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Understanding cognitive processing in intact brains is the subject of intense research efforts that aim to resolve individual and network activity of neuronal cells across different layers of the brain. While efforts to record a large number of individual cellular activity in intact brains are underway, the network-level coordinated activity of neurons result in long-range, low frequency oscillations that carry significant electrophysiological information and is the gold standard for recording neural correlates of cognition from animals and humans. Recently, recording of individual cellular activity, commonly referred to as single units, with high signal-to-noise ratio from the cortical surface was accomplished. Critical to this milestone in electrophysiology was the use of organic microelectrode arrays that (1) possess superior electrochemical junction characteristics enabling them to have contact diameters that are similar to neuronal sizes yet while maintaining low electrochemical impedances and low noise, and (2) enable conformal coverage of thin parylene C device carrier layers to the brain curvature. The small contact diameter, and therefore listening sphere, its low noise, and its intimate contact with the surface of the brain are all attributed as essential conditions to permit the recording of single unit activity from the brain’s surface. This thesis appraises the development of novel microelectrode arrays that record single units from the brain’s surface, and their application in recording brain activity from anesthetized and awake animal models. The first part of the dissertation discusses the application of Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate, commonly known as PEDOT:PSS – a semiconductive polymer with excellent electrochemical properties – as well as microelectrode contacts that employ large surface area one-dimensional nanostructures, to the electrophysiological investigations in songbird experiments. Significantly, we observed strong correlation of surface-recorded single units with spectrotemporal features of replayed birdsongs across trials and that were also validated with simultaneously implanted depth electrodes. This finding has implications for minimally destructive brain-machine interfaces that can make use of surface-recorded units. Additionally, we carried out systematic investigations to understand the influence of the electrode contact diameter and the contact material on resolving single unit activity from the surface of the brain. Our initial results suggest that contacts with lower impedances result in higher signal amplitude as well as higher biological noise amplitude, due to their sensitivity and that amplitude of single units generally decreases with diameter.While acute recordings can streamline testing of neurotechnologies, chronic recordings are important for applications in which subjects can ultimately engage in behavioral experiments. To this end, the last part of this dissertation concerns with the development and optimization of a chronically stable device form factor. This device leverages the transparency of the parylene C substrate to perform simultaneous electrophysiological recording and multi-photon imaging of neuronal activity in awake mice. We recorded stimulus-evoked calcium indicator responses that correlated with local field potential (LFP) response and higher frequency multi-and single unit activity. This dissertation encompasses advances in the scalable, monolithic fabrication procedure for high-yield PEDOT:PSS microelectrode arrays on parylene C substrates and their utility of electrocorticography (ECoG) recording capability of neuronal activity from intact brains.

Fabrication of heteroatom-doped graphene electrodes remains a challenging endeavor, especially on flexible substrates. Precise chemical and morphological control is even more challenging for patterned microelectrodes. We herein demonstrate a scalable process for directly generating micropatterns of heteroatom-doped porous graphene on polyimide with different backbones using a continuous-wave infrared laser. Conventional two-step polycondensation of 4,4'-oxydianiline with three different tetracarboxylic dianhydrides enabled the fabrication of fully aromatic polyimides with various internal linkages such as phenylene, trifluoromethyl or sulfone groups. Accordingly, we leverage this laser-induced polymer-to-doped-graphene conversion for fabricating electrically conductive microelectrodes with efficient utilization of heteroatoms (N-doped, F-doped, and S-doped). Tuning laser fluence enabled achieving electrical resistivity lower than ∼13 Ω sq–1 for F-doped and N-doped graphene. Finally, our microelectrodes exhibit superior performance for electrochemical sensing of dopamine, one of the important neurotransmitters in the brain. Compared with carbon fiber microelectrodes, the gold standard in electrochemical dopamine sensing, our F-doped high surface area graphene microelectrodes demonstrated 3 order of magnitude higher sensitivity per unit area, detecting dopamine concentrations as low as 10 nM with excellent reproducibility. Hence, our approach is promising for facile fabrication of microelectrodes with superior capabilities for various electrochemical and sensing applications including early diagnosis of neurological disorders.

The heterogeneous structure that exists in virtually all hydrogels has a significant influence on the resulting strength and toughness. While the internal structure has been observed with electron microscopy, it is difficult to measure the in situ local polymer concentration in the native swollen state. In this study, a modified microelectrode technique (MET) was employed to measure the Donnan potential of a heterogeneous hydrogel with a phase-separated structure. With this method, we succeeded in observing quantitative in situ polymer concentrations ranging from 10.2 mu mol/L to several hundred mmol/L. From the obtained concentration profiles, we could successfully evaluate the internal phase-separated structure with a resolution of less than 0.8 mu m. Using MET, we could estimate the average activity coefficient of the hydrogel, and we found a difference in concentration between the dense and sparse phases. We demonstrate that MET is a powerful method that can locally and quantitatively measure the polyelectrolyte concentration distribution within hydrogels. Furthermore, this method can be applied to cells and organs in vivo due to their similarities with polyelectrolytes. Enabling the in situ determination of the internal structures of biomaterials could have important implications toward the characterization of damaged and diseased tissues on the local scale.

The assessment of candidate materials for redox flow batteries requires effective diagnostic techniques for monitoring the evolution of electrolyte state of charge and state of health to interrogat...

