Table of contents

Since the birth of modern day medicine, during the times of Hippocrates in ancient Greece, the profession has developed from the rudimentary classification of disease into a rigorous science with an inspiring capability to treat and cure. Scientific methodology has distilled clinical diagnostic tools from the early arts of prognosis, which used to rely as much on revelation and prophecy, as intuition and judgement [1]. Over the past decade, research into the interactions between proteins and nanosystems has provided some ingenious and apt techniques for delving into the intricacies of anatomical systems.

In vivo biosensing has emerged as a vibrant field of research, as much of medical diagnosis relies on the detection of substances or an imbalance in the chemicals in the body. The inherent properties of nanoscale structures, such as cantilevers, make them well suited to biosensing applications that demand the detection of molecules at very low concentrations. Measurable deflections in cantilevers functionalised with antibodies provide quantitative indicators of the presence of specific antigens when the two react. Such developments have roused mounting interest in the interactions of proteins with nanostructures, such as carbon nanotubes [3], which have demonstrated great potential as generic biomarkers. Plasmonic properties are also being exploited in sensing applications, such as the molecular sentinel recently devised by researchers in the US. The device uses the plasmonic properties of a silver nanoparticle linked to a Raman labelled hairpin DNA probe to signal changes in the probe geometry resulting from interactions with substances in the environment. Success stories so far include the detection of two specific genes associated with breast cancer [4].

A greater understanding of how RNA interference regulates gene expression has highlighted the potential of using this natural process as another agent for combating disease in personalized medicine. However, the large molecular weight, net negative charge and hydrophilicity of synthetic small interfering RNAs makes it hard for the molecules to cross the plasma membrane and enter the cell cytoplasm. Immune responses can also diminish the effectiveness of this approach. In this issue, Shiri Weinstein and Dan Peer from Tel Aviv University provide an overview of the challenges and recent progress in the use of nanocarriers for delivering RNAi effector molecules into target tissues and cells more effectively [5].

Also in this issue, researchers in Korea report new results that demonstrate the potential of nanostructures in neural network engineering [6]. Min Jee Jang et al report directional growth of neurites along linear carbon nanotube patterns, demonstrating great progress in neural engineering and the scope for using nanotechnology to treat neural diseases.

Modern medicine cannot claim to have abolished the pain and suffering that accompany disease. But a comparison between the ghastly and often ineffective iron implements of early medicine and the smart gadgets and treatments used in hospitals today speaks volumes for the extraordinary progress that has been made, and the motivation behind this research.

References

[1] Wallis F 2000 Signs and senses: diagnosis and prognosis in early medieval pulse and urine texts Soc. Hist. Med.13 265–78

[2] Arntz Y, Seelig J D, Lang H P, Zhang J, Hunziker P, Ramseyer J P, Meyer E, Hegner M and Gerber Ch 2003 Label-free protein assay based on a nanomechanical cantiliever array Nanotechnology14 86–90

[3] Gowtham S, Scheicher R H, Pandey R, Karna S P and Ahuja R 2008 First-principles study of physisorption of nucleic acid bases on small-diameter carbon nanotubes Nanotechnology19 125701

[4] Wang H-N and Vo-Dinh T 2009 Multiplex detection of breast cancer biomarkers using plasmonic molecular sentinel nanoprobes Nanotechnology20 065101

[5] Weinstein S and Peer D 2010 RNAi nanomedicines: challenges and opportunities within the immune system Nanotechnology21 232001

[6] Jang M J, Namgung S, Hong S, and Nam Y 2010 Directional neurite growth using carbon nanotube patterned substrates as a biomimetic cue Nanotechnology21 235102

RNAi, as a novel therapeutic modality, has an enormous potential to bring the era of personalized medicine one step further from notion into reality. However, delivery of RNAi effector molecules into their target tissues and cells remain extremely challenging. Major attempts have been made in recent years to develop sophisticated nanocarriers that could overcome these hurdles. This review will present the recent progress with the challenges and opportunities in this emerging field, focusing mostly on the in vivo applications with special emphasis on the strategies for RNAi delivery into immune cells.

