Chem. Int. Ed.52 12684-7

[6] Meredith P and Sarna T 2006 The physical and chemical properties of eumelanin Pigment cell research19 572-94

[7] Pezzella A, d'Ischia M, Napolitano A, Palumbo A and Prota G 1997 An integrated approach to the structure of Sepia melanin. Evidence for a high proportion of degraded 5, 6-dihydroxyindole-2-carboxylic acid units in the pigment backbone Tetrahedron53 8281-6

Introduction

Stimulus-responsive hydrogels represent sensor elements with a high application potential for the detection of the concentration of a solved species. In combination with a piezoresistive pressure sensor, the hydrogel's analyte-dependent swelling pressure is transformed into an electrical output signal. In the past, numerous sensors with sensitivities to various analytes, like e.g. ethanol, glucose and pH, have been researched using this sensor principle [1]. However, the time span until a final steady-state value of the sensor's output signal is reached is typically in the range of minutes to hours due to the excessive diffusion processes associated with the gel's volume phase transition and visco-elastic behaviour.

State of the art

Previous strategies for shortening the response time mostly addressed reducing the hydrogel layer's dimensions, which concurrently results in a reduction of sensitivity. The measurement method of force compensation using a bisensitive hydrogel represents a sensitivity-preserving approach. The concept of force compensation with a bisensitive hydrogel is to counteract the swelling of the hydrogel with a second stimulus, in this case the temperature. A closed-loop configuration is used to control the temperature with a Peltier element in a way that the hydrogel is continuously kept at a fixed swelling state (Figure 1a). The applied temperature is therefore directly proportional to the analyte concentration to be measured and thus represents the sensor output signal containing the measurement information [2]. By using this configuration, the time-consuming diffusion processes can be reduced significantly. In a previous work, a force-compensated sensor utilizing a bisensitive hydrogel enabled a response time reduction of up to 70% [3].

Method

In [3] an interpenetrating polymer network (IPN) is used as a bisensitive hydrogel, which is sensitive both to the ion concentration c_Na⁺ of a saline solution (measurand) and to the temperature ϑ (compensation parameter). This IPN showed sufficient compressive strength for the operation under the influence of the pressure sensor membrane's restoring force. However, its sequential two-step synthesis complicates the gel structuring process. With regard to enable gel synthesis, gel structuring and gel bonding within one single process step, a single-step synthesis that yields a bisensitive gel with similar compensatory and mechanical properties is desirable. In this work a semi-interpenetrating polymer network (semi-IPN) is presented, which fulfils these requirements. According to IUPAC it is called [net-P(AMPS-co-NiPAAm)]-sipn-PAMPS. It consists of a single statistical copolymer network based on N-isopropylacrylamide (NiPAAm) and 2-acrylamido-2-methylpropane sulfonic acid (AMPS) in which long polymer strands of the sulfonic acid (PAMPS) are incorporated, thus contributing to an improvement of the mechanical properties. A second cross-linking reaction is omitted in this way.

Materials

NiPAAm (Acros Organics) was purified by recrystallization from n-hexane while AMPS (Sigma Aldrich), PAMPS (average molecular weight: 2,000,000 g/mol, mass fraction of the solution: 15 wt% in water, Sigma Aldrich), N,N'-methylenebisacrylamide (BIS, Merck) and N,N,N',N'-tetramethylethylenediamine (TMEDA, Sigma Aldrich) were used without further purification. The initiator sodium peroxodisulphate (NaPS, Riedel-de Haën) was used as a 0.84 molar aqueous solution (1.00 g in 5.0 ml of water).

Synthesis

The semi-IPN was synthesized by redox-initiated free radical polymerization in water in an argon atmosphere. NiPAAm (1057.3 mg, 9.343 mmol), AMPS (59.9 mg, 0.289 mmol), BIS (59.4 mg, 0.385 mmol), PAMPS (363.3 mg of the solution) and NaPS (57.3 µl of the stock solution, 0.048 mmol) were dissolved in 7.9 ml deionized water. Sodium hydroxide solution NaOH (600 ml of a stock solution with concentration 1 mol/l) was added to have predominantly basic conditions. The solution was degassed and cooled in iced water for 10 min. After initiating the polymerization with TMEDA (7.3 µl, 0.048 mmol) the pregel solution with a total volume of 10 ml was filled into polymerization vials and cooled at 15 °C for 3 h. Finally, the semi-IPN hydrogel was cleaned for three days with deionized water to remove polymerization residues. The bisensitive free-swelling characteristics were measured by investigating the mass-based swelling degree Q_m as a function of c_Na⁺ and ϑ according to [2]. Flat cylindric samples (diameter: 15 mm, thickness: 3 mm) were fabricated to compare the ultimate compressive strength with the state-of-the-art IPN hydrogel using a rheometer (Anton Paar Physica MCR 301).

Results and Conclusions

Figure 1b shows, that the semi-IPN hydrogel exhibits the desired bisensitive swelling characteristic. For a defined operating point at Q_m ≈ 8, there is an almost linear relation between the measured variable 'ion concentration c_Na⁺' (scaled logarithmically) and the compensation parameter 'temperature ϑ' for the indicated operating range of the sensor (Figure 1c).

Excited at the same stimulus parameters, the semi-IPN samples showed a significant higher compressive strength (> 40 N) than the IPN samples (22.3 ± 4.5 N), possibly due to a denser copolymer network as well as the additional polymer strands present in the network.

Exemplary sensor measurements in the force compensation mode using the bisensitive semi-IPN hydrogel are illustrated in Figure 1d. A significant response time reduction of more than 50% compared to the usual deflection method is also achieved with this hydrogel. Hence, the results prove the suitability of the novel hydrogel within the sensor and lay the foundation for a simplified and reproducible fabrication of the hydrogel layer directly on the sensor's socket.

References

[1] A. Richter, G. Paschew, S. Klatt, J. Lienig, K.-F. Arndt, H.-J. Adler, Sensors 8(1):561-581 (2008), doi: 10.3390/s8010561.

[2] S. Binder, A. T. Krause, B. Voit, G. Gerlach, IEEE Sensors Letters 1(6) (2017); doi: 10.1109/LSENS.2017.2774922.

[3] S. Binder, G. Gerlach, Technisches Messen 86(4):227-236 (2019); doi: 10.1515/teme-2019-0004.

Figure 1

We will present our recent results on the design of semiconducting material, dielectric receptor matrices, and stabilizing and amplifying circuit structures for detection of volatile analytes in the atmosphere and proteins in aqueous solution. Besides our natural interest in designing materials that respond more strongly to analytes of interest than to likely interferents, we also emphasize the use of chemical and electronic amplification methods to increase the ratio of the desired responses to the drift (signal/noise ratio). Printable materials, especially polymers, are emphasized for the responsive layers. The use of multiple sensing elements, typically field-effect transistors (FETs), to create patterns of responses increases the selectivity of the information, either by narrowing the classes of compounds providing the responses, distinguishing time-dependent from dose-dependent responses, and/or increasing the ratio of analyte responses to environmental drifts. As a specific example, using pairs of FETs, in series or in parallel, allows device drifts to be substantially canceled while analyte responses are maintained and even reinforced. This strategy has led to significant improvements in the use of polymer-based FETs to detect pollutant gases such as nitrogen dioxide and ammonia. To increase the stability of systems used to detect analytes in solution, we sometimes separate the sensing surface from the output device in an arrangement known as a remote gate. We show that the output device may be an organic-based or a silicon-based transistor, and can respond to electrochemical potential changes at the sensing surface arising from a variety of chemical interactions. This type of configuration was applied to the understanding of vapor sensors and the effect of receptor polarity on the detection of brain injury biomarker proteins. New details about the mechanisms for sensor responses to analytes can be obtained from remote gate configurations, including connection of interfacial voltages and charge densities in responsive polymer semiconductors.

Introduction

The eight-carbon aromatic isomers ethylbenzene and m-, p-, and o-xylene are difficult to separate from one another due to similarities in molecular structure and physicochemical properties. Separating these isomers is often necessary for industrial chemical synthesis [1]. Additionally, each isomer displays slightly different toxicity [2]. However, in drinking water guidelines, only data for total xylenes is provided because separate quantification of each isomer without the use of sophisticated spectroscopic or chromatographic methods is difficult. Furthermore, for most sensors based on sorption into polymer coatings, polymer/water partition coefficients for these analytes are much lower than polymer/air partition coefficients, resulting in low sensitivity and poor selectivity in their liquid-phase sensing.

One method for addressing the above issues is to design multi-component sensor coatings that highlight the small variations in isomer structures. Such coatings can be designed by selecting coating components based on their chemical and physical properties, as well as the properties of the target analytes [3]. Properly designed coatings will show favorable sensing parameters (sensitivity, partial selectivity) in liquid-phase measurements compared to commercially available single-component polymers.

Initial results indicate that selectivity of multi-component coatings can be significantly higher, thus enabling identification of chemical isomers, which were previously not (or barely) distinguishable in the liquid phase, with limits of detection in the low parts-per-billion (ppb) by weight. Furthermore, by utilizing advanced sensor signal processing [4] to analyze sensor data, minute response differences between the isomers ethylbenzene and the three xylenes can be uniquely identified, even in solutions of multiple analytes.

Sensor Coating Design

The design of chemical sensor coatings should select properties of the coating components, in light of the target analytes, that predict and control sensing behavior. The sensing mechanism utilized here relies on bulk absorption of target analytes into polymer coatings. Polarity/dipole moment and polarizability of coating and target isomers affect the absorption process and, as a result, the sensitivity of the coated sensor to the analyte. Multi-component coatings using polymer-plasticizer blends to generate Hansen solubility parameters (HSP) that favor strong coating-analyte interactions, i.e. favorable coating/water analyte partition coefficients, were designed for this work. These coatings exhibit significantly increased sensitivity and partial selectivity to target isomers compared to single-component polymers, such as poly(epichlorohydrin) or poly(isobutylene). As a result, minute variations in analyte properties (polarity/dipole moment, polarizability, etc.) can be detected at lower analyte concentrations. The designed coatings consist of blends of polystyrene (PS) and one of two plasticizers, diisooctyl azelate (DIOA) or ditridecyl phthalate (DTP). Identification of ethylbenzene and xylene is demonstrated for each polymer-plasticizer pair, with sensitivities for ethylbenzene and each xylene isomer in good agreement with trends in dipole moments and polarizabilities.

Method

Solutions of multi-component coatings were prepared with varying plasticizer-to-polymer weight ratios (given below) and with varying concentrations of polymer-plasticizer blend in the solvent. Coatings were deposited onto SH-SAW sensor devices via spin coating for use in direct liquid-phase measurements. Coating thicknesses were determined by profilometry. Coated sensors were exposed to diluted aqueous solutions of target analytes in flow-through measurements. The concentrations of analyte solutions were independently confirmed using a gas-chromatograph photoionization detector (GC-PID) system. Frequency responses of coated sensors are used to extract sensing parameters such as sensitivity, response time constant, and viscoelastic properties of the coatings. Extracted sensing parameters for each isomer serve as inputs for an advanced estimation-theory-based sensor signal-processing technique that quantifies mixtures.

Results and Conclusions

Table 1 shows relative energy difference (RED) values for pairs of coatings and analytes calculated using Equation 1, as well as dipole moment, polarizability, and measured sensitivity and response time constant for each isomer. The polymer-plasticizer blend coatings selected are 17.5% DIOA-PS and 30% DTP-PS. RED values for each pair of materials are well below 1.0, indicating excellent miscibility. While differences between isomers are relatively small, the measured variation in responses is highlighted with an appropriate multivariate signal-processing method. The extracted average sensitivity and average response time constant for each coating/analyte pair, shown in Table 1, correlate well with the trends in analytes' dipole moments and polarizabilities. High sensitivities to ethylbenzene and xylene isomers are observed. Responses of the DIOA-PS coating to ethylbenzene and total xylenes are easily distinguishable from one another. Figure 1 shows single-analyte response curves for the DTP-PS coating for ethylbenzene and m-, p-, and o-xylene. Sensing parameters were extracted from the responses, thus allowing minute differences to be clearly observed. It is demonstrated that DTP-PS coatings show partial selectivity between ethylbenzene, m-, p-, and o-xylene. Figure 2 shows the response curve of a multi-analyte solution of the three xylene isomers, with estimated and measured concentrations for each isomer in the mixture in Table 2. Experimental responses and extracted results strongly support that selectivity to each xylene isomer can be achieved with appropriate sensor coating design.

References

[1] Y. Yang, P. Bai, X. Guo, Separation of Xylene Isomers: A Review of Recent Advances in Materials, ACS Sens., 56, 14725-14753 2017; doi: 10.1021/acs.iecr.7b03127

[2] Safety Data Sheets for ethylbenzene and m-, p-, and o-xylene, available online: https://hazard.com/msds/

[3] P. Adhikari, L. Alderson, F. Bender, A.J. Ricco, F. Josse, Investigation of Polymer-Plasticizer Blends as SH-SAW Sensor Coatings for Detection of Benzene in Water with High Sensitivity and Long-Term Stability, ACS Sens., 2, 157-164 2017; doi: 10.1021/acssensors.6b00659

[4] K. Sothivelr, F. Bender, F. Josse, E.E. Yaz, A.J. Ricco, Quantitative Detection of Complex Mixtures using a Single Chemical Sensor: Analysis of Response Transients using Multi-Stage Estimation, ACS Sens., 4, 1682-1690, 2019; doi: 10.1021/acssensors.9b00564

Figure 1

Alcoholic and phenolic hydrogen-bond (HB) acidic absorbents activated by fluorine chemistries have been previously developed at the U.S. Naval Research Laboratory and elsewhere to augment sorbent HB acidity, reduce sorbent HB basicity and target complementary HB basicity of a wide range of hazardous target chemicals. A significant limitation of HB sorbents developed to date has been the propensity for sorbent self-association. This intermolecular bonding between sorbent molecules hinders sorbate access to active HB acid sites in the sorbent, limiting its overall efficacy. Sorbent self-association is evidenced by broadened hydroxyl peaks in the mid-infrared (MIR) region, which can obscure important absorption frequencies that appear upon absorption of an analyte into the sorbent. In this current work our aim is to develop improved HB acidic sorbent compounds which minimize undesired sorbent self-association in order to apply these sorbents to infrared- and Raman-based sensing devices for chemical threat detection.

A series of new HB acidic sorbents have been synthesized and the subsequent sorbent-sorbate interactions have been characterized by a number of methods. MIR spectroscopy has been used to help elucidate sorbent-analyte vapor interactions. The newly synthesized sorbents have been challenged with various analyte vapors, including toxic industrial chemicals, chemical warfare agent simulants, and background interferents. A particular focus of these characterization efforts has been to observe the spectral changes that occur in the hydroxyl region of the MIR upon exposure of a sorbent material to an analyte vapor. Analyte binding of an HB base occurs principally at the sorbent hydroxyl site. The resulting redshift of the hydroxyl stretching frequency is characteristic of the basicity of the analyte.

These sorbent materials are specifically designed to be selective toward hazardous chemicals through complementary hydrogen-bonding interactions between sorbent and analyte molecules. Generally, common interferents, such as hydrocarbons, have little or no hydrogen-bond basicity, while hazardous chemicals of interest have moderate to high basicity. More strongly HB basic analytes trigger larger redshifts of the hydroxyl absorption frequency. Benchtop FTIR characterization has confirmed that these newly designed sorbent materials are responsive to threat chemicals of interest at low concentrations and largely unresponsive to interferent chemicals, even at relatively high concentrations.

Based on the strong affinity of these sorbents to threat chemicals of interest and the significant spectral changes that occur in the MIR upon formation of the hydrogen-bonded complex, these sorbent materials make useful candidates for MIR sensing applications. A frequency shift of the hydroxyl stretch indicates a sorbate has formed a HB with the sorbent. The magnitude of the frequency shift correlates with the basicity of the analyte, which is indicative of the class of compound to which the newly bound chemical belongs. In a sensing application, this feature can provide an alert that a hazardous chemical is present, even if it is an unknown threat. While the hydroxyl region allows for class specificity of unknown compounds, the fingerprint region complexity may facilitate specific analyte recognition. At present, this work has been focused on analysis of the hydroxyl region and distinction of different classes of compounds, but future efforts will turn to the fingerprint region to provide an avenue for specific chemical identification.

Raman spectroscopy has also been used to characterize these sorbent materials. Specifically, a technique known as waveguide-enhanced Raman spectroscopy (WERS) has been used, which features the use of highly evanescent, low-loss waveguides with the sorbent material as a top cladding.² WERS can be achieved using an incredibly small footprint with a sorbent-functionalized nanophotonic waveguide that is approximately a few centimeters long. Using WERS, the differential Raman spectra of the sorbent material interacting with different chemical warfare agent simulants has been measured at parts-per-billion detection levels. The spectra exhibit extrapolated three-sigma detection limits as low as 3 ppb. Continuing efforts are focused on adapting this technique to photonic integrated circuit-based fabrication and chip-scale Raman spectroscopy for trace chemical vapor detection.

This presentation will highlight the design of these next-generation sorbents as a tool to facilitate MIR- and Raman-based sensing of threat chemicals. It will focus on analyzing sorbent-analyte spectral interactions and discuss how to exploit these features to develop MIR- and Raman-based sensors.

References:

1. Roberts, C. A.; McGill, R. A. Bisphenol hypersorbents for enhanced detection of, or protection from, hazardous chemicals. U.S. Patent Application 2019/0134601 A1, 2019.

2. Tyndall, N. F.; Stievater, T. H.; Kozak, D. A.; Koo, K.; McGill, R. A.; Pruessner, M. W.; Rabinovich, W. S.; Holmstrom, S. A. Optics Letters, 2018, 43, 4803-4806.

Introduction

We have been using a dye-doped plasticized poly(vinyl chloride) (PVC) membrane for various optical sensor applications such as ion-sensing [1], bioassay [2] and immunoassay [3]. PVC membranes are mainly composed of 30-33wt% PVC, 60-66wt% plasticizer and a rest of components are functional molecules like a lipophilic dye and ionophore. The PVC membrane responds by color change based on bulk extraction or interfacial reaction. In order to improve sensitivity, increasing the membrane thickness and dye concentration in the PVC membrane is necessary. However, increase in the membrane thickness causes a slower response, and increase in dye concentration causes dye precipitation due to the low solubility of dye. To solve these problems, we have developed ionic liquid-based dye (IL-dye), which was an ionic liquid composed of a pH indicator dye, as the plasticizer. The PVC membrane sensor using IL-dye allowed to contain unusually high concentration of dye and the absorbance sensitivity was significantly improved with much thinner membrane, compared with that of conventional one [4]. On the other hand, direct fluorescence measurements for sensitive analysis using this membrane is generally difficult due to the concentration quenching.

Recently, luminescent solid or liquid materials using Förster resonance energy transfer (FRET) from large amounts of FRET donor molecules to small amounts of FRET acceptor molecules were reported, where efficient FRET behavior and highly bright acceptor fluorescence were observed [5]. Thus, by combining this technique with PVC membrane sensors based on IL-dyes, demonstration of highly-sensitive fluorescence-based analysis compared with that of conventional PVC membrane-based optical sensors is expected.

Here, we developed a highly-sensitive FRET-based ion measurement system using highly-fluorescent IL-dye that we developed recently (Figure 1). A pyrene-based ionic liquid, [P₆₆₆₁₄][HP-SO₃] (Figure 2(a)), which had the bright fluorescent characteristic originated from pyrene eximer, was used as the FRET donor and plasticizer, and fluorescein derivative, [P₆₆₆₁₄][12-DCF] (Figure 2(b)), was chosen as the FRET acceptor. To maximize the sensitivity of FRET-based sensing, donor and acceptor ratio was optimized. Then, FRET-based anion sensing scheme, coextraction of proton and anion, was demonstrated as a proof of concept.

Method

Ionic liquid composed of lipophilic phosphonium cation and pyrene or fluorescein derivative anion was synthesized based on ion-exchange reaction using [P₆₆₆₁₄][Cl] and each anion. Plasticized PVC membrane was prepared based on spin-coating (1600 rpm, 20 s) on the poly(ethylene terephthalate) (PET) film using the THF cocktail containing 10 wt% PVC and 90 wt% [P₆₆₆₁₄][HP-SO₃], where 0-5 mol% of [P₆₆₆₁₄][12-DCF] was doped. Then, the fluorescence spectrum (λ_ex = 348 nm) and excitation spectrum (λ_em = 560 nm) of each PVC membrane was measured to investigate the FRET behavior and optimal acceptor concentration. Finally, as the demonstration of ion sensing, FRET response toward different pH solutions (50 mM phosphate buffer containing 100 mM NaCl) was evaluated.

Results and Discussion

The molar ratio of phosphonium and dye in synthesized [P₆₆₆₁₄][HP-SO₃] was characterized as 1 : 1 (mol/mol) by ¹H NMR measurement. The fluorescence spectra of the PVC membrane containing acceptor showed FRET efficiency of close to 100% at 0.5 mol% of acceptor. From the fluorescence and excitation spectra, the amplification factor (AF) of acceptor fluorescence was calculated by equation (1) where I^ex_D and I^ex_A are fluorescence intensities at excitation wavelengths of donor and acceptor in the excitation spectrum of the PVC membrane without acceptor, I^ex_D-FRET and I^ex_A-FRET are those of the PVC membrane with acceptor, I^em_D and I^em_D-FRET are fluorescence intensities at the donor emission wavelength in the fluorescence spectra of the PVC membrane without or with acceptor, respectively[5]. In this case, AF was larger when smaller amounts of acceptor were doped. Especially, the largest AF (approximately 6) was obtained in the 0.01 mol% acceptor condition. That means the fluorescence intensity per an acceptor molecule was amplified 6-fold. On the other hand, fluorescence intensity (I_A) of acceptor calculated by equation (2) was the largest at the 0.5 mol% acceptor condition. Thus, 0.5 mol% acceptor condition was determined to be optimal donor and acceptor ratio (Figure 3). In this experiment, I_A was compared with that of conventional PVC membrane prepared with 2-nitrophenyl octyl ether (NPOE) as the plasticizer under the same membrane thickness condition (200 nm). As the result, FRET-based fluorescence of PVC membrane was larger than that of conventional one in all cases of acceptor concentration. Especially in 0.5 mol% acceptor condition, 12-fold fluorescence intensity was observed (Figure 3). That is supposed the change of fluorescence intensity between fluorescence on and off state is expanded to 12-fold when the chemical structure change of acceptor is caused by responding to analytes. Finally, proposed PVC membrane was applied for ion measurement in aqueous solutions. In fluorescence spectra under the several pH conditions, the obvious changes of spectra, which was obtained by highly-efficient FRET system, were successfully observed under the constant chloride concentration. In this case, spectral change was caused by coextraction of proton and chloride anion, and that result means the present FRET-based system can detect the very small amounts of acceptor molecules that change their molecular structure. Thus, FRET-based system proposed in this study is expected to improve the sensitivity of various PVC membrane-based optical sensors for ions, biomolecules and proteins.

References

[1] H. Hisamoto et al., Anal. Chem., 2004, 76, 3222.

[2] H. Hisamoto et al., Anal. Chim. Acta., 2006, 556, 164.

[3] S. Funano et al., Analyst, 2015, 140, 1459.

[4] T. Mizuta et al., Sens. Actuators B, 2018, 258, 1125.

[5] N. Melnychuk et al., J. Am. Chem. Soc., 2018, 140, 10856.

Figure 1

Introduction

Recently, conductive metal-organic frameworks (cMOFs), having electrical conductivity with ultra-high specific surface area, have attracted much attention in diverse applications. In particular, cMOFs are promising materials for gas sensors, because their high surface area facilitates surface reactions of gas molecules, which can be transduced by electrical signals. However, cMOFs-based gas sensors are still suffering from some challenges, such as low response and poor detection limits [1]. On the other hand, bimetallic nanoparticles (BNPs) are known to have superior activities for surface reactions than single-elemental counterparts. In this regard, we envisioned that ultra-small BNPs can be encapsulated in the cavities of cMOFs and these BNPs-decorated cMOFs (BNP@cMOFs) can exhibit exceptionally high surface reactivity with efficient electrical responses.

