Editors’ Choice—Review—3D Printing: An Innovative Trend in Analytical Sensing

Dalton L. Glasco; Anjaiah Sheelam; Nguyen H. B. Ho; Art Matthew Mamaril; Melissa King; Jeffrey G. Bell

doi:10.1149/2754-2726/ac5c7a

Society finds itself at a point where the collection, analysis and interpretation of data is of paramount importance. As such, there is a concerted effort to exploit the newest technologies towards data collection through the development of diverse and robust sensors^1–4 that collect various chemical,^5–7 biological,^8–10 and physical^11–13 information. Of particular interest are sensors and/or devices which are deployable at the point-of-use (POU)^14–16 or point-of-care (POC).^17–20 A breakthrough in POC sensing came in the 2000s from the Whitesides group,²¹ through their use of paper as the substrate for the sensor's functional components. Being mass-produced, the use of paper in constructing analytical devices allowed for the development of sensors which are (i) low-cost, (ii) capable of storing and transporting chemical reagents, and (iii) easily disposed of through incineration (important when analyzing biological samples).^22–25 While many analytical techniques have successfully been implemented at the POC,^26–28 electrochemical approaches (e.g., amperometric,^29,30 potentiometric,^31–33 voltammetric,^34–36 etc) have been used more frequently owing to their sensitivity, reliability, and their ability to be miniaturized and integrated with electronics.³⁷ Furthermore, recent advances in the development of low-cost and miniaturized potentiostats have allowed researchers to entirely leave the laboratory setting to perform measurements.^38–41 Coupling the rise of portable potentiostats with powerful smartphones has drastically altered the traditional landscape of healthcare, by allowing for decentralized diagnostics through the instantaneous transmission of data (i.e., diagnostic results) from the field to the appropriate healthcare practitioner. While we now have at our disposal the tools to perform measurements reliably outside of the traditional laboratory setting, the process of fabricating sensors is currently experiencing a revolution owing to the emerging technology of 3D printing.^42–44

3D printing is an additive manufacturing technique where many types of materials are used to build structures,^45–47 scaffolds,^48–50 and even sensors.^51–53 3D printing is a generalized term for the many different techniques used to additively produce these designs.⁵⁴ For most 3D printing techniques, a design is produced using computer aided design (CAD) software. A standard tessellation language (.stl) file is used to transfer the design to the corresponding 3D printing (or slicing) software. Slicing software is used to cut a 3-dimensional design into appropriate thickness layers for the 3D printer to create the design.^55–57 Once the design is sliced, the 3D printer fabricates the design according to the desired spatial dimensions. With its inherent versatility, it should be no surprise that 3D printing has begun to permeate academic research, making profound impacts in fields which are taking advantage of the ability to rapidly prototype and iterate devices.^58,59

In this review, we focus primarily on the application of 3D printing towards the fabrication of the active sensing element used in the development of physical and electrochemical sensors. Here we have summarized and discussed the different approaches and applications researchers have used towards 3D printing sensors composed of various materials. Electrochemical sensors which use 3D printed material directly, or after a modification step, to perform an analytical measurement are receiving substantial attention. Interesting examples of 3D printed physical sensors for various applications and their role in increasing the functionality of soft robots is discussed in relation to their in-field applications. Although sensor components such as housings, microfluidics, conductive traces, etc, have been 3D printed, they are outside the primary scope of this review and will only briefly be discussed. Lastly, innovations in the field of energy storage are discussed as it pertains to the 3D printing of anodes and/or cathodes. While our aim in this review is to give a thorough treatment on the progress and application of 3D printing towards the development of electrochemical and physical sensors, we direct readers to other outstanding reviews which specifically focus on the different types of 3D printing: i) stereolithography,⁵⁵ ii) fused-deposition modeling,⁵⁶ and iii) selective laser sintering.⁵⁷ We also direct the readers to interesting reviews related to the role of 3D printing in energy storage/conversion applications.^60,61

Key Milestones in the Development of 3D Printing Technology

Solid-freeform technology, (i.e., additive manufacturing) is popularly known as 3D printing. 3D printing is a "bottom-up" fabrication method which produces structures with defined shape via layer-by-layer deposition and curing. In the early 1980s at the University of Colorado, Charles W. Hull, who was motivated by imperfections in product design, began the laborious task of developing a new technology which would mitigate such imperfections.⁶² In 1986, he patented his first invention on the technique of stereolithography. Hull developed a.stl file format for use in CAD software to transfer it to anywhere in the world through the internet. Hull also developed the first 3D printer, the stereolithography apparatus, and introduced the first commercially available 3D printer, the SLA-250. The first printed 3D object was a small black-eye wash cup using stereolithography.