The unfolding dynamics of a protein, ubiquitin, pinned in several uniform flows, was studied at low and high flow rates in an all-atom style through a non-equilibrium molecular dynamics approach with explicit water molecules included. Atomic hydrodynamic force components on individual amino acids, as a function of time, due to the collisional interactions with the flowing water molecules were calculated explicitly. The protein conformational change in response to those time-varying forces was computed completely at the high flow rate up to nanosecond until the fully stretched state was reached. The end-to-end length of the single ubiquitin protein molecule at high flow rate is smoothly increasing. The step-like jumps between metastable states that describe the µm ms ^{− 1} scale force pulling experiments conducted on polyubiquitins at low flow rates, are not seen at the high flow speeds necessary to computationally probe the ns nm ^{− 1} scale regime. No unfolding was observed in the low flow rate atomic computations at nanosecond scale while partial and complete unfolding was observed in the coarse-grained low flow rate computations at microsecond scale. Examination of the all-atom computation of the time variation of the hydrodynamic forces on, and the velocity components of, the protein molecule unveiled to some extent the details of the complexity of the hydrodynamic friction variation in the nm ns ^{− 1} regime of high rate flow-driven protein unfolding. This demonstrates quantitatively that all-atom computations are more suitable than the Langevin equation or Brownian dynamics methods for probing the interaction dynamics and resulting conformational dynamics of protein unfolding in strong flows on nm ns ^{− 1} time/length scales while the reverse is true for investigation of slow, diffusively driven systems.

Researchers have made extensive efforts to mimic or reverse-engineer in vivo neural circuits using micropatterning technology. Various surface chemical cues or topographical structures have been proposed to design neuronal networks in vitro. In this paper, we propose a carbon nanotube (CNT)-based network engineering method which naturally mimics the structure of extracellular matrix (ECM). On CNT patterned substrates, poly-L-lysine (PLL) was coated, and E18 rat hippocampal neurons were cultured. In the early developmental stage, soma adhesion and neurite extension occurred in disregard of the surface CNT patterns. However, later the majority of neurites selectively grew along CNT patterns and extended further than other neurites that originally did not follow the patterns. Long-term cultured neuronal networks had a strong resemblance to the in vivo neural circuit structures. The selective guidance is possibly attributed to higher PLL adsorption on CNT patterns and the nanomesh structure of the CNT patterns. The results showed that CNT patterned substrates can be used as novel neuronal patterning substrates for in vitro neural engineering.

Ultrasmall superparamagnetic iron oxide (USPIO) particles are very useful for cellular magnetic resonance imaging (MRI), which plays a key role in developing successful stem cell therapies. However, their low intracellular labeling efficiency, and biosafety concerns associated with their use, have limited their potential usage. In this study we develop a novel system composed of RBC-derived vesicles (RDVs) for efficient delivery of USPIO particles into human bone marrow mesenchymal stem cells (MSCs) for cellular MRI in vitro and in vivo. RDVs are highly biosafe to their autologous MSCs as manifested by cell viability, differentiation, and gene microarray assays. The data demonstrate the potential of RDVs as intracellular delivery vehicles for biomedical applications.

Bifunctional nanoprobes with both magnetic and optical contrast have been developed for ultra-sensitive brain tumor imaging at the cellular level. The nanoprobes were synthesized by simultaneously incorporating a magnetite nanoparticle cluster and fluorescence dyes into silica encapsulation by a sol–gel approach under ultrasonic treatment. The nanoprobes maintain superparamagnetic behavior at room temperature and possess enhanced transverse relaxivity and good photostability. As a glioma targeting ligand, chlorotoxin was covalently bonded to the surface of the nanoprobes. In vitro cellular uptake assays demonstrated that the nanoprobes were highly specific, taken up by human U251-MG glioma cells via receptor-mediated endocytosis. The labeled glioma cells were readily detectable by both MR imager and confocal laser scanning microscopy.