Integrated sensors in “on-a-chip” in vitro cellular models are a necessity for granularity in data collection required for advanced biosensors. As these models become more complex, the requirement for the integration of electrogenic cells is apparent. Interrogation of such cells, whether alone or within a connected cellular framework, are best achieved with microelectrodes, in the form of a microelectrode array (MEA). Makerspace microfabrication has thus far enabled novel and accessible approaches to meet these demands. Here, resin-based 3D printing, selective multimodal laser micromachining, and simple insulation strategies, define an approach to highly customizable and “on-demand” in vitro 3D MEA-based biosensor platforms. The scalability of this approach is aided by a novel makerspace microfabrication assisted technique denoted using the term Hypo-Rig. The MEA utilizes custom-defined metal microfabricated microelectrodes transitioned from planar (2D) to 3D using the Hypo-Rig. To simulate this transition process, COMSOL modeling is utilized to estimate transitionary forces and angles (with respect to normal). Practically, the Hypo-Rig demonstrated a force of ~40N, as well as a consistent 70° average angular transitionary performance which matched well with the COMSOL model. To illustrate the scalability potential, $3\times 3$ , $6\times 6$ , and $8\times 8$ versions of the device were fabricated and characterized. The 3D MEAs, demonstrated impedance and phase measurements in the biologically relevant 1 kHz range of 45.4 $\text{k}\Omega $ , and −34.6° respectively, for polystyrene insulated, $\sim 70~\mu \text{m}$ sized microelectrodes. [2021-0121]

Effective methods for rapid sorting of cells according to their viability are critical in T-cells based therapies to prevent any risk to patients. In this context, we present a novel microfluidic device that continuously separates viable and non-viable T-cells according to their dielectric properties. A dielectrophoresis (DEP) force is generated by an array of castellated microelectrodes embedded into a microfluidic channel with a single inlet and two outlets; cells subjected to positive DEP forces are drawn towards the electrodes array and leave from the top outlet, those subjected to negative DEP forces are repelled away from the electrodes and leave from the bottom outlet. Computational fluid dynamics is used to predict the device separation efficacy, according to the applied alternative current (AC) frequency, at which the cells move from/to a negative/positive DEP region and the ionic strength of thesuspension medium. The model is used to support the design of the operational conditions, confirming a separation efficiency, in terms of purity, of 96% under an applied AC frequency of 1.5 × 106 Hz and a flow rate of 20 µl/h. This work represents the first example of effective continuous sorting of viable and non-viable human T-cells in a single-inlet microfluidic chip, paving the way for lab-on-a-chip applications at the point of need.

Neural implantation with a microscale electrode permits a real-time neuromoduration to enhance the treatment of neural disorders. However, the penetration of a neural microprobe into soft brain tissues always resulted in the invasive tissue damage and mechanical tissue-device friction, which further induced the extensive chronic inflammation that limited the device lifetime. To develop a biocompatible and biocompliant neural implant, this study presented a smart substrate with bioinspired nacre-like structure that can exhibit ultra-hydroresponsive mechanical strength transition, sustained anti-inflammatory drug delivery, and anti-biofouling ability. An organic-inorganic composite, called LOG-P, was synthesized with oligo proanthocyanidin (OPC)-intercalated Ca–Al layered double hydroxide (Ca–Al-LDH) and graphene oxide (GO), followed by crosslinked with linear structural polyvinyl alcohol (PVA) to form a brick-and-mortar architecture. LOG-P exhibited strong mechanical strength of ~ 5 GPa in Young's modulus at dehydrated state, while showing ~99% decrease of Young's modulus when getting hydrated. In addition, the intercalation of OPC in LDH led to zero-order release with duration up to 80 days. LOG-P with negatively charged surfaces inhibited the adhesion of astrocytes, while the released OPC led to robust neuronal cell viability. Finally, integrated with Ag circuits by aerosol jet printing, the fabricated LOG-P-based microelectrode arrays showed stable electroactivity, also permitting a complete penetration into brain-tissue phantoms without bending. Such organic-inorganic nanocomposite-based neural interface with physical, chemical, and biological compatibility was expected to be a revolutionary platform for development of next-generation neural implants.

Polydopamine (PDA)-based biomimetic materials have attracted much attention due to the outstanding adhesion and biocompatibility, etc. However, developing a generalized and simple approach for the patternable polymer coatings in a liquid environment and the secondary modification for high-resolution electrodes are challengeable. Herein, A high-performance flexible microelectrode arrays (fMEAs) for biomedical applications based on novel platinum nanowire (PtNW) was proposed using PDA as the bioinspired adhesive buffer layer between the polymer substrate and the nanowire layer. The PDA film was patternable and selectively grafted on the flexible PI substrate using the micro-contact printing ( $\mu $ CP) technique, followed by the reduction of PtNW on patterned PDA in chloroplatinic acid (H2PtCl6) by in situ electroless deposition. The as-fabricated PI-PDA/PtNW electrode has greatly reduced the electrochemical impedance at 1 kHz by 99.54% compared with that of PI-Ti/Pt using the conventional sputtering method, and also increased the charge storage capacity (CSCc) by 27 times. At the same time, the adhesion between the metal layer (PDA/PtNW or Ti/Pt) and the PI substrate was evaluated using both intense ultrasonic bath and torsion fatigue test. The results showed that PDA was very effective as the adhesive layer by significantly enhancing both mechanical adhesion and impedance stability when suffering mechanical stress. These achievements are of great interest for robust flexible electronics for implantable or wearable biomedical applications.

A highly sensitive amperometric Prussian blue-based hydrogen peroxide sensor was developed using 3D pyrolytic carbon microelectrodes. A 3D printed multielectrode electrochemical cell enabled simultaneous highly reproducible Prussian blue modification on multiple carbon electrodes. The effect of oxygen plasma pre-treatment and deposition time on Prussian blue electrodeposition was studied. The amperometric response of 2D and 3D sensors to the addition of hydrogen peroxide in μM and sub-μM concentrations in phosphate buffer was investigated. A high sensitivity comparable to flow injection systems and a detection limit of 0.16 μM was demonstrated with 3D pyrolytic carbon microelectrodes at stirred batch condition.