In 1992, Scott Crump patented another important and more affordable technique in 3D printing called fused-deposition modeling (FDM).⁶³ Soon after in 1993, Michael Cima and Emanuel Sachs, from Massachusetts Institute of Technology patented a machine named "3D printer," which could print metal, plastic, and ceramic materials.⁶⁴ The interest in, and development of 3D printers was amplified with the emergence of several companies such as DTM corporation, Z corporation, solidscape and object geometries. Remarkably, companies such as Organovo and Helisys can print objects composed of living human tissue,^65,66 whereas other industrial sectors such as the aerospace and automotive industries, have used 3D printing to prototype aircraft and automotive parts.^67,68 Governmental agencies have also exploited 3D printing technology to rapidly print, and manufacture firearms and it was in the early 2000s when dental implants and prosthetics were fabricated,^69,70 that 3D printing was introduced to the medical device field. Owing to its fast prototyping, inexpensive, and flexible design capability, 3D printing became extremely popular in electrochemical energy storage and conversion.⁷¹ For example, in 2015 Arenas et al. utilized 3D printing to define electrolyte flow channels and fabricated a redox flow battery.⁷² The first glucose dehydrogenase biosensor was fabricated by Adams et al. in 2018, which was reported to show a linear detection between 0–400 mg dL⁻¹ of glucose.⁷³ In 2020, using a dual-extruder 3D printer, the Kokkinos group fabricated an electrochemical cell-on-a-chip in a single-step process.⁷⁴ An interesting advancement occurred in 2020, when Joao et al. introduced a 3D printing pen capable of printing a biodegradable carbon black/polylactic acid (PLA)-based filament, which was used for on-site detection of Pb and Cu ions in aqueous and hydroethanolic media.⁷⁵ Figure 1 highlights some of the significant advancements in the development of 3D printing technology as well as its application in the field of analytical sensing.

**Figure 1.** Timeline illustrating some of the important milestones relating to 3D printing technology and its application in the fabrication of sensors.
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A search in the Web of Science database using the keyword "3D printing," shows approximately 54300 research articles (including 2600 review articles) have been published to date. The number of publications/reviews vs year is shown in Figs. 2a and 2b. It can be observed from these figures that a steep increase in publications began in 2014. This data indicates the use of 3D printing in various applications, including electrochemical sensing, physical sensing, energy storage and application, food industry, automotive, military, and other industries.

**Figure 2.** The exponential growth rate of publications on 3D printing. (a) Research articles and (b) reviews. (Source: Web of Science, keyword: "3D Printing" in topic.)
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Types of 3D Printing

Fused-deposition modelling

Fused deposition modeling (FDM) is one of the major commercial versions of 3D printing.⁷⁶ This technique uses extruded material to form layered structures which are built into a desired pattern or design. FDM is a filament-based technique where diverse materials such as acrylonitrile butadiene styrene (ABS),⁷⁷ polylactic acid (PLA),⁷⁸ polystyrene,⁷⁹ polycarbonates,⁸⁰ polyethylene terephthalate (PET),⁸¹ polyvinyl alcohol (PVA),⁸² polyamide (i.e., Nylon),⁸³ polycaprolactone (PCL),⁸⁴ polybutylene terephthalate (PBT),⁸⁵ and polyglycolic acid (PGA)⁸⁶ can be printed owing to their inertness (i.e., no chemical reactions occur) in the fabrication process. Conductive thermoplastics have also become commercially available providing a unique platform for fabrication of carbon-based electrodes for electrochemical sensing. Briefly, the fabrication process takes the desired filament material and extrudes it (i.e., squeezes out) through a heated nozzle that reaches the glass transition temperature for the material causing it to temporarily liquify, allowing it to be extruded into layers which can be quickly cooled and resolidified. As each new layer builds upon the previously extruded layer, the semi-liquid form fuses to the preceding layer before solidifying. Sacrificial support structures are generally used for complex designs to prevent any deformations or print fails. FDM systems are considerably less robust than other techniques due to the lack of chemical fusing. Additionally, when compared to other 3D printing techniques currently available, FDM printing has the lowest resolution.⁸⁷ Although resolution is printer dependent, extruder nozzles are the primary mechanism for adjusting resolution (i.e., smaller extruder nozzles lead to higher resolution). The feature resolution of FDM is typically on the order of 500 μm. The primary benefits of FDM printing which drive its utility and application are its high print-material versatility and its low-cost. Since the filaments are extruded through controllable nozzles, multiple nozzles can be outfitted to the device, allowing for simultaneous multi-material printing.^88–90 An FDM printer is typically much less expensive than stereolithography (SLA) based 3D printers, which is an important consideration if the fabricated products are to be used, for example, in point-of-care (POC) applications.