A strategy to bind bacterial cells to surfaces in a directed fashion via dip-pen nanolithography (DPN) is presented. Cellular attachment to pre-designed DPN generated microarrays was found to be dependent on the shape and size of the surface feature. While this observation is likely due in part to a dense, well formed mercaptohexadecanoic acid (MHA) monolayer generated via DPN, it may also simply be due to the physical shape of the surface structure. Motile Pseudomonas aeruginosa bacterial cells were observed to bind to DPN generated mercaptohexadecanoic acid/poly-L-lysine (MHA/PLL) line patterns, 'blocks' made up of eight lines with 100 nm spacings, with ∼ 80% occupancy. Cellular binding to these 'block' surface structures occurs via an electrostatic interaction between negatively charged groups on the bacterial cell surface and positively charged poly-L-lysine (PLL) assemblies. These data indicate that these DPN generated 'block' surface structures provide a promising footprint for the attachment of motile bacterial cells that may find utility in cell based biosensors or single cell studies.

This paper investigates the influence of resonant and nonresonant plasmonic nanostructures, such as arrays of silver and aluminum nanoparticles in the forward scattering configuration, on the optical absorption in a thin-film amorphous silicon solar cell. It is demonstrated that nonresonant coupling of the incident sunlight with aluminum nanoparticles results in higher optical absorption in the photoactive region than resonant coupling with silver nanoparticle arrays. In addition, aluminum nanoparticles are shown to maintain a net positive enhancement of the optical absorption in amorphous silicon, as compared to a negative effect by silver nanoparticles, when the nanoparticles are oxidized.

Magnetic field detection with extremely high spatial resolution is crucial to applications in magnetic storage, biosensing, and magnetic imaging. Here, we present the concept of using a spin torque oscillator (STO) to detect magnetic fields by measuring the frequency of the oscillator. This sensor's performance relies predominantly on STO properties such as spectral linewidth and frequency dispersion with magnetic field, rather than signal amplitude as in conventional magnetoresistive sensors, and is shown in measured devices to achieve large signal to noise ratios. Using macrospin simulations, we describe oscillator designs for maximizing performance, making spin torque oscillators an attractive candidate to replace more commonly used sensors in nanoscale magnetic field sensing and future magnetic recording applications.

Memristive devices, which exhibit a dynamical conductance state that depends on the excitation history, can be used as nonvolatile memory elements by storing information as different conductance states. We describe the implementation of a nonvolatile synchronous flip-flop circuit that uses a nanoscale memristive device as the nonvolatile memory element. Controlled testing of the circuit demonstrated successful state storage and restoration, with an error rate of 0.1%, during 1000 power loss events. These results indicate that integration of digital logic devices and memristors could open the way for nonvolatile computation with applications in small platforms that rely on intermittent power sources. This demonstrated feasibility of tight integration of memristors with CMOS (complementary metal–oxide–semiconductor) circuitry challenges the traditional memory hierarchy, in which nonvolatile memory is only available as a large, slow, monolithic block at the bottom of the hierarchy. In contrast, the nonvolatile, memristor-based memory cell can be fast, fine-grained and small, and is compatible with conventional CMOS electronics. This threatens to upset the traditional memory hierarchy, and may open up new architectural possibilities beyond it.