Adenosine triphosphate (ATP) is an important rapid signaling molecule involved in a host of pathologies in the body. Historically, ATP is difficult to directly detect electrochemically with fast-scan cyclic voltammetry (FSCV) due to limited interactions at bare carbon-fibers. Systematic investigations of how ATP interacts at electrode surfaces is necessary for developing more sensitive electrochemical detection methods. Here, we have developed gold nanoparticle (AuNP), and platinum nanoparticle (PtNP) modified carbon-fiber microelectrodes coupled to FSCV to measure the extent to which ATP interacts at metal nanoparticle-modified surfaces and to improve the sensitivity of direct electrochemical detection. AuNP and PtNPs were electrodeposited on the carbon-fiber surface by scanning from -1.2 to 1.5 V for 30 s in 0.5 mg/mL HAuCl

The effects of current density and electrode-normal magnetic fields on the growth and detachment characteristics of a single bubble on vertical microelectrode surface have been investigated. A high-speed camera was used to capture the bubble evolution behavior and the bubble contact characteristic parameters were extracted and analyzed with OpenCV-Python program. The results reveal that an apparent bubble coalescence behavior occurs at low current densities and can be gradually inhibited with increasing current density. With the increase of current density, the bubble growth rate, departure diameter, working electrode potential and potential fluctuations increase, while the bubble growth time first increases and then decreases continuously. The upper microelectrode surface is more easily covered than the lower microelectrode surface. The whole microelectrode can be completely covered when the current density exceeds a certain limit with and without magnetic fields. The external magnetic fields can obviously promote the bubble detachment behavior within a relatively large current density range.

Purpose The purpose of this paper is to visualize protein manipulation using dielectrophoresis (DEP) as a substantial perspective on being an effective protein analysis and biosensor method as DEP is able to be used as a means for manipulation, fractionation, pre-concentration and separation. This research aims to quantify DEP using an electrochemical technique known as cyclic voltammetry (CV), as albumin is non-visible without any fluorescent probe or dye. Design/methodology/approach The principles of DEP were generated by an electric field on tapered DEP microelectrodes. The principle of CV was analysed using different concentrations of albumin on a screen-printed carbon electrode. Using preliminary data from both DEP and CV methods as a future prospect for the integration of both techniques to do electrical quantification of DEP forces. Findings The size of the albumin is known to be 0.027 µm. Engineered polystyrene particle of size 0.05 µm was selected to mimic the DEP actuation of albumin. Positive DEP of the sample engineered polystyrene particle was able to be visualized clearly at 10 MHz supplied with 20 Vpp. However, negative DEP was not able to be visualized because of the limitation of the apparatus. However, albumin was not able to be visualized under the fluorescent microscope because of its translucent properties. Thus, a method of electrical quantification known as the CV technique is used. The detection of bovine serum albumin (BSA) using the CV method is successful. As the concentration of BSA increases, the peak current obtained from the voltammogram decreases. The peak current can be an indicator of DEP response as it correlates to the adsorption of the protein onto the electrodes. The importance of the results from both CV and DEP shows that the integration of both techniques is possible. Originality/value The integration of both methods could give rise to a new technique with precision to be implemented into the dialyzers used in renal haemodialysis treatment for manipulation and sensing of protein albumin.

Microelectrodes for electrokinetic detection have been employed to manipulate and collect nanomaterials and biomaterials. However, the process of microelectrode patterning has been researched in the semiconductor fabrication process, which is expensive and time-consuming. Here, we demonstrate dielectrophoretic trapping of 200 nm fluorescent polystyrene nanoparticles and $\lambda $ -deoxyribonucleic acid with SYBR gold using dielectrophoretic trapping onto an interdigitated circular electrode (ICE). For dielectrophoretic trapping, an ICE is designed and an ordered flexible printed circuit board (FPCB), possessing a non-porous polyimide substrate, is constructed. The ICE FPCB could identify the dielectrophoretic trapping conditions and simulate them by the finite element method. The fluorescent molecules in the ICE FPCB are dielectrophoretically trapped at the finger edges of the ICE when a peak-to-peak voltage of 12 V is applied at 6 kHz for 15–20 min. Moreover, monitoring of the dielectrophoretic trapping effect of SYBR gold eliminated the false negative detection error.

Tunable microlens arrays (MLAs) with controllable focal lengths have been extensively used in optical sensors, biochips, and electronic devices. The commonly used method is electrowetting on dielectric (EWOD) that controls the contact angle of the microlens to adjust the focal length. However, the fabrication of tunable MLAs at the microscale remains a challenge because the size of MLAs is limited by the external electrodes of EWOD. In this study, a highly integrated planar annular microelectrode array was proposed to achieve an electrowetting tunable MLA. The planar microelectrode was fabricated by electrohydrodynamic jet (E-jet) printing and the liquid microlens was then deposited in situ on the microelectrode. This method could realize 36 tunable liquid microlenses with an average diameter of 24 μm in a 320 × 320 μm2 plane. The fabricated tunable MLAs with higher integration levels and smaller sizes can be beneficial for cell imaging, optofluidic systems, and microfluidic chips.

As continues increasing the COVID-19 infections, there is an urgent need for developing fast, simple, selective, and accurate COVID-19 biosensors. A highly uniform gold (Au) microcuboid pattern was used as a microelectrode that allowed monitoring a small analyte. The electrochemical biosensor was used to monitor the COVID-19 S protein within a concentration range from 100 to 5 pmol L-1; it showed a lower detection limit of 276 fmol L-1. Finally, the developed COVID-19 sensor was used to detect a positive sample from a human patient obtained through a nasal swab; the results were confirmed using the PCR technique. The results showed that the SWV technique showed high sensitivity towards detecting COVID-19 and good efficiency for detecting COVID-19 in a positive human sample.