Here, for the first time, we report the combination of cMOFs with ultra-small BNPs in order to translate bimetallic synergies for surface reactions into cMOFs-based chemiresistors. As a proof of our concept, we fabricated 2 nm-sized Pt–Ru BNPs encapsulated in cMOFs (PtRu@cMOFs). PtRu@cMOFs-based sensors show hugely improved NO₂ sensing performances at room temperature in air, in terms of response, cross-selectivity, and detection limits.

Method

Cu₃(HHTP)₂, a typical cMOF, is prepared by hydrothermal method using copper(II) acetate and HHTP. The Cu₃(HHTP)₂ has numerous rigid pores with a diameter of 2 nm, which act as an encapsulation site for BNPs. Two kinds of metal precursors, RuCl₃ and K₂PtCl₄, are added in the suspension of Cu₃(HHTP)₂ in deionized water. Then, the suspension is stirred for 30 min to bind heterogeneous metal ions with the cavities of Cu₃(HHTP)₂. The metal ions are electrostatically bound to oxygen groups in HHTP of Cu₃(HHTP)₂. Subsequently, the metal precursors are reduced with sodium borohydride (NaBH₄), resulting in ultra-small (~2 nm) PtRu BNPs encapsulated in the cavities of Cu₃(HHTP)₂. The prepared PtRu@cMOFs are used as a chemiresistor for NO₂ detection, in order to utilize bimetallic synergies in Pt–Ru nanocatalysts for chemiresistive sensing.

Results and Conclusions

We investigated the morphology of PtRu NPs in PtRu@cMOFs by using transmission electron microscopy (TEM) analysis. TEM image showed that ~2 nm PtRu NPs were well dispersed in the cMOF-matrix. X-ray photoelectron spectroscopy (XPS) analysis was conducted to confirm the formation of Pt–Ru BNPs. In the region of Pt and Ru spectra, PtRu@cMOFs display shifts of Pt⁰ 4f and Ru⁰ 3p peaks compared to monometallic counterparts. As reported in previous literature, these peak shifts indicate the interaction between atomic Pt and Ru in bimetallic Pt–Ru, demonstrating the formation of Pt–Ru BNPs in cMOFs.

To investigate bimetallic synergy of Pt–Ru BNPs in cMOFs-based chemiresistive sensing, the resistance changes (ΔR/R₀) of PtRu@cMOFs in response to exposures of NO₂ 2 ppm are compared with those of pristine cMOFs, Ru@cMOFs, and Pt@cMOFs. Importantly, PtRu@cMOFs showed hugely improved NO₂ responses compared to pristine cMOFs, Pt@cMOFs, and Ru@cMOFs, demonstrating the superior catalytic effect of Pt–Ru BNPs on NO₂ sensing. Responses of PtRu@cMOFs-based sensors were measured in 0.2–3 ppm of NO₂. The sensors showed high responses of 46.8% to 1 ppm, which is the regulatory permissible NO₂ exposure limit designated by the occupational safety and health administration (OSHA) in U.S.A. Moreover, PtRu@cMOFs exhibited 8-fold higher responses to NO₂ than other analytes, demonstrating the ultrahigh cross-selectivity. Furthermore, PtRu@cMOFs showed superior sensing response compared to the state-of-art NO₂ sensors in air at room temperature.

In conclusion, we have demonstrated the synthesis of BNPs embedded in cMOFs, which have superior NO₂ sensing performances. The cavities of cMOFs do not only act as a binding site of metal precursors but also suppress the growth of BNPs during the chemical reduction, generating ultra-small (~ 2nm) PtRu BNPs in cMOFs. PtRu@cMOFs exhibit greater NO₂ responses compared to their monometallic counterparts. These outstanding sensing performances are attributed to the bimetallic synergies of Pt and Ru in Pt–Ru BNPs with highly porous and conductive matrix. Our approaches provide general and facile methods to create various beneficial BNPs in versatile cMOFs [2].

References

[1] Campbell, M. G., Liu, S. F., Swager, T. M., Dincă, M. Chemiresistive sensor arrays from conductive 2D metal–organic frameworks. J. Am. Chen. Soc. 137, 13780–13783 (2015).

[2] Xu, C., Wang, L., Mu, X., Ding, Y. J. L. Nanoporous PtRu alloys for electrocatalysis. Langmuir 26, 7437–7443 (2010)

The stability of gold surfaces modified with DNA self assembled monolayers has drawn increasing attention as the lifespan of the created sensors is an important consideration for biosensor development and applications.^1–4 In this study, we investigated the thermal stability of a mixed self assembled monolayer (SAMs) composed of a short alkythiol and alkythiol modified DNA immobilized on a single crystal gold bead electrode at either open circuit potential (OCP) or by electrodeposition.^5,6 Using in-situ fluorescence microscopy and electrochemical measurements, different SAMs with varied surface properties were studied, and the relative stability towards increasing temperatures was evaluated. The results show that the stability strongly depends on the preparation method, the DNA coverage and on the underlying surface crystallography. The single crystal bead electrode enabled study of a number of surface crystallographies in a self-consistent manner. For the surfaces made without potential control, the {111} regions were the least thermally stable surface and completely desorbed from the gold surface after heating to 85 °C in some cases. On the other hand, {100} is the most stable region on which SAMs can survive higher than 85 °C in buffer. The {110}, {210} and {311} surfaces were also studied. The surfaces with hexagonal symmetry were less stable than those with square or rectangular symmetry. The different methods used to prepare the DNA SAM also showed significant changes in the stability. In general, SAMs made with potential assisted deposition showed higher stability than those made at OCP. This unique finding can be used to comment on typical sensor surface which are polycrystalline flat gold surfaces composed of a variety of grains and grain boundaries. These results may help to explain the irreproducible results from the DNA SAMs and such as the reported inconsistent results during DNA mismatch discrimination while the solution was heated during experiment.⁷ Modifying the method used to prepare the DNA SAMs and carefully controlling the composition of the gold substrate may result in significant improvements in the SAM stability. Moreover, increasing the thermal stability will result in longer term storage stability.^8,9

References

(1) Brittain, W. J.; Brandsetter, T.; Prucker, O.; Rühe, J. ACS Appl. Mater. Interfaces

2019, 11, 39397–39409.

(2) Civit, L.; Fragoso, A.; O'Sullivan, C. K. Electrochem. commun. 2010, 12, 1045–1048.

(3) Flechsig, G. U.; Peter, J.; Hartwich, G.; Wang, J.; Gründler, P. Langmuir 2005, 21,

7848–7853.

(4) Ge, D.; Wang, X.; Williams, K.; Levicky, R. Langmuir 2012, 28, 8446–8455.

(5) Leung, K. K.; Gaxiola, A. D.; Yu, H.-Z.; Bizzotto, D. Electrochim. Acta 2018, 261,

188–197.

(6) Yu, Z. L.; Casanova-Moreno, J.; Guryanov, I.; Maran, F.; Bizzotto, D. J. Am. Chem.

Soc. 2015, 137, 276–288.

(7) Xu, X.; Makaraviciute, A.; Kumar, S.; Wen, C.; Sjödin, M.; Abdurakhmanov, E.; Danielson,

U. H.; Nyholm, L.; Zhang, Z. Anal. Chem. 2019, 91, 14697–14704.

(8) McAteer, K.; Simpson, C. E.; Gibson, T. D.; Gueguen, S.; Boujtita, M.; El Murr, N. J.

Mol. Catal. - B Enzym. 1999, 7, 47–56.

(9) Young Choi, J.; Yang, I. M. Pharm. Anal. Acta 2016, 07 .

Figure 1

Figure 1

Föster Resonance Energy Transfer (FRET) is a powerful technique used to probe close-range molecular interactions. Physically, the FRET phenomenon manifests as a dipole–dipole interaction between closely juxtaposed fluorescent molecules (10–100 Å). For instance, after photoexcitation, a fluorophore may de-excite through direct emission with a bathochromic spectral shift. However, in the presence of a nearby acceptor, the donor non-radiatively transfers energy to the acceptor molecule, resulting in quenched donor fluorescence. With the advent of genetically encoded fluorescent molecules, this method has found widespread biological applications as a spectroscopic atomic-scale ruler, biochemical reaction kinetics and chemical sensor. [1] Our effort is to employ this FRET technique to make a prototype device for highly sensitive detection of environment pollutant.

Among the most common environmental pollutants, nitroaromatic compounds (NACs) are of particular interest because of their durability and toxicity. That's why, sensitive and selective detection of small amounts of nitroaromatic explosives, in particular, 2,4-dinitrotoluene (DNT), 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenol (TNP) has been a key challenge due to the increasing threat of explosive-based terrorism and the need of environmental monitoring of drinking and waste water. In addition, the excessive utilization of TNP in several other areas such as burn ointment, pesticides, glass and the leather industry resulted in environmental accumulation, and is eventually contaminating the soil and aquatic systems. To the date, A great number of elegant methods, including fluorimetry, gas chromatography, mass, ion-mobility and Raman spectrometry have been successfully applied for explosive detection. Among these efforts, fluorescence-quenching methods based on the mechanism of FRET show good assembly flexibility, high selectivity and sensitivity. [2]

Recently, our group has reported a highly fluorescent dansyl copolymer poly[(Methyl methacrylate)-co-(Dansyl-alanine methacryloyloxyethyl ester)], P[(MMA-co-(Dansyl-Ala-HEMA)], DCP for sensitive detection of NACs. [3] Here our alternative approach to increase fluorescence sensing efficiency by exciting the fluorophore DCP through Förster resonance energy transfer (FRET). In this paper, we report a polymer-polymer FRET-based sensor system for the highly selective detection of NACs, such as TNP, DNT and TNT. The sensor system is composed of a copolymer Poly[(N,N-dimethylacrylamide)-co-(Boc-Trp-EMA)] (RP) bearing tryptophan derivative in the side chain as donor and dansyl tagged copolymer P(MMA-co-Dansyl-Ala-HEMA) (DCP) as an acceptor. Initially, the inherent fluorescence of RP copolymer is quenched by non-radiative energy transfer to DCP which only happens once the two molecules are within Förster critical distance (R₀). The excellent spectral overlap (J_λ= 6.08×10¹⁴ nm⁴M^-1cm^-1) between donors' (RP) emission profile and acceptors' (DCP) absorption profile makes them an exciting and efficient FRET pair i.e. further confirmed by the high rate of energy transfer from RP to DCP i.e. 0.87 ns^-1 and lifetime measurement by time correlated single photon counting (TCSPC) to validate the 64% FRET efficiency. This FRET pair exhibited a specific fluorescence response to NACs such as DNT, TNT and TNP with 5.4, 2.3 and 0.4 mM LODs, respectively. The detection of NACs occurs with high sensitivity by photoluminescence quenching of FRET signal induced by photo-induced electron transfer (PET) from electron-rich FRET pair to electron-deficient NAC molecules. The estimated stern-volmer constant (K_SV) values for DNT, TNT and TNP are 6.3 × 10³, 7.6 × 10³ and 2.2 × 10⁴ M^-1, respectively, this is approximately 6 orders of higher magnitude than the previous report. [3] The mechanistic details of molecular interactions are established by time-resolved fluorescence, steady state fluorescence and absorption spectroscopy confirmed that the sensing process is of mixed type, i.e. both dynamic and static quenching as lifetime of FRET system (0.73 ns) is reduced to 0.55, 0.57 and 0.61 ns DNT, TNT and TNP, respectively.

Consequently, our results suggest a promising and potential approach to use FRET- and PET-based fluorescent probe to detect NACs with higher sensitivity. It's simple and rich methodology opens up the possibility of designing optical sensor of various NACs in one single platform for designing multimodal sensor for environmental monitoring and future field based study.

Reference:

1. Jares-Erijman, E.A. et al. Nat. Biotechnol. 2003, 21, 1387.

2. Sun, X. et al. Chem. Soc. Rev. 2015, 44, 8019.

3. Kumar, V. et al.Sci. Rep. 2019, 9 (1), 7269.

Figure 1

Electrocatalytic performance of metal nanoparticles (NPs) has been studied to apply for electrochemical devices such as fuel cells and electrochemical sensors. We have developed metal NPs embedded carbon film electrodes by co-sputtering of metal and carbon [1]. Various kinds of metals including Pt, Pd, Au, Ni, Cu and their alloys can be fabricated in the carbon film by using unbalanced magnetron (UBM) sputtering and applied for detecting hydrogen peroxide, glucose [1], heavy metals [2,3] and sugar markers [4, 5]. The electrocatalytic activity of metal NPs can be modulated by changing electronegativity of neighbor materials. Here, we proposed two electrode structures to modulate the electrocatalytic activity of metal NPs by forming metal NPs on hybrid carbon film electrodes, The electrodes were then applied applied for detecting small organic molecules such as alcohols and sugars.

The first electrode structure is Ni(OH)₂ NPs electrodeposited on the surface of nitrogen terminated carbon film electrodes. The carbon film was formed by UBM sputtering and the surface was treated by N₂ plasma. After treatment, the NiNPs were electrodeposited by applying negative potential(Fig.1 left figure of Electrode Fabrication). The size of NiNPs became smaller by decreasing potential from -1000 to -1300 mV. By taking account of this property, we adjusted the potential to obtain similar NiNPs size on both N₂ plasma treated and untreated carbon surfaces. After deposition, the potentials of both electrodes were cycled between 0 and 0.70 V (vs Ag/AgCl) to form surface Ni(OH)₂. The redox reaction peaks of Ni(OH)₂ oxidation and NiOOH reduction shifted positive and negative directions, respectively at Ni(OH)₂ modified untreated carbon film(Fig.1 centor figure of Electrode Fabrication). with increasing potential scan rate. In contrast , peak separation increase at Ni(OH)₂ modified N₂ plasma treated carbon film is greatly decreased suggesting fast redox reaction. We applied both electrodes for electrocatalytic oxidation of glucose in alkaline media(Fig.1 left of Applications). The oxidation current of glucose at Ni(OH)₂ modified N₂ plasma treated carbon film electrode shows much larger current than that at Ni(OH)₂ modified N₂ untreated carbon film electrode. The current of former electrode continued to slightly increase when the glucose concentration is around 7 mM. In contrast, the current of latter electrode was saturated below 3 mM.

The other structure we proposed was fabricated by electroplating the Ni onto PdNPs or AuNPs embedded carbon film electrodes. By using the overpotential difference between PdNPs and carbon surface, we successfully electrodeposited NiNPs selectively only on the embedded PdNPs, resulting Ni-Pd heterodimer structure on the electrode surface(Fig.1 right of Electrode Fabrication). The average size of deposited NiNPs onto PdNPs is smaller than that deposited on the pure carbon film electrode because the embedded PdNPs worked as growth core of NiNPs. We cycled the potential in strong alkaline solution to form Ni(OH)₂ on the surface of NiNPs. The oxidation peak potential of Ni(OH)₂ /Pd heterodimers, which corresponds to surface NiOOH formation reaction, slightly increases with increasing the scan rates from 1 mV/s to 100 mV/s. In contrast, the oxidation peak potential of Ni(OH)₂ NP modified pure carbon film(Fig.1 center figure of Electrode Fabrication) shifted more positively (about 0.2 V) with increasing the scan rate, which suggests that the oxidation and reduction cycle of Ni(OH)₂ /Pd heterodimer is much faster than that of Ni(OH)₂ NP. Both electrodes were applied to electrochemically oxidize methanol. When the concentration of methanol is below 1M, the sensitivity of Ni(OH)₂ NP modified carbon film electrode is relatively higher than that at Ni(OH)₂ /Pd heterodimer modified carbon film electrode. However, the curent at Ni(OH)₂ /Pd heterodimer modified electrodes was superior to that at Ni(OH)₂ NP modified electrode when the methanol concentration was higher than 1 M (Fig.1 right figure of Applications). This could be due to the fast regeneration of catalytic sites (NiOOH) resulting in higher turnover rates for methanol oxidation reaction. The above behavior of Ni(OH)₂ /Pd heterodimer modified carbon film electrode could be more suitable for energy device such as fuel cell electrode and Ni(OH)₂ modified carbon film electrode is more suitable to detect alcohol sensing electrode.

In conclusion, the electrocatalytic activity of NiNPs can be largely modulated by changing substrates, suggesting that the design of electrode surfaces are very important to realize high performance electrodes for chemical sensors.

References

[1] T. You, O. Niwa, M. Tomita, S. Hirono," Characterization of platinum nanoparticle- embedded carbon film electrode and its detection of hydrogen peroxide", Anal. Chem.,75 (2003) 2080.

[2] D. Kato, T. Kamata, D. Kato, H. Yanagisawa, O. Niwa, "Au nanoparticle-embeded carbon films for electrochemical As³⁺ detection with high sensitivity and stability", Anal. Chem., 88 (2016) 2944.

[3] S. Shiba, S. Takahashi, T. Kamata, H. Hachiya, D. Kato, O. Niwa, "Selective Au Electrodeposition on Au Nanoparticles Embedded in Carbon Film Electrode for Se(IV) Detection" Sensors and Materials., 31 (2019) 1135.

[4] S. Shiba, D. Kato, T. Kamata, O. Niwa," Co-sputter deposited Nickel-Copper bimetallic nanoalloy embedded carbon films for electrocatalytic biomarker detection", Nanoscale, 8 (2016) 12887.

[5] S. Shiba, R. Maruyama, T. Kamata, D. Kato, O. Niwa, "Chromatographic determination of sugar probes used for gastrointestinal permeability test by employing nickel-copper nanoalloy embedded in carbon film electrodes", Electroanalysis, 30 (2018) 1407.

Figure 1

There is an increasing need for on-site and real-time analyses of complex gas mixtures in many application fields such as industry, air quality, security and medicine. One challenge consists in developing complete and portable multi-gas analysis systems allowing in situ and real-time quantitative analysis of complex gas mixtures. A promising approach is based on the integration of resonating devices on silicon chips by using "standard" microelectronic technologies. The fabrication of these gravimetric gas sensors based on Nano Electro Mechanical System (NEMS) requires the use of a chemical sensitive layer to ensure a better collection and concentration of the target molecules. This enhances the sensitivity in conjunction with the limit of detection. The integration of a chemical sensitive layer on to NEMS fabricated on Si wafers leads to specific material requirements.

• The use of solvent is prohibited in order to avoid the degradation of the Si nanocantilevers due to capillarity forces,

• Very thin film thickness (less than few hundred of nanometers) should be deposited on the Si beam in order to avoid filling the gap between the resonant cantilever and the electrodes,

• The deposition technique should provide good uniformity over a large surface (typically on 200 mm Si wafers) for a collective sensor fabrication.

• And the material should be optimized to absorb the highest level of targeted gas for a given thickness, reversibly and quickly.

In this work, the objective was to develop materials deposited using microelectronic compatible techniques in order to detect light alkanes and aromatic volatile organic compounds such as BTEX (for Benzene, Toluene Ethylbenzene and Xylene). Organosilicate materials are potentially good candidates for this application especially because they are nonpolar or weakly polar materials. In order to better understand the impact of the material chemistry on the detection of hydrocarbon gas and optimize the sensitivity of the chemical layer, a large panel of organosilicate thin films were deposited by different chemical vapor deposition (CVD) techniques. First, SiOCH were deposited by Plasma Enhanced Chemical Vapor Deposition (PECVD), this technique being the most used in the microelectronic industry for dielectric thin-film deposition. Several precursors (diethoxymethylsilane, trimethylsilane or octamethyltrisiloxane) and deposition conditions were used in order to vary their chemical composition and their physical properties. In these SiOCH, the carbon content is mainly under the form of methyl groups bonded to silicon. At the same time, to allow a better flexibility in term of chemical functions, filament assisted chemical vapor deposition (FACVD) was used for the deposition of organosilicate thin films. Indeed, FACVD allow a better control over the precursor fragmentation pathway in comparison to plasma-based techniques. Then, it is possible to add polar groups (such as ethoxy to in case of FACVD of methyltriethoxysilane) or to introduce siloxane rings in the materials (in case of initiated CVD of cyclosiloxane). Finally, the introduction of additional porosity was investigated as another way to potentially improve the sensitivity of the chemical sensitive layers. By using a porogen approach, it is possible to introduce up to 40 % porosity in a PECVD SiOCH. Using a foaming approach, we can go even further (> 50 %). Film properties after deposition and after potential annealing were investigated using multiple characterization techniques (ellipsometry, FTIR and Tof-SIMS). Porosity was characterized by ellipsometric porosimetry and grazing incidence small angle X-ray Scattering. In these material, pores (if any) are nanometrics and porosity is mainly open and interconnected. Thin film response under toluene or pentane exposures was studied using Quartz Crystal Microbalance functionalized with the different SiOCH.

Through the synthesis and characterization of these various SiOCH thin films, the role of hydrophobicity, carbon content and specific chemical bonding can be highlighted. It is shown that the hydrophobic nature of SiOCH materials composed of a Si-O-Si backbone with methyl groups bonded to silicon, combined with the presence nanoporosity, lead to very high sensibility. The presence of isolated polar bonds such as ethoxy groups seems beneficial especially for BTEX detection. High partition coefficients toward toluene and pentane can be obtained, at least ten time higher than those measured on more classical polymers such as PDMS. Both deposition techniques (PECVD or FACVD) are able to produce good chemical sensitive layers for the detection of light alkanes and aromatics VOCs and these organosilicates constitute promising solution for the functionalization of NEMS-based gas sensors.

Acknowledgment: Developments on FACVD were performed in the frame of a collaboration with TEL, US-Technology Development Center, America.

Introduction

Ammonia (NH₃), a major industrial commodity (142 Mt in 2017 [1]), is toxic as well as a tracer for food spoilage detection and important breath marker for impaired kidney function [2]. As a result, there is a strong interest in selective sensors that detect NH₃ concentrations over a large range: from 250 to 2900 ppb in mouth-exhaled breath down to few ppb in indoor air at high relative humidity. Also, it occurs usually in gas mixtures containing a myriad of compounds requiring also high NH₃ selectivity. Most promising as a solid-state and low-cost sensor material is CuBr featuring high selectivity and sensitivity to low NH₃ concentrations (e.g. 20 ppb [3]) even at room temperature. However, current fabrication methods usually result in micro-sized CuBr particles [3] and rather dense film morphologies [4] that could impede efficient NH₃ diffusion in the film and interaction with the CuBr surface. Here, we introduce a novel fabrication route yielding highly porous and nanostructured CuBr films for improved NH₃ sensitivity and fast response dynamics at room temperature.

Methods

Porous and nanostructured CuBr films are obtained by a flame-aerosol based method on interdigitated electrodes. Their sensing performance was evaluated at room temperature in gas mixtures prepared with high-resolution mass flow controllers, as described in detail elsewhere [5]. In brief, analyte gases (i.e. NH₃, isoprene, ethanol, methane, acetone, hydrogen, acetic acid, methanol, formaldehyde and CO) were supplied from calibrated cylinders (10 or 50 ppm in synthetic air, PanGas) and dosed to dry synthetic air (Pangas 5.0, C_nH_m and NO_x ≤ 100 ppb) with calibrated mass flow controllers. Humidity was added by bubbling dry synthetic air through distilled water and admixing it to the analyte flow. All transfer lines were made of inert Teflon to minimized analyte gas adsorption and heated to 55 °C to avoid water condensation. The sensor film resistance was continuously monitored with a multimeter (Keithley, Integra Series 2700, USA).

Results and Conclusions

The porous CuBr films were tested for sensing of 5 - 5000 ppb NH₃ at 90% RH (Figure 1a). When exposed to 5000 ppb of NH₃, the resistance rapidly increases from 47 kΩ to 13 MΩ corresponding to a response (S) of 276. When exposed to NH₃, the Cu⁺ as charge carriers are immobilized by forming that results in the observed resistance increase. Remarkably, this interaction is rapid and reversible even at room temperature, as indicated by the full recovery of the initial resistance baseline (dashed line, Figure 1a) and in line with literature [3]. Most impressively, NH₃ concentrations down to 5 ppb (see also inset of Figure 1a for higher magnification) are detected and can be distinguished clearly from 10 and 20 ppb. The signal-to-noise-ratio (SNR, > 70) is remarkable and should enable the detection of even lower concentrations with an extrapolated lower limit of detection (LOD) of 210 parts-per-trillion (ppt) considering a typical SNR of 3. This is superior to state-of-the-art room temperature NH₃ sensors: For instance, polyaniline sensors detect 40 ppb NH₃ at ≥ 90% RH [6], but these are usually for single-use only as they recover too slowly.

