Electrochemical aptamer sensors will soon be backed by two decades of research since they were first introduced in 2005, and have yet to achieve the commercial success seen for continuous enzymatic glucose monitors. At the University of Cincinnati, we have hypothesized that the biggest barriers holding back electrochemical aptamer sensors are three fold: (1) 1-2 week high-accuracy longevity is now the expected performance benchmark; (2) there has been little research done on adapting aptamer sensors onto the commercially and clinically proven ‘plastic needle strip’ approach used in most glucose monitors; (3) while there have been dozens of in-vivo demonstrations for aptamer sensors, they have targeted easier to sense analytes instead of the most clinically impactful analytes. This presentation will review the latest progress on all three of these barriers. The presentation will review fundamental electrode, monolayer, and measurement designs now allowing record multi-month operation. The presentation will also highlight our recent in-vivo results (rats, pigs, humans) and the progression towards a wearable monitor that is very similar to a modern glucose monitor. Lastly, this presentation will summarize the significant remaining challenges for sensing of the most clinically important analytes, which are often in the pM to nM range, and often medium to large size molecules such as peptide hormones and proteins. While challenges remain, the breakthroughs of just the past 2 years suggests that multi-week monitoring with electrochemical aptamer sensors is a near-term reality.

Due to their high specificity and selectivity, receptor-based biosensors play an important role in real-time health monitoring. However, maintaining an ideal homeostatic sensor environment while correcting for the physiological variability of biofluids is imperative. Biological media contain an abundance of interfering species which if not addressed, can render the biosensor inoperable. Enzyme-based electrochemical sensors are particularly susceptible to redox-active interferences as these increase analyte detection limits, making physiological measurements a challenge. For this reason, extensive research has been applied to develop various strategies to mitigate such interferences. Here we present a novel conductive membrane encapsulation strategy designed to mitigate redox-active interferences while allowing redox-inactive target analyte to pass through unaltered to the sensor surface. This redox-active mitigation strategy is highly generalizable as the potential across the conductive membrane can be easily modified. Using a first-generation glucose oxidase sensor as a model interferent-sensitive system, we have shown a 72 percent reduction in redox-active interference and an 8-fold decrease in detection limit upon implementation of our conductive membrane strategy.

Redox cycling (RC) is a powerful tool capable of amplifying faradaic currents in electroanalytical measurements, thus allowing an enhancement of sensitivity through fast multiple sequential oxidation and reduction reactions of a redox-active analyte. Present state-of-the-art RC devices are mostly based on planar electrode geometries either in 2D or 3D configurations, requiring cleanroom facilities and expensive microfabrication techniques. Here, the electrochemical elaboration and characterization of a 3D coaxial macroporous twin-electrode is reported, obtained by following a low-cost bottom-up approach. A nanoengineered highly organized porous material is the basis for the design of two threaded cylindrical porous gold microelectrodes with a gap in the micrometer range that can be fine-tuned. The potentials of the outer and inner electrodes are biased at values above and below the redox potential of the analyte so that a given molecule can participate several times in the electron exchange reaction by shuttling between both electrodes. The resulting signal amplification, combined with a straightforward synthesis strategy of the electrode architecture, allows envisioning numerous (bio)electroanalytical applications.

Conventional wisdom suggests that widely utilized self-assembled alkylthiolate monolayers on gold are too unstable to last more than several days when exposed to complex fluids such as raw serum at body temperature. Demonstrated here is that these monolayers can not only last at least 1 week under such harsh conditions but that significant applied value can be captured for continuous electrochemical aptamer biosensors. Electrochemical aptamer biosensors provide an ideal tool to investigate monolayer degradation, as aptamer sensors require a tightly packed monolayer to preserve sensor signal vs background current and readily reveal fouling by albumin and other solutes when operating in biofluids. Week-long operation in serum at 37 °C is achieved by (1) increasing van der Waals interactions between adjacent monolayer molecules to increase the activation energy required for desorption, (2) optimizing electrochemical measurement to decrease both alkylthiolate oxidation and electric-field-induced desorption, and (3) mitigating fouling using protective zwitterionic membranes and zwitterion-based blocking layers with antifouling properties. This work further proposes origins and mechanisms of monolayer degradation in a logical stepwise manner that was previously unobservable over multiday time scales. Several of the observed results are surprising, revealing that short-term improvements to sensor longevity (i.e., hours) actually increase sensor degradation in the longer term (i.e., days). The results and underlying insights on mechanisms not only push forward fundamental understanding of stability for self-assembled monolayers but also demonstrate an important milestone for continuous electrochemical aptamer biosensors.