Objective: Understanding the in vivo force and tissue dimpling during micro-electrode implantation into the brain are important for neuro-electrophysiology to minimize damage while enabling accurate placement and stable chronic extracellular electrophysiological recordings. Prior studies were unable to measure the sub-mN forces exerted during in vivo insertion of small electrodes. Here, we have investigated the in vivo force and dimpling depth profiles during brain surface membrane rupture (including dura) in anesthetized rats. Methods: A μN-resolution cantilever beam-based measurement system was designed, built, and calibrated and adapted for in vivo use. A total of 244 in vivo insertion tests were conducted on 8 anesthetized rats with 121 through pia mater and 123 through dura and pia combined. Results: Both microwire tip sharpening and diameter reduction reduced membrane rupture force (insertion force) and eased brain surface penetration. But dimpling depth and rupture force are not always strongly correlated. Multi-shank silicon probes showed smaller dimpling and rupture force per shank than single shank devices. Conclusion: A force measurement system with flexible range and μN-level resolution (up to 0.032 μN) was achieved and proved feasible. For both pia-only and dura-pia penetrations in anesthetized rats, the rupture force and membrane dimpling depth at rupture are linearly related to the microwire diameter. Significance: We have developed a new system with both μN-level resolution and capacity to be used in vivo for measurement of force profiles of various neural interfaces into the brain. This allows quantification of brain tissue cutting and provides design guidelines for optimal neural interfaces.

Multivariate analysis is carried out for single-walled carbon nanotubes (SWNTs) functionalized with a cobalt octaethyl porphyrin (CoOEP) chemiresistive sensor device for selective and simultaneous detection of multiple analytes. The chemiresistor was prepared on Si/SiO2 substrate with photolithographically patterned gold microelectrodes having a 3-µm gap. SWNTs were aligned dielectrophoretically and functionalized with CoOEP by drop-casting. The aligned and CoOEP-functionalized SWNTs were characterized with electrical (I–V method), structural, spectroscopic, and morphological techniques, and sensor performance was investigated in a chemiresistive sensing modality. The fabricated sensor shows response towards acetone, dichloromethane, methyl ethyl ketone, ethanol, and methanol, with a lower detection limit of 5 ppm, which is far below the OSHA permissible exposure limit for each analyte, and demonstrates fast response and recovery. The multivariate analysis viz. principal component analysis and linear discrimination analysis reveals high discriminating capability of SWNTs functionalized with the CoOEP chemiresistive sensor towards these analytes, which could be used as an intelligent electronic nose (E-nose). This type of intelligent E-nose can address the crucial need for monitoring environmental pollution in industries, homes, buildings, etc.

Graphene microelectrode arrays (MEAs) have emerged as a viable neurointerfacing tool for their combined benefits in mechanical, electrical, and optical properties. To evaluate their promise for high-resolution neurointerfacing applications, here we presented a 28- $\mu \text{m}$ pitched, poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)-coated graphene MEA that can achieve one order higher spatial resolution than previous graphene MEAs in both neurostimulation and optogenetic electrophysiology. The electroplated PEDOT:PSS layer improved the impedance and the charge-injection capacity of the graphene electrodes by 40–60 times (sub-100 $\text{k}\Omega $ , >1.31 mC/cm2 and maintained low light-induced artifacts among them (sub-3 $\mu$ V). As a result, our MEA was able to stimulate neuronal ensemble with single electrodes and record optogenetically evoked neural spikes with high signal-to-noise ratios. These results shed light on the possible use of PEDOT:PSS-coated graphene MEAs toward high-resolution interrogation of neural activity.

This work develops a technology for actuating droplets of any size without the requirement for high voltages or active control systems, which are typically found in competitive systems. The droplet actuation relies on two microelectrodes separated by a variable gap distance to generate an electrostatic gradient. The physical mechanism for the droplet motion is a combination of liquid dielectrophoresis and electrowetting. Investigating the system behavior as a function of the driving frequency identified the relative contribution of these two mechanisms and the optimum operating conditions. A fixed signal frequency of 0.5 kHz actuated various liquids and contaminants. Droplet actuation was demonstrated on several platforms, including linear, radial-symmetric, and bilateral-symmetric droplet motion. The electrode designs are scalable and can be fabricated on a flexible and optically transparent substrate: these key advancements will enable consumer applications that were previously inaccessible. A self-cleaning platform was also tested under laboratory conditions and on the road. This technology has significant potential in microfluidics and self-cleaning platforms, for example, in the automotive sector to clean body parts, camera covers, and sensors.

An SU-8 probe with an array of nine, individually addressable gold microband electrodes (100 μm long, 4 μm wide, separated by 4-μm gaps) was photolithographically fabricated and characterized for detection of low concentrations of chemicals in confined spaces and in vivo studies of biological tissues. The probe’s shank (6 mm long, 100 μm wide, 100 μm thick) is flexible, but exhibits sufficient sharpness and rigidity to be inserted into soft tissue. Laser micromachining was used to define probe geometry by spatially revealing the underlying sacrificial aluminum layer, which was then etched to free the probes from a silicon wafer. Perfusion with fluorescent nanobeads showed that, like a carbon fiber electrode, the probe produced no noticeable damage when inserted into rat brain, in contrast to damage from an inserted microdialysis probe. The individual addressability of the electrodes allows single and multiple electrode activation. Redox cycling is possible, where adjacent electrodes serve as generators (that oxidize or reduce molecules) and collectors (that do the opposite) to amplify signals of small concentrations without background subtraction. Information about electrochemical mechanisms and kinetics may also be obtained. Detection limits for potassium ferricyanide in potassium chloride electrolyte of 2.19, 1.25, and 2.08 μM and for dopamine in artificial cerebral spinal fluid of 1.94, 1.08, and 5.66 μM for generators alone and for generators and collectors during redox cycling, respectively, were obtained.