The porous CuBr sensor was tested with isoprene, ethanol, methane, acetone, hydrogen, acetic acid, methanol, formaldehyde and carbon monoxide (CO), all at a concentration of 1 ppm and 90% RH (Figure 1b). Most remarkably, the sensor responds strongest to NH₃ with selectivity > 30 with CO being the highest one (> 290). This is similar to thermally deposited CuBr films with a CeO₂ overlayer [3] for some of these analytes. Other NH₃ sensors feature lower selectivities to these analytes. In fact, polymer-based PEDOT:PSS nanowires [7] are quite sensitive to ethanol (NH₃ selectivity ~15 vs. CuBr ~40).

In conclusion, such nanostructured and porous CuBr films are quite attractive for wearable breath analyzers [8] and detectors for distributed air and food quality monitoring networks with stringent power requirements.

References

[1] United States Geological Survey: Mineral Commodity Summaries - Nitrogen Statistics and Information, 2019.

[2] Davies, S.; Spanel, P.; Smith, D., Quantitative analysis of ammonia on the breath of patients in end-stage renal failure. Kidney Int., 52 (1997) 223-228.

[3] Li, H.-Y.; Lee, C.-S.; Kim, D. H.; Lee, J.-H., Flexible Room-Temperature NH3 Sensor for Ultrasensitive, Selective, and Humidity-Independent Gas Detection. ACS Applied Materials & Interfaces, 10 (2018) 27858-27867.

[4] Bendahan, M.; Lauque, P.; Seguin, J.-L.; Aguir, K.; Knauth, P., Development of an ammonia gas sensor. Sens. Actuators B, 95 (2003) 170-176.

[5] Güntner, A. T.; Righettoni, M.; Pratsinis, S. E., Selective sensing of NH₃ by Si-doped α-MoO₃ for breath analysis. Sens. Actuators B, 223 (2016) 266-273.

[6] Hibbard, T.; Crowley, K.; Kelly, F.; Ward, F.; Holian, J.; Watson, A.; Killard, A. J., Point of Care Monitoring of Hemodialysis Patients with a Breath Ammonia Measurement Device Based on Printed Polyaniline Nanoparticle Sensors. Anal. Chem., 85 (2013) 12158-12165.

[7] Tang, N.; Zhou, C.; Xu, L.; Jiang, Y.; Qu, H.; Duan, X., A Fully Integrated Wireless Flexible Ammonia Sensor Fabricated by Soft Nano-Lithography. ACS Sens., 4 (2019) 726-732.

[8] Güntner, A. T.; Abegg, S.; Königstein, K.; Gerber, P. A.; Schmidt-Trucksäss, A.; Pratsinis, S. E., Breath Sensors for Health Monitoring. ACS Sens., 4 (2019) 268-280.

Figure 1

Detection of different gases in power transformer oil is essential to accurately examine and understand different problems and faults in the transformer system. Especially, during situations like corona discharge and arcing, evolution of hydrogen gas can be hazardous due to its highly flammable and explosive nature. Therefore, development of high-performance gas sensors targeted for hydrogen gas over a wide range of concentrations is very important.

We suggest a facile and effective fabrication method of hydrogen sensing composite material based on palladium and nickel alloy with nanofiber structures originated from electrospinning. PdNi alloy, with further decoration with platinum nanoparticles as catalysts via apo-ferritin templating, shows greatly enhanced sensitivity and response time. Conventionally, Palladium is widely used as hydrogen sensors due to its well-known phase transition to PdH_x, α-PdH_x at hydrogen concentration below 1%, and β-PdH_x at hydrogen concentration above 2%. However, huge volume expansion associated from this transformation limits its lifetime and reduces its long-term performance. In this work, nickel alloying effectively decreases the lattice parameters of the alloy, while increasing the stability during repetitive exposure to high concentration to hydrogen gas. Furthermore, formation of grain boundaries to compensate the lattice contraction induced by nickel alloying, high surface area from its nanofiber structure and gas dissociation and activation properties of platinum nanoparticles improves the sensor's sensitivity toward hydrogen gas [1]. Nickel in the lattice also acts as pinning points to effectively suppress the grain growth of the alloy during high temperature annealing and reduction processes, which further improves its sensitivity and response time. This facile fabrication and decoration methods allow us to produce a highly sensitive and rapidly responding hydrogen gas sensor with enhanced long-term stability compared to the conventional Pd based hydrogen gas sensors.

Reference

[1] D. H. Kim, ACS Nano 13, 6071–6082 (2011); doi:10.1021/acsnano.9b02481

Introduction

The early detection of explosive gas atmospheres is highly relevant for industrial process measurement technology and avoids the endangerment of people. In the field of safety technology, catalytic combustion sensors, so-called »pellistors«, are used to detect flammable gases such as hydrocarbons or hydrogen. Pellistor sensors measure the heat produced from catalytic oxidation of the gas by detecting the resistance alteration of a Pt-based heater induced by temperature changes using a Wheatstone bridge circuit. The heat generated is related to the kind and concentration of gas by specific combustion enthalpy [1]. The major advantages of catalytic sensors are simple operation principle, easy installation and calibration. However, state-of-the-art pellistors have some disadvantages, such as high operation temperatures of over 400°C, high-power consumption and high susceptibility to catalyst poisons. High-power consumption limits the usage of pellistors in mobile applications because of the short battery lifetime. Reducing operating temperature will contribute to decrease the power consumption.

The primary gas recognition element of the pellistor is the catalytic layer. To reduce the operation temperature high active catalysts are required. Especially for detection of methane, which is one of the most inert combustible gases, catalysts of high activity or particularly high working temperatures of at least 450°C are mandatory. For this reason, a reliable detection of methane is the most important challenge. Catalysts implemented in nowadays pellistors were developed already in 1960s and contain Pd or/and Pt nanoparticles stabilized on a porous metal oxide support in its active chemical and physical state. Alumina and, to a lesser extent, zirconia are commonly used due to its high surface area and thermal stability [2]. However, some reports show that the application of metal oxides like CeO₂ as support can lead to an improved sensor performance due to high oxygen storage and release ability [3]. The researches in the field of catalytic combustion provided many further evidences that especially metal oxides with spinel structures as Co₃O₄, Ni_xCo_3-xO₄, Co_3-xCu_xO₄, Co_3-xZn_xO₄ etc., can contribute to catalytic combustion of methane and therefore considerably decrease the temperature for catalytic reaction [4]. New catalysts have the potential to considerably improve the performance of pellistors.

This research focuses on the development of alternative, highly active catalysts based on spinels for catalytic detection of methane in the low-temperature range. Catalytic activity was investigated by Simultaneous Thermogravimetry-Differential Thermal Analysis (TG-DTA, termed as STA) coupled with Quadrupole Mass Spectrometer (STA-QMS).

Method

STA (NETZSCH, STA 409 CD-QMS 403/5 SKIMMER) is a calorimetric method to monitor the heat consumption (endothermic) or release (exothermic DTA signal) occurring by different processes. Heat release during exothermic oxidation reaction is measured by comparison the temperature of sample placed in an alumina crucible with that of reference crucible after calibration and signal normalization. In contrast to a pellistor, in which each element of the sensor including electronics, contacts and catalytic layer, etc. influences the formation of the sensing signal, STA shows unaffected thermal signal originating from catalytic reaction. Additionally, the complex preparation steps as in case of pellistor can be avoided. Thermal analysis like DSC [5] and DTA ensure comparable conditions for appropriate testing and investigation of different catalytic materials. QMS allows the analysis of gaseous residues and reaction products by ionization.

For catalyst investigation, Co₃O₄ spinel doped with nickel (synth. NiCo₂O₄) and palladium (4wt% Pd/synth. Co₃O₄) were synthesized according to [4]. For comparison, commercial Co₃O₄ (comm. Co₃O₄) was used.

Results and Conclusions

Co₃O₄ spinel and his derivatives have been chosen for the investigation of catalytic activity. The thermal behavior of investigated oxides in synthetic air (reference) and in 1 vol% CH₄ is shown in Fig. 1a. The mass spectrum presented for mass ion m/z of 44 for NiCo₂O₄ (Fig. 1b) confirms the CO₂ evolution by CH₄ injection into the chamber as a result of catalytic reaction.

Figure 1: (a) DTA signal of four investigated catalysts at four temperatures (red line) measured successively in synthetic air (gray background) and 1vol% CH₄ (green background); (b) simultaneously recorded mass spectrum (STA-QMS) of mass ion 44 from the NiCo₂O₄ sample.

Spinel NiCo₂O₄ and 4wt% Pd/synth. Co₃O₄ (Fig. 1a) reveal first traces of activity already at 250°C, while undoped commercial Co₃O₄ shows a minor signal at 300°C first. Certainly, with temperature increasing the behavior changes. Consequently, NiCo₂O₄ is a preferred catalyst for low operation temperature. It shows higher activity at lower temperatures, whereas at higher temperatures (450°C) Pd doped Co₃O₄ catalysts prevail in catalytic activity.

Especially doped NiCo₂O₄ spinel exhibited excellent catalytic activity towards methane oxidation. The structure-properties relation will be presented and discussed.

References

[1] J.B.Miller, Catalytic Sensors for Monitoring Explosive Atmospheres. IEEE Sens J. 1 (2001) 88–93. doi:10.1109/JSEN.2001.923591

[2] G.Korotcenkov, Handbook of Gas Sensor Materials; Springer, Vol. 1 (2014). doi.org:10.1007/978-1-4614-7165-3

[3] Y.Wang, M.M.Tong, D.Zhang, Z.Gao, Improving the Performance of Catalytic Combustion Type Methane Gas Sensors Using Nanostructure Elements Doped with Rare Earth Cocatalysts. Sensors. 11 (2011) 19–31. doi:10.3390/s110100019.

[4] F.Tao, J.Shan, L.Nguyen, et al. Understanding complete oxidation of methane on spinel oxides at a molecular level. Nat Commun. 6 (2015) 7798. doi:10.1038/ncomms8798

[5] J.Loskyll, W.F.Maier, K.Stoewe. Application of a Simultaneous TGA-DSC Thermal Analysis System for High-Throughput Screening of Catalytic Activity. ACS Comb. Sci. 14 (2012) 600−604. doi:10.1021/co3000659.

Figure 1

We study the electrical characterization at room temperature (RT) of black phosphorus nanoflakes decorated with nickel nanoparticles (Ni/bP). The latter has been exposed to different concentrations of NO₂ at RT in a dry air environment highlighting fast and stable response over the time. This latter characteristic is particularly relevant since environmental instability of exfoliated BP has been an issue so far, under ambient conditions few-layer BP degrades completely in less than a week, preventing its applications in several fields.

Introduction

In the rapidly emerging field of layered two-dimensional (2D) functional materials, bP, the all P-counterpart of graphene, is a potential candidate for various applications e.g., nanoscale optoelectronics, rechargeable ion batteries, electrocatalysts, thermoelectrics, solar cells, and sensors [1]. bP has been reported to exhibit superior chemical sensing performance. In particular, bP is selective for the detection of paramagnetic molecules, e.g., NO₂, in addition to high sensitivity at a limit of detection (LOD) of ppb levels.[2] In this work, by applying a multiscale characterization approach we demonstrated a stability and functionality improvement of Nickel-decorated bP (Ni/bP) films for gas sensing prepared by a simple, reproducible and affordable deposition technique. Furthermore, we studied possible electrical activity of these films for their employment as functional layers in gas sensors by exposing them to different gaseous compounds (NO2, CO2, H2, NH3, CO, Benzene, etha-nol, ethylene, Formaldehyde) in different relative humidity (RH%) conditions. Moreover, the influence in sensing perfor-mance of nickel nanoparticle (NP) dimensions in related to the decoration technique and the film thickness were investigated.

Materials and Methods

Black phosphorus microcrystals were suspended in dimethylsulfoxide and kept under ultrasonication for several hours. The exfoliated bP nanosheets were decorated with nickel nanoparticles following two different procedures: 1) preformed Ni NPs were immobilized on bP, 2) Ni NPs were grown directly on bP flakes. Electrical conductance measurements have been performed on Ni/bP flakes deposited via spin coating on Al₂O₃ substrates with built-in interdigitated gold electrodes, in order to better control the film thickness. Electrical conductance measurements have been performed at RT (25±2°C) by exposing the sensing film to certified mixtures of NO₂ diluted in dry air (20% O₂ and 80% N₂) with different NO₂ concentration ranging from 200 ppb to 1 ppm.

Results and Conclusions

Exfoliated black phosphorus nanoflakes decorated with nickel nanoparticles (Ni/bP) have been prepared and characterized with particular attention to the role of Ni nanoparticle dimension in the sensing mechanism. Electrical activity towards different concentrations of NO₂ at room temperature in a dry air environment highlighted fast and stable response over the time. This latter characteristic is particularly relevant since environmental instability of exfoliated BP has been an issue so far, under ambient conditions few-layer bP degrades completely in less than a week, preventing its applications in several fields. In situ grown Ni/bP (2) shows stable response during all the four weeks measurements period with no dependence of the response on the film thickness. Ni decoration effectively suppress ambient degradation, for at least 1 week in Ni/bP (1) and over 4 weeks in Ni/bP (2) in ambient conditions. This result highlighted that Ni/bP (2) sensor can be practically used under ambient conditions for a reasonable period without performance degradation of the devices.The obtained results pave the way for the use of chemically exfoliated bP flakes for gas sensing applications, avoiding the use of a time-consuming technique for the exfoliation and for the fabrication of the metallic contacts, like electron beam lithography, focused ion beam lithography, etc.

References

[1] Batmunkh, M.; Bat-Erdene, M.; Shapter, J. G. Phosphorene and Phosphorene-Based Materials - Prospects for Future Applications. Adv. Mater. 2016, 28, 8586– 8617.

[2] Donarelli, M.; Ottaviano, L.; Giancaterini, L.; Fioravanti, G.; Perrozzi, F.; Cantalini, C. Exfoliated black phosphorus gas sensing properties at room temperature. 2D Mater. 2016, 3, 025002

Figure 1: (a) Electrical characterization at room temperature of bP, Ni/bP (1) and Ni/bP (2) devices in dry conditions with five different concentration of NO2. (b) Calibration curve of Ni/bP based sensors in dry condition.

Figure 1

Introduction

Metal sulfides have been proved to be highly sensitive to low concentration NO₂ due to their unique structure and electrical properties, among which SnS₂ has been widely studied to make use of its narrow band gap, large surface-to-volume ratio and large electronegativity. However, it has been proved that the low sensitivity of pure SnS₂ to NO₂ at the room temperature is still far from sufficient practical values. Therefore, the fabrication of nanocomposites based on SnS₂ with heterojunctions have been studied as promising candidate materials for gas sensors with practical applications. For instance, Gu and his coworkers reported that the sensing properties of formed SnO₂/SnS₂ nanohybrids improved obviously compared with commercial pristine SnS₂ nanosheets and Hao further promoted the progress by decorating the surface of SnS₂ nanoflowers with SnO₂ nanoparticles.

Under the inspiration from the above studies, herein cerium was later introduced into the one-step synthesis process of SnS₂/SnS heterostructures to effectively modulate the sensing property. In previous studies, Ce-doped SnS₂ nanoflakes were successfully synthesized and exhibited higher photocatalytic efficiency than that of un-doped SnS₂ due to the porous architecture and reduced energy bandgap after Ce-doping. Ce-doped SnS₂ nanoflowers were also studied as anode electrodes materials for lithium ion batteries, whose reversible capacities and cycling performance is the best among the synthesized Ce SnS₂ compounds because of larger lattice space provided by the larger-radius cerium ions replacement of Sn⁴⁺ for lithium intercalation and deintercalation. Besides, it has been found that Ce dopants can effectively tune the optical gaps and produce the magnetic ground state.

Experimental

Synthesis of SnS@SnS₂ nanoparticles

The pure SnS@SnS₂ nanoparticles were synthesized by a hydrothermal reaction. In experiment, 0.902 g of SnCl₂·2H₂O and 1.805 g of thiourea were dissolved in a stoichiometric ratio of 1:3 in 32ml Milli-Q water under vigorous stirring to form a white homogeneous solution. Then, the obtained homogeneous solution was transferred into a 50 mL Teflon-lined stainless-steel autoclave and kept at 200 °C for 8 h. Then, the autoclave was allowed to cool down to room temperature naturally. The formed SnS@SnS₂ nanoparticles were washed with ethanol and water by centrifugation (8 000 rpm) three times, respectively, then dried at 60 °C for several hours in air to obtain the final product named SnS@SnS₂-0.

Synthesis of Ce³⁺ doped SnS@SnS₂ nanoparticles

The Ce³⁺ doped SnS@SnS₂ nanoparticles are synthesized in the same method. The only difference is that different amounts of Ce(OOCCH₃)₃·5H₂O were added with SnCl₂·2H₂O and thiourea to obtain the homogeneous solution. The synthesized Ce³⁺ doped SnS@SnS₂ with molar ratios of Ce³⁺ to tin (Ce/Sn) in the precursors of 0.005, 0.01, 0.02 and 0.04 were named SnS@SnS₂-0.5, SnS@SnS₂-1, SnS@SnS₂-2 and SnS@SnS₂-4 respectively.

Results and Conclusions

In this study, the synthesized SnS₂ bulk nanocomposites are randomly arranged with a great many SnS quantum dots dispersing on the surface. At the interfaces between SnS₂ and SnS phases, accumulation layers are formed and p-n heterojunctions come into existence. Besides, it has been proved that cerium is mainly found in SnS quantum dots to achieve the lowest formation energy. Therefore, the number of SnS quantum dots can be modulated by the doping concentration. Furthermore, the number of heterojunctions, the baseline resistance and the sensing properties can be effectively controlled.

In conclusion, the pristine SnS@SnS₂ nanocomposites and Ce-doped SnS@SnS₂ nanocomposites with different doping proportions were all synthesized by a simple one-step hydrothermal method. Due to the combined action of SnS@SnS₂ p–n heterojunctions and high specific surface, 1at.% Ce-doped SnS@SnS₂ sensor had obviously improved sensing sensitivity with lower baseline resistance compared to pristine SnS@SnS₂ and exhibited the best gas sensitivity of 31 with response/recovery time of 19s/63s to 10 ppm NO₂ at room temperature. The reason was that Ce-doping could effectively modulate the number and size of SnS quantum dots, thereby regulating the number of the SnS@SnS₂ p-n heterojunction and specific surface to enhance the gas sensitivity, which was consistent with the DFT calculating results. The replacement of some Sn²⁺ by Ce³⁺ also increased the electron concentration and made contributions to the decrease of baseline resistance. By changing the proportion of Ce precursors, the sensing performance can be effectively modulated and finally achieve the ideal sensing material for NO₂ gas sensing at room temperature.

References

[1] Joo, J.; Na, H. B.; Yu, T.; Yu, J. H.; Kim, Y. W.; Wu, F. X.; Zhang, J. Z,; Hyeon, T. Cheminform 2003, 34, 11100-11104.

[2] Raouf, M.; Nasiri, M. Materials Science in Semiconductor Processing 2015, 40, 293-301.

[3] Lhuillier, E.; Pedetti, S.; Ithurria, S.; Nadal, B.; Heuclin, H.; Dubertret, B. Accounts of Chemical Research 2015, 48, 22-30.

[4] Andrea, G.; Barbara, F.; Vincenzo, G.; Gaiardo, A.; Fabbri, B.; Guidi, V.; Bellutti, P.; Giberti, A.; Gherardi, S.; Vanzetti, L.; Malagù, C.; Zonta, G. Sensors 2016, 16, 296-314.

[5] Yang, S.; Jiang, C.; Wei, S. Applied Physics Reviews 2017, 4, 021304-021338.

[6] Choi, S. J.; Kim, I. D. Electronic Materials Letters 2018, 14, 221-260.

Figure 1

Introduction

Over the past few decades, researchers have devoted considerable effort to the integration of synthetic receptors into chemical sensing platforms. In general, molecularly imprinted polymers (MIPs) have been developed for targets ranging from small molecules to proteins while surface imprinted polymers (SIPs) are generally used to detect larger entities such as microorganisms or whole cells [1]. These synthetic receptors have been combined with traditional electrochemical, optical or microgravimetric readout approaches to create sensors for various applications including medical diagnostics and environmental screening [2]. In 2012, a surprisingly versatile readout tool for label-free sensing was developed; the so-called heat-transfer method (HTM) [3]. The technique was originally developed for the detection of point mutations in DNA but was soon extended towards chemical sensing by coating the chips with synthetic receptors. In this way, it can be used for a wide variety of applications ranging from e.g. bacteria detection in urine samples for UTI diagnosis to cardiac biomarker testing in serum [4-5].

The benefit of these thermal chemical sensing platforms over existing state-of-the-art technology lies in the unique combination of highly selective synthetic receptors and a low-cost, user-friendly readout platform that requires minimal instrumentation. The challenges towards commercial application mainly involve standardizing and upscaling the MIP/SIP synthesis procedure as well as the limited sensitivity of the readout approach. However, progress is being made in both aspects in recent years.

Method

Bacteria imprints were made by spin coating aluminum chips with semi-cured polyurethane layers. Template bacteria are immobilized onto a PDMS stamp and pressed into the polyurethane layer that was cured over-night. Removal of the stamp and template leads to a SIP containing microcavities that are complementary to the template. Thermal resistance over the solid-liquid interface was monitored by sending a thermal wave through the chip with an average temperature of 37.0°C and an amplitude of 0.1 °C. The phase shift of the transmitted thermal wave at 0.03 Hz was analyzed in function of the bacteria concentration in spiked urine samples [4].

MIPs can be made in a more reproducible manner than SIPs, through the so-called solid phase synthesis approach. MIP nanoparticles were obtained by immobilizing selected cardiovascular biomarkers onto glass beads that were packed in a column. Radical polymerization was performed at room temperature and the colum was eluded at different temperatures. The particles that elute at elevated temperatures were retained, as their affinity for the target is the highest. The MIP particles were directly immobilized onto the surface of the thermocouples for thermal resistance measurements.

Results and Conclusions

The results shown in Figure 1a illustrate that the phase shift observed in the transmitted thermal wave will increase when exposing the SIP-coated aluminum chip to the target bacterium, in this case E. coli. These findings can be explained by the fact that bacteria binding to the cavities in the SIP layer will displace the urine (water-based so a good thermal conductor) that was previously present, leading to an increase of the thermal-resistance at the solid-liquid interface and a tempered propagation of the thermal wave that was send through the chip.

The experiments using the nano-sized MIP particles for biomarker illustrate that it is possible to multiplex the thermal analysis for the detection of cardiac biomarkers in serum. The data in figure 1b show that the thermal resistance of the MIP particles at the interface only change when exposed to their target (red, ST2). Exposing the MIPs to a similar cardiac biomarker (blue, H-FABP) results in a response that is similar to the response of the non-imprinted reference channel (black) with no significant change in the phase shift observed.

References

[1] S. Piletsky, et al. MIP-based Sensors in Molecularly Imprinted Sensors. Elsevier, 339-354 (2012); DOI: https://doi.org/10.1016/B978-0-444-56331-6.00014-1.

[2] K. Eersels, et al. A Review on Synthetic Receptors for Bioparticle Detection Created by Surface-Imprinting Techniques—From Principles to Applications. ACS Sens. 1, 1171-1187 (2016); DOI: 10.1021/acssensors.6b00572

[3] B. van Grinsven, K. Eersels, et al. The Heat-Transfer Method: A Versatile Low-Cost, Label-Free, Fast, and User-Friendly Readout Platform for Biosensor Applications. ACS Appl. Mater. Interfaces 6, 13309-13318 (2014); DOI: https://doi.org/10.1021/am503667s

[4] E. Steen Redeker, K. Eersels, et al. Biomimetic Bacterial Identification Platform Based on Thermal Wave Transport Analysis (TWTA) through Surface-Imprinted Polymers. ACS Infect. Dis. 3, 388-397 (2017); DOI: 10.1021/acsinfecdis.7b00037.