Stereolithography

Stereolithography (SLA) is the most foundational form of 3D printing currently available and requires a photocurable resin that polymerizes by a UV light source (commonly a UV laser).⁹¹ There are two configurations of SLA printing: i) a conventional geometry, otherwise known as a "free platform configuration" and ii) an inverted geometry, also known as a "top-down configuration." In the free platform configuration, the desired structure is printed on a build platform that begins at the top of a reservoir tank (containing the photocurable resin) and moves downward into the resin after each layer is printed, until the pre-determined number of layers have formed. The top-down configuration uses a platform which begins immersed at the bottom of the reservoir tank, near a transparent optical window, where the photocurable resin is cured layer by layer as the platform is raised from the optical window. A movable laser (or a fixed laser with mirrors) is used to polymerize the resin at the working surface into a solid form. Each 2D layer solidifies and melds into the previous layer, creating a continuous solid object. Interestingly, many alternate forms of SLA are reported in the literature.^92–94 For example, a modification of the laser optics of conventional SLA 3D printers to a system known as two-photon polymerization (2PP) greatly improves the feature resolution, down to the nanometer scale. Here, a laser sends pulses that initiate two-photon absorption and polymerization on a very small volume of the photopolymer. Of all the 3D printing techniques currently available, 2PP has the best resolution and is appropriate to create high-quality optical surfaces and microstructures of considerable complexity.⁹⁵ Unfortunately, 2PP has two major drawbacks prohibiting its widescale use: i) a potentially insurmountable high cost (price) and ii) the advanced technical knowledge required for end users. Another modified SLA type 3D printing technique is digital light processing stereolithography (SLA-DLP), which uses a digital micromirror as the laser source projector. Using the digital micromirror as the projector can simultaneously impinge upon and polymerize the entire build surface as opposed to rastering with a single source, significantly increasing build speed.⁹⁶ Other variations of SLA that have been developed and reported in the literature include modifications such as incorporating an infrared (IR) laser and thermally curable resins.⁹⁷ It should be noted that relying on photocuring resins as the fundamental operating principle, limits the range of materials that SLA-type systems can print (compared to other techniques), as polymers such as polyethylene glycol diacrylate (PEG-DA)⁹⁸ or polymethyl methacrylate (PMMA)⁹⁹ typify the type of materials used. Good resolution and the rigid construction offered by SLA make SLA the most standard method of fabricating in 3D printed devices in research settings.¹⁰⁰

Selective laser sintering

Selective laser sintering (SLS) was the first powder-based 3D printing technique. SLS relies on a CO₂ laser to selectively sinter (or melt) a fine powder at the active fabrication surface.¹⁰¹ The fabrication surface (i.e., build platform) can then be lowered, allowing for a roller (from a powder container) to re-spread a fresh powder coating onto the surface for the fabrication of the subsequent layer. SLS based printers commonly have print resolutions around 100 μm, which is fundamentally determined by the particle size of the active layer as well as the focal spot of the laser, similar to SLA printing.¹⁰² Among the main categories of 3D printing types (e.g., FDM, SLA, and SLS), SLS routinely delivers the strength and durability of standard industrially fabricated parts, and the products usually retain the properties of the bulk materials. Components made of metal or metal alloys are best suited to SLS. The sequential addition of new layers of powder makes SLS quite capable of multi-material printing, adding extra levels of complexity to a design.¹⁰³ Significant limitations for printing polymer microfluidic or optical components arise from un-sintered material that remains on the surface or in small channels, along with the higher inherent surface roughness of the technique. Table I compares the various 3D printing technologies (e.g., FDM, SLA and SLS) with respect to their advantages, cost, types of printable materials and resolution range.

Table I. Comparison of several 3D printing styles used in analytical chemistry.

Method	Materials	Benefits	Drawbacks	Cost	Resolution range
FDM, FFF	Thermoplastic filament, Conductive filament, nanoparticle infused filament, fiber-reinforced filament,	Low cost, high speed, simplicity	Mechanical strength, Limited material (thermoplastics)	$200–$1500	50–200 μm
SLA, DLP	Photocurable monomer resins, hybrid polymer-ceramics	Fine resolution, high quality	Very limited materials, slow printing, partly expensive	$400–$5000	10–100 μm
SLS, SLM	Metallic powders, alloys, limited polymers, ceramics,	Fine resolution, high quality	Slow printing, expensive, high porosity in binding method	$10,000–$175,000	80–250 μm

FFF—Fused filament fabrication, SLM—Selective laser melting.

Electrochemical Sensors

Ready-to-use sensing elements

For the purposes of this review, "ready-to-use" sensing elements (e.g., electrodes, membranes, etc) are defined as being untreated/unmodified (e.g., activated, complexed, coated, etc) prior to use. The attachment or incorporation of the "as-printed" sensing element into a device or sensor housing does not preclude its classification as "ready-to-use." As mentioned previously, 3D printing has influenced many fields with the ability to rapidly incorporate and print low-cost material to fabricate customizable structures and devices.^104,105 In the realm of analytical electrochemistry, 3D printing was primarily used for creating electrode housings,¹⁰⁶ scaffolds,¹⁰⁷ structures,¹⁰⁸ etc, due to the ease in which one could print rigid and nonconductive materials. However, over the past ∼5 years, 3D printing has exploded into the field of electroanalysis owing to advancements relating to the printability of conductive polymers and plastics.^109,110 3D printing has provided a streamlined methodology to fabricate conductive electrodes, and recently, ion-selective membranes (ISMs). By far, FDM 3D printing has led the surge in the fabrication of electrochemical sensing elements due to the ease in which conductive material (e.g., carbon fiber, metallic nanoparticles, etc) can be introduced into extrudable plastics. Particularly interesting is the work of the Kokkinos group, who demonstrated this capability using a dual extrusion process.⁷⁴ This work fabricated an entirely 3D printed sensor where a nonconductive PLA filament was used to print the holding platform while a carbon-based PLA filament was used to print the working, counter, and reference electrodes. Dual extrusion FDM printing allows for multi-material fabrication simultaneously in a single printing process. Figure 3 illustrates the printing process (Fig. 3a), a computer aided design of the device (Fig. 3b), and the fully printed device (Fig. 3c).