Recently, miniaturized electrochemical biosensors have the advantage of real-time monitoring and label-free detection of biomarkers. However, controlled manipulation of reagent samples for specific immobilization of biomarkers remains a challenge to attend high-resolution microfluidic biosensor. Here, we designed a microfluidic channel and valves integrated electrochemical biosensor for the detection of β-amyloid (1–42) biomarker, one of the most neurotoxic peptides present in the cerebrospinal fluid, and a possible marker for the detection of Alzheimer's disease. The formation of the antibody-antigen complexes on gold microelectrode integrated inside the fluidic chambers was presented in the developed biosensor, and all the measurements are carefully controlled using pneumatic valves integrated with the device. The demonstrated microfluidic electrochemical biosensor exhibits a linear response towards various β-amyloid antigen concentrations from 2.2 pM to 22 μM, with an enhanced detection limit of 1.62 pM. The developed technology offers an advantage of minimal reagent sample and suitable environment for miniaturized and sensitive detection of biomarkers, could also be used for the detection of other biomarkers with high efficiency.

Conductive polymers have been intensively investigated as materials for electrodes in flexible electronics due to their favorable biocompatibility and reliable electrochemical stability. Nevertheless, patterning of conductive polymers for the fabrication of devices and in various electronics applications confronts multifarious limitations and challenges. Here, we present a simple but efficient strategy to obtain conductive polymer microelectrodes via utilization of surface-tension-confined liquid patterns. This method shows universality for various oxidizers and conductive polymers, high resolution, stability, and favorable compatibility with different surfaces and materials. The developed method has been demonstrated for creating conductive polymer microelectrodes with a customized reaction process, defined geometry, and flexible substrates. The obtained microelectrodes were assembled into flexible capacitive sensors. Thus, the method realizes a facile approach to conductive polymer microelectrodes for flexible electronics, biomedical applications, human activity monitors, and electronic skin.

Thin-film polymer microelectrode arrays (MEAs) facilitate the high-resolution neural recording with its superior mechanical compliance. However, the densely packed electrodes and interconnects along with the ultra-thin polymeric encapsulation/substrate layers give rise to non-negligible crosstalk, which could result in severe interference in the neural signal recording. Due to the lack of standardized characterization or modeling of crosstalk in neural electrode arrays, to date, crosstalk in polymer MEAs remains poorly understood. In this work, the crosstalk between two adjacent polymer microelectrodes is measured experimentally and modeled using equivalent circuits. Importantly, this study demonstrated a two-well measuring platform and systematically characterized the crosstalk in polymer microelectrodes with true isolation of the victim channel and precise control of its grounding condition. A simple, unified equation from detailed circuit modeling was proposed to calculate the crosstalk in different environments. Finite element analysis (FEA) analysis was conducted further to explore the crosstalk in more aggressively scaled polymer electrode threads. In addition to standardizing neural electrode array crosstalk characterization, this study not only reveals the dependence of the crosstalk in polymer MEAs on a variety of key device parameters but also provides general guidelines for the design of thin polymer MEAs for high-quality neural signal recording.

Microelectrodes for hydrogen permeation measurements were fabricated by photolithography. Although the application of a positive-type photoresist coating was effective for the formation of a circle-shaped pattern with a diameter of several tens of micrometers on an iron surface, the coating had poor adhesion to the iron surface and poor durability in an H2SO4 solution. However, the addition of a silica coating derived from tetraethoxysilane (TEOS) on the iron surface as an inner layer resulted in improvement of durability as well as resistance of the coating. Furthermore, the introduction of a layer derived from a mixture of TEOS and glycidyl 3-trimethoxysilylpropyl ether (GPTMS) between the inner layer derived from TEOS and the photoresist coating resulted in long durability showing a large impedance of more than 10(9) Omega cm(2) for 4x10(5) s in an H2SO4 solution. Cathodic polarization of the microelectrode on the iron surface revealed that the hydrogen evolution reaction (HER) rate is dependent on the plane orientation of the surface. HER rate on an SCM435 steel surface also strongly depended on the microstructure and hardness of the local surface.

The feature size and resolution of inkjet printing is limited by nozzle size, jetting volume and ink spreading. This study proposes a unique inkjet printing method for controlling feature sizes such as line width and thickness for the fabrication of mciro metal electrodes. To form the micro metal electrodes, we printed silver (Ag) ink inside a hydrophilic track formed by a printed non-wettable patterns. The minimum line width of the printed Ag could be reduced up to 18 μm by using the jetted ink droplet of 35 ± 4.2 μm diameter, which is twice the line width. To increase the thickness of the microelectrode, Ag ink was repeatedly printed layer-by-layer, and the thickness could be increased to 1 μm for an 18 μm width. After optimizing the printing conditions for a straight line, the fabrication of a micro-grid electrode was demonstrated, by first printing a horizontal electrode pattern, then a vertical electrode pattern was printed by repeating the proposed printing method. Also, we investigated the sheet resistance of the Ag grid-printed ITO-coated glass substrate by changing the grid space distance.