A key approach for designing bioinspired machines is to transfer concepts from nature to man-made structures by integrating biomolecules into artificial mechanical systems. This strategy allows the conversion of molecular information into macroscopic action. Here, we describe the design and dynamic behaviour of hybrid bioelectrochemical swimmers that move spontaneously at the air-water interface. Their motion is governed by the diastereomeric interactions between immobilized enantiopure oligomers and the enantiomers of a chiral probe molecule present in solution. These dynamic bipolar systems are able to convert chiral information present at the molecular level into enantiospecific macroscopic trajectories. Depending on the enantiomer in solution, the swimmers will move clockwise or anticlockwise; the concept can also be used for the direct visualization of the degree of enantiomeric excess by analysing the curvature of the trajectories. Deciphering in such a straightforward way the enantiomeric ratio could be useful for biomedical applications, for the read-out of food quality or as a more general analogue of polarimetric measurements.

Electrochemical biosensors promise a simple method to measure analytes for both point-of-care diagnostics and continuous, wearable biomarker monitors. In a liquid environment, detecting the analyte of interest must compete with other solutes that impact the background current, such as redox-active molecules, conductivity changes in the biofluid, water electrolysis, and electrode fouling. Multiple methods exist to overcome a few of these challenges, but not a comprehensive solution. Presented here is a combined boron-doped diamond electrode and oil–membrane protection approach that broadly mitigates the impact of biofluid interferents without a biorecognition element. The oil–membrane blocks the majority of interferents in biofluids that are hydrophilic while permitting passage of important hydrophobic analytes such as hormones and drugs. The boron-doped diamond then suppresses water electrolysis current and maintains peak electrochemical performance due to the foulant-mitigation benefits of the oil–membrane protection. Results show up to a 365-fold reduction in detection limits using the boron-doped diamond electrode material alone compared with traditional gold in the buffer. Combining the boron-doped diamond material with the oil–membrane protection scheme maintained these detection limits while exposed to human serum for 18 h.

Biofuel cells (BFCs) are electrochemical devices that rely on the transformation of chemical energy into electricity through biochemical pathways, however delivering only moderate or low power and voltage. This intrinsic limitation narrows their potential applications for driving electronics and thermodynamic systems with higher energy demands than what can be delivered by the BFCs alone. Nevertheless, coupling BFCs to electronic circuits, able to raise their voltage, allows circumventing these drawbacks. In this proof-of-concept study, we demonstrate an unconventional way of achieving highly efficient electrochemical corrosion protection of an iron surface in a chloride rich medium. The required protecting cathodic potential is generated by a self-powered bioelectronic system, consisting of a BFC, which can, despite its low voltage output (0.3 V), completely prevent interfacial corrosion if it is combined with an electronic boost converter.

Graphene‐based composites have received attention as part of the drive towards next‐generation electronic and energy‐storage technologies. However, current graphene synthesis methods are limited by complex, time‐consuming, toxic, costly, and/or often low‐yield procedures. The synthesis of a novel stretchable graphene‐polyurethane‐poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate ink aimed at printing wearable electronics is reported. The procedure is based on low‐cost high‐yield production of high‐performance graphene ink produced by laser induction of polyimide film followed by harvesting the graphene. Screen printing is used to fabricate flexible and intrinsically stretchable micro‐supercapacitors (S‐MSCs) printed on different substrates. The resulting graphene‐based printed S‐MSCs display a remarkably high capacitive performance and attractive mechanical resiliency. High specific areal capacitance, above 23 mF cm −2 , is achieved, which is the highest areal capacitance reported for highly stretchable, printed graphene supercapacitors. A repeated (200 cycles) stretchability beyond 100% is obtained while maintaining more than 85% of the S‐MSCs' original capacitance. This unique and highly scalable graphene ink synthesis method holds considerable promise for application in low‐cost graphene‐based chemical formulation, especially in the field of printed and wearable electronics toward multifunctional, energy‐storage systems capable of withstanding severe mechanical deformation while maintaining their optimal electrochemical performance.