**Figure 3.** (a) Schematic representation of the 3D printing fabrication for a single-step cell-on-a-chip device using a dual extruder FDM printer. (b) CAD dimensions of the 3D printed device (cm). (c) Comparison photograph of the 3D printed device to a coin. Reproduced from V. Katseli, A. Economou, and C. Kikkinos, *Talanta*, **208**, 120388 (2020). Copyright 2022 with permission from Elsevier.
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Once fabricated, the device was used to detect caffeine and paracetamol in both pharmaceutical tablets as well as urine. Using the electrochemical technique of differential pulse voltammetry (DPV), this group obtained detection limits of 2.01 μM for caffeine and 2.84 μM for paracetamol, respectively. The Kokkinos group demonstrated the robustness of this device by simultaneously measuring both caffeine and paracetamol in pharmaceutical formulations (96% and 101% recovery, respectively) and urine (97% and 103% recovery, respectively). Although FDM 3D printing has led the way with fabrication of conductive based electrochemical sensors, SLA has begun to make an impact in fabricating sensing components that FDM has not yet established.

Recent work by the Bell group has demonstrated the capability of SLA 3D printing technology to fabricate ready to use ISMs.¹¹¹ Previously, ISMs were primarily fabricated using polyvinyl chloride (PVC) based membranes (to ensure structural support), however, throughout the years several groups utilized other polymers for the support material. This work demonstrated the novelty of 3D printing a photocurable ISM cocktail that includes all ISM components (e.g., plasticizer, ion-exchanger, etc) along with a flexible acrylate based photocurable resin. Figure 4a illustrates the 3D printing process of the ISM and fabrication of both solid-contact and liquid-contact ion-selective electrodes (ISEs). Proof-of-concept demonstrations focused on the model ion tetrabutylammonium which was measured using both solid-contact (Fig. 4b) and liquid contact (Fig. 4c) ISE configurations, as well as a paper-based ISE (Figs. 4d, 3e). The work further probed the robustness of using 3D printing for fabricating ISMs for other analytes such as i) benzalkonium, a common preservative used in eye drops and hand sanitizer, ii) bilirubin, an important biomarker of liver health, and iii) potassium, an important blood electrolyte. Each ISE resulted in excellent reproducibility, selectivity, and covered the necessary detection ranges for biologically relevant levels for each target analyte. All additives were incorporated into the 3D printable resin prior to printing allowing for a ready to use membrane after printing. Furthermore, the authors demonstrated the mass-production capabilities by printing 121 disk-shaped ISMs in approximately 30 min.

**Figure 4.** (a) Schematic representation of the 3D printing fabrication of ISMs and ISEs. (b) Schematic illustration of a solid contact ISEs and (c) a liquid contact ISE. (d) Schematic of a paper-based device incorporating a 3D printed ISM and (e) a 4-point calibration curve for the analysis of the tetrabutylammonium cation. Modified from D. L. Glasco, N. H. B. Ho, A. M. Mamaril, and J. G. Bell, *Anal. Chem.*, 93, 15826 (2021). Copyright 2022 with permission from American Chemical Society.
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Interestingly, the Subannajui group used an FDM 3D printer to fabricate electrodes by blending PLA with i) carbon nanotubes (CNT), ii) CNT/copper (Cu) and iii) CNT/zinc oxide (ZnO) composites.¹¹² As a result, the 3D printed conductive electrodes based on CNT/PLA composites were used to perform electronic tongue analysis. They found that the 3D printed electrodes were electrochemically distinct and sufficiently stable over multiple cyclic voltammetry measurements and able to distinguish the voltammetric signals from various electroactive species (e.g., ferrocyanide, H₂O₂, and NAD⁺). Each sensor composition was found to provide good limits of detection for all three species in the micromolar range with the optimal compositions of each electrode providing limits-of-detection (LOD) of 5.3, 2.9, and 1.2 μM for H₂O₂, NAD⁺, and ferrocyanide respectively. This research provided a low cost and time-efficient method while using inexpensive instrumentation where it is beneficial for preliminary observations and on-site investigation. The Munoz group has taken a unique approach to fabricate ready-to-use electrochemical sensors for forensic based studies with 3D printing. Using FDM printing they fabricated a sampling sensor for heavy metal analysis as it relates to gunshot residue.¹¹³ This group incorporated a 3D printed electrochemical cell using nonconductive PLA filament (housing) and a graphene/PLA composite filament (sampling electrode) for the sampling working electrode. Gunshot residue was collected onto the electrode surface which could then be added to the electrochemical cell and analyzed through square-wave anodic stripping voltammetry. The 3D printed sensors produced dynamic ranges of 50–1500 μg l⁻¹ and LODs of 0.5 and 1.8 μg l⁻¹ for Pb²⁺ and Sb³⁺, respectively.

The ability to directly use the as-fabricated sensors is highly dependent on the purity and functionality of material being printed. Recently, it has been found that metal impurities (e.g., Fe and Ti) in commercially available filaments drastically influence the electrochemical characteristics of the corresponding 3D printed sensors.¹¹⁴ For example, the Pumera group found that Fe, Ti and Al impurities in commercially available graphene/PLA composite filaments leads to enhanced catalysis towards water splitting.¹¹⁵ As such, it is imperative to fully characterize the composition of all sensors fabricated in order to gain insights and to fully understand all factors leading to the sensor's activity.