Lithium metal secondary batteries (LMBs) have extremely high energy densities and are considered the most promising energy storage and conversion systems in the future. We start with the formation and growth process of the Li metal deposited layer to reveal and clarify the reasons for the apparent comprehensive performance of the Li metal anode. Specifically, under the conditions of ether electrolyte and typical additives, the apparent Coulombic efficiency, micromorphology of the deposition layer, SEI information, and the kinetic mechanism of the Li plating/stripping process under a series of current density conditions are studied. The results show that in the electrolyte containing LiNO

The constant development and improvement of microelectromechanical systems (MEMS) have been given a great opportunity to develop new reliable microsystems devices for biomedical research. This article presents a locally addressable 2-D arrayed indium–tin oxide microelectrode platform with integrated thin-film transistors (TFTs) for biological and chemical sensing. Microelectrode arrays (MEAs) using TFT have the advantage of being transparent with a high density of microelectrodes on a large surface. In vitro 2-D electrical measurements on 28 parallel-connected lines selected from a 22 500 MEA were successfully performed with heart cells for the first time. Observation of cell contraction was performed simultaneously with an inverted microscope. Voltammetry and amperometry measurements were also demonstrated using the transparent microelectrodes as working electrodes and an integrated Ag/AgCl reference electrode. Due to its unique features, we believe that the TFT platform can provide more understanding of the key communication between heart cells, and large-scale cardiovascular and nervous systems. As a result, the platform offers unique access to versatile lab-on-a-chip devices that integrate many measurement techniques on one chip for the study of cell cultures, tissues, and organoids.

A needle electrochemical sensor was developed based on a nitrogen-doped graphene (NDG) microelectrode for the analysis of salicylic acid (SA) in plants. Self-supporting NDG microelectrodes were synthesized by electron-assisted hot filament chemical vapor deposition using ethanol and nitrogen as the C and N sources, respectively. The formation mechanism of the NDG microelectrodes is discussed by analyzing the ethanol decomposition and nitrogen-doping processes. The microelectrodes were composed of few-layered NDG nanosheets, and the N content of the nanosheets varied in the 0.96–12.5 at% range. Furthermore, a novel needle sensor was constructed based on a cylindrical three-electrode system consisting of a Pt wire, optimized NDG microelectrode, and Ti tube with diameters of approximately 0.3, 0.9, and 1.5 mm, respectively, arranged concentrically. The needle sensors were also assembled into a parallel array consisting of four sensors. At a pH range of 4.5–7.5, the NDG-microelectrode-based needle sensor array exhibited a low detection limit (0.32–0.14 μA μM−1, S/N = 3), wide linear range (1–500 μM), and excellent reproducibility, selectivity, and stability for the detection of SA. The NDG-based needle sensors and sensor arrays are reliable electrochemical platforms for the detection of SA in plant tissue both in vivo and in vitro.

Relatively low efficiency is the biggest obstacle to the popularization of water electrolysis, which is a particularly feasible way to produce super-pure hydrogen. Imposing a magnetic field can increase the hydrogen production efficiency of water electrolysis. However, the enhancement's detailed mechanism still lacks an insightful understanding of the bubbles' micro vicinity. Our recent work aims to understand why the micro-magnetohydrodynamic (MHD) convection hinders single bubbles' detachment on the microelectrode. A water electrolysis experiment by microelectrode is performed under an electrode-normal magnetic field, and dynamic analysis of the single bubble growing on microelectrodes is performed. The variation of bubble diameter with time in the presence or absence of the magnetic field was measured, and the forces acting on the bubble were quantified. The result shows that the micro-MHD convection, induced by Lorentz force, can give rise to a downward hydrodynamic pressure force that will not appear in large-scale MHD convection. This force can be of the same magnitude as the surface tension, so it dramatically hinders bubbles' detachment. Besides, the Kelvin force provides a new potential way for further improving the efficiency of water electrolysis.

The purpose of this paper is to design an efficient and low cost electrocoagulation reactor in which aluminum microbipolar electrodes are used and kept in suspension by an axial helical agitator. When compared to a conventional electrocoagulation reactor operated in the same conditions, the new electrocoagulation reactor shows significantly improved performance in batch mode. The use of this new electrocoagulation reactor in continuous mode and at the optimum operating conditions, Viz. Rotation speed = 300 rpm, CNaCl = 1 g/L, i = 180 A/m2, R = 10 mg dye/g of aluminum particles, allowed the dye concentration to reach a plateau with an abatement percentage of approximately 96%. The flocs that were formed appeared to be stable after 1 h.

The optrode integrated with light sources and electrical recording electrodes presents significant advantages. However, the performance of the optrode is still hindered by photoelectric artifact generated by optical stimulation. A controlled electrodeposition method of Pt-Black/PEDOT-GO (graphene oxide doped poly(3,4-ethylene-dioxythiophene)) double layer on gold microelectrode is developed for noise reduction in this work. The microscopic characterization shows that Pt-Black can increase the adhesion of PEDOT-GO to the substrate and prevent it from spreading around, thereby avoiding short circuits in adjacent microelectrodes. Moreover, the electrochemical measurements show that Pt-Black/PEDOT-GO can decrease impedance and improve electrochemical performance dramatically. Finally, the bench noise recordings show that Pt-Black/PEDOT-GO can simultaneously reduce background noise, photovoltaic noise and photoelectrochemical noise to less than $100~\mu \text{V}$ .

Silicon-based platinum (Pt) and silver (Ag) microelectrodes are constructed using photolithography technique and used in detecting arsenic activity in different electrolytes. Pt and Ag have good properties either as a working, a counter, or a reference electrode due to their low electrical resistance, high melting point, and high chemical stability. This chemical sensor has the ability to detect the changes in the level or activity of arsenic in electrolytes. Patterning these metals by wet chemical or dry etching is not a feasible process as these metals cannot be etched properly. The lift-off process can be applied to ease the etching process, but it has a major problem whereby the metal particles or ears may remain at the edges at the end of the process. The process variables, particularly the resist slope, were investigated to reduce possible defects using an image reversal resist. The thickness and angle of the resist side wall were measured by SEM. The effects of many factors that may influence or resist steep angle formation were analyzed and optimized with the Design of Experiment (DOE) technique to achieve the target recipe of resist angle < 60°. The lower angle of the resist side wall resulted in a better percentage yield of good electrode pattern after the lift-off process. The ability of fabricated microelectrode and influence of supporting electrolytes in arsenic determination were discussed.