Complementary NAND and NOR gates composed of p-channel HgTe-nanocrystal (NC) films and n-channel HgSe-NC films were constructed on back-gate patterned plastic substrates. The NAND gate was made of two HgTe-p-channel thin film transistors (TFTs) in parallel and two HgSe-n-channel TFTs in series. The NOR gate was built up with both two HgSe-n-channel TFTs in parallel and two HgTe-p-channel TFTs in series. The mobility and on/off ratio for the p-channel TFTs were estimated to be 0.9 cm² V ^{− 1} s ^{− 1} and 10, respectively, and those for the n-channel TFTs were measured to be 1.8 cm² V ^{− 1} s ^{− 1} and 10², respectively. The NAND and NOR gates were operated with gains of 1.45 and 1.63 and transition widths of 7.8 and 6.2 V, respectively, at room temperature in air. In addition, the operations of the NAND and NOR logics are reproducible for up to 1000 strain cycles.

In this work we present and discuss the nanopatterning of rutile TiO₂ single crystal surfaces following their irradiation with energetic heavy ions through a stencil mask of Ni filled self-ordered porous anodic alumina. After etching in HF a corrugated surface morphology is obtained composed of parallel alternate furrows and ridges (or nanobars) 50 nm in diameter and with 100 nm pitch. In addition, isolated, but collapsed, TiO₂ nanorods are seen lying on the patterned surface. The stability of the nanopatterned surface under high temperatures treatments and crystalline properties are analyzed.

Silicon oxide nanodot arrays were fabricated using functionalized block copolymer templates and selective silylation. A polystyrene-b-poly(acrylic acid/acrylic anhydride) (PS-b-PAA/AN) thin film containing spherical nanodomains was used as a template to build nanoscopic silica structures. A PS-b-PAA/AN thin film was prepared by acid-catalyzed thermal deprotection of polystyrene-b-poly(tert-butyl acrylate) on an SU-8 resist film containing a photoacid generator. This resulting film has excellent solvent and thermal resistance due to crosslinked anhydride linkages in carboxyl-functionalized PAA/AN block domains. Silicon was introduced by spin-spraying of hexamethyldisilazane (HMDS) over the entire surface of a self-assembled PS-b-PAA/AN thin film. HMDS was selectively reacted with carboxylic acid groups in spherical domains of a PAA/AN block. SiO₂ nanodot arrays were generated by oxygen reactive ion etching.

A p-type ethanol sensor with a response time of ∼ 8.3 s at room temperature was produced by SnO₂:Sb nanowires. The electrical properties of p-type SnO₂ nanowires are stable with a hole concentration of 1.544 × 10¹⁷ cm ^{− 3} and a field-effect mobility of 22 cm² V ^{− 2} S ^{− 1}. X-ray photoelectron spectroscopy (XPS) and Hall measurement revealed that as-synthesized nanowires exhibit p-type behavior. A comprehensive investigation of the p-type sensing mechanism is reported.

Metal and semiconductor nanorods polarized by an external electric field tend to align parallel to this field. We derived the equation of motion for this alignment, taking into account electrostatic forces, thermal fluctuations and viscous resistance of the liquid the nanorods are suspended in. It was solved for a strong ac electric field, as well as for the combination of strong dc and weak ac fields. The results were used for calculations of the capacity of the nanorod solution, its frequency dispersion and dependence on the field strength. Modification of the nanorod absorption spectra under the influence of an electric field was also considered. It was shown that metal nanorods in laser radiation, with the frequency belonging to the interval between longitudinal and transverse plasmon modes, tend to align perpendicular, rather than parallel, to the optical electric field.

We present an effective, low cost protocol to reduce the toxicity of gold nanorods induced by the presence of cetyltrimethylammonium bromide (CTAB) on their lateral surface as a result of the synthesis process. Here, we use thiolated methoxy-poly(ethylene) glycol (mPEG–SH) polymer to displace most of the CTAB bilayer cap from the particle surface. The detoxification process, chemical and structural stability of as-prepared mPEG–SH-conjugated gold nanorods were characterized using a number of techniques including localized surface plasmon resonance (LSPR), transmission electron microscopy (TEM) and surface-enhanced Raman spectroscopy (SERS). In view of future applications as near-infrared (NIR) nanoheaters in localized photothermal therapy of cancer, we investigated the thermal behaviour of mPEG–SH-conjugated gold nanorods above room temperature. We found a critical temperature at around 40 °C at which the adsorbed polymer layer is susceptible to undergo conformational changes. Additionally, we believe that such plasmonic nanoprobes could act as SERS-active carriers of Raman tags for application in cellular imaging. In this sense we successfully tested them as effective SERS substrates at 785 nm laser line with p-aminothiophenol (pATP) as a tag molecule.