[5] M. Peeters, et al. Thermal Detection of Cardiac Biomarkers Heart-Fatty Acid Binding Protein and ST2 Using a Molecularly Imprinted Nanoparticle-Based Multiplex Sensor Platform. ACS Sens. (2017); DOI: 10.1021/acssensors.9b01666.

Figure 1

Contemporary gas monitoring scenarios for industrial safety, environmental surveillance, medical diagnostics, personal wellness, and other applications demand sensors with higher accuracy, enhanced stability, and often lower power; all in unobtrusive formats and at low cost [1-3]. Unfortunately, available sensors based on traditional detection principles often have not only inadequate accuracy and stability but also have relatively high power demands, pushing the limits of existing detection concepts where we are reaching their fundamental performance limits. These limitations of available sensors drive the innovative designs of new generation of sensors.

We are focusing on development of new principles of gas sensing based on multiparameter signal excitation and detection resulting in a new generation of gas sensors based on the multivariable response principles. Design criteria of these individual sensors involve a sensing material with multi-response mechanisms to different gases and a multivariable transducer with independent outputs to recognize these different gas responses.

In our talk, we will discuss our different sensor types that operate over the electromagnetic spectrum ranging from the radio-frequency to microwave and to optical regions. We will discuss new performance capabilities of the developed sensors using two broad examples of our recent developments.

In the first example, we will discuss our multivariable sensors in the radio-frequency and microwave spectral regions [4-6]. We are implementing impedance spectroscopy and diverse types of sensing materials and transducers with the goals of improving gas-selectivity of our sensors and rejection of interferences. Examples of our sensing materials in these spectral regions include conjugated and dielectric polymers, ligand-functionalized metal nanoparticles, metal oxides, and carbon allotropes. Examples of our transducers include resonant and non-resonant structures.

In the second example, we will discuss our multivariable sensors in the optical spectral region [7-11]. We are implementing our bio-inspired three-dimensional nanomaterials with the visible-light reflectance or transmittance measurements with the goals of improving gas-selectivity of our sensors and enhancing sensor stability. Examples of our sensing materials operating in the optical spectral region include polymeric and inorganic nanostructures functionalized based on our design rules for multi-gas detection using individual sensors.

Our developments resulted in sensors with previously unavailable performance characteristics in wearable, stationary, airborne and other formats where our multivariable sensors independently quantify up to four individual gases in complex mixtures, reject interferences with up to 2,000,000-fold overloading in concentrations over the analytes, and enhance sensor-response stability. Such performance characteristics are attractive when selectivity advantages of classic gas chromatography, ion mobility, and mass spectrometry instruments are canceled by requirements for no consumables, low power, low cost, and unobtrusive form factors for Internet of Things, Industrial Internet, and other applications. We will conclude with a perspective for future needs in fundamental and applied aspects of gas sensing and with the 2030 roadmap for ubiquitous gas monitoring.

[1] Bogue, R. Towards the trillion sensors market. Sensor Rev.34, 137-142 (2014).

[2] Alexander, M., Bernhart, W., Rossbach, C. & Nölling, K. Smart Strategies for Smart Sensors. (Roland Berger GMBH, 2017).

[3] Potyrailo, R. A. Ubiquitous wearable and disposable chem-bio sensors: markets demands and innovative technology solutions. (Sensors Expo & Conference, San Jose, CA, June 26-28, 2018).

[4] Potyrailo, R. A., Surman, C., Nagraj, N. N. & Burns, A. Materials and Transducers Toward Selective Wireless Gas Sensing. Chem. Rev.111, 7315–7354 (2011).

[5] Potyrailo, R. A. Multivariable sensors for ubiquitous monitoring of gases in the era of Internet of Things and Industrial Internet. Chem. Rev.116, 11877–11923 (2016).

[6] Potyrailo, R. A. Toward high value sensing: monolayer-protected metal nanoparticles in multivariable gas and vapor sensors. Chem. Soc. Rev.46, 5311-5346 (2017).

[7] Potyrailo, R. A. et al. Morpho butterfly wing scales demonstrate highly selective vapour response. Nature Photonics1, 123-128 (2007).

[8] Potyrailo, R. A. et al. Discovery of the surface polarity gradient on iridescent Morpho butterfly scales reveals a mechanism of their selective vapor response. Proc. Natl. Acad. Sci. U.S.A.110, 15567–15572 (2013).

[9] Potyrailo, R. A. et al. Towards outperforming conventional sensor arrays with fabricated individual photonic vapour sensors inspired by Morpho butterflies. Nature Commun.6, 7959 (2015).

[10] Potyrailo, R. A., Karker, N., Carpenter, M. A. & Minnick, A. Multivariable bio-inspired photonic sensors for non-condensable gases. J. Opt.20, 024006 (2018).

[11] Potyrailo, R. A. et al. Multi-gas sensors for enhanced reliability of SOFC operation. ECS Transactions91, 319-328 (2019).

Chemicals and materials with active ionic species are widely employed in various chemical and electrochemical applications such as solvents, catalysts, sensors, fuel cells, batteries, atomic switches, etc. Ionic liquids (IL) are liquids often composed of bulky organic cations or anions whereas conductive polymers are solids with dopant ions in a rigid organic framework. In this presentation, I will discuss the fundamental research of ionic liquid and conductive polymer interface electrochemistry for sensor applications. Being composed entirely of ions and with a broad structural and functional diversity i.e., bifunctional (organic/inorganic), biphasic (solid/liquid), and biproperty (solvent/electrolyte) materials, ionic liquids have the complementing attributes and the required variability to allow a systematic design process across many components to enhance sensing capability for miniaturized gas sensor system implementation. Being composed with dopant ions in a rigid organic framework, the unique properties of conductive polymers allow ease of functionalization with bio-recognition elements and enable label free electrochemical, optical and mass sensing technologies for study bio-interactions on a single platform. The simplicity of the demonstrated detection principles could yield forward-thinking solutions to many sensors challenges, especially miniaturization and robustness that is essential for their integration with engineering advancements such as portable electronics, networked sensing and next-generation monolithic implementation of autonomous sensors with the performance, cost, power, and operational lifetime characteristics to suit a broad range of applications.

Fast scan cyclic voltammetry (FSCV) and carbon-fiber microelectrodes (CFMEs) have been utilized used to detect several important neurochemicals in vivo. However, this method is limited due to the ability to discriminate dopamine from several of its metabolites. PEDOT, Nafion, and Polyethyleneimine modified microelectrodes will be utilized to detect physiologically low levels of neurotransmitters that also resist surface fouling and have high temporal resolution to detect fast changes of neurotransmitters. Furthermore, novel electrode coatings and waveforms will also be utilized to detect several neurotransmitter metabolites such as dopamine, norepinephrine, normetanephrine, 3-methoxytyramine (3-MT), homovanillic acid (HVA), 3,4 dihydroxyphenylacetic acid (DOPAC), and other metabolites. Currently, dopamine is thought to be an important neurotransmitter concerning several disease states such Parkinson's disease, drug abuse (amphetamine, cocaine, etc.), and even for gambling and sex-disorders. However, dopamine is metabolized on a subsecond timescale, and studies have pointed to the importance of neurotransmitter metabolites in these disease states apart from dopamine. Presently, there is no method to selectively co-detect these neurotransmitter metabolites of dopamine utilizing FSCV. Through several waveform modifications and polymer electrode coatings, we develop a novel method to tune the detection of dopamine and said metabolites, which will help differentiate dopamine and respective metabolites through the shapes and positions of their respective cyclic voltammograms. Preliminary measurements have also been made in zebrafish retina showing the application of this technique in biological tissue. The co-detection and differentiation of dopamine metabolites and dopamine will have many implications in better understanding complex disease, behavioral, and pharmacological states.

Moreover, within the greater neuroscience community, there has long been a critical need for the development of versatile and affordable multichannel sensors for the detection of neurotransmitters. Little success has been achieved in developing and commercializing these multielectrode arrays used specifically for the detection of neurotransmitters with voltammetry in multiple brain regions.

The brain is by far the most heterogeneous organ, and it is critically important to monitor various brain regions simultaneously in order to understand complex pharmacological, drug, and behavioral states. For example, several studies have shown significant differences in electrical activity and neurotransmitter concentrations in disparate brain regions such as the striatum, hippocampus, and prefrontal cortex among others. Therefore, it is critically important to make high temporal resolution neurochemical measurements to study the phasic firing of neurons in several brain regions concurrently. FSCV allows for high temporal measurements (< 100 msec) of neurotransmitter levels. Some of the many applications of this technique could be measuring neurochemical changes during epileptic seizures with simultaneous EEG measurements in rodents, drug abuse studies, measuring robust dopamine increases during deep brain stimulation in Parkinsonian models, and possibly many others.

This work will also discuss the development of multielectrode arrays (MEAs) for neurotransmitter detection with fast scan cyclic voltammetry in multiple brain regions simultaneously. Parylene and silicon insulated carbon fiber microelectrode arrays were shown to be able to measure neurochemicals in multiple brain regions simultaneously when coupled with multichannel potentiostats. Moreover, we have utilized techniques such as plasma enhanced chemical vapor deposition (PECVD) to deposit conductive carbon nanospikes onto the surface of existing metal multielectrode arrays to give them dual functionality as neurotransmitter sensors with FSCV in addition to being used primarily for electrical stimulation and recording. Other assays have shown the utility of electrodepositing carbon nanotubes and polymers such as PEDOT to coat metal arrays with carbon to give them dual sensing capabilities. This BRAIN Initiative funded work will allow us to further understand complex brain heterogeneity by making measurements in multiple brain regions simultaneously.

Nanochannels, such as ion channels, are present in many biological functions and can control ion flow through the channel for cellular function. The trigger of the ion flow can be achieved through changes of pH, voltage, or others variables. Ion channels are important to studying some diseases, however, biological ion channels are embedded in fragile lipid bilayer membranes making them difficult to study. This research is focused on creating a synthetic nanochannel that employs the internal diameter of carbon nanotubes (CNTs) as pores. The CNTs are naturally hydrophobic and studies have shown fast water transport though the CNTs making them a good material for synthetic ion channels. We will assemble 10⁷ channels in parallel to each other within a CNT fiber. This approach will allow easy assembly of the nanochannels for exploration of their capabilities and limitations. This project looks at the diameter correlation to ion dimensions as well as the size selectivity of the nanochannels. Preliminary work has been focused on electrochemical measurements that confirm flow of ions through the CNT nanochannels. Blank samples show current flow close to zero, while samples containing the CNT nanochannel show current flow higher then 4 nA.

Heterojunctions of two-dimensional materials have been attracting considerable attention because of their outstanding tunable optical and electrical properties. Taking the composites of CeO₂/graphene and SnO₂/graphene as examples, the interfacial effects on the electronic states and gas sensing properties are studied. For the CeO₂/graphene composites, the electron is transferred from graphene onto CeO₂ {111} facets showing the Schottky contact, but from CeO₂ {100} facets onto graphene resulting in Ohmic contact. Furthermore, since CeO₂{100} surface is the polar surface, and NO₂ is a polar molecule, the interactions between NO₂ and CeO₂ with {100} polar facets should be stronger thus promoting adsorption of NO₂. The internal electric field near the polar surface promotes charge separation and accelerates charge exchange between NO₂ and the composites. As a result, the CeO₂ {100}/graphene composites deliver substantially enhanced gas sensing performance to NO₂, as compared to CeO₂ {111}/graphene composites. It was also found that oxygen vacancies (O_v) have significant influences on the gas sensing performance. According to the first-principle calculations, the tunable electronic states and enhanced gas sensing performances owing to interfacial effects can be well understood.

Protein analysis has found widespread applications in biomedical fields (e.g., disease diagnosis and precision medicine), especially recently in point-of-care testing (POCT). Conventional protein analysis is large-equipment-dependent, which limits its applications in POCT. Herein, we proposed a strategy using a shaped liquid entity, termed liquid plasticine (LP), as a platform to perform isoelectric focusing (IEF)-based protein analysis. The LP-IEF system mainly consisted of a separation channel, a catholyte module and an anolyte module, which were all in the form of self-standing liquid micro-containers with specific shapes and connected together. The basic functions of the LP-IEF system were examined using three standard proteins, with the results showing a clear separation, 10-folds concentration, and a resolution of 0.03 pH, meaning that this system could serve for pretreatment and analysis of proteins from complex physiological samples. The developed LP-IEF system was further demonstrated as a colorimetric quantitative analytical platform of clinical microalbuminuria with a relative error of <9.4% compared to the results obtained by the traditional clinical detection methods. Moreover, the LP-IEF system was coupled to MALDI-TOF-MS and successfully used to identify a-1-microglobulin/bikunin precursor (AMBP) in clinical diabetic urines. The LP-IEF system proposed in this work opens a flexible, versatile, and low-cost way for POCT of proteins, which could inspire many practical applications in future.

References

[1] J. C. Niu, T. Zhou, L. L. Niu, Z. S. Xie, F. Fang, F. Q. Yang, Z. Y. Wu, Simultaneous Pre-concentration and Separation on Simple Paper-based Analytical Device for Protein Analysis, Analytical and bioanalytical chemistry 410.6 (2018): 1689-1695. Doi:10.1007/s00216-017-0809-5.

[2] X. G. Li, H. X. Shi, Y. Y. Hu, Rod-shaped Liquid Plasticine for Gas Diffusion Detection, Soft matter, 15(15), 3085-3088. Doi:10.1039/c9sm00362b.

Introduction

Quantum dots (QDs) have become attractive tools in bioanalysis because of their advantageous optical and electrochemical properties. This relates to applications exploiting fluorescence, electrochemiluminescence or photocurrent generation [1]. For the latter case QDs are immobilized on conductive electrodes. By light excitation charge carriers are formed inside the nanoparticles which can be used for photocurrent generation. Signal chains can be constructed when appropriate donor or acceptor components are present in solution. The special feature of such electrodes is that the response is triggered by illumination of the sensing electrode [1]. In this study, a light-addressable photoelectrochemical sensor was built by coupling QDs with oxidases to detect different enzyme substrates.

Results and Conclusions

At first CdSe/ZnS QDs have been immobilised via a dithiol compound on gold electrodes. Two different enzymes, glucose oxidase (GOD) and sarcosine oxidase (SOD) have been deposited on this QDs-electrode at spatially well resolved places. Here small spots have been achieved by a dropping method. A laser beam is moved over the spots to detect photocurrents. Since oxygen can act as electron acceptor at the illuminated QDs the photocurrent is correlated to the oxygen concentration in solution. By action of the enzymes in the presence of the corresponding substrate a competitive situation for oxygen is created in front of the QD layer and thus, the photocurrent decreases [2, 3]. Since this happens in a concentration dependent way, analysis of the enzyme substrate is feasible.

Furthermore, due to the spatially separated immobilisation of the two enzymes, an independent read-out of the two enzyme reactions is possible. The results indicate good lateral resolution and selectivity of the multi-detection system without any crosstalk between the two sensing regions and also without any response at regions, which have not been modified with an enzyme [4].

After that, the possibility of an imaging of the enzyme spot by photocurrent measurement has been studied. When the laser is moved over the spot of GOD with a constant speed, the size of the spot can be determined from the photocurrent - time curve (with a defined moving speed). The photocurrent correlates to different local enzyme activities. Consequently, an imaging of the enzyme activity distribution on the surface has also been achieved by this method.

References

[1] F. Lisdat, D. Schäfer, A. Kapp, Analytical and Bioanalytical Chemistry 405 (2013) 3739-3752

[2] M. Riedel, et al., Chem. Phys. Chem. 2013, 14, 2338-2342.

[3] J. Tanne et al., Anal. Chem. 2011, 83, 7778-7785.

[4] S. Zhao et al., ACS Applied Materials & Interfaces, 2019, Vol. 11 (24), p. 21830-21839

Introduction

Acetic acid is a key tracer in chocolate and coffee processing defining their final taste. Additionally, it is a promising breath marker for cystic fibrosis and gastro-oesophageal reflux disease as breath concentrations are significantly increased with 170 ppb [1] and 85 ppb [2], respectively, compared to healthy humans (48 ppb). However, current sensors lack ppb to ppm level sensitivity with high selectivity to detect relevant acetic acid concentrations accurately in gas mixtures at high humidity (90%). Here, we present an acetic acid selective gas sensor able to detect lowest ppb-level concentrations. It consists of doped ZnO nanoparticles whereas doping level, particle & crystal size as well as film morphology were subsequently optimized in a flame spray pyrolysis (FSP) reactor.

Method

ZnO nanoparticles with different (0 - 10 mol%) doping contents were produced by flame spray pyrolysis (FSP) and directly deposited [3] onto water-cooled Al₂O₃ sensor substrates forming a highly porous sensing network. The mechanical stability of the nanoparticles on the Al₂O₃ was fortified by in-situ annealing [4] with a particle-free xylene flame followed by annealing at 500 °C for 5 h in an oven. The sensors were mounted onto Macor holders, placed in a sensing chamber and installed in an evaluation setup described elsewhere [5]. The sensors were heated to 250 - 450 °C and tested on 1 ppm acetic acid, acetone, ethanol and ammonia at relative humidity ranging from 10 to 90%.

Results and Conclusions

Figure 1a shows a top view SEM of the sensing film for ZnO doped with 1 mol% transition metals. The doping thermally stabilizes the particles during high temperature treatment and preserves the highly porous nanostructured sensing network typical for FSP. In specific, it consists of aggregates and agglomerates of individual nanoparticles with particle sizes ~35 nm (Figure 1a, inset), as determined by nitrogen adsorption from filter-collected powders and ideal for gas sensing due to the high available surface area.

Figure 1b shows the sensor response to 1 ppm acetic acid, ethanol, acetone and H₂ as a function of the doping content. Additionally, the doping with 1 mol% increases the sensor response to acetic acid and selectivity to ethanol and acetone compared to pure ZnO (Figure 1b). That way, even concentrations down to 50 ppb were detectable at 50% relative humidity (RH), unprecedented by other acetic acid sensors. Note that at higher doping contents, the responses to all analytes decrease again, most likely due to the isolating character of segregated transition metal phases.

As a result, an inexpensive acetic acid detector has been developed that could be easily incorporated into a portable breath analyzer, used for food processing monitoring or incorporated into orthogonal arrays [6].

References

[1] Smith, D.; Sovova, K.; Dryahina, K.; Dousova, T.; Drevinek, P.; Spanel, P., Breath concentration of acetic acid vapour is elevated in patients with cystic fibrosis. J Breath Res (2016).

[2] Dryahina, K.; Pospisilova, V.; Sovova, K.; Shestivska, V.; Kubista, J.; Spesyvyi, A.; Pehal, F.; Turzikova, J.; Votruba, J.; Spanel, P., Exhaled breath concentrations of acetic acid vapour in gastro-esophageal reflux disease. J Breath Res (2014).

[3] Mädler, L.; Roessler, A.; Pratsinis, S. E.; Sahm, T.; Gurlo, A.; Barsan, N.; Weimar, U., Direct formation of highly porous gas-sensing films by in situ thermophoretic deposition of flame-made Pt/SnO₂ nanoparticles. Sensor Actuat B-Chem (2006), 283-295.

[4] Tricoli, A.; Graf, M.; Mayer, F.; Kuhne, S.; Hierlemann, A.; Pratsinis, S. E., Micropatterning layers by flame aerosol deposition-annealing. Adv Mater (2008), 3005-3010.

[5] Güntner, A. T.; Righettoni, M.; Pratsinis, S. E., Selective sensing of NH₃ by Si-doped a-MoO₃ for breath analysis. Sensor Actuat B-Chem (2016), 266-273.

[6] Pineau, N. J.; Kompalla, J. F.; Güntner, A. T.; Pratsinis, S. E., Orthogonal gas sensor arrays by chemoresistive material design. Microchim Acta (2018).

Figure 1

The defect-tolerant nature of lead halide perovskites renders high PLQYs by simply confining them in nanopores. In view of this character, a fluorescence turn-on and wavelength-shift dual responsive methylamine (MA) gas sensor is achieved using HPbBr₃/PbBr₂@SiO₂ nanospheres (NSs). In this composite, the hydrophobic silica shell not only provides mesopores for the penetration of MA gas, but enhances the moisture stability of the MAPbBr₃ perovskite nanocrystals generated after reacted with MA gas, improving the sensing performance. When exposed to the MA gas, the fluorescence is rapidly turned on due to the formation of MAPbBr₃ perovskite nanocrystals. The enhanced photoluminescence is linearly with the MA concentration in the range of 0.08 – 6.3 μM with a LOD of 3.1 nM (S/N = 3). In addition, the photoluminescence peak is consistently red-shift from 478.7 nm to 510.6 nm when the MA concentration is increased from 0.083 to 6.3 µM. Correspondingly, the emission color is changed from weak blue to cyan, and to bright green, which imparts the potential for colorimetric sensing. By combining the turn-on and wavelength-guide sensing modes, this MA sensor is more flexible and the result is more reliable.

Figure 1

Room temperature ionic liquid (RTIL) is a unique chemical which possesses exceptional physical and chemical properties. It is viscous in nature and the general architecture consists of a long chain cation and a long/short chain anion seated side by side, in a zwitter ion format. The cation and anion are equi-charged species makes the compound electrically neutral in nature (Hallett and Welton 2011).The density of RTIL is higher than water and it possesses negligible vapor pressure, which enables it for many important applications. One of the most important properties of RTIL is its low volatility and high thermal stability (up to 400K) compared to other organic solvents, attracts the scientific community and hence RTIL is extensively used in various applications like energy, catalysis, chemo and bio sensing, gas sensing etc (Marsh et al. 2004). Most of the RTIL is non-conducting in nature due to its high viscosity (>50cP), and restrains the charge distribution. While few RTIL possess low viscosity and very high conductivity. This complex relation between viscosity and ionic conductance is easy understood by Walden's rule which suggests that mostly long alkyl chain hydrocarbon cation based RTIL possesses lower conductivity (Schreiner et al. 2010). The electrochemical stability of cation generally follows this order (Fig.1):

Whereas the anion follows this order (Fig.2):

Any one combination of above cation and anion may not have desired chemical, electrical or electrochemical property (Liang et al. 2002). RTIL consists of one Common cation with two different anions that can show separate electrical and electrochemical property. For example, 1-ethyl-3-methyl imidazolium (EMIM+) based cation when constituted with thiocyanate (SCN-) has an ionic conductivity >20mS/cm but the electrochemical stability is 2.9 V, whereas the same cation when coupled with has an ionic conductivity of 12 mS/cm whereas the electrochemical stability is 4.3 V which is much higher compared to thiocyanate (Fro et al. 2008). It is found that EMIM+ based RTIL with these two different anions: and are suitable for electrochemical application.

Phenylpiperidines are a chemical class of drugs with a phenyl moiety directly attached to piperidine. (Fig3)

Fig.3: Chemical structure of 1-phenyl-pipyridine

These agents have an important role in many aspects of medicine including anesthesia and pain medicine. Pharmacological effects associated with phenylpiperidines are vastly different, yet similar; they include morphine-like activity in some derivatives, while in others they exert potent central nervous system effects. One of the famous subclass of Phenylpiperidines are fentanyl analogs, which is currently one of the most worrying factor for scientific community.

In this paper, we have tried to explore an electrochemical sensor for detection of different compounds based on 1-phenyl-pipyridine using a specific RTIL [EMIM] [BF₄]. A commercially available screen printed electrode was functionalized with RTIL and a DC based electroanalytical technique was implemented to obtain sensor performance to detect N-phenyl-N-(piperidin-4-yl) propionamide used as a 1-phenyl-pipyridine analogue with high specificity. The LOD of this system has been calculated to be 0.5 ppm.

Fig 4: (a) Experimental protocol (b) Square wave voltammetry result shows distinct peak for the Norfentanyl analog.