The development and field validation of newly designed nanostructured gold-plated gel-integrated microelectrode (Au-GIME) arrays applied to the direct in situ square wave anodic stripping voltammet...

In many biological systems, pH can be used as a parameter to understand and study cell dynamics. However, measuring pH in live cell culture is limited by the sensor ion specificity, proximity to the cell surface, and scalability. Commercially available pH sensors are difficult to integrate into a small-scale cell culture system due to their size and are not cost-effective for disposable use. We made PHAIR—a new pH sensor that uses a micro-wire format to measure pH in vitro human airway cell culture. Tungsten micro-wires were used as the working electrodes, and silver micro-wires with a silver/silver chloride coating were used as a pseudo reference electrode. pH sensitivity, in a wide and narrow range, and stability of these sensors were tested in common standard buffer solutions as well as in culture media of human airway epithelial cells grown at the air–liquid interface in a 24 well cell culture plate. When measuring the pH of cells grown under basal and challenge conditions using PHAIR, cell viability and cytokine responses were not affected. Our results confirm that micro-wire-based sensors have the capacity for miniaturization and detection of diverse ions while maintaining sensitivity. This suggests the broad application of PHAIR in various biological experimental settings.

The discovery of electrochemical switching of the Lα phase of chlorpromazine hydrochloride in water is reported. The phase is characterized using polarizing microscopy, X-ray scattering, rheological measurements, and microelectrode voltammetry. Fast, heterogeneous oxidation of the lyotropic liquid crystal is shown to cause a phase change resulting from the disordering of the structural order in a stepwise process. The underlying molecular dynamics is considered to be a cooperative effect of both increasing electrostatic interactions and an unfolding of the monomers from “butterfly”-shaped in the reduced form to planar in the oxidized form.

In this paper, a procedure to release SU-8 layers from glass substrates using typical undesirable effects is described. The proposed process can be used as lift off or stripping. The releasing method consists in taking advantage of the undesired thermal delamination, and the effect of UV overexposure on the delamination temperature, which are considered undesirable effects. This implies the use of SU-8 for both structural and lift off using the same facilities, without any additional photoresist, material, remover or developer. In this way, the fabrication of a glass/gold microelectrodes array (MEA) for cell culture applications is carried out as a proof of concept. The MEA is composed of gold tracks of 1.5 mm width and 8 electrodes with radii between 25 and 500 $$\upmu \hbox {m}$$ at its ends. The SU-8 photoresist is also used as an insulation layer releasing the pads and the electrodes. Finally, biological experiments with neuroblastoma cells SK-N-SH cultured on the MEA surface were carried out in order to validate and demonstrate the biocompatibility of both the MEA and the process. The fabrication and biological results were successful, showing a normal cell proliferation over the developed MEA.

The influence of interfacial pH between AISI 4135 steel and seawater under different polarization potentials on the formation of calcareous deposits has been studied. An interfacial pH of 9.61 at −0.9 V vs. SCE using state of the art iridium oxide microelectrode was found to be the critical pH for the precipitation of magnesium hydroxide. Calcareous deposits with a double-layer structure comprising an inner-brucite layer and an outer-aragonite layer were found to form at potentials between −1.0 V and −1.2 V vs. SCE. Furthermore, the facilitation of hydrogen permeation into steel induced by the formation of calcareous deposits was verified using the Devanathan-Stachurski electrochemical test. The mechanism of calcareous deposits facilitates hydrogen permeation into steel is related to its inhibition on hydrogen recombination and escape processes.

Controlled electrical stimulation is essential for evaluating the physiology of cardiac tissues engineered in heart-on-a-chip devices. However, existing stimulation techniques, such as external platinum electrodes or opaque microelectrode arrays patterned on glass substrates, have limited throughput, reproducibility, or compatibility with other desirable features of heart-on-a-chip systems, such as the use of tunable culture substrates, imaging accessibility, or enclosure in a microfluidic device. In this study, indium tin oxide (ITO), a conductive, semi-transparent, and biocompatible material, was deposited onto glass and polydimethylsiloxane (PDMS)-coated coverslips as parallel or point stimulation electrodes using laser-cut tape masks. ITO caused substrate discoloration but did not prevent brightfield imaging. ITO-patterned substrates were microcontact printed with arrayed lines of fibronectin and seeded with neonatal rat ventricular myocytes, which assembled into aligned cardiac tissues. ITO deposited as parallel or point electrodes was connected to an external stimulator and used to successfully stimulate micropatterned cardiac tissues to generate calcium transients or propagating calcium waves, respectively. ITO electrodes were also integrated into the cantilever-based muscular thin film (MTF) assay to stimulate and quantify the contraction of micropatterned cardiac tissues. To demonstrate the potential for multiple ITO electrodes to be integrated into larger, multiplexed systems, two sets of ITO electrodes were deposited onto a single substrate and used to stimulate the contraction of distinct micropatterned cardiac tissues independently. Collectively, these approaches for integrating ITO electrodes into heart-on-a-chip devices are relatively facile, modular, and scalable and could have diverse applications in microphysiological systems of excitable tissues.