This paper presents the synthesis of CuO nanowires using a localized thermal heating method in ambient air. It employs local heat sources defined in micro-resistive heaters fabricated by a standard polysilicon-based surface micromachining process instead of a global furnace heating. Since the synthesis is performed globally at room temperature, the presented process is compatible with standard CMOS. The synthesized CuO nanowires are characterized by scanning electron microscopy, transmission electron microscopy and high resolution transmission electron microscopy. It is found that this approach provides a simple method to locally synthesize suspended CuO nanowires on polysilicon microbridges on silicon substrates, thus allowing for integration of CuO nanowires into silicon-based devices. It provides a significant step towards the process integration of CuO nanowires with MEMS to realize functional devices.

Nearly monodisperse CuCr₂Se₄ hexagon-shaped nanoparticles with crystallite sizes from 15.1 to 24.3 nm were synthesized by thermal decomposition of metal chlorides and selenium powder in oleylamine. In addition, the 'flower'-shaped CuCr₂Se₄ nanoparticles with a crystallite size 19.8 nm were also fabricated under similar conditions using heptanoic acid. Magnetic measurements show that all samples reveal ferromagnetic behavior below 350 K. The 'flower'-shaped nanoparticles have saturation magnetization, coercivity and remanent magnetization higher than the hexagon-shaped nanoparticles. However, the Curie temperature of the 'flower'-shaped nanoparticles (≈380 K) is somewhat lower than in the hexagon-shaped nanoparticles (420–430 K). These phenomena may be associated with the shape and surface anisotropy which would exert a tremendous influence on the particle's magnetic properties.

Mixed single-walled and multi-walled carbon nanotube membrane (buckypaper) was incorporated onto the surface of polyimide/carbon fibre composites via a compression moulding process. Flammability was investigated by cone calorimeter tests under an external radiant heat flux of 50 kW m ^{− 2}. The burning residue was analysed with scanning electron microscopy and thermogravimetric analysis. The buckypaper survived the burning test and decreased the peak heat release rate by 40%, reduced the total heat release by 26%, produced 82% less smoke release and resulted in 33% less mass loss. The directly mixed carbon nanotubes (5 wt% multi-walled carbon nanotubes) yielded 38% less peak heat release rate, only 3.7% less total heat release, 28% more smoke release and no change in mass loss. Compared to direct mixing of carbon nanotubes into the resin, the use of buckypaper is more efficient in fire retardancy improvement; it yielded further delay of ignition, lower heat release rate, further reduced heat release, lower mass loss and less smoke release. The buckypaper worked as an excellent physical barrier, obstructing the flow of heat and oxygen to the inner polymer resin. The as-prepared buckypaper greatly improved the fire retardancy of polyimide matrix carbon fibre composites.

We demonstrate the application of scattering-type scanning near-field optical microscopy (s-SNOM) for infrared (IR) spectroscopic material recognition in state-of-the-art semiconductor devices. In particular, we employ s-SNOM for imaging of industrial CMOS transistors with a resolution better than 20 nm, which allows for the first time IR spectroscopic recognition of amorphous SiO₂ and Si₃N₄ components in a single transistor device. The experimentally recorded near-field spectral signature of amorphous SiO₂ shows excellent agreement with model calculations based on literature dielectric values, verifying that the characteristic near-field contrasts of SiO₂ stem from a phonon–polariton resonant near-field interaction between the probing tip and the SiO₂ nanostructures. Local material recognition by s-SNOM in combination with its capabilities of contact-free and non-invasive conductivity- and strain-mapping makes IR near-field microscopy a versatile metrology technique for nanoscale material characterization and semiconductor device analysis with application potential in research and development, failure analysis and reverse engineering.