References:

Fro AP, Kremer H, Leipertz A (2008) Density , Refractive Index , Interfacial Tension , and Viscosity of Ionic Liquids [ EMIM ][ EtSO 4 ], [ EMIM ][ NTf 2 ], [ EMIM ][ N ( CN ) 2 ], and [ OMA ][ NTf 2 ] in Dependence on Temperature at Atmospheric Pressure. J Phys Chem B 112:12420–12430

Hallett JP, Welton T (2011) Room-Temperature Ionic Liquids: Solvents for Synthesis and Catalysis. 2. Chem Rev 111:3508–3576. https://doi.org/10.1021/cr1003248

Liang C, Yuan C-Y, Warmack RJ, et al (2002) Ionic Liquids: A New Class of Sensing Materials for Detection of Organic Vapors Based on the Use of a Quartz Crystal Microbalance. Anal Chem 74:2172–2176. https://doi.org/10.1021/ac011007h

Marsh K., Boxall J., Lichtenthaler R (2004) Room temperature ionic liquids and their mixtures—a review. Fluid Phase Equilib 219:93–98. https://doi.org/10.1016/j.fluid.2004.02.003

Schreiner C, Zugmann S, Hartl R, Gores HJ (2010) Fractional Walden Rule for Ionic Liquids: Examples from Recent Measurements and a Critique of the So-Called Ideal KCl Line for the Walden Plot †. J Chem Eng Data 55:1784–1788. https://doi.org/10.1021/je900878j

Figure 1

We demonstrate a facile approach to deposit Pt/IrO₂ composite films via a bipolar pulsing deposition technique in which the Pt ions are electrochemically reduced and the IrO₂ colloids are electrophoretically deposited. The composite Pt/IrO₂ films are subjected to both potential pulse and differential pulse voltammetry to detect the presence of dopamine (DA) and ascorbic acid (AA) for bio-sensing applications. In human's body, a critical concentration of DA is used as an indicator for onset of Parkinson's disease. Unfortunately, the existence of AA would interfere with the detection of DA due to their similar oxidation potential. By fabricating a composite of Pt and IrO₂, a lower detection limit with a minimized interference of DA and AA could be achieved. Electrochemical parameters relevant to the preparation of Pt/IrO₂ films are optimized and the resulting morphology and composition are analyzed by SEM and EDS. The oxidation state of Pt and Ir are determined by XPS. The electrical resistance and electrochemical surface area of Pt/IrO₂ films are recorded by impedance spectroscopy and electrochemical analysis.

Carbon Nanotubes (CNTs) are the emerging materials because of their extraordinary physical and chemical properties. Diverse applications, such as chemical and biochemical sensors, electronic devices, nanocontainer lithium ion batteries, thermally stable materials, and many others have been proposed and tested. The properties of carbon nanotubes depend on their structure, such as diameter, defect density, length, chirality, number of walls, etc. Regrowth of nitrogen-doped carbon nanotubes (N-CNTs) from open end of carbon nanotube fiber is our initial focus to achieve using Chemical Vapor Deposition (CVD) method. Incorporation of Nitrogen into carbon nanotube structure leads to high surface area and high density of defects. N-doped CNTs has excellent performance in oxygen reduction reactions and enhance the energy storage capabilities of Lithium ion batteries. Fe-Al bimetallic nanoparticles synthesized by electrochemical process lead to the N-CNTs growth by CVD which is proved by initial investigation. Fabrication of electrode using N-CNTs fiber is easy because of their high conductivity, large surface area, and strong mechanical strength. The application of the electrode and necessary data will be discussed in final presentation.

Introduction

Despite graphene shows outstanding electronic and physicochemical properties to be employed as a gas sensor, its implementation in commercial devices still faces many issues. The main drawbacks that are limiting real applications are the low sensitivity and selectivity towards gas molecules of graphene in its pristine form. In consequence, further modifications are needed to enhance these essential gas-sensing parameters. One of the easiest and most effective strategies is the decoration of graphene (or other carbon nanomaterials) with metal or metal-oxide nanoparticles [1], an approach that has been extensively studied by many researchers.

In contrast, perovskites are promising materials that despite showing rich surface chemistry have attracted limited research interest for gas sensing until now. Probably because of their inherent problems, such as high degradation in contact with ambient moisture or their stability problems even at moderate working temperatures. Nevertheless, we recently reported the first use of graphene loaded with perovskite nanocrystals [2] to detect NO₂ and NH₃. Our approach has been demonstrated as a novel option to employ perovskites in dry and humid air, instead of their use in inert atmospheres by employing nitrogen without ambient moisture [3]. Here we deepen our study by analyzing, for the first time, a wide range of perovskite-graphene hybrids for gas sensing.

Methods

Chemical-sensitive films composed by graphene nanolayers loaded with different perovskite nanocrystals are developed. In particular, five different perovskite nanocrystals are synthesized and studied. Considering the general formula of perovskites (ABX₃), we started with the perovskite nanocrystal already employed as a gas sensor in our previous work, which is MAPbBr₃ (1). Thus, as our main objective is to analyze the effect on the gas sensing properties of the different elements in perovskites, first we change the cation A, obtaining two different perovskites with caesium (CsPbBr₃) (2) and formamidinium (FAPbBr₃) (3). After that, two new nanocrystals are obtained by changing the anion X, replacing the bromide by iodine (MAPbI₃) (4) and chlorine (MAPbCl₃) (5). Different synthesis processes are performed to obtain the five nanocrystals, but all of them show diameters below to 10 nm, which are found suitable for the decoration of graphene.

Characterization

All the nanomaterials employed in this work are characterized in depth employing techniques such as X-Ray Photoelectron Microscopy (XPS) to obtain detailed information about the graphene functional groups; High-Resolution Transmission Electron Microscopy (HR-TEM) to analyze the nanocrystal size and its interplanar distances; Field Emission Scanning Electron Microscope (FESEM) to evaluate the spatial nanocrystal distribution over the graphene nanolayers; and finally, an X-Ray Diffraction (XRD) analysis to study the crystalline structure of perovskites. Afterwards, the films developed are integrated in gas sensing devices, which are placed in an airtight Teflon chamber connected to calibrated bottles of nitrogen dioxide, ammonia, benzene and toluene. Consecutive gas dilutions are performed in order to obtain different analyte concentrations. With these results, the effect of the cation and anion in the detection of pollutant gases and vapors was studied at low concentrations. Full details will be given at the conference.

Results and Conclusions

The resulting hybrid nanomaterials, i.e. graphene loaded with perovskite nanocrystals have been demonstrated as great options for room-temperature operated gas sensing, entailing to low-power consumption devices. Additionally, the high instability of perovskites over time is clearly ameliorated here, thanks to the highly hydrophobic character of graphene, which protects the nanocrystals from the effect of ambient moisture. As a result, we can take advantage of the outstanding perovskite properties by increasing the stability and the sensor shelf-life. Also, sensitive, reproducible, reversible and remarkably stable responses to nitrogen dioxide, ammonia and VOCs can be obtained (see Figure 1) for sensors operated room temperature. Even, higher sensitivity can be obtained to both, electron donor and electron-withdrawing gases, thanks the presence of perovskite nanoparticles in comparison to their bare graphene counterparts. The reason probably is because perovskites can act as ambipolar charge transporters. These results will allow a better understanding about the role in the sensing mechanism of the different perovskite components, and constitutes a novel approach to employ perovskites in gas sensors, showing a high potential to improve the performance of other usual graphene decorations. For instance, despite the good results reported by loading graphene with metal oxides, usually these are associated with high cost (derived from the use of noble metals) and high working temperatures. Conversely, the decoration of graphene with perovskite nanocrystals opens a new low-cost production concept linked to low-power consumption devices.

References

[1] J. Casanova-Cháfer, E. Navarrete, X. Noirfalise, P. Umek, C. Bittencourt, E. Llobet, Gas Sensing with Iridium Oxide Nanoparticle Decorated Carbon Nanotubes, Sensors. 19 (2019) 113. doi:10.3390/s19010113.

[2] J. Casanova-Cháfer, R. García-Aboal, P. Atienzar, E. Llobet, Gas Sensing Properties of Perovskite Decorated Graphene at Room Temperature, Sensors. 19 (2019) 4563. doi:10.3390/s19204563.

[3] C. Bao, J. Yang, W. Zhu, X. Zhou, H. Gao, F. Li, G. Fu, T. Yu, Z. Zou, A resistance change effect in perovskite CH₃NH₃PbI₃ films induced by ammonia, Chem. Commun. 51 (2015) 15426–15429. doi:10.1039/c5cc06060e.

Figure 1

Introduction

Recently, reduced graphene oxide (RGO) has been studied and used in many fields due to their intrinsic properties and its easy of fabrication. RGO has high surface area, lots of dangling bonds, oxygen functional groups and defects that contribute enhancement of absorption and interactions with target gases [1]. Also, RGO is retaining flake size and initial graphene oxide layer ratios. Because of those advantages, many researches have been conducted to improve gas sensing properties by synthesizing RGO nanosheets (NSs)-based nanocomposites. In this study, we discussed enhanced gas sensing abilities by incorporating RGO or graphene NSs to metal oxide nanofibers (NFs) and nanoparticles (NPs). First, RGO NSs were incorporated to SnO₂ NFs for enhanced gas sensing abilities. By varying the weight percent of RGO NSs to SnO₂ NFs, the optimal 0.44 wt% of RGO NSs showed highest response to NO₂ gas. Also metal NPs such as Au, Pd, and Pt were functionalized to further increase their gas selectivity to CO, C₆H₆, and C₇H₈ gases. Likewise, RGO NSs were loaded to ZnO NFs and enhanced their H₂ gas sensing ability. Then, for the selective detection of CO and C₆H₆ gases, Au and Pd NPs were functionalized on RGO NSs incorporated ZnO NFs. When RGO NSs were incorporated with CuO NFs, sensing abilities of CuO NFs to H₂S gas were enhanced by balancing the electrons between CuO NFs and RGO NSs. At the end, by utilizing the enriched electrons in graphene NSs, SnO₂ and ZnO powders were mixed with graphene NSs and irradiated with microwaves. As fabricated SnO₂-graphene and ZnO-graphene composites were highly sensitive and selective to NO₂ gas.

Method

For the fabrication of RGO, graphite powder was used as starting material and graphene oxide (GO) was produced using Hummers method. The process of graphite oxidation was conducted by stirring graphite (1g) with H₂SO₄ (46 ml) containing KMnO₄ (12 g) and H₃PO₄ (12 g) to facilitate exfoliation and separation of graphene sheets. After repeating the washing and filtration obtained a very fine brown powder was dried in a vacuum oven. In order to reduce exfoliated GO NSs, the powder was mixed with hydrazine monohydrate and the mixture was heated at 150^oC for 24h. A homogenous RGO NSs suspension was prepared in dimethylformamide (DMF) by sonication. The procedure to synthesize RGO NSs loaded SnO₂ NFs using electrospinning is as follows. First, PVAc was dissolved in mixed solvent composed of ethanol (20 g) and DMF (15 g). Then, SnCl₂2H₂O (2.7 g) and RGO NSs 0.44 wt% were added to the PVAc solution, and stirred for 10 h. Prepared solution was loaded into a syringe equipped with a 21-gauge stainless steel needle with an inner diameter of 0.51 mm. Feed rate, applied voltage, and distance between the tip of needle and collector were fixed at 0.03 mL/h, 15 kV, and 20 cm. Similarly, for the fabrication of RGO NSs loaded ZnO and CuO NFs, zinc acetate (Zn(CH₃CO₂)₂ and copper acetate (Cu(CH₃CO₂)₂) were used as the source materials. For the functionalization of Au, Pd, and Pt NPs, aqueous solution of HAuCl₄nH₂O, PdCl₂, and H₂PtCl₆nH₂O were dissolved in a mixed solution of acetone and 2-propanol, and then exposed to UV radiation for 1 min. To the next, for the fabrication of graphene-SnO₂ and graphene-ZnO nanocomposites, mixture of SnO₂, ZnO nanopowders and graphene were uniformly dispersed in ethanol for 1 h and dried. The dried powder mixture s were put into an alumina crucible and treated by a microwave heating process with a power of 1 kW for 5 min. For sensing tests, double-layer electrode comprising an Au layer (300 nm thick) and a Ti layer (50 nm thick) were deposited on the specimens using sputtering at room temperature.

Results and Conclusions

In the gas sensing test, improved sensing performance was identified by using RGO-based nanocomposites. Sensor response to CO and NO₂ gases of RGO NSs-loaded SnO₂ NFs were superior to those of pure SnO₂ NFs. Also, by incorporating Au NPs to RGO NSs-loaded SnO₂ NFs, sensor response to 5 ppm CO gas was changed from 17.0 to 27.4. Likewise, functionalization of Pd and Pt NPs enhanced the sensing properties of RGO NSs-loaded SnO₂ NFs and showed high response of 12.3 and 16.0 to 5 ppm of C₆H₆ and C₇H₈ gases. Incorporation of RGO NSs to ZnO NFs increased gas response of ZnO NFs to all gases and especially showed extremely high response of 2524.0 to 10 ppm H₂ gas at 400^oC. By decoration Au and Pd NPs on RGO NSs-loaded ZnO NFs, sensor response to 1 ppm CO and C₆H₆ gases showed high response of 23.5 and 11.8. When RGO NSs were loaded on CuO NFs, the sensor response of 0.5 wt% RGO NSs-loaded CuO NFs showed highest response to 10 ppm H₂S gas. Finally, as the extremely enhanced selective NO₂ sensor, SnO₂-graphene and ZnO-graphene composites showed high response of 24.66 and 12.57 to 1ppm NO₂ gas. These enhanced sensing properties will be attributed to the creation of defects due to microwave irradiation, increased surface area and generation of heterojunctions and homojunctions.

References

[1] J. H. Kim, A. Mirzaei, Y. Zheng, J. H. Lee, J. Y. Kim, H. W. Kim, S. S. Kim, Enhancement of H₂S sensing performance of p-CuO nanofibers by loading p-reduced graphene oxide nanosheets, Sensors and Actuators B: Chemical 281, 453-461 (2019); doi: 10.106/j.snb.2018.10.144

Most polymeric materials are insulators. They can be rendered conductive by the addition of appropriate fillers [1]. To obtain the desired conductivity and to ensure spatial homogeneity of the composite, excellent dispersion of the fillers is considered necessary [1,2]. To prepare the composite, solution casting has been widely used and past work suggests that it can adequately disperse the filler in a polymer matrix [3,4]. However, the method involves long preparation times and large quantities of organic solvents, and is not easily scalable. Melt mixing [4-6] offers an attractive alternative as past work [4,5] suggests that it can yield polymer nanocomposites with conductivities similar to that of solution cast samples. They however utilized laboratory scale batch mixing but industrial scale compounding is often performed using melt extrusion [6]. Therefore, in this work, we have investigated the feasibility of twin-screw melt extrusion for nanocomposite preparation by comparing the electrical conductivity of multiwalled carbon nanotubes (MWCNT) filled acrylonitile-butadiene-styrene (ABS) nanocomposites thus prepared to those obtained using internal batch mixing.

First, we measured the electrical conductivity of the polymer nanocomposites prepared by the two methods. As can be seen from Fig. 1, for the samples prepared using the batch mixer, the conductivity exhibited a rapid increase of several orders of magnitude upon addition of a small quantity of MWCNT (less than 1 vol%). Upon further addition of MWCNT, the conductivity increase became less steep. The observed behavior is consistent with results in the literature [1,4] and can be interpreted using percolation theory, which suggests that the sharp increase in the conductivity observed at a certain volume fraction arises because the filler forms a conducting path that percolates across the polymer matrix [1]. Unexpectedly however, for the samples prepared using the twin screw extruder, the results were markedly different in that very little increase in conductivity was observed. If the above interpretation using percolation theory [1] is well founded, this suggests the absence of a percolation path consisting of the MWCNT.

Due to van der Waals attraction, MWCNT tend to aggregate into micron scale clusters. During nanocomposite preparation these clusters must be broken down to facilitate the dispersion of the MWCNT in the matrix. As sufficient dispersion is believed to be necessary for the formation of the conducting path [1,2], we performed dynamic viscoelasticity measurements of the samples prepared by both methods to assess the dispersion state of MWCNT. At 0.227 vol% MWCNT, the storage modulus, G', at low frequencies is lower for the samples prepared using the batch mixer when compared to that prepared using the extruder. Following [1,4], this can be taken to suggest that the dispersion of the MWCNT is poorer in the extruded samples and can be hypothesized to be the reason for the low conductivity. Upon increasing the MWCNT content, the low frequency G' of the samples prepared by both methods differed little from each other and exhibited a plateau. A low frequency plateau in G' is typically considered indicative of the presence of a network structure [1,4]. Data in Fig. 2 would suggest that, at the higher volume fractions, both preparation methods results in the formation of a MWCNT network structure. However, the conductivity values for the two methods are vastly different. If high electrical conductivity cannot arise in the absence of a percolating path, that would suggest the absence of a network structure and directly contradicts the implications of the rheology data. Future work will focus on resolving this contradiction using other methods to characterize the dispersion of the MWCNT in the ABS matrix.

[1] R. M. Mutiso and K. I. Winey, in Polymer Science: A Comprehensive Reference, edited by K. Matyjaszewski and M. Möller, (Elsevier, Amsterdam, 2012), pp. 327.

[2] M. H Kim et al., Korea – Australia Rheology Journal, 31, 179 (2019).

[3] M. H. Al-Saleh, H. K. Al-Anid, and Y. A. Hussain, Composites Part A: Applied Science and Manufacturing, 46, 53 (2013).

[4] S. K. Sukumaran et al., Journal of The Electrochemical Society, 166, B3091 (2019).

[5] S. Dul, A. Pegoretti, and L. Fambri, Nanomaterials, 8, 674 (2018).

[6] A. Dorigato, V. Moretti, S. Dul, S. H. Unterberger, and A. Pegoretti, Synthetic Metals, 226, 7 (2017).

Fig.1 Variation of σ with ϕ: comparison of nanocomposites prepared using a twin-screw extruder (■) and using an internal batch mixer (●).

Fig. 2 Variation of G' with ω at 200℃ for several ϕ: melt extrusion (solid symbols) and batch mixing (hollow symbols). The data for neat ABS is also shown.

Figure 1

Melamine (MA) is non-edible synthetic chemical intentionally added to foodstuffs such as milk and milk products including infant formula as the fake source of protein. Many evidences confirmed that this molecule is primarily responsible for kidney failure by forming kidney stones and then blocking the renal tubes. Therefore, a simple, sensitive and rapid method for online quantification of MA can avoid the consumption of milk products contaminated with MA and possible health risks resulted both socially and economically. The present work reports the development of a chemical sensor from aniline (ANI) and acrylic acid (AA) copolymer films by using concurrent electrochemical polymerization method using MA as a template. After optimization of important parameters and template removal, the performance of the film formed was studied by cyclic and differential pulse voltammetry. The proposed sensor showed a linear current response with various concentrations of MA. The linear range, limit of quantification and limit of detection were 0.1-200 x10^-9 M, 5.73x10^-11M, 1.72 x10^-11M respectively. The sensitivity and selectivity of the sensor achieved may attribute to the synergistic effect of different functional units found on the polymer composite. These functional units competitively bind the template with non-covalent interactions. The sensor was also applied to analyze milk samples and obtained a recovery of 95.87-105.63% with RSD 1.11-2.23%. The good stability and reusability as well as strong affinity to the imprint molecule make the imprinted copolymers the promising functional materials for future sensor development.

There is a current need for an inline arsenic sensing system that can continuously sample aquifer water quality for well drilling and ground water monitoring applications. Concentrations of arsenic oxyanions above 10 μg/L in drinking water are considered dangerous by the World Health Organization [1]. Levels above this in daily consumption can lead to renal toxicity and a condition known as Arsenicosis, which produces lesions on the skin. We are currently developing an Au thin film, As stripping voltammetry flow cell sensing to meet this challenging need. Our findings show that use of gold (Au) nanofilm electrodes physically vapor deposited (PVD) onto porous carbon papers can detect concentrations below 10 μg/L of arsenite, As (III), in water. The nanofilms were characterized by SEM, X-ray diffraction and with X-ray fluorescence with a measured loading of approximately 13 μg of Au per 1 cm² of carbon paper in each electrode. The PVD method increases the manufacturability of aqueous arsenic sensors because it is facile, scalable, and uses much less Au than screen printing methods. Linear stripping voltammetry (LSV) was used in a three-electrode configuration to create a calibration curve for standard additions of 5, 10, 25, 50 and 75 μg/L As (III). The resulting plot of peak area versus concentration resulted in a linear correlation. The capacitance of PVD deposited Au nano films was significantly less than that of Au nanoparticles on XC72 carbon, produced via solution precipitation methods. The lower capacitance enables the detection of low concentrations of As without the need for the application of more complex pulse voltammetry methods.

References

1. WHO, Arsenic in Drinking Water. 2011, World Health Organization.

This research work reports the chemical spray synthesis and nitrogen dioxide (NO₂) and hydrogen (H₂) gas sensor applications of bismuth ferrite (BiFeO₃, abbreviated as BFO) and tungsten-doped bismuth ferrite (W-BiFeO₃, abbreviated as BWFO) nanostructures. The influence of tungsten-doping on the structure, morphology, surface area and the NO₂ and H₂ gas sensors properties was examined and compared with pristine BFO. W-doping was confirmed by X-ray diffraction, energy-dispersive X-ray and Fourier-transform infrared spectroscopy measurements. Based on the results obtained, a model demonstrating the gas sensing performance difference for the BFO and BWFO nanostructures was also proposed. At dilute concentrations (100 ppm) of NO₂ and H₂, BWFO displayed enhanced sensitivity (sensor response) compared to BFO, which can be accounted for by a change in morphology, structure and surface area.

Introduction

A low-cost chemical sensor for ammonia (NH₃) detection is highly demanded nowadays for several important applications. Two-dimensional (2D) nanomaterials such as graphene/reduced graphene oxide (rGO), transitional metal dicharcogenides, black phosphor and transition metal carbonitride (MXene) have found a promising application in the fields of gas sensing electronics at room temperature due to their unique microstructure, electrical properties and excellent gas adsorptions ability. Decoration of the secondary phase such as noble metals and metal oxide nanocrystals to form heterojunctions with two-dimensional materials can effectively improve the inadequacy of two-dimensional materials based gas sensors. It takes advantages of the difference in the Fermi level of each phase to make the electrons transfer from one material to the other and thus enriching the electron concentration on the surface of one material that is dominant in the electrical transport. In this way, more ionized oxygen is chemisorbed, leading to the improvement of the gas sensing properties [1].

In this work, 2D MXene heterojunctions incorporated with SnO₂ nanoparticles have been synthesized by using hydrothermal method. The as-fabricated MXene/SnO₂ heterojunction based chemiresistive-type sensor showed excellent sensitivity to different concentrations of ammonia from 0.5-100 ppm at room temperature. The response has about 20 times higher than those reported in literature to 100 ppm NH₃ and an excellent selectivity.

Preparation and characterizations

The Ti₃AlC₂ was purchased directly from Beijing Forsman Corp. The concentrated hydrochloric acid (HCl) was diluted to 9M. 2g of lithium fluoride (LiF) was added into 20ml diluted hydrochloric acid and stirred with magnetic mixer. 2g Ti₃AlC₂ was slowly and evenly dispersed in the solution over a period of several minutes and subsequently stirred at 35℃ for 48h to obtain the MXene. 70 mg of MXene powder was dispersed in 30ml of deionized water after grinding and sonicated for 30min. 73.5mg of stannic chloride pentahydrate (SnCl₄·5H₂O) was added into the suspension and stirred with magnetic stirrer at room temperature. The suspension was then loaded in a 50ml Teflon-lined autoclave. The autoclave was sealed and heated in an KSL-1200X hydrothermal system at 180℃ for 12h to obtain the MXene-SnO₂ hybirds. The samples were then characterized by XRD, SEM, XPS, Raman and TEM-ED. The MXene/SnO₂ based chemirestive-type sensor was measured by a static volumetric method. The resistance of the sensor is directly measured by a digital multimeter (Agilent 34410A). The responses of the sensors were defined as the relative change in the resistances of the sensors in the air and those in the tested gas.