Post-modified sensors

The ability to modify electrode surfaces with conductive polymers, nanomaterials, and biological recognition elements (i.e., enzymes, antibodies, aptamers, etc) has been extremely rewarding in the development of electrochemical sensors which are both sensitive and selective towards specific target analytes.^116,117 As such, electrochemical sensors have been used to detect diverse analytes in various complex matrices such as biological fluid (e.g., blood, urine, saliva, sweat, and tears) and environmental samples. In this section, we highlight advancements made in the fabrication of electrochemical sensors utilizing 3D printed surfaces which have undergone post-processing to modify the surface of the electrochemical sensor for specific applications. The ability to easily modify 3D printed electrode materials has allowed researchers to expand the list of target analytes which can be detected using sensors fabricated using 3D printing. While an optimal scenario would permit the printing of a sensor which contains the complete functionality required to perform the desired measurement, barriers in the currently available 3D printer technology need to be overcome for this to be realized.

Regardless of barriers imposed simply by printer technology, 3D printing has still made an impact in electrochemical sensing through post-modification of the 3D printed material. For example, SLS printing is proving particularly useful in the fabrication of customizable metallic electrodes. Research performed by the Pumera group has provided insightful and important advancements in the 3D printing of metallic biosensors in recent years.¹¹⁸ A recent study by this group utilizes the ability of SLS printing to fabricate a unique stainless-steel helical electrode that was post-modified using electroplating. Electrodes were electroplated with gold and bismuth and subsequently used to detect heavy metals through anodic stripping voltammetry (ASV), a technique which is an established approach to detect trace heavy metals.

Figure 5 displays a computer aided design of the helical design (Fig. 5a), a steel 3D printed electrode (Fig. 5b), a gold electroplated steel electrode (Fig. 5c), and a bismuth electroplated electrode (Fig. 5d). Measurements with these novel sensors resulted in improved reproducibility, linearity, and sensitivity compared to conventional glassy carbon electrodes for lead and cadmium analysis. Although glassy carbon electrodes resulted in better limits-of-detection, this unique approach shows the potential to compete with conventional electrode materials.

The versatility and rapid prototyping ability of 3D printing allow researchers to address important and impactful societal concerns in a streamlined manner. Of particular relevance is the dramatic effect that the COVID-19 pandemic had on all aspects of society throughout the world. Here, the ability to diagnose COVID-19 quickly and accurately was a task that many researchers in the field of analytical chemistry embarked upon. Munoz and Pumera applied their knowledge with 3D printing and immunosensing to fabricate a 3D printed immunosensor for the detection of COVID-19.¹¹⁹ Figure 6 displays the fabrication process of the immunosensor with the post modified 3D printed electrode. Utilizing the ability of FDM printing and availability of graphene-based filament the authors developed a novel diagnostic tool to detect COVID-19 through competitive immunocomplexes.

**Figure 6.** (a) Schematic of a 3D printed electrochemical COVID-19 immunosensor fabrication process. (b) Indirect competitive assay used for detecting the COVID-19 recombinant protein. Reproduced from J. Munoz and M. Pumera, *Chem. Engineering J.*, **425**, 131433 (2021). Copyright 2022 with permission from Elsevier.
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This device utilized electrochemical impedance spectroscopy to determine the Δratio (i.e., Δratio = (R_A − R₀)/R₀ where R₀ and R_A is the charge transfer resistance, R_ct, before and after incubation of antibody/antigen mixture, respectively) calibration of COVID-19 protein which covered a range of 1–10 μg ml⁻¹. Comparing the specified protein to serum showed significant overlap with a spike analysis that was completed that provided a 103% recovery.

While FDM 3D printers have been the primary vehicle used to fabricate sensors, the Venton group used a unique approach to develop a sensor used to measure dopamine levels.¹²⁰ The authors demonstrate the ability to post modify a carbon-based, non-conductive material into a conductive pyrolyzed carbon electrode. Using a photopolymerizable carbon-based resin, they first printed non-conductive microstructures, which were converted into conductive nano-electrodes through pyrolysis, for neurotransmitter analysis. During pyrolysis, carbon-containing substances decompose under high heat (in the absence of oxygen) to produce glassy carbon-like materials with conductive properties. They were able to use the post-modified 3D printed sensors to analyze dopamine using fast-scan cyclic voltammetry after stimulation in an adult fly brain. These interesting electrochemical sensors were able to reproducibly detect stimulated dopamine from 10 to 50 μM. While SLA 3D printing has rarely been used in the fabrication of sensors, most resins are carbon based and can therefore be easily converted into conductive electrodes using the pyrolysis approach.

An important contribution to the aim of 3D printing entire devices in a single print was realized by the O'Neil group, who utilized dual extrusion FDM printing to fully 3D print an all-in-one device consisting of a housing, microfluidic channel, and electrodes.¹²¹ Using PLA as a nonconductive filament for the housing that holds the microfluidic channel, and a graphene/PLA filament O'Neil presented a device to measure catechol using amperometry. Once the device was printed the working electrode was post modified through the electrodeposition of a gold film. The authors successfully measured catechol from 5.1–103 μM with extremely reproducible results. Not only does this work provide a 3D printed sensing element, but they combine it with microfluidics in a one-step fabrication method. While individually the sensing components and housing/fluidic channels can be fabricated using 3D printing, the advancement in 3D printing technology (i.e., the use of dual extruders for multi-material printing) has only recently given researchers the ability to simultaneously print both components. The analytical characteristics of a variety of 3D printed electrochemical sensors can be found in Table II.