Ammonia was produced electrochemically from nitrogen/air in aqueous alkaline electrolytes by using a Fe2O3/TiO2 composite catalyst under room temperature and atmospheric pressure. At an applied potential of 0.023 V versus reversible hydrogen electrode, the rate of ammonia formation was 1.25 × 10-8 mmol mg-1 s-1 at an overpotential of just 34 mV. This rate increased to 2.7 × 10-7 mmol mg-1 s-1 at -0.577 V. The chronoamperometric experiments on Fe2O3/TiO2/C clearly confirmed that Fe2O3 along with TiO2 shows superior nitrogen reduction reaction activity compared to Fe2O3 alone. Experimental parameters such as temperature and applied potential have a significant influence on the rate of ammonia formation. The activation energy of nitrogen reduction on the employed catalyst was found to be 25.8 kJ mol-1. Real-time direct electrochemical mass spectrometry analysis was used to monitor the composition of the evolved gases at different electrode potentials.

A new wearable potentiometric tattoo biosensor for real-time on-body monitoring of G-type nerve agents simulant is described. The skin-worn flexible biosensor responds rapidly and selectively to the fluorine-containing organophosphates (OP) nerve agent simulant diisopropyl fluorophosphate (DFP, a model OP analyze) in both liquid and vapor phases. The epidermal potentiometric OP biosensor relies on the pH-sensitive polyaniline (PANi) coating on a flexible printed transducer for monitoring the proton release during the enzymatic hydrolysis of DFP by enzyme organophosphate hydrolase (OPH). The sensing electrodes are screen printed on a temporary tattoo paper and are interfaced to a conformal electronic interface that provides wireless data transmission. The skin-worn OP potentiometric sensor can withstand severe mechanical strains without compromising its analytical performance. The biosensor displays a wide dynamic range, fast response and high selectivity towards DFP (including efficient discrimination against organophosphate pesticides), and good reproducibility. The attractive performance of the new wearable biosensor indicates considerable promise for on body threat detection towards rapid warning regarding potential exposure to G-series nerve agents.

Current methods to create 3D structures are limited to few materials and designs, are costly, and have low processing throughput. Planar designs (of printed sacrificial, flexible, and guiding layers) fabricated by thick film technique that can reversibly fold between their 2D and 3D forms through compressive buckling and selective bonding is reported in this work. Versatile ink compositions based on a wide variety of materials (e.g., carbonaceous, polymers, and nanomaterials) are used along with screen printing technique for creating variety of desired 3D structures, such as spirals, squares, and spikes. Various composite inks are printed onto substrates containing a printed sacrificial layer for selective binding, and the substrate can be prestretched for a controlled buckling process. Removal of the sacrificial layer and release of the strained substrate leads to the folding of the flat printed structures into targeted respective 3D architectures. Such use of planar screen-printed layers to create 3D shapes brings several technological advantages, including broad selection of materials, large-scale processing at low cost, and incorporation of numerous functional technologies. The successful control of such printed 3D architectures offers a promising route to enable numerous applications based on large variety of materials.

Flexible epidermal tattoo and textile-based electrochemical biosensors have been developed for vapor-phase detection of organophosphorus (OP) nerve agents. These new wearable sensors, based on stretchable organophosphorus hydrolase (OPH) enzyme electrodes, are coupled with a fully integrated conformal flexible electronic interface that offers rapid and selective square-wave voltammetric detection of OP vapor threats and wireless data transmission to a mobile device. The epidermal tattoo and textile sensors display a good reproducibility (with RSD of 2.5% and 4.2%, respectively), along with good discrimination against potential interferences and linearity over the 90–300mg/L range, with a sensitivity of 10.7µA∙cm3∙mg−1 (R2 = 0.983) and detection limit of 12mg/L in terms of OP air density. Stress-enduring inks, used for printing the electrode transducers, ensure resilience against mechanical deformations associated with textile and skin-based on-body sensing operations. Theoretical simulations are used to estimate the OP air density over the sensor surface. These fully integrated wearable wireless tattoo and textile-based nerve-agent vapor biosensor systems offer considerable promise for rapid warning regarding personal exposure to OP nerve-agent vapors in variety of decentralized security applications.

To design original electrochemical devices, self-assembly and growth processes can be coupled to create a wide range of sophisticated architectures with interesting functionalities. In this work, we present a convergent strategy for the fabrication of a miniaturized, macroporous, and coaxial two-electrode electrochemical cell with tunable porosity, thickness, and distance between individually addressable macroporous electrodes. The assembly presents a platform that could be used for the fabrication of high-performance electrochemical devices such as miniaturized (bio)fuel cells, sensors, and batteries.