Results and Conclusions

Fig.1a shows the XRD of the prepared samples. Appearance and down-shift of the peak at ~10 oC indicates the successful achievements of MXene and thus the MXene-SnO₂ composite heterojunctions [2-3].Fig.1 (b-c) show the micrographs of the surface morphology of the MXene and heterojunctions. The etched MXene material has obvious layered structure with sizes ranging from 2 μm to 4 μm. The thickness of MXene is about 75 nm indicating the sample contains about 100 single layers of MXene. The granular SnO₂ nanoparticles are intimately attached to the surface of MXene. Fig.2 (b) shows the Raman spectra of MXene and Mxene/SnO₂ heterojunction. The appearance of both D-band and G-band in the MXene/SnO₂ heterojunction sample indicated that MXene remained well during the hydrothermal reaction. Fig.2(c) shows the Ti core level (2p) spectra of the MXene and MXene/SnO₂. Ti - X corresponds to titanium carbide or titanium oxynitride. Fig.2d indicates that the peaks at 530.1 and 532 eV correspond to oxygen vacancies and O=C-OH, respectively, suggesting that these and surface-adsorbed oxygen tend to form more active sites, thereby enhancing sensing capability.

The sensors using MXene/SnO₂ heterojuction shows excellent response and selectivity to low-level NH₃ from 0.5-9 ppm at RT (Fig.3). Since the work function of MXene (4.465 eV) was slightly lower than that of SnO₂ (4.7 eV), Schottky-type junctions were formed across MXene/SnO₂ interfaces (Fig.4). Electrons would transfer from SnO₂ to MXene, and the depletion layer was deepened on the surface of MXene. MXene could then chemically adsorb more oxygen, and the response of the MXene/SnO₂ heterojunction was thus significantly enhanced.

References

[1] J. M.Walker, S. A.Akbar, P. A.Morris, Synergistic Effects in Gas Sensing Semiconducting Oxide Nano-Hetero- structures: A review, Sens. Actuators B 2019, 286, 624-640. doi: 10.1016/j.snb.2019.01.049

[2] S.J.Kim,H-J.Koh, C. E. Ren, O.Kwon, K.Maleski,S-Y.Cho, B.Anasori, Ch-K.Kim, Y-K.Choi, J. Kim, Y.Gogotsi, H-T.Jung, Metallic Ti₃C₂T_X MXene Gas Sensors with Ultrahigh Signal-to-Noise Ratio, ACS Nano 2018, 12, 986−993.doi: 10.1021/acsnano.7b07460.

[3] E. Lee, A.Vahidi, B. C. Prorok,Y. S. Yoon, M.Beidaghi, D-J.Kim, Room Temperature Gas Sensing of Two-Dimensional Titanium Carbide, ACS Appl. Mater. Interf. 2017, 9, 37184-37190.doi: 10.1021/acsami. 7b11055.

Figure 1

Hydrogen is one of the most important "next generation energy sources", which is free for environment pollution, with water as the only emission. Due to the danger of hydrogen explosion when mixed with air, as well as the low specific heat capacity of hydrogen, the temperature required for combustion can be reached immediately even a little heat absorbed. Therefore, it's necessary to search an effective way to monitor hydrogen leakage at room temperature.

In this study, the Pd based hydrogen sensor was investigated. During the transduction process, volumetric expansion occurred due to the hydrogen absorption at room temperature to achieve safe hydrogen detection. Previous research indicated that Pd/Ni alloy films/ nanofibers can achieve higher catalytic activity, stability and sensitivity than pure Pd films/nanofibers due to the synergistic effect between Pd and Ni^1,2,3. But both the films and nanofibers structures have limited specific surface area and therefore limited exposed hydrogen adsorption sites. To overcome these problems, we fabricated the porous Pd nanotubes alloyed with Ni by using Polyvinylpyrrolidone (PVP) and SiO₂ templates electrospinning route, then the PVP and SiO₂ templates were selectively removed by calcination and etching⁴, respectively. The sensing performance was measured by monitoring the resistance curves of sensing platform at various hydrogen concentrations. Compared to Pd/Ni nanofibers structures, tubular structures achieved lower LOD and higher sensitivity which are attributed to the high surface area and abundant hydrogen adsorption active sites. High performance Pd/Ni nanotubes can be successfully fabricated in an effective and facile approach for hydrogen detection at room temperature. At last, the effects of the concentration of Ni in Pd on the sensing performance was also investigated.

References

1. Guangyang Bao et al, "Synergistic effect of the Pd–Ni bimetal/carbon nanofiber composite catalyst in Suzuki coupling reaction." Org. Chem. Front., 2019, 6,352.

2. Wang, Boyi et al. "Palladium Nanofiber Networks Hydrogen Sensor and Hydrogen-Actuated Switches: Proceedings of the 5th International Conference on Sustainable Design and Manufacturing (KES-SDM-18)." 10.1007/978-3-030-04290-5_12.

3. Feng, Li et al. "Pd–Ni Alloy Nanoparticles as Effective Catalysts for Miyaura–Heck Coupling Reactions." The Journal of Physical Chemistry C 2015 119 (21), 11511-11515 DOI: 10.1021/jp510988m

4. Peresi Majura Bulemo et al, "Mesoporous SnO2 Nanotubes via Electrospinning−Etching Route:Highly Sensitive and Selective Detection of H2S Molecule." October 17, 2019 at 10:40:01 (UTC).

Motivation

Cell signaling proteins have been widely regarded as some of the most powerful biomarkers for cancer diagnosis because they are real therapy related molecules. Extracellular vesicles, exosomes, transport proteins to promote tumor growth and are stable in biofluids at room temperature.^[1] Hence, detection of exosomal proteins (e.g., cluster of differentiation (CD) 9, CD 63, CD 81) would be easily deployed at the point-of-care (POC) diagnostic. A successful electrochemical biosensor is generally determined by electrodes and their modification as well as specific bio-recognition elements (BREs).

Graphene like MoS₂ has emerged in biosensing applications owing to their intriguing properties, such as good catalytic properties, interesting metallic-to-semiconducting transition from 1T to 2H phase, and good biocompatibility.^[2] However, a particularly vexing problem for MoS₂ as the sensing materials is the structural instability that the exfoliated or ultrathin two dimensional (2D) MoS₂ is hard to be retained in in their freestanding state. The surface modification technologies, such as growth of building blocks could transfer the 2D to relatively stable 3D nanoarchitectures, in which each component can also exert different function.

Herein, we demonstrate a nanostructure consisting of zinc oxide (ZnO) nanowires (NWs) array grown on 2D MoS₂forming a new nanoarchitecture (ZnO-MoS₂) providing high specific surface area and good electron transport capability. Then, zeolitic imidazolate framework 90 (ZIF-90) thin films are in-situ deposited onto ZnO NWs by using ZnO as precursor to directly react with imidazole-2-carboxyaldehyde (ICA). The integrated hybrid nanostructure, denoted as ZIF-90-ZnO-MoS₂, possesses not only effective mass transport and electron transduction capabilities but also covalent bio-conjugation of BREs through the aldehyde group on the bridging ICA ligand in ZIF-90. Of particular note is the ZnO NWs array is an indispensable part of the hybrid nanostructure, since the in-situ growth of ZIF-90 and effective integration with layered MoS₂ is still a challenge. Through the cooperation of three different kinds of building blocks, from signal generation, amplification to transduction could be achieved in an integrated nanoarchecture.

Results and Discussion

Figure 1a displays the scanning electron microscope (SEM) image of obtained ZIF-90-ZnO-MoS₂ nanohybrid, from which the ordered NWs array is uniformly grown onto 2D MoS₂ material. The higher magnification SEM (Figure 1b) and transmission electron microscopy (TEM) (Figure 1c) images show that the length and diameter of vertical ZnO NWs are 1.5 μm and 50 nm, respectively. Further high resolution TEM (HR-TEM) (Figure 1d) characterization demonstrates that the NWs are consisted of highly crystal ZnO core with the diameter of about 25 nm and ZIF-90 sheath with the thickness of about 12 nm.

A FITC-labeled goat anti-human immunoglobulin G (IgG) is employed to verify our hypothesis. The inset of Figure 1e shows the fluorescence microscopy image of microelectrode immobilized with FITC-labeled goat anti-human IgG. It can be seen that only the region deposited with ZIF-90-ZnO-MoS₂ nanohybrid visualizes green fluorescence. This result illustrates ZIF-90-ZnO-MoS₂ nanohybrid possesses the capability of direct covalent bio-conjugation of antibody. And the results shown Figure 1e further confirm the developed hybrid material could effectively detect signaling protein.

We next fabricated a microfluidic electrochemical microsensor chip, and the configuration is shown in Figure 1f. The microsensor chip is composed of a polydimethylsiloxane (PDMS) layer sealed with screen-printed electrodes. The microsensor is consisted of five electrodes, including counter electrode (CE), reference electrode (RE) and three different working electrodes. Among the three working electrodes, electrode 1 and 2 are locally deposited with fabricated ZIF-90-ZnO-MoS₂ nanohybrid material as the test electrodes, and electrode 3 is printed with carbon conductive ink for the background signal deduction. The micro-channels on the chip are employed for the simultaneous immobilization of bio-recognition antibodies as well as dual detection of exosome markers (CD63 and CD9). From Figure 1g, our fabricated microsensor chip shows obvious response towards NCI-H 1650, and almost no signal for other cells supernatant (NCI-H 1650: human non-small cell lung cancer cells, 16 HBE: human bronchial epithelial cells, HFL-1: human fetal lung fibroblast-1 and HUVEC: human umbilical vein endothelial cells).

Conclusion

In summary, the ZIF-90-ZnO-MoS₂ nanohybrid integrated with different kinds of building blocks realizes the cooperation of multi-function, including covalent bio-conjugation of antibodies, signal generation and transduction. To further combine with microfluidic electrochemical microsensor chip, the simultaneous immobilization of bio-recognition antibodies and dual detection of exosome markers can also be acquired.

References

[1] Cormac Sheridan, Nature Biotechnology 2016, 4, 359.

[2] Varnika Yadav, Shounak Roy, Prem Singh, Ziyauddin Khan and Amit Jaiswal, Small 2019, 15, 1803706.

Figure 1

Introduction

Compact and low-cost gas sensors are urgently sought in emerging applications including indoor air monitoring[1], search and rescue[2], and medical diagnostics[3]. While chemo-resistive sensors feature remarkable sensitivities to detect even parts-per-billion (ppb) concentrations, a key limitation is selectivity, impeding commercial use[4]. An important interfering molecule is ethanol due to its omnipresence in the environment at high concentrations. In specific, ethanol concentrations may reach high parts-per-million (ppm) levels released from disinfectants and cleaning agents[5], thus exceeding trace level concentrations of target analytes such as acetone in breath analysis (500 ppb in healthy humans[6]) or carcinogenic benzene in indoor air (8 h exposure limit of 50 ppb in the EU[7]) by orders of magnitudes. This is particularly problematic, as most sensors (e.g. carbon-based or metal-oxide sensors) are sensitive to ethanol. Thus, ethanol interference is a major concern even for sensors with rather high selectivity to ethanol.

A simple approach to mitigate ethanol interference is through interface design, i.e., by combining sensors with a modular filter. Thereby, the filter is placed before the sensor to pre-select complex gas mixtures. Particularly suitable are catalytic filters[8], as they allow continuous conversion of active species into inactive species, while target analytes remain unscathed. State-of-the-art catalytic filters, however, do not allow to distinguish between volatile organic compounds such as ethanol and acetone. Here, we explore the use of a highly selective flame-made nano-catalyst as packed bed filter for the removal of ethanol in gas mixtures at high relative humidity (RH).

Method

Nano-catalyst filters were installed before flame-made Si-doped WO₃[3] sensors. The performance of the filter-sensor system was characterized with a gas mixing setup at high RH (90%) and calibrated gas standards. Finally, the filter was tested as proof of concept with the breath of an alcohol-intoxicated volunteer. Therefore, a single volunteer consumed 150 mL of red wine prior to experiments. Thereafter, ethanol concentrations were investigated in three consecutive breath pulses both with and without the activated nano-catalyst with a proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS).

Results and Conclusions

The sensor response to breath-relevant 0-1 parts per million (ppm) acetone in presence of 0-20 ppm ethanol at 90 % RH is shown in Figure 1. Without the activated filter, the sensor clearly detects even low acetone concentrations (0.25 ppm) in absence of ethanol with high response (4) and signal to noise ratio > 100 (Figure 1a, squares). However, when testing gas mixtures with additional 5 (triangles), 10 (diamonds) or 20 (stars) ppm of ethanol, the sensor response is shifted upwards, resulting in an overestimation of acetone concentration. In contrast, with the activated filter, the interference of ethanol is reduced significantly, for example by 88% in case of 20 ppm ethanol only (stars) (Figure 1b). The residual error (e.g., 25% at 0.5 ppm acetone with 20 ppm ethanol) can be attributed to the formation of H₂ during ethanol oxidation.

Figure 2 shows the ethanol concentration profile for three consecutive exhalations of an alcohol-intoxicated volunteer without (0 ≤ t ≤ 3 min) and with (t > 3 min) the nano-catalyst filter. Without filter, ethanol concentrations reach 185 ppm as measured by PTR-ToF-MS. Most importantly, with filter, such high ethanol concentrations are removed completely even in the complex gas mixture of breath (> 800 compounds[9]). As a result, this filter presents a simple and inexpensive solution to the long-standing challenge of interference of chemical sensors by high concentrations of ethanol. Due to its compact and modular design, it can be flexibly combined with any type of gas sensor and integrated into portable devices for wide applicability.

References

[1] C. S. Lee, Z. Dai, D. H. Kim, H. Y. Li, Y. M. Jo, B. Y. Kim, H. G. Byun, I. Hwang, and J. H. Lee, Highly discriminative and sensitive detection of volatile organic compounds for monitoring indoor air quality using pure and Au-loaded 2D In₂O₃ inverse opal thin films, Sensors Actuators, B Chem., 273, (2018) 1–8.

[2] A. T. Güntner, N. J. Pineau, P. Mochalski, H. Wiesenhofer, A. Agapiou, C. A. Mayhew, and S. E. Pratsinis, Sniffing Entrapped Humans with Sensor Arrays, Anal. Chem., 90, (2018) 4940–4945.

[3] A. T. Güntner, N. A. Sievi, S. J. Theodore, T. Gulich, M. Kohler, and S. E. Pratsinis, Noninvasive Body Fat Burn Monitoring from Exhaled Acetone with Si-doped WO₃-sensing Nanoparticles, Anal. Chem., 89, (2017) 10578–10584.

[4] A. T. Güntner, S. Abegg, K. Königstein, P. A. Gerber, A. Schmidt-Trucksäss, and S. E. Pratsinis, Breath Sensors for Health Monitoring, ACS Sens., 4, (2019, 268–280.

[5] V. Bessonneau and O. Thomas, Assessment of exposure to alcohol vapor from alcohol-based hand rubs, Int. J. Environ. Res. Public Heal., 9, (2012) 868–879.

[6] C. Turner, P. Španěl, and D. Smith, A longitudinal study of ammonia, acetone and propanol in the exhaled breath of 30 subjects using selected ion flow tube mass spectrometry, SIFT-MS, Physiol. Meas., 27, (2006) 321–337.

[7] ECHA - European Chemicals Agency, Opinion on scientific evaluation of occupational exposure limits for benzene.

[8] M. Fleischer, S. Kornely, T. Weh, J. Frank, and H. Meixner, Selective gas detection with high-temperature operated metal oxides using catalytic filters, Sensors Actuators, B Chem., 69, (2000) 205–210.

[9] B. De Lacy Costello, A. Amann, H. Al-Kateb, C. Flynn, W. Filipiak, T. Khalid, D. Osborne, and N. M. Ratcliffe, A review of the volatiles from the healthy human body, J. Breath Res., 8, (2014), 014001 (29pp).

Figure 1

Introduction

Photoelectrochemical (PEC) analysis is a sensing technology that combines photochemistry and electrochemistry effectively. Nowadays, most of PEC analysis use ultraviolet/visible light as a light source [1]. Compared with visible/ultraviolet light, near-infrared (NIR) owns a strong penetrating ability and can directly penetrate tissue, glass and plastic packaging, thus has a good prospect in practical application. However, only a few researchers use NIR light as a light source for the PEC sensing platforms. The biggest problem is difficult to find a photovoltaic material that can absorb NIR efficiently while having high efficiency of PEC conversion due to the longer wavelength and less energy of NIR. Thereby, exploring some new NIR PEC materials is conducive to the development of advanced PEC sensing platforms.

NIR Response of PEC Biosensor for MC-LR

Silver sulfide (Ag₂S) is a narrow-band semiconductor material with high chemical stability. Its band gap is about 1.1 eV, thus is capable absorb light in the NIR region [2]. AuNPs have good electrical conductivity and SPR effect. This paper developed an unlabeled PEC biosensor of MC-LR based on AuNPs/Ag₂S/FTO. The sensor utilized an antibody as a capture probe immobilized on the surface of the AuNPs/Ag₂S/FTO to recognize the target selectively. After adding MC-LR to the detection system, the fabricated composite electrode absorbed the inactive MC-LR, which would cause steric effects and limit the surface electron transfer, resulting in a decrease in photocurrent. Therefore, the MC-LR can be detected quantitatively based on the decrease in the intensity of the photocurrent. The sensor reveals a large detection range, high sensitivity, good selectivity and excellent stability.

Method

For the preparation of AuNPs/Ag₂S/FTO, polyvinylpyrrolidone was dissolved in ethylene glycol first, and then added with potassium iodide and sodium sulfide under stirring to obtain Ag₂S cubes. The above Ag₂S suspension was then dropped onto the FTO surface and dried at room temperature [3]. After that, 5 μL of AuNPs were added to the surface of Ag₂S/FTO and dried at 60 ℃ to obtain AuNPs/Ag₂S/FTO. For determination of MC-LR, chitosan and glutaraldehyde were used to immobilize antibodies. After activation, 50 μL of 50 μg L^–1 MC–LR Ab was dropped onto the electrode and then incubated at 37 °C for 4 h. After incubation, the Ab/AuNPs/Ag₂S/FTO was rinsed with phosphate buffer solution containing 0.05 % Tween–20 solution and then incubated in 1 % (w/v) BSA solution to block the unbound sites. The final electrode was incubated into 50 μL of 5 μg L^–1 MC–LR solutions for 1 h at 37 °C, followed by washing with the phosphate buffer solution for three times.

Results and Conclusions

The typical SEM images were employed to characterize the morphology and microstructure of the as-prepared AuNPs/Ag₂S/FTO electrodes. As showed in Fig. 1A, the Ag₂S on the surface of the electrode exhibited unique cubic arrangement with a size of 4.5 µm (inset of Fig. 1A). After modification of AuNPs, the SEM image also showed clearly that the original cubic morphology of Ag₂S, and the PEI-stabilized Au NPs were spherical in shape with diameters of 20-45 nm (inset of Fig. 1B), indicating that AuNPs solution only forms a film on the surface of Ag₂S, which does not destroy the original cubic shape of Ag₂S. To evaluate the PEC behaviors of the modified electrodes, the I-t curves were recorded by our homemade NIR responsive PEC system under a bias potential of 0.6 V with the excitation light at 980 nm (Fig. 2). We found that by immobilizing Ab, BSA blocking and incubation with the target analyte MC-LR, the photocurrent was gradually reduced, which can be attributed to the inhibition of interface electrons transfer by these modified substances on the BSA/Ab/AuNPs/Ag₂S/FTO electrodes. Based on the reduction effect of this signal, the quantitative analysis of MC-LR can be achieved.

References

[1] B.C.Li, Y.F.Chen, A.H.Peng, X.M.Chen, X.Chen, Improved photoelectrochemical properties of tungsten oxide by modification with plasmonic gold nanoparticles for the non-enzymatic sensing of ethanol, Journal of colloid and interface science. 537 (2019): 528-535. doi: 10.1016/j.jcis.2018.11.061

[2] R.Y.Li, W.W.Tu, H.S.Wang, Z.H.Dai, Near-infrared light excited and localized surface plasmon resonance-enhanced photoelectrochemical biosensing platform for cell analysis, Analytical chemistry 90.15 (2018): 9403-9409. doi: 10.1021/acs.analchem.8b02047

[3] J.B.Zeng, M.Li, A.Liu, F.F.Teng, T.Zeng, W.Duan, M.M.Li, M.F.Gong, C.Y.Wen, Y.D.Yin, Au/AgI dimeric nanoparticles for highly selective and sensitive colorimetric detection of hydrogen sulfide. Advanced Functional Materials 28.26 (2018): 1800515. doi:10.1002/adfm.201800515

Figure 1

Signal-stimulated (bio)molecular release has been extensively studied and reported in numerous research papers, reviews and books,¹ being motivated by various biomedical and biotechnological applications. Among many other molecular, biomolecular and nano-size species, DNA molecules have been studied for the signal-controlled release, being highly important for gene delivery therapy, biosensors, biochips, unconventional biocomputing, and for many other applications. Various signals triggering DNA release have been used including application of altering electromagnetic field, photochemical capture and release of DNA, thermally stimulated release of DNA, etc. Electrochemically triggered DNA release is particularly attractive due to its simple realization and versatility. Specifically, these developed systems are designed for different release processes triggered by various signals (electrical, biomolecular, illumination, etc.), thus representing a general interfacial platform for controlled release of different biomolecules and nano-size species.²

Herein, we report on the DNA releasing system controlled by local/interfacial pH changes triggered by a very small potential applied to reduce oxygen bioelectrocatalytically with the help of immobilized bilirubin oxidase (Box). Notably, the DNA release was only a convenient model, while the developed approach can be adapted to the electrically stimulated release of any negatively charged (bio)molecules or nano-species.³

1. Li, X.; Jasti, B. R. Design of Controlled Release Drug Delivery Systems, McGraw-Hill Education, New York, 2005.

2. Masi, M.; Bollella, P.; Katz, E. Electroanalysis2019, 31, in press, published on-line (DOI: 10.1002/elan.201900377).

3. Masi, M.; Bollella, P.; Katz, E. ACS Applied Materials and Interfaces2019, Submitted.

Introduction

Surface molecular imprinting [1,2] is one of the preferred techniques when it comes to generating biomimetic recognition for sensing bioanalytes. Limiting oneself to the surface of the respective molecularly imprinted polymer (MIP) usually is no problem, because biospecies are usually large enough that few binding events lead to measurable sensor responses, e.g. for mass-sensitive bacteria detection [3]. However, the detection limits of quartz crystal microbalances (QCM) do usually not meet the needs for detecting contamination of real-life samples when it comes to pathogen detection. The (geometrical) limitation of surface MIP in that regard makes it necessary to think about suitable systems for pre-concentration prior to the sensor measurement. Herein, we report Raman Microscopy studies on bacteria surface MIP aiming at visualizing different areas of the polymer and distinguishing between different species bound to the surface. Furthermore, we assess the binding properties of MIP resulting from Pickering emulsion polymerization [4] as a possible approach to selectively pre-concentrate bacteria.

Experimental

For molecular imprinting, we chose a non-pathogenic strain of Escherichia coli (E. coli) as a model species. We prepared surface MIP of two different morphologies based on polystyrenes cross-linked with divinyl benzene utilizing azo-bisisobutyronitrile (AIBN) as a radical initiator. For MIP thin films, we prepared respective mixtures of monomer and crosslinker, pre-polymerized at 70°C, and then spin-coated onto the respective devices. In parallel, we prepared stamps comprising E. coli on their surfaces. Then, we pressed the stamp into the oligomer thin films on the respective surface and cured the system at 80°C over night. We took all spectra on a confocal Raman Microscopy system (WiTec alpha300RAS) at an excitation wavelength of l=532nm. Chemometric data evaluation relied on the software package Solo&Mia by Eigenvector. For Pickering emulsion, we prepared mixtures of styrene and divinylbenzene and used bacteria to emulsify them in either distilled water, or a suitable buffer system (e.g. 10mM PBS) and polymerized the bacteria stabilized droplets at 37°C. Then, we removed E. coli cells from the polymer surface via solvent extractions in acetic acid + SDS, water and methanol.