Table II. 3D printed electrochemical sensors used for analytical analyses.

Printed Component	3D Printing Method	Material Used	Post Modification	Analysis Technique	Analyte	Detection Range	Limit of Detection	References
Ion-Selective Membrane	SLA	Photocurable resin premixed with ISM components	—	Potentiometry	TBA⁺	8–1 × 10⁴ μM	—	111
					Bilirubin	8–1 × 10⁴ μM	—
					Benzalkonium	16–1 × 10⁴ μM	—
					Potassium	61–1 × 10⁶ μM	—
Immunoassay electrode	FDM	conductive graphene/PLA	Immersion in DMF then electrochemically activated followed by immunocomplexing	Charge Transfer Resistance	COVID-19 recombinant protein	—	0.5 ± 0.1 μg ml⁻¹	119
Pyrolyzed Electrodes	DLW	Carbon-based photocurable resin	Pyrolysis	DPV	Dopamine	10–50 μM	177 ± 21 nM	120
Carbon Electrode	FDM	Nonconductive PLA filament (housing)	—	DPV	Caffeine	0–116 μM	2.84 μM	74
		Carbon-based PLA filament (electrode)			Parcetamol	0–149 μM	2.01 μM
Carbon Black Electrode	FDM	Carbon black PLA	—	DPV	Serontonin	—	—	122
Steel, Au, Bi plated electrodes	SLS	Stainless steel powder	Electroplated with Au and Bi films	ASV	Lead	50–300 ppb	3.53 ppb	118
					Cadmium	50–300 ppb	9.35 ppb
Graphene/PLA sampling electrode	FDM	PLA filament (electrochemical cell)	—	ASV	Lead	50–1500 μg l⁻¹	0.5 μg l⁻¹	113
		Graphene/PLA filament (electrode)			Antimony	50–1500 μg l⁻¹	1.8 μg l⁻¹
CNT, CNTCu, CNT/ZnO PLA electrodes	FDM	CNT, CNT/Cu, and CNT/ZnO doped PLA filament	—	Cyclic Voltammetry	Ferrocyanide	—	1.2 μM	112
					H₂O₂	—	2.9 μM
					NAD⁺	—	5.3 μM
Graphene/PLA electrodes	FDM	PLA Filament (housing)	Electrodeposition Au film	Amperometry	Catechol	5.1–103 μM	—	121
		Graphene/PLA filament (electrode)
Carbon-based PLA E-Ring	FDM	Flexible PLA (E-Ring housing)	—	Chronoamperometry	Glucose	12.5–400 μM	—	123
		Carbon-based PLA filament (electrode)
Ag conduction element and electrode	Micro Extrusion	Ag doped filament	Drop casted ISMs onto electrode surface	Potentiometry	Potassium	100–1 × 10⁵ μM	—	124
					Calcium	100–1 × 10⁵ μM	—
					Sodium	1000–1 × 10⁵ μM	—

DLW—Direct Laser Writing, DPV—Differential Pulse Voltammetry, ASV—Anodic Striping Voltammetry.

Wearables

Wearable sensors are rapidly emerging as effective POC devices which can provide real-time monitoring of various electrolytes and biomarkers found in biological fluids, most commonly, sweat.^125,126 Indeed, 3D printing is beginning to play a profound role in the development of such wearable devices, and here we will discuss some important contributions relating to the incorporation of 3D printed sensors into wearable devices. The use of low-cost materials, simplicity in fabrication, and rapid testing capabilities, are key characteristics that successful POC devices contain and 3D printing has begun providing these characteristics for wearable sensors. The Kokkinos group introduced a novel electrochemical glucose sensor that did not rely on any enzymatic reactions.¹²³

Figure 7 shows the dual extrusion FDM printing process where a non-conductive, flexible filament is used for the ring housing while a carbon-based filament is utilized to fabricate the conventional 3-electrode set up (e.g., working, counter, and reference electrodes). In using a miniature potentiostat that can be directly controlled by a smartphone, this unique wearable sensor provides a non-invasive detection of glucose in sweat through a self-monitoring process. Measurements of glucose with the ring-based wearable sensor yielded a detection range from 12.5–400 μM, without interference from common electroactive metabolites in sweat, covering the physiological relevant range. This approach resulted in a cost-effective, easy to use, rapid analysis of glucose, an important biomarker of diabetes, which can effectively be used at the point-of-care.

Another advancement in wearable sensing was demonstrated by the Esfandyarpour group, where they fabricated a multiplexed 3D printed electrochemical sensor for detection of important electrolytes in sweat.¹²⁴ Figure 8 illustrates a schematic of the wearable sensor for Ca²⁺, K⁺, and Na⁺ ion detection. A polydimethylsiloxane (PDMS) fluidic channel was used to absorb sweat into the detection well where the 3D printed sensors and reference electrode are housed.