Zinc oxide (ZnO) thin films were grown on uncoated and zinc-coated Corning glass substrates by pulsed-laser deposition (PLD). X-ray diffraction measurements revealed that the as-deposited films are polycrystalline having preferential orientation along the [0002] and [] directions. Transmittance spectroscopy verified that the as-deposited films are transparent with a direct bandgap of about 3.28 eV at room temperature. Piezoresponse imaging and local hysteresis loop acquisition were performed to characterize the piezoelectric and possible ferroelectric properties of the films. The out-of-plane (effective longitudinal, ) and in-plane (effective shear, ) coefficients were estimated from the local piezoresponse based on the comparison with LiNbO₃ single crystals. Measurements of all three components of piezoresponse (one longitudinal and two shear signals) allowed constructing piezoelectric maps for polycrystalline ZnO and to relate the variation of piezoelectric properties to the crystallographic and grain structure of the films. A shifted piezoresponse hysteresis loop under high voltages hints at the possible pseudoferroelectricity, as discussed recently by Tagantsev (2008 Appl. Phys. Lett. 93 202905).

This paper reports dependency of specific heat and ballistic thermal conductance on cross-sectional geometry (tube versus rod) and size (i.e., diameter and wall thickness), in free-standing isotropic non-metallic crystalline nanostructures. The analysis is performed using dispersion relations found by numerically solving the Pochhammer-Chree frequency equation for a tube. Estimates for the allowable phonon dispersion relations within the crystal lattice are obtained by modifying the elastic acoustic dispersion relations so as to account for the discrete nature of the material's crystal lattice. These phonon dispersion relations are then used to evaluate the specific heat and ballistic thermal conductance in the nanostructures as a function of the nanostructure geometry and size. Two major results are revealed in the analysis: increasing the outer diameter of a nanotube while keeping the ratio of the inner to outer tube radius (γ) fixed increases the total number of available phonon modes capable of thermal population. Secondly, decreasing the wall thickness of a nanotube (i.e., increasing γ) while keeping its outer diameter fixed, results in a drastic decrease in the available phonon mode density and a reduction in the frequency of the longitudinal and flexural acoustic phonon modes in the nanostructure. The dependency of the nanostructure's specific heat on temperature indicates 1D, 2D, and 3D geometric phonon confinement regimes. Transition temperatures for each phonon confinement regime are shown to depend on both the nanostructure's wall thickness and outer radius. Compared to nanowires (γ = 0), the frequency reduction of acoustic phonon modes in thinner walled nanotubes (γ = 0.96) is shown to elevate the ballistic thermal conductance of the thin-walled nanotube between 0.2 and 150 K. At 20 K, the ballistic thermal conductance of the thin-walled nanotube (γ = 0.96) becomes 300% greater than that of a solid nanowire. For temperatures above 150 K, the trend in ballistic thermal conductance inverts. The greater number of phonon modes in nanostructures with increased outer diameter and wall thickness is shown to have a larger contribution to ballistic thermal conductance when compared to the increased contribution from the frequency reduction of acoustic phonon modes in thinner walled nanotubes.

We have demonstrated the fabrication of horizontally aligned carbon nanotube (CNT) bundles on Si substrate for interconnect line application. By controlling the catalyst thickness, we fabricated multi-walled CNT and few-walled CNT bundles with different diameters. We measured the resistances of the CNTs as a function of the length and the diameter. The dependence of the contact resistance between the CNT and the metal on the CNT diameter was extracted from the resistance plots. We investigated and experimentally validated the relationship between the diameter and the mean free path of the CNT.