Results and Discussion

In a first step it was essential to clarify if one can use the Raman spectra of different bacteria species and polymer, to differentiate between those, respectively. Polymer and bacteria spectra obviously differ from each other enough to distinguish them by the naked eye. However, this is not the case for the Raman emission spectra of different bacteria species, because they all contain nucleic acids, proteins, and lipids. Therefore it is necessary to rely on chemometric strategies – modified partial least squares discriminant analysis (PLS-DA) in the concrete case – to achieve such goal. This is indeed possible: Fig. 1A shows the outcome for four different bacteria species, namely Escherichia coli, Lactococcus lactis, Bacillus cereus and Staphylococcus epidermidis that clearly demonstrates separation of the species according to their spectral properties. Knowing the specific spectral ranges also allows for generating false-color images showing which areas of a bacteria MIP surfaces reveal pure polymer and which parts contain bacteria of different species. It is even possible to go one step further: Comparing AFM and false color so-called RamanTV images (see Fig. 1B) for an example of the latter) demonstrates that the Raman microscope is even useful for distinguishing polymer surface and imprinted cavities. For such micrometer-sized analytes, the combination of Raman microscopy and AFM hence allows for generating maps showing all possible types of surfaces, i.e. polymer matrix as well as both unoccupied cavities and different bacteria species present at the polymer surface. This opens the perspective of directly visualizing occupancy and selectivity of the respective MIP.

AFM turned out useful to visualize such imprints not only on flat surfaces, but also on curved ones: Figure 1C) and 1D) reveal an imprinted site on the surface of a miroparticle resulting from emulsion polymerization, Fig. 1E) an SEM image showing occupied and empty cavities. One can generate such cavities in different polymer matrices, for instance when replacing divinyl benzene as a cross-linker by trimethyolylpropane trimethacrylate (TRIM), or ethylene glycol dimethacrylate (EGDMA). In both cases, the respective imprinted surface reveal cavities that fit the size and shape of the template bacteria. Scanning electron microscopy also revealed that bacteria re-occupy those cavities if one exposes the particles to to bacteria suspensions. This leads to two conclusions: first, one can tune polymer properties without destroying the emulsion structure necessary for Pickering emulsion. This is of interest for bringing the artificial system closer to physiological conditions. Second, those particles are inherently suitable for selectively pre-concentrating those species from larger samples.

References

[1] O. Hayden, P. A. Lieberzeit, F. L. Dickert. Artificial Antibodies for Bioanalyte Detection—Sensing Viruses and Proteins. Adv. Funct. Mater. 16 (2006) 1269-1278; DOI: 10.1002/adfm.200500626

[2] P. Cornelis et al., Sensitive and specific detection of E. coli using biomimetic receptors in combination with a modified heat-transfer method, Biosens. Bioelectron. 136 (2019) 97-105; DOI: 10.1016/j.bios.2019.04.026

[3] R. Samardzic et al., Quartz Crystal Microbalance In-Line Sensing of Escherichia Coli in a Bioreactor Using Molecularly Imprinted Polymers. Sens. Lett. 12 (2014) 1152-1155; DOI:10.1166/sl.2014.3201

[4] X. Shen et al. Bacterial imprinting at pickering emulsion interfaces. Angew. Chem. Intl. Ed. 53 (2014) 10687-10690; DOI: 10.1002/anie.201406049

Figure 1

External signal-stimulated release of (bio)molecules is used in many biotechnological and biomedical applications¹. It has been well documented over decades, resulting in vast group of physical and chemical systems functioning differently and reacting to different signals. Among various molecule-releasing systems responding to different activating signals (e.g.; optical, magnetic, chemical, mechanical, temperature change, etc.); electrochemical systems is one of the most important and interesting research fields. Besides systems controlled by electrostatic attraction/repulsion of molecules at polarized electrode surfaces^2,3, more sophisticated systems that are able to release only specific molecules are based on molecular and supramolecular systems can be tailored. In the latter case, selected molecules are included in complex structures assembled at electrode surfaces and disassembled upon electrochemical processes. Some of these systems have electrochemically cleavable covalent bonds (e.g., disulfide bonds), which results in the release of the connected molecules upon redox reaction. While the electrochemical cleavage of bonds based on the redox transformations is a very powerful and successful approach in clean model systems, it may be significantly complicated in the presence of other redox species appearing in complex biological media. Thus, more universal approaches to the electrochemically stimulated cleavage of chemical bonds should be investigated. Herein we report a new linker with a hydrolysable phenolic ester bond at basic pH (~8-10) for electrode modification. Basic pH locally produced at the electrode surface upon electrochemical reduction of oxygen resulted in the hydrolytic cleavage of the phenolic ester bond and release of the immobilized fluorescent dye used as a model compound⁴.

ǂ These authors equally contributed to the work

References:

1. Katz, E., Pingarron, J. M., Mailloux, S., Guz, N., Gamella, M., Melman, G., & Melman, A. Substance release triggered by biomolecular signals in bioelectronic systems.The journal of physical chemistry letters, 2015, 6(8), 1340-1347.

2. Sempionatto, J. R., Gamella, M., Guz, N., Pingarrón, J. M., Pedrosa, V. A., Minko, S., & Katz, E. Electrochemically Stimulated DNA Release from a Polymer‐Brush Modified Electrode. Electroanalysis, 2015, 27(9), 2171-2179.

3. Masi, M., Bollella, P., & Katz, E. Biomolecular Release Stimulated by Electrochemical Signals at a Very Small Potential Applied. 2019, Electroanalysis. Accepted manuscript.

4. Bellare, M.; Kadambar, V. K.; Bollella, P.; Katz, E. and Melman, A; Electrochemically stimulated molecule release associated with interfacial pH changes Commun., 2019, 55, 7856-7859.

Electrochemical aptamer-based (E-AB) sensors are a technology that enables precise measurements of specific molecular targets in the body. They have been demonstrated to support real-time therapeutic drug monitoring and feedback-controlled drug dosing in living animals. However, one drawback of E-AB sensors is the rapid degradation of their sensing interface upon continuous interrogation in biological fluids by, for example, voltammetry. Over time, the faradaic current from their aptamer-attached redox reporter decreases, and the currents from charging the electrical double-layer increase beyond the faradaic current, thus preventing signaling. The latter effect is due to progressive desorption of electrode-passivating alkyl thiol monolayers employed in these sensors. This progressive degradation limits their in-vivo operational life to hours, a period too short for monitoring the vast majority of drugs in humans, which generally have half-lives on the order of days. In response, our laboratory is investigating novel monolayer chemistries that extend the operational life of E-AB sensors without compromising their sensing performance or biocompatibility. In this presentation, I will discuss the effects that different monolayer chemistries have on E-AB sensing performance and how they extend the in-vitro operational life of E-AB sensors for days in undiluted biological fluids.

Typically, DNA SAMs used for electrochemical based sensing are prepared without controlling the gold electrode potential[1]. Applying a potential during DNA deposition enables control over the coverage and DNA organization[2-4]. These characteristics are determined by the composition of the immobilization buffer, the immersion time, the DNA concentration, the extent of backfilling with a small alkylthiol and whether deposition occurs on a bare or alkythiol coverage gold surface[3-4]. Few studies have explored the influence of the underlying surface crystallography. Here, we show the possibilities of using electrochemical potential control to manipulate the characteristics of the DNA SAM. Moreover, the use of a single crystal gold bead electrode, coupled with the use of a fluorophore tagged DNA and fluorescence microscopy, enables examination of the influence of the underlying surface crystallography on the DNA SAM prepared. Various constant potentials were used as well as using a square-wave potential perturbation during deposition. There are significant differences in the DNA SAM produced under these conditions. In some cases, the DNA coverage was low on the <111> surfaces, higher on more open or atomically rough regions. In other cases, the coverage was higher on the <100> surfaces as compared to the other regions. The use of constant positive or negative potentials (vs SCE) resulted in significant differences in the relative coverages among regions of different atomic arrangements (Fig 1). In addition, a significant difference was observed between immobilization buffers that contain Cl and those that are Cl free. Also, the use of constant or square-wave potential perturbations resulted in significantly different local organizations of DNA in the SAM. Examples of these types of DNA SAM surfaces will be presented with some conclusions on the implications for use on polycrystalline planar gold surfaces.

References:

[1] Xiao, Y.; Lai, R. Y.; Plaxco, K. W. Preparation of Electrode-Immobilized, Redox-Modified Oligonucleotides for Electrochemical DNA and Aptamer-Based Sensing. Nat. Protoc.2007, 2 (11), 2875–2880.

[2] Jambrec, D.; Kayran, Y. U.; Schuhmann, W. Controlling DNA/Surface Interactions for Potential Pulse‐Assisted Preparation of Multi‐Probe DNA Microarrays. Electroanal.2019, 410, 3.

[3] Leung, K. K.; Gaxiola, A. D.; Yu, H. Z.; Bizzotto, D. Tailoring the DNA SAM Surface Density on Different Surface Crystallographic Features Using Potential Assisted Thiol Exchange. Electrochim. Acta2018, 261, 188–197.

[4] Leung, K. K.; Yu, H. Z.; Bizzotto, D. Electrodepositing DNA Self-Assembled Monolayers on Au: Detailing the Influence of Electrical Potential Perturbation and Surface Crystallography. ACS Sens.2019, 4 (2), 513–520.

Figure 1:

Figure 1

Introduction

Nicotinamide Adenine Dinucleotide (reduced form), NADH is a very important redox compound that is essential for metabolic reactions and ATP production in all living cells. Intracellular NADH metabolism is also important to consider the cancer treatment. Intracellular NADH has been conventionally measured by WST assay using a cell membrane-permeable redox mediator, 1-methoxy PMS (1-Methoxy-5-methylphenazinium methylsulfate) and a water soluble tetrazolium to form formazan. This colorimetric method is very easy and useful for cell counting and cytotoxicity test. However, WST assay is time-consuming and then it is not able to apply for evaluation of acute cytotoxicity by chemical compounds including drugs and pollutants. On the other hand, some research groups have already shown that electrochemical method with double mediator system is useful to monitor rapidly intracellular NADH level corresponding to the cell viability [1-5].

In this paper, we would like to report the usefulness of the electrochemical interface using a small screen printed carbon electrode (SPCE) and a new double mediator system combining 1-methoxy PMS and ferricyanide. It was demonstrated that our electrochemical interface was available for faster and wide range of mammalian cell counting as compared with WST assay. Furthermore our method could be applied to acute cytotoxicity test on mammalian cells. The optimization of measurement condition is mentioned in the presentation and the advantages of our new double mediator system against other double mediator system are also discussed in the presentation.

Method

We used PC12 cell (Rat adrenal pheochromocytoma cell line) as a mammalian cell sample. The cells were grown in culture flasks containing DMEM with 5% FBS and 10%HS at 37℃ with 5% CO₂ atmosphere. For the cell counting experiment, the medium was exchanged to HBSS before experiments. Cells were removed from the bottom of culture flask by trypsin treatment and suspended in HBSS. After measurement of cell density of the original cell suspension with a hemocytometer, cell suspension was exactly diluted to prepare various density of cell suspension. Each diluted cell suspension was taken in a well of 96 well plate and final concentration of 500 μM potassium ferricyanide and 10 μM 1-metoxy PMS solution were added in a drop wise to the cell suspension. After incubation for 10 minutes, a SPCE (working electrode area is 1 mm²) was immersed into the cell suspension and chronoamperometric measurement was immediately performed by potential application at +0.5V vs. Ag/AgCl reference electrode on the SPCE. The electrochemical measurement was carried out using a potentiostat (Multi-Autolab Cabinet, Metrohm Autolab).

We further tried to test the acute cytotoxicity of oxamic acid that is a famous inhibitor of anaerobic glycolysis. Acute cytotoxicity test was carried out with the same electrochemical instrument by following procedure. Each concentration of oxamic acid/HBSS was prepared and added into PC12 cell/HBSS suspension (5.5 x 10⁵ cells /well) in a well (final concentration of oxamic acid: 0 to 20 mM) and the cell suspension was incubated for 1hour. And then potassium ferricyanide (final 500 mM) and 1-metoxy PMS (final 10 μM) solutions were added into the cell suspension. After incubation for more 10 minutes, a SPCE was immersed into the cell suspension and chronoamperometric measurement was immediately performed by potential application at +0.5V.

Results and Conclusions

In the first place, it was demonstrated that our electrochemical interface with a new combination of double mediator system was very useful for very wide range of cell counting. The amperometric oxidation current showed very good linearity vs. the number of viable cells in the range from 7500 to 964000 cells/well (Data is not shown). The result strongly supported the combination of 1-methoxy PMS and ferricyanide is effective to monitor intracellular NADH level and to speculate the cell viability.

Therefore, in the second place, we applied our electrochemical interface to test the acute toxicity by oxamic acid. The inset of Figure 1 shows the decrease of oxidation current of the double mediator system after 1 hour oxamic acid treatment. The decrease of oxidation current was clearly dependent on the concentration of oxamic acid. It indicated that intracellular NADH level corresponding to the cell viability was rapidly decreased by oxamic acid treatment. This result suggested that our electrochemical interface with a new double mediator system might be useful to evaluate acute cytotoxicity of drugs.

References

[1] A. Heiskanen, J. Yakovleva, C. Spégel, R. Taboryski, M. Koudelka-Hep, J. Emnéus, T. Ruzgas, Amperometric monitoring of redox activity in living yeast cells: comparison of menadione and menadione sodium bisulfite as electron transfer mediator, Electrochem Commun, 6 (2004) 219-224.

[2] A. Heiskanen, C. Spégel, N. Kostesha, S. Lindahl, T. Ruzgas J. Emnéus, Mediator-assisted simultaneous probing of cytosolic and mitochondrial redox activity in living cells, Anal Biochem, 384 (2009) 11-19.

[3] R.Y.A. Hassan, U. Bilitewski, A viability assay for Candida albicans based on the electron transfer mediator 2,6-dichlorophenolindophenol, Anal Biochem, 419 (2011) 26-32.

[4] M. Rahimi, H.Y. Youn, D.J. McCanna, J.G. Sivak, S.R. Mikkelsen, Application of cyclic biamperometry to viability and cytotoxicity assessment in human corneal epithelial cells, Anal Bioanal Chem, 405 (2013) 4975-4979.

[5] Y. Matsumae, Y. Takahashi, K. Ino, H. Shiku, T. Matsue, Electrochemical monitoring of intracellular enzyme activity of single living mammalian cells by using a double-mediator system, Anal Chim Acta, 842 (2014) 20-26.

Figure 1

Molecularly imprinted polymers (MIPs) are known as an alternative for antibodies in immunosensors with high stability and low production cost. MIP approach relies on polymerization in the presence of a template molecule and subsequent template removal. In this process, the template molecule is exactly the same as the target molecule leading to a good selectivity for the biomimetic sensor [1]. The integration of MIPs with nanomaterials enables ultrasensitive sensors for various analytes. Besides, nanomaterials with uniform distribution and suitable morphology provide a wide linear range of detection for the sensor [1]. In particular, the controlled electrodeposition of gold can supply gold nano-micro islands (NMIs) with remarkable electrochemical behavior and high active surface area [2, 3]. However, it is found that the modification of an electrode surface using electrochemically reduced graphene oxide (ERGO), as a facile and fast method, not only increases the surface area but also improves its electrochemical behavior [4]. Herein, we describe a surface modification strategy based on indium tin oxide (ITO) electrode coated with ERGO to increase the surface active sites for nucleation and deposition of NMI. For this aim, we electrochemically reduced graphene oxide (GO) by one cycle in cyclic voltammetry (CV) with a scan rate of 100 mV s^-1 in the range of -0.6 to -2 V_Ag/AgCl. The succeed of the electrochemical reduction was confirmed through I_D/I_G ratio in Raman spectroscopy and observing the enhanced electrochemical behavior in CV and electrochemical impedance spectroscopy (EIS) tests. The gold layers were deposited at 0 and -0.4 V_Ag/AgCl in 5, 50 and 100 mM HAuCl₄ solutions for 50 and 300 s. The surface area of the resulted structures was also determined by integrating the reduction peak in CV tests in 50 mM H₂SO₄ solution [2]. The results showed that the gold structure deposited from 100 mM HAuCl₄ at 0 V_Ag/AgCl for 50 s provided a significant surface area (0.47 cm²) on the electrode surface of 1 mm diameter, while this value for gold nanoparticles, as the common form of gold nanostructure in electrochemical biosensing, was determined only 0.063 cm². This noticeable increase in surface area can result in a wide linear range of detection as well as excellent electrochemical behavior in biosensing applications. Scanning electron microscopy (SEM) of NMI structures deposited on both ITO and ERGO/ITO electrodes indicated a shrub-like structure because of the concentration polarization governed during gold deposition. Transmission scanning electron microscopy (TEM) of the NMI displayed Au (113) as the main crystalline plane. Based on the chronoamperometry plots, the gold deposition mechanism on the surface of both electrodes was according to the instantaneous deposition mode [2]. However, the electrode background surface indicated that the ERGO/ITO was uniformly covered by gold. This was attributed to the higher nucleation sites on the ERGO-modified electrode, which was confirmed by the increase of double-layer formation time (t_max). Accordingly, several nucleation stages on the chronoamperometry plot during NMI deposition on the ERGO/ITO electrode, were related to the formation of gold shrub-like structures with more needle-shaped structures. Finally, electropolymerization of a thin layer of o-phenylenediamine in the presence of Heart-fatty acid binding protein (H-FABP) as the template molecule and its subsequent removal was applied to make a biomimetic sensor. In this study, we demonstrated that the biomimetic developed electrode with high surface area, low production cost, and facile and fast synthesis method is acceptably selective to H-FABP against other cardiac biomarkers and serum proteins.

KEYWORDS: Electrodeposition; Electrochemically reduced graphene oxide; Electrochemical sensors; Gold nano-micro islands; Molecularly imprinted polymers.

References

[1] R. Gui, H. Jin, H. Guo, Z. Wang, Recent advances and future prospects in molecularly imprinted polymers-based electrochemical biosensors, Biosens. Bioelectron. 15 (2018) 56-70.

[2] S. Mahshid, A. H. Mepham, S. S. Mahshid, B. BurgessI, T. SaberiSafaei, E. H. Sargent, S. O. Kelley, Mechanistic Control of the Growth of Three-Dimensional Gold Sensors, The Journal of Physical Chemistry C 120 (2016) 21123-21132.

[3] M. Jalali, T. Abdel Fatah, S. S. Mahshid, M. Labib, A. S. Perumal, S. Sara Mahshid, A Hierarchical 3D Nanostructured Microfluidic Device for Sensitive Detection of Pathogenic Bacteria, Small 14 (2018) 1801893.

[4] A. Sanati, M. Jalali, K. Raeissi, F. Karimzadeh, M. Kharaziha, S. S. Mahshid, S. Mahshid, A review on recent advancements in electrochemical biosensing using carbonaceous nanomaterials, Microchimica Acta 186 (2019) 773.

Nanomaterials with enzyme‐like activities, or nanozymes, have attracted lots of attention recently due to their advantages such as low cost, superior activity, and high stability. The complex structure and composition of nanozymes has led to extensive investigation of their catalytic sites at an atomic scale, and to an in‐depth understanding of the biocatalysis mechanisms.

Single-atom catalysts (SACs) offer the unique feature of maximum atomic utilization, providing a potential pathway to improve the catalytic activity of nanozymes. Recently, we have demonstrated a Fe-N-C single-atom nanozyme (SAN) that exhibits high peroxidase-like activity. The SAN consists of atomically dispersed Fe─Nx moieties hosted by metal–organic frameworks (MOF) derived porous carbon. Due to high single-atom active Fe dispersion and the large surface area of the porous support, the SAN provided a high specific activity which was almost at the same level as natural horseradish peroxidase (HRP). Besides, the Fe-N-C based SAN presented much better storage stability and robustness against harsh environments compared with natural enzymes. The biosensing applications of the SAN and their major challenges will be discussed.

References:

1. L. Jiao, H. Yan, Y. Wu, W. Gu, C. Zhu, D. Du, Y. Lin. When Nanozymes Meet Single-Atom Catalysis. Angew. Chem. Int. Ed. 2019, doi.org/10.1002/ange.201905645

2. C. Zhu, S. Fu, Q. Shi, D. Du, Y. Lin. Single-Atom Electrocatalysts. Angew. Chem. Int. Ed. 2017, 56, 13944-13960.

3. N. Cheng, J. Li, D. Liu, Y. Lin, D. Du. Single-Atom Nanozyme Based on Nanoengineered Fe-N-C Catalyst with Superior Peroxidase-Like Activity for Ultrasensitive Bioassays. Small, 2019, 1901485.

4. X. Niu, Q. Shi, W. Zhu, D. Liu, H. Tian, S. Fu, N. Cheng, S. Li, J. N Smith, D. Du, Y. Lin. Unprecedented peroxidase-mimicking activity of single-atom nanozyme with atomically dispersed Fe-Nx moieties hosted by MOF derived porous carbon. Biosensors & Bioelectronics, 2019, 142, 111495.

5. Y Wu, L Jiao, X Luo, W Xu, X Wei, H Wang, H Yan, W Gu, BZ Xu, D Du, Y. Lin, C. Zhu. Oxidase‐Like Fe‐N‐C Single‐Atom Nanozymes for the Detection of Acetylcholinesterase Activity. Small, 2019, 15, 1903108

6. L Jiao, W Xu, H Yan, Y Wu, C Liu, D Du, Y Lin, C Zhu. Fe-NC Single-Atom Nanozyme for the Intracellular Hydrogen Peroxide Detection. Anal. Chem., 2019, 91, 11994-11999

Aggregation of tau proteins underlies several neurodegenerative diseases, notably Alzheimer's disease (AD). Protein aggregation is a complex multi-step process where normal soluble proteins self-assemble in an ordered fashion into higher order conglomerates of low solubility. Experimental evidence suggests that not only the large tau aggregates, known as neurofibrillary tangles (NFTs), are involved in neuronal death, but also small tau oligomers are more likely contributed to the neuronal toxicity.^1-3 While in the recent years substantial progress has been made in the design of drugs that interfere with tau aggregation, there is a lack of methods available that allow rapid screening of potential drug candidates which is critical for the future successful clinical trial.^4-6 The heterogeneous nature of protein aggregation is the key challenge for testing the aggregation inhibition.

Our previous studies showed the capability of surface-based electrochemistry to monitor the conformational changes of tau film on the gold surface by interrogating the electrochemical properties of tau-modified surface using the ferro/ferricyanide redox couple.⁷ We also clearly demonstrated that electrochemistry is a highly useful tool to monitor tau-metal and tau-tau interactions.⁷ Thus, we proposed that this approach can be expanded to monitor changes in the current/impedance as a result of the interaction of surface-linked tau proteins with tau protein in solution or with drug candidates. The former will provide information about tau dimerization and aggregation, while the latter will give information about tau-drug interactions and can potentially be further developed into a drug screening tool by following two different strategies. The first approach examines the affinity of the drug to bind to tau, followed by determining the effectiveness of the drug to prevent the tau dimerization. The second strategy monitors tau oligomerization and aggregation in an attempt to examine the inhibitory activity of potential drug candidates.

We utilized Screen printed gold electrodes to reduce the sample size and the preparation time. A commercially available tau aggregation inhibitor, Cpd16 (amino thienopyridazine) was chosen to evaluate the developed biosensor. Since the orientation of the protein molecules on the surface has a significant impact on the efficiency and robustness of the biosensor, two different approaches were employed to anchor tau proteins on the electrode surface. First, full-length tau protein was chemically linked to the gold surface using lipoic acid N-hydroxysuccinimide ester (Lip-NHS), in which tau molecules randomly immobilize on the gold electrode. Although, results obtained from this approach was promising, non-specific adsorption is one of the biggest challenges that might have contributed to the false positive results. Therefore, biotin-tagged tau proteins were immobilized on the gold surface through the anchor NeutrAvidin to provide an oriented self-assembled monolayer as a biorecognition element. The non-specific adsorption can be minimized by this approach due to highly specific interaction of biotin with NeutrAvidin. This is the first report of using biotin-tagged tau for modification of a protein-based electrochemical biosensor. The oriented film has the advantages of higher sensitivity and reproducibility compared to the random orientation film on the gold surface. Also, the time for surface modification was significantly reduce by this approach.