**Figure 8.** (a) Schematic demonstration of an all-inclusive integrated wearable (AIIW) top view. (b) Image of a flexible AIIW patch including 3D printed ion sensors along with a wearable-microfluidic sample handling (WMFSH). (c) Schematic illustration of individual components assembly into a AIIW patch. (d) Cross-sectional schematic of a AIIW patch attached to the skin during sweat collection. (e) Schematic illustration of 3D printed electrodes, electrodes membrane, PDMS substrate, an adhesive layer, and WMFSH unit integration into a AIIW patch. Reproduced from T. Kim, Q. Yi, E. Hoang, and R. Esfandyarpour, *Adv. Mater. Tech.*, 6, 2001021 (2021). Copyright 2022 with permission from Advanced Materials Technologies.
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The 3D printed sensor consists of a 3D printed silver-based filament for the electrode and electrical connection where the electrode was then modified through the addition of drop casted ion-selective membranes for Ca²⁺, K⁺, and Na⁺. Each sensor was monitored through potentiometric measurements and provided detection ranges from 100 mM to 100 μM for potassium and calcium while sodium provided a range of 100 mM to 1 mM. Selectivity for each sensor showed limited interference from other common electrolytes found in sweat. Direct sweat analysis provided stable measurements over hundreds of seconds for each sensor. With the implementation of fluidic channels, the ability to transfer sweat to the sensors was accomplished with ease and could be replenished over time while volumes of previously measured sweat could flow out the exit wells.

While the number of wearable devices which incorporate 3D printed sensing elements is currently sparse, the rising interest in 3D printing, coupled with the growing interest for real-time monitoring of important health biomarkers, suggests that fully 3D printed wearable devices will soon be realized. In fact, several other research groups are actively working in this area, alluding to the incorporation of their sensors into wearables.^127–129 One interesting example comes from Woo Soo Kim and his cohort that have produced many 3D printable sensors that can be easily translated to a wearable substrate for on-body analysis.¹²⁷ In a recent study Kim's group discusses the ability to 3D print a conductive carbon nanofiber-silver nanowire (CNF-AgNW) ink that is integrated for an ion-selective field effect transistor (ISFET) for the detection of several electrolytes (e.g., K⁺, Ca²⁺, and NH₄ ⁺). Kim post modified the conductive CNF-AgNW electrode with ISMs selective for each corresponding ion. This work provided a proof-of-concept demonstration of 3D printable CNF-AgNW ink for the use of ISFET electrochemical sensing. These examples highlight the potential of 3D printing to revolutionize the fabrication of wearable sensors which are low-cost, highly reproducible, and selective.

Physical Sensors

With the increased demand to quantify and monitor diverse parameters, sensors capable of acquiring physical information (e.g., shear, pressure, temperature, etc) are becoming more ubiquitous in society, and have begun to be integrated into wearable consumer electronics,¹³⁰ soft robots,¹³¹ electronic skins,¹³² and smart medical prosthetics.¹³³ As the demand for these applications grows, so do the requirements and criteria for the development and effective implementation of physical sensing devices. Physical sensors have been developed and fabricated from different materials and methods.¹³⁴ Flexible substrates and materials have been increasingly utilized in these applications, because of the adaptability and conformability offered to the surfaces with different geometries and topologies. In prior literature, piezoelectric, resistive, capacitive and optical devices have been constructed and demonstrated, with mechanical sensing capacities on a variety of flexible substrates, including elastomeric nanocomposites and primarily deformable polymeric films (e.g., polyimide/PI, polyvinylidene fluoride/PVDF or poly(3,4-ethylenedioxythiophene): polystyrene sulfonate, PEDOT:PSS.¹³⁵ One of the prime challenges in the development of physical sensors is the fabrication process itself, where common approaches utilize techniques such as photolithography, lamination, spin-coating, solution casting, vacuum filter deposition, and inkjet printing. These techniques are often complex, not amenable to modification, and time-consuming. As such, it is not surprising that 3D printing, with its ability to rapidly print and protype devices, has begun to be heavily relied upon in the fabrication of physical sensors.¹³⁶

An interesting example of using 3D printing to fabricate a flexible strain sensor, shown in Fig. 9, was published by Xiao et al.¹³⁷ Here, the authors developed a high-performance strain sensor using a UV curable composite consisting of multiwalled carbon nanotubes (MWCNTs) and a highly stretchable elastomer (epoxy aliphatic acylate and aliphatic urethane diacrylate). The authors found that the MWCNT/elastomer composite delivered a sensitivity of 8.939 with a linearity up to 45% strain, when using 2 wt% of MWCNTs. The sensor could measure strain between 0.01% and 60% which maintaining a high mechanical durability over 10000 cycles. As a demonstration of potential application for the 3D printed strain sensor, the authors fabricated a 4 × 4 sensor array to measure the distribution of external stimuli as shown in Fig. 9g.

**Figure 9.** (a) DLP 3D printer diagram. (b) Schematic illustration of DLP printing for a strain sensor array. (c) Images of strain sensor array size and compressibility. (d) Image of ECUST logo printed using MWCNT/EA composition. (e) Image of ECUST logo printed using EA material. (f) Schematic representation for a 4 × 4 strain sensor array fabrication. (g) Image of a 4 × 4 strain sensor array. Reproduced from T. Xiao, C. Qian, R. Yin, K. Wang, Y. Gao, and F. Xuan, *Adv. Mater. Tech.*, 6, 2000745 (2020). Copyright 2022 with permission from Advanced Materials Technologies.
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Alsharari et al. developed a method to 3D print porous, soft pressure sensors using an FDM printer (Fig. 10).¹³⁸ The sensors, which are composed of multiple layers, showed both a high tactile sensitivity (0.7145 kPa⁻¹ at 0.5 kPa) and a wide sensing range (0.1 kPa–200 kPa). To explore the utility of the 3D printed soft, pressure sensors, the authors investigated a variety of applications ranging from finger bending/pressing to the addition of incremental weights (placing a series of coins on top of the sensors). According to the authors, such applicability coupled with the soft and flexible nature of the sensors suggests that the sensors could be incorporated into wearable devices or have applications in the field of robotics.