Controlling the interface between biological tissues and electrodes remains an important challenge for the development of implantable devices in terms of electroactivity, biocompatibility, and long-term stability. To engineer such a biocompatible interface a low molecular weight gel (LMWG) based on a glycosylated nucleoside fluorocarbon amphiphile (GNF) was employed for the first time to wrap gold electrodes via a noncovalent anchoring strategy, that is, self-assembly of GNF at the electrode surface. Scanning electron microscopy (SEM) studies indicate that the gold surface is coated with the GNF hydrogels. Electrochemical measurements using cyclic voltammetry (CV) clearly show that the electrode properties are not affected by the presence of the hydrogel. This coating layer of 1 to 2 μm does not significantly slow down the mass transport through the hydrogel. Voltammetry experiments with gel coated macroporous enzyme electrodes reveal that during continuous use their current is improved by 100% compared to the noncoated electrode. This demonstrates that the supramolecular hydrogel dramatically increases the stability of the bioelectrochemical interface. Therefore, such hybrid electrodes are promising candidates that will both offer the biocompatibility and stability needed for the development of more efficient biosensors and biofuel cells.

Rationally designed hierarchical macro-/microporous HKUST-1 electrodes were prepared via an electrochemical deposition–dissolution technique with the motivation to overcome diffusion limitations that typically occur for conventional microporous MOFs. A colloidal crystal of silica spheres was prepared by the Langmuir–Blodgett (LB) technique. Using this crystal as a template, macroporous copper electrodes with a controlled number of pore layers were prepared via electrodeposition. After the removal of the template, the synthesis of HKUST-1 was performed via partial anodic dissolution of the copper surface in the presence of an organic linker, leading to the deposition of HKUST-1 on the electrode surface with the designed macroporous structure. The macroporous Cu electrodes do not only behave as structural templates but are also the Cu source for the formation of MOFs. The applied potential and deposition time allow the characteristics of the porous layer to be fine-tuned. The developed synthesis is rapid, occurs under mild conditions and therefore opens up various potential applications including catalysis, separation and sensing based on these hierarchical materials.

A bottom-up approach is proposed for the design of a fully integrated miniaturized electrochemical cell with independently addressable cylindrical macroporous electrodes. The presented strategy allows excellent control over the pore size, the thickness of each macroporous electrode, as well as their separation gap. Such coaxial architectures are potentially suitable for the elaboration of miniaturized electrochemical devices such as (bio)fuel cells, supercapacitors, or biosensors. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

We are developing a cell-based bioelectronic glucose sensor that exploits the multi-parametric sensing ability of pancreatic islet cells for the treatment of diabetes. These cells sense changes in the concentration of glucose and physiological hormones and immediately react by generating electrical signals. In our sensor, signals from multiple cells are recorded as field potentials by a micro-electrode array (MEA). Thus, cell response to various factors can be assessed rapidly and with high throughput. However, signal quality and consequently overall sensor performance rely critically on close cell-electrode proximity. Therefore, we present here a non-invasive method of further exploiting the electrical properties of these cells to guide them towards multiple micro-electrodes via electrophoresis. Parameters were optimized by measuring the cell's zeta potential and modeling the electric field distribution. Clonal and primary mouse or human β-cells migrated directly to target electrodes during the application of a 1 V potential between MEA electrodes for 3 minutes. The morphology, insulin secretion, and electrophysiological characteristics were not altered compared to controls. Thus, cell manipulation on standard MEAs was achieved without introducing any external components and while maintaining the performance of the biosensor. Since the analysis of the cells' electrical activity was performed in real time via on-chip recording and processing, this work demonstrates that our biosensor is operational from the first step of electrically guiding cells to the final step of automatic recognition. Our favorable results with pancreatic islets, which are highly sensitive and fragile cells, are encouraging for the extension of this technique to other cell types and microarray devices.

Two electrodes in one are obtained based on a bottom-up approach leading to a fully integrated microelectrochemical cell with independently addressable coaxial electrodes, as described by A. Kuhn and co-workers in article 1500192. The inherent macroporosity ensures tunable high surface areas for both cylindrical electrodes, thus allowing efficient transport and conversion of electroactive molecules. Such coaxial architectures are desirable for miniaturized electrochemical devices such as (bio)fuel cells, supercapacitors or biosensors.