For both surface modification, a range of different electrochemical techniques has been exploited to study tau-tau interaction as well as tau-Cpd16 interaction by monitoring the redox activities of ferro/ferricyanide redox couple. Also changes in the film resistance as a result of such biomolecular interactions were conveniently monitored by electrochemical impedance spectroscopy. Circular dichroism spectroscopy and transmission electron microscopy were utilized as supporting techniques to monitor tau aggregation kinetics. The IC₅₀ of Cpd16 obtained from the developed biosensors is comparable with the reported IC₅₀, which shows the ability of this biosensor to predict the IC₅₀ of the drug candidate for the in vitro model of AD.

This project represents a significant achievement that contributes to our understanding of tau protein aggregation and provides a highly sensitive analytical tool that makes it possible to rapidly screen drug candidates that target tau aggregation. It can be expected that such a tool will be critical to identify the efficient drug candidates for AD therapy.

References:

1. Ross, C. A., and Poirier, M. A. (2005) Opinion: What is the role of protein aggregation in neurodegeneration? Nat. Rev. Mol. Cell Biol. 6, 891–898.

2. Ross, C. A., and Poirier, M. A. (2004) Protein aggregation and neurodegenerative disease. Nat. Med. 10, S10–S17.

3. Baggett, D.W., Nath, A. (2018) The Rational Discovery of a Tau Aggregation Inhibitor. Biochemistry, 57 (42), 6099-6107.

4. Panza, F. et al. (2016) Tau aggregation inhibitors: The future of Alzheimers pharmacotherapy? Expert Opinion on Pharmacotherapy, 17 (4), 457-461.

5. Seidler, P.M.et al. (2018) Structure-based inhibitors of tau aggregation. Nature Chemistry, 10 (2), pp. 170-176.

6. Rickard, J.E., Horsley, D., Wischik, C.M., Harrington, C.R. (2017) Assays for the screening and characterization of tau aggregation inhibitors. Methods in Molecular Biology, 1523, 129-140.

7. Ahmadi, S., Ebralidze, I. I., She, Z., and Kraatz, H. B. (2017) Electrochemical studies of tau protein-iron interactions—Potential implications for Alzheimer's disease. Electrochim. Acta 236, 384–393

Figure 1

Single-walled carbon nanotubes (SWCNTs) are an emerging building block for nanoscale sensors and labels because of their unique photophysical properties. Semiconducting SWCNTs fluoresce in the tissue transparency near infrared (nIR) window (840 – 1650 nm) and do not bleach. Due to their 1D nature small perturbations in their environment strongly affect their fluorescence. The major challenges in using SWCNTS for sensing is on the one side their purification and on the other side a tailored surface chemistry for molecular recognition and photophysical signal transduction. Cellular metabolites such as first messengers are important biomolecules used by cells to exchange both energy and information but up to day there are many such molecules for which no sensors exist. DNA is a versatile macromolecule to functionalize and solubilize SWCNTs. Furthermore, DNA acts as a conformational quantum yield switch, which makes it a good candidate to impart signal transduction. However, different sensing strategies are known, but general recognition capabilities need to be further explored. Here, we present three different approaches with DNA to tailor SWCNT surface chemistry and detect biologically important metabolites.

Firstly, we tuned the sensitivity of ssDNA/SWCNTs against the neurotransmitter dopamine and different plant polyphenols by changing systematically the DNA sequence. In a more rational approach, we engineered DNA strands conjugated to small peptide sequences. In order to enable a ratio-specific linkage, we determined the amount of bound DNA on the SWCNT surface, which was further observed to play an important role in maintaining colloidal stability of the modified ssDNA/SWCNT conjugates. Finally, aptamer-based approaches were used to combine stable surface modification with target selective binding.

For all these approaches we demonstrated via nIR-fluorescence spectroscopy and nIR-fluorescence microscopy that tailoring these nanosensors resulted in an increased specificity against their targets, ranging from small chemical communication compounds (dopamine, H₂O₂) to cell wall components and secreted enzymes.

Nanoporous anodic alumina (NAA) attracts interest in nanotechnology[1]. Its physical and chemical properties combined with a cost-effective and scalable production make it a good for nanotechnology-related applications. Its high and tuneable surface-to-volume ratio as well as its interesting optical properties[2] have been used as the basis of different biosensing schemes. Biosensing, and specifically optical biosensing is of great interest in health and environmental applications. The reflection interference spectroscopy (RIfS) method based on NAA has demonstrated its ability in detecting many kinds of molecules [3,4].

Biosensors engineered with aptamers as a bioreceptor are called aptabiosensors. Thrombin Binding Aptamer (TBA) has a well-known binding process and high affinity and is one of the most studied aptamers. Thrombin is the key factor of blood coagulation, whose activity is important in wounds and in blood circulation. The free thrombin-binding aptamer remains as a random-coil state in the absence of thrombin, while in the presence of thrombin the protein attaches to the aptamer changing its conformation to quadruplex. In this study we assess the capabilities of NAA with the inner pore surfaces modified with TBA to detect specifically the thrombin protein by means of the RIfS method.

We prepared NAA with the usual anodization conditions under oxalic acid electrolyte to obtain porous layers with uniform pore diameter and with a thickness that permits the measurement with RIfS in a flow-cell where the different species in solution can be introduced. The experiments consisted of monitoring the change in effective optical thickness (EOT, the quantitative characteristic parameter obtained from RIfS) in the different steps of the biosensing process. Figure 1 shows SEM pictures of the NAA platforms prepared.

The NAA pore surfaces were initially functionalized with (3-aminopropyl)triethoxysilane (APTES) and then the surface mas modified in a three-step procedure monitored in real time thanks to the RIfS method. Figure 2 shows the change in EOT as a function of time during the surface functionalization of NAA: the covalent attachment of Sulfo-NHS-Biotin and subsequent streptavidin attachment (stages 1 and 2 in the figure) and the final immobilization of TBA in the pore walls of NAA (step 3 in the plot).. First, the flow of the Sulfo-NHS-Biotin solution produced a considerable increase in EOT. Then, a further increase in EOT is observed with the infiltration of streptavidin. Finally, EOT also shows clearly the immobilization of biotinylated TBA.

The aptamer-functionalized NAA substrates were employed to detect human thrombin protein. For this purpose, different substrates were used in RIfS experiments with human thrombin protein at different concentrations. Figure 3 shows one example of the evolution of the EOT signal upon infiltration of a 1.35 µM thrombin solution. Results show that after obtaining a baseline with constant EOT corresponding to the flow of binding buffer, the thrombin solution is injected causing a rapid increase in EOT, at a rate of 0,05 nm/s. After this increase a stable value is reached after 3600 s, with an absolute change in EOT of ∆EOT = 28 nm. The experiment corresponding to Figure 3 has been repeated for a set of concentrations to obtain a sensitivity curve of the aptamer-functionalized NAA and to determine the lower limit of detection. With this, the dissociation constant of the aptamer-thrombin reaction is determined as K_d = 0,9 µM, the sensitivity to be m = 45.5 nm/µM and the LOD = 72 nM.

Finally, in order to demonstrate the specificity of the NAA platform, experiments replacing the flow of thrombin by the flow of a different but similar protein, Bovine Serum Albumin (BSA) were conducted showing a much lower response. Furthermore, thrombin flow experiments with NAA lacking the aptamer functionalization step were also performed to demonstrate the protein does not bind non-specifically to the NAA inner pore walls.

[1] Josep Ferré-Borrull, et al., Nanomaterials, vol. 7, p. 5225 (2014).

[2] Josep Ferré-Borrull et al., in NANOPOROUS ALUMINA: FABRICATION, STRUCTURE, PROPERTIES AND APPLICATIONS, Springer Series in Materials Science, vol. 219, p. 185 (2015).

[3] Laura Pol et al., Nanomaterials, vol. 9, p.478 (2019).

[4] Laura Pol et al, Sensors, vol. 19, p. 4543 (2019).

Figure 1

Permanent doping of semiconductors and low-dimensional structures to modulate their electronic properties is a well-established concept. Even in cases where doping of thin films by analytes (e.g. carbon nanotubes by ammonia) is applied in sensors, it is only reversed by physical removal of dopant molecules, e.g. heating. We have introduced the concept of molecular switches as chemical dopants for thin nanocarbon (or other 2D-materials) films. These molecules can be switched between doping and non-doping states in the presence or absence of a particular analyte. They impart selectivity not only due to their change in doping behavior, but also by physically blocking other potential dopants in the analyte solution from interacting with the conductive film. The resulting structures can act as chemiresistive films.

Chemiresistive sensors are a well-established technology for gas-phase sensing applications. They are simple and economical to manufacture, and can operate reagent-free and with low or no maintenance. Unlike electrochemical sensors they do not require reference electrodes. While in principle they can be made compatible with aqueous environments, only a few such examples have been demonstrated. Challenges include the need to prevent electrical shorts through the aqueous medium and the need to keep the sensing voltage low enough to avoid electrochemical reactions at the sensor. We have built a chemiresistive sensing platform for aqueous media. The active sensor element consists of a percolation network of low-dimensional materials particles that form a conducting film, e.g. from carbon nanotubes, pencil trace, exfoliated graphene or MoS₂. The first member of that platform was a free chlorine sensor.[1-3] We are currently working to expand the applicability of our platform to other relevant species, in particular anions and cations that are commonly present as pollutants in surface and drinking water.[4] Our sensors can be incorporated into a variety of systems and will also be suitable for online monitoring in remote and resource-poor locations.

[1] L. H. H. Hsu, E. Hoque, P. Kruse, and P. R. Selvaganapathy, A carbon nanotube based resettable sensor for measuring free chlorine in drinking water. Appl. Phys. Lett. 106 (2015) 063102.

[2] E. Hoque, L. H. H. Hsu, A. Aryasomayajula, P. R. Selvaganapathy, and P. Kruse, Pencil-Drawn Chemiresistive Sensor for Free Chlorine in Water. IEEE Sens. Lett. 1 (2017) 4500504.

[3] A. Mohtasebi, A. D. Broomfield, T. Chowdhury, P. R. Selvaganapathy, and P. Kruse, Reagent-Free Quantification of Aqueous Free Chlorine via Electrical Readout of Colorimetrically Functionalized Pencil Lines. ACS Appl. Mater. Interfaces 9 (2017) 20748-20761.

[4] P. Kruse, Review on Water Quality Sensors. J. Phys. D 51 (2018) 203002.

Figure 1

Single-walled carbon nanotubes (SWCNTs) non-covalently modified with DNA have been widely implemented as probes for near-infrared molecular sensing and imaging in biological systems. However, these constructs show poor stability in biomolecule-rich, in vivo environments leading to attenuation of sensor response. To study the relevant interactions that occur between DNA-SWCNTs in a biological environment, we develop a method to capture real-time binding behavior of fluorophore-labeled biomolecules, utilizing the SWCNT surface as a fluorescence quencher. We apply this assay to monitor corona dynamics of proteins adsorbing on single-stranded DNA (ssDNA) functionalized SWCNT dopamine sensor. We show the proteins albumin and fibrinogen adsorb to varying degrees on the ssDNA-SWCNT surface. Fibrinogen adsorption was 168% greater than that of albumin on a mass basis. Furthermore, fibrinogen induced more DNA desorption than albumin. These results are recapitulated by the respective kinetic rate constants for adsorption and desorption, calculated by fitting experimental adsorption data to a competitive adsorption model. Greater fibrinogen adsorption and induced DNA desorption coincide with a 78.2% reduction in dopamine response compared to 52.2% for albumin. We use this method to further study the passivation of ssDNA-SWCNTs with PEGylated phospholipid, a molecule shown to improve biocompatibility of nanoparticle platforms. The non-covalent interaction causes marginal desorption of DNA but significantly reduces subsequent adsorption of fibrinogen. The mitigated protein adsorption by phospholipid-PEG coincides with a reduction in sensor response attenuation. This methodology presents a generic yet robust protocol to track solution-phase competitive adsorption of multiple chemical species on a nanoparticle surface and to relate these phenomena to sensor efficacy.

Using soft materials (e.g., paper, hydrogel) to replace the traditional hard materials (e.g., glass, silicon) as substrates have become a recent trend in developing point-of-care testing (POCT) platforms. And through integration of the soft materials with electrochemical or electric devices can further extend the applications of POCT. In our recent work, we used four kinds of soft materials, including paper, PDMS, hydrogel and liquid marble, as the new soft substrates of POCT platforms and realized their new applications in POCT. For example, by integration of the electrodes and hydrophobic channels on paper through simply writing method using home-made pens, the fabricated paper-based electrochemical devices have been successfully applied to detect glucose in artificial urine and melamine in sample solutions. By fabrication of MWNTs/PDMS fibers as multifunctional sensors and integration them on a glove, the measurement of gesture recognition and temperature have been realized by the "smart" glove. Through injection of liquid metal into the 3D helical structure of hydrogel and combination the hydrogel with electronic sensing device, the temperature, UV sensing and EMG signal detections have been performed by the wearable, multifunctional hydrogel device. By using liquid marble as a separator and small device for isoelectric focusing, the POCT separation and analysis of proteins have been realized. The proposed new soft platforms show wide application potential in POCT.

References

[1] H. Liu, M. X. Li, S. B. Liu, P. P. Jia, X. J. Guo, S. S. Feng, T. J. Lu, H. Y. Yang, F. Li, F. Xu, Spatially Modulated Stiffness on Hydrogel for Soft and Stretchable Integrated Electronics, Material Horizons. 2019, DOI: 10.1039/C9MH01211G.

[2] Z. D. Li, H. Liu, X. C. He, F. Xu, F. Li, Pen-on-Paper Strategies for Point-of-Care Testing of Human Health, Trac-Trends Anal. Chem. 108 (2018) 50-64. doi.org/10.1016/j.trac.2018.08.010

[3] H. Liu, M. X. Li, C. Ouyang, T. J. Lu, F. Li, F. Xu, Bio-friendly, Stretchable, and Reusable Hydrogel Electronics as Wearable Force Sensors, Small. 14 (2018) 1801711. doi: 10.1002/smll.201801711

Fundamental knowledge about protein aggregation is critical for the understanding of many neurodegenerative diseases. Protein aggregation can be difficult to comprehensively study by traditional characterization techniques which may require sample pretreatment and alter the native state of the samples being studied. There is a great need for native state "in solution" measurements of protein monitoring in the biomedical field. We have utilized single-particle collision electrochemistry (SPCE) for the early tracking of lysozyme (Lyz) aggregation states by electrochemically analyzing lysozyme modified silver nanoparticle (Lyz-AgNPs) and their oxidation currents. When the modified nanoparticles collide with a microelectrode at a high enough potential, they can be oxidized at the surface of the electrode. Information can be extrapolated from the electrochemical data and help aid in the determination of particle stability and coverage. Our electrochemical determination method was compared to other measurements from UV-Vis spectroscopy, circular dichroism (CD) and atomic force microscopy (AFM) to validate our findings and determine the strutural changes of lysozyme protein on the surface of silver nanoparticles. This work demonstrates that this electrochemical technique could potentially be used to screen protein samples for formation of aggregates.

Serotonin is an important neurotransmitter involved in various functions of the nervous, blood, and immune system. In general, detection of small biomolecules such as serotonin in real time with high spatial and temporal resolution remains challenging with conventional sensors and methods. In this work, we designed a near-infrared (nIR) fluorescent nanosensor (NIRSer) based on fluorescent single-walled carbon nanotubes (SWCNTs) to image the release of serotonin from human blood platelets in real time. The nanosensor consists of a nonbleaching SWCNT backbone, which is fluorescent in the beneficial nIR tissue transparency window (800–1700 nm) and a serotonin binding DNA aptamer. The fluorescence of the NIRSer sensor (995 nm emission wavelength for (6,5)-SWCNTs) increases in response to serotonin by a factor up to 1.8. It detects serotonin reversibly with a dissociation constant of 301 nM ± 138 nM and a dynamic linear range in the physiologically relevant region from 100 nM to 1 μM. As a proof of principle, we detected serotonin release patterns from activated platelets on the single-cell level. Imaging of the nanosensors around and under the platelets enabled us to locate hot spots of serotonin release and quantify the time delay (21–30 s) between stimulation and release in a population of platelets, highlighting the spatiotemporal resolution of this nanosensor approach. In summary, we report a nIR fluorescent nanosensor for the neurotransmitter serotonin and show its potential for imaging of chemical communication between cells.

Carbon nanotubes (CNTs) are widely used in neuroscience research for its excellent properties such as high conductivity, electrochemical stability, biocompatibility, mechanical compatibility with tissues, tunable mechanical and chemical properties. CNTs are investigating for its performance as neuronal scaffolds to support neural tissues, neuron growth and differentiation as well as neural stimulating and recording electrodes to control and monitor neural activity in both vitro and in vivo environments. Surprisingly neurons show a better interaction with CNTs when neurons are grown on CNT substrates. Previous research has shown neuronal differentiation on pristine CNT and CNT composites and the alignment of neurites on CNT substrates. Current research focus on interaction of neurons at the interface of pristine CNT films with aligned and cross hatch patterned CNT layers prepared from multi-walled CNT arrays. CNTs have nano scale surface roughness and contribution of alignment of CNTs can retain and adhere neurons without any adhesive proteins. As an initial step to study the interaction of neurons with CNT films, the effect of different CNT alignment on neuron adhesion and neurite development was chosen. PC12 cell line was used to study neuron adhesion and neurite alignment on CNT substrates. It is a commonly used neuronal cell model due to its ability to attain sympathetic neurons characteristics in the presence of nerve growth factor (NGF) in low serum medium. For the study, CNT films were prepared as aligned and in cross hatch pattern on PET sheets. After sterilization with UV irradiation, PC12 cells were seeded and cultured at a density of 20 000 cells/mL on CNT films and allowed to differentiate in NGF medium. For comparison poly l lysine (PLL) coated CNT films were used. Fig 1(Left) shows SEM image of a differentiating PC12 cell on PLL coated film of aligned CNTs and Fig 1(Right) shows SEM image of a differentiating PC12 cell on a crosshatch patterned CNT film with no adhesive coating. While neurites of PC12 cells align with the CNTs on aligned CNT film as states in the literature, pristine CNTs in crosshatch pattern were also able to hold the cells without any surface adhesive coating and allow differentiation of cells. Also PC12 cells tend to show random alignment on crosshatch patterned CNTs and adhere well due to higher degree of porosity and surface roughness. As pristine CNT films were able to hold PC12 cells, the interface properties will be further evaluated by impedance spectroscopy.

Figure 1

Introduction

Viruses are not only infectious agents, they are also known as promising functional building blocks for application in nano- and biotechnologies. The tobacco mosaic virus (TMV) was the first studied plant virus and is widely distributed; it infects vegetables, like tomato, bell pepper, beans and other members of the family Solanaceae, while it is totally harmless for mammals [1]. It is one of the most studied plant viruses and its genome is completely sequenced, whereby genetical and chemical modification is easy. TMV has a nanotube-like shape with a length of 300 nm, an outer diameter of 18 nm and an inner diameter of 4 nm. Since it possesses a high chemical and physical robustness, it can be integrated with different electronic transducers for bio- and chemical sensing applications [2].

Recently, we presented a TMV-based amperometric glucose biosensor [3] and a potentiometric penicillin biosensor [4]. TMV was used as enzyme nanocarrier for the enzyme glucose oxidase and penicillinase, respectively [3,4]. The sensitivity and detection limit of these biosensors, among others, depend on the density of TMVs on the sensor surface. The surface density of the immobilized TMVs is strongly influenced by the electrostatic interactions between the charged TMVs and sensor surface as well as by the inter-TMV-nanotubes repulsion, which could be changed by varying the pH value and the ionic strength of the TMV solution. In this study, we investigated an impact of the pH value and ionic strength of the TMV solution on the surface density of TMV nanotubes immobilized onto Ta₂O₅-gate capacitive field-effect electrolyte-insulator-semiconductor (EIS) sensors.

Materials and Methods

TMV particles modified with biotin-linker molecules (TMV_Bio), which serve as binding sites for streptavidin-conjugated enzymes, have been immobilized onto capacitive field-effect EIS sensors with Ta₂O₅ as transducer layer, as shown in Fig. 1. Immobilization was performed from TMV_Biosolutions with different values of pH between pH 3.0 and pH 9.5 and ionic strength between 0.1 mM and 750 mM. The sensors have been electrochemically characterized before and after TMV_Bio immobilization by capacitance-voltage- and constant-capacitance methods, respectively. In addition, the density of the immobilized TMVs and morphology of the sensor surface has been investigated by means of scanning electron microscopy (SEM).

Results and Conclusions

The TMV_Bio density on the Ta₂O₅ sensor surface was influenced by varying the pH value (as exemplarily shown in Fig. 1) and ionic strength (not shown) of the TMV_Bio solution. The amplitude of the field-effect sensor signal correlates well with the density of the immobilized TMV_Bionanotubes. Thus, optimized conditions for the high-density immobilization of TMV_Bio nanotubes onto the Ta₂O₅ surface and thereby enhanced biosensing have been found. Details of the experiments and the obtained results will be presented and discussed.

Figure 1: Measurement set-up with schematic layer structure of the capacitive EIS sensor modified with negatively charged TMV_Bio particles (a). SEM images of the Ta₂O₅-sensor surface modified with TMV_Bio nanotubes at pH 4.5 (b) and pH 7.0 (c), respectively.

Acknowledgements

The authors like to thank Dr. Claudia Koch and Rebecca Hummel, Stuttgart, for scientific and technical support.

References

[1] X. Z. Fan, E. Pomerantseva, M. Gnerlich, Tobacco mosaic virus: A biological building block for micro/nano/bio systems, Journal of Vacuum Science & Technology A. 31 (2013) 050815. doi: 10.1116/1.4816584.

[2] M. Knez, M. Sumer, A. Bittner, C. Wege, H. Jeske, D. Hoffmann, K. Kuhnke, K. Kern, Binding the tobacco mosaic virus to inorganic surfaces, Langmuir 20 (2004) 441–447. doi: 10.1021/la035425o.

[3] M. Bäcker, C. Koch, F. Geiger, F. Eber, H. Gliemann, A. Poghossian, C. Wege, M. J. Schöning, Tobacco mosaic virus as enzyme nanocarrier for electrochemical biosensors, Sensors and Actuators B: Chemical 238 (2017) 716– 722. doi: 10.1016/j.snb.2016.07.096.

[4] A. Poghossian, M. Jablonski, C. Koch, T. S. Bronder, D. Rolker, C. Wege, M. J. Schöning, Field-effect biosensor using virus particles as scaffolds for enzyme immobilization, Biosensors and Bioelectronics 110 (2018) 168–174. doi: 10.1016/j.bios.2018.03.036.

Figure 1

Glassy carbon electrodes (GCE) were modified by cysteamine-capped gold nanoparticles (AuNp@cysteamine) and PAMAM dendrimers generation 4.5 bearing 128-COOH peripheral groups (GCE/AuNp@cysteamine/PAMAM), in order to be tested as electrochemical detector of uric acid (UA) in human serum samples. The results showed that concentrations of UA detected by cyclic voltammetry with GCE/AuNp@cysteamine/PAMAM were comparable (deviation <±10%; limits of detection and quantification were 1.7×10^-4 and 5.8×10^-4 mg/dL, respectively) to those concentrations obtained using the typical uricase-based enzymatic method [1]. Furthermore, results of UA detected by DC-potential amperometry demonstrated that the presence of dendrimers in the GCE/AuNp@cysteamine/PAMAM system minimizes ascorbic acid and serum proteins interferences during UA oxidation, thus improving the electrocatalytic activity of the gold nanoparticles. On the other hand, GCE/AuNp@cysteamine/PAMAM were employed for detecting UA in serum donated by pregnant women having gestational hypertension or preeclampsia (the group of "cases") and from health pregnant women (the "control" group). The new data confirmed significant differences between the detected UA levels (p<0.001) in the groups of "cases" (6.2±0.5mg/dL) and "control" (4.2±0.9mg/dL), respectively. Therefore, these results demonstrated that the employment of GCE/AuNp@cysteamine/PAMAM - based amperometric detectors as non-enzymatic devices for early diagnosis of preeclampsia constitute a highly reliable route.

References:

[1] A.S. Ramírez-Segovia, J.A. Banda-Alemán, S. Gutiérrez-Granados, A. Rodríguez, F.J. Rodríguez, L.A. Godínez, E. Bustos, J. Manríquez, Analytica Chimica Acta, 812 (2014) 18-25.