**Figure 10.** (a) Schematic representation of a multi-layered pressure sensor. (b) A 3D printing schematic using dual extrusion FDM printing for sensor fabrication. (c) Demonstration schematic of post processing removal of support material. Reproduced from M. Alsharari, B. Chen, and W. Shu, *Adv. Electron. Mater.*, 8, 2100597 (2021). Copyright 2022 with permission from Advanced Electronic Materials.
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While the field of soft robotics has been dramatically influenced by the rise in 3D printing technology, the work by the Tolley group investigated the incorporation of 3D printed soft resistive sensors into a soft gripper.¹³⁹ As a proof-of-concept demonstration, the authors 3D printed a soft gripper with embedded sensors and measured the static response observed while the gripper was holding various objects. Figures 11a–11e shows the soft gripper holding a plastic strawberry, pencil, can of spam, toy peg and plastic banana, respectively. Although this study highlights the versatility of 3D printing by being able to fabricate the soft robot as well as the corresponding sensors, the authors note that the need for high-sensitivity electronics (to perform the measurements) as well as drift in the observed readings need to be addressed in future research. Table III highlights examples of 3D printed physical sensors.

**Figure 11.** Sensor readings for a pneumatic gripper embedded with strain sensors across S1, S2, and S3 for a (a) plastic strawberry, (b) pencil, (c) can of spam, (d) toy peg, and (e) plastic banana in a 3D perspective (f) and 2D perspective (g). Reproduced from B. Shih, C. Christianson, K. Gillespie, S. Lee, J. Mayeda, Z. Huo, and M. T. Tolley, *Front. Robot. AI*, 6, (2019).
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Table III. 3D printed physical sensors used for various applications.

Printed Component	3D Printing Method	Material Used	Property analyzed	Range	References
Capacitive Sensor	FDM	Thermoplastic polyurethane	Temperature	10 °C–40 °C	140
		AlfaOhm (PLA)-based filament with CNT
Flexible strain sensor	FDM	Carbon infused thermoplastic polyurethane	Strain	10 N for shear forces	141
				50 N for normal forces
Strain Sensor	FDM	Conductive PLA ProtoPasta filament	Dynamic Strain	Up to 800 Hz	142
Spatial Capacitance Sensor	FDM	PLA	Capacitance	—	143
Soft Pressure Sensor	FDM	Carbon black thermoplastic polyurethane (CBTPU)	Pressure	0.1–200 kPa	138
Flexible Strain Sensor	DLP	MWCNT/elastomer (epoxy aliphatic acrylate and aliphatic urethane diacrylate)	Strain	∼60% strain	137

Conclusions and Future Perspectives

In this review we presented several important contributions relating to 3D printed electrochemical and physical sensors. The explosive rise in the use of 3D printers to fabricate sensing devices is rapidly altering the landscape in which researchers can prototype and validate sensors. Using 3D printing to fabricate sensors has the following primary benefits: i) precise control over shape and spatial dimensions of the sensing elements, ii) reduced fabrication time, iii) affordability, iv) mass production capabilities, and v) reproducibility. While 3D printing has proved itself to be advantageous in the fabrication of electrochemical and physical sensors, there are several issues which need to be addressed before 3D printing can be used to its full potential. Of particular importance is printer/material compatibility. Currently, there are a limited number of commercially available photocurable polymers (for SLA printers) and filaments (for FDM printers). Simply expanding the catalogue of 3D printable materials will lead to the fabrication of sensors with added functionality, which will open the door for the sensing of diverse analytes. To achieve this added functionality, active collaborations between materials chemists and analytical chemists must be formed. These collaborations should aim to develop filaments and resins with new features such as the incorporation of nanomaterial, conductive polymers, piezoelectric materials, etc. Although the technology of 3D printers has progressed to a point where many of them have become remarkably affordable, further reductions in cost will allow them to become more ubiquitous in academic research labs. Furthermore, the ability to combine 3D printing mechanisms (e.g., SLA and FDM type printing) into a single printer will streamline efforts towards the goal of creating complete devices in a single print. For example, flexible wearable devices would benefit from the ability to print electronics into flexible polymers. Interestingly, 3D printing has also permeated the energy storage/conversion research field, where work on the fabrication of anodes and cathodes for Li-ion batteries and solid-state supercapacitors have already been reported.^144,145 With ongoing research and development with 3D printing technology at the core, it is not impractical to imagine entire sensing devices (including sensor components, interfaces, electronics, power sources, etc) to be printed with a single "click." Considering the ability of 3D printers to deliver highly reproducible sensors with decreased cost and fabrication time, the continued incorporation of 3D printing into sensor design and development will provide a much-needed gateway between academic research and the commercialization of these sensors.

Editors' Choice—Review—3D Printing: An Innovative Trend in Analytical Sensing

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Abstract

Key Milestones in the Development of 3D Printing Technology