Bioelectric medicine treatments target disorders of the nervous system unresponsive to pharmacological methods. While current stimulation paradigms effectively treat many disorders, the underlying mechanisms are relatively unknown, and current neuroscience recording electrodes are often limited in their specificity to gross averages across many neurons or axons. Here, we develop a novel, durable carbon fiber electrode array adaptable to many neural structures for precise neural recording. Carbon fibers ( $6.8~\mu \text{m}$ diameter) were sharpened using a reproducible blowtorchmethod that uses the reflection of fibers against the surface of a water bath. The arrays were developed by partially embedding carbon fibers in medical-grade silicone to improve durability. We recorded acute spontaneous electrophysiology from the rat cervical vagus nerve (CVN), feline dorsal root ganglia (DRG), and rat brain. Blowtorching resulted in fibers of 72.3 ± 33.5-degree tip angle with $146.8~\pm ~17.7~\mu \text{m}$ exposed carbon. Observable neural clusters were recorded using sharpened carbon fiber electrodes fromrat CVN ( $41.8~\mu \text{V}_{\text {pp}}$ ), feline DRG ( $101.1~\mu \text{V}_{\text {pp}}$ ), and rat brain ( $80.7~\mu \text{V}_{\text {pp}}$ ). Recordings from the feline DRG included physiologically relevant signals from increased bladder pressure and cutaneous brushing. These results suggest that this carbon fiber array is a uniquely durable and adaptable neural recordingdevice. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closed-loop neural control of therapeutic treatments and monitoring systems.

In the neuromuscular system, signal transmission from motor neurons (MNs) to innervated muscle fibers is crucial for their synaptic function, viability, and maintenance. In order to better understand human neuromuscular junction (hNMJ) functionality, it is important to develop on-a-chip devices with human cells. To investigate this cell network, microfluidic platforms are useful to grow different cell types in isolated compartments. Such devices have already been developed to study in vitro neuronal circuitry. Here, we combined microfluidics with two techniques: soft lithography and custom microelectrodes array (MEA). Our goal was to create hNMJs on a specific pattern of electrodes to stimulate pre-synaptic axons and record post-synaptic muscle activity. Micromachining was used to create structurations to guide muscle growth above electrodes, without impairing axon propagation, therefore optimizing the effectiveness of activity recording. Electrodes were also arranged to be aligned with the microfluidic chambers in order to specifically stimulate axons that were growing between the two compartments. Isolation of the two cell types allows for the selective treatment of neurons or muscle fibers to assess NMJ functionality hallmarks. Altogether, this microfluidic/microstructured/MEA platform allowed mature and functional in vitro hNMJ modelling. We demonstrate that electrical activation of MNs can trigger recordable extracellular muscle action potentials. This study provides evidence for a physiologically relevant model to mimic a hNMJ that will in the future be a powerful tool, more sensitive than calcium imaging, to better understand and characterize NMJs and their disruption in neurodegenerative diseases.

We report a novel reversible bonding technique for liquid metal (LM) microelectrode fabrication in this study. This technique greatly simplifies the process of LM micro-electrode fabrication and can be used to achieve the rapid fabrication of LM blind-end electrodes. Three kinds of treatments, including heat treatment, plasma treatment and heat/plasma treatment, were tested for bonding strength. The experimental results showed that the heat/plasma treatment has the strongest bonding strength. All the three treatments can be completely released by simple water treatment. This handy fabrication method can help to integrate micro-liquid metal electrodes vertically in a microchannel. At the end of this work, this fabrication method was used to integrate liquid metal thermocouples in a microchannel, which greatly shortened the fabrication time and lowered the cost compared with traditional deposition or sputtering methods.

The imaging resolution of scanning electrochemical microscopy (SECM) depends strongly on the tip electrode size and the tip-substrate distance. Herein, etched glass encapsulation was applied to fabricate a gold disk electrode, and the size of the tip electrode was accurately determined from the steady-state limiting current. Referring to the theoretical research carried out by our predecessors, the formula for the imaging resolution was derived, followed by the imaging of gold spots and cells with the prepared microelectrodes of different sizes and with different tip-substrate distances. A depth scan was performed to generate 2D current maps of the gold spot relative to the position of the microelectrode in the x-z plane. Probe approach curves and horizontal sweeps were obtained from one depth scan image by simply extracting vertical and horizontal cross-sectional lines, and further characterized by comparison with simulated curves through modeling of the experimental system. The experimental results were basically consistent with the theory, revealing that the highest imaging resolution can be obtained with the smallest tip electrode when d/a = 1, and when the size of the tip electrode is fixed the smallest tip-substrate distance can give the highest imaging resolution.

Conducting polymers (CPs) are emerging as one of the most promising functional materials for bioelectronics and biointerfaces due to their high biocompatibility, intrinsic electrical and ionic conductivity, tunable mechanical properties and the capability of being functionalised through chemical modification. For bioelectronics applications, there is an increasing demand for miniaturisation of the devices, which will not only enable the exploring of, for example, the stimuli-response of single cells and the electrophysiological mapping at a cellular resolution, but also benefit the advanced clinical diagnostics and therapeutic applications, especially when implantable and other wearable medical devices are needed. One critical step for miniaturising CP-based bioelectronic devices is the microfabrication of CPs. Driven by this demand, a variety of microfabrication techniques have been developed or adapted to CPs. As a result, a wide range of CP microelectrodes in both 2D and 3D formats have been successfully fabricated and successfully employed in a variety of bioelectronic applications, ranging from the acquisition of biological information (sensing and recording), controlling the physiological behaviour (stimulation) of cells and tissues to biomimetic applications such as artificial muscles. These CP-integrated microbioelectronic devices bring about unprecedented possibilities and exciting prospects for fundamental research and clinical applications of organic bioelectronics. This review addresses the recent advancements in the fabrication techniques of 2D and 3D CP microelectrodes and the applications of such electrodes in bioelectronic devices. We aim at providing insights into these emerging techniques that may inspire the development of the next generation of bioelectronics.

Extracellular vesicles (EVs) are small entities that are released by most cell types. EVs are important form of intercellular communication and a rich source of biomarkers for a wide variety of diseases. Many methods for EVs isolation have been utilized, however, most of them have significant drawbacks including lengthy processing time, high cost, shortfalls in selectivity and surface marker dependency. In consideration of these issues, this paper discussed on the dielectrophoresis (DEP) microelectrode method designed to rapidly isolate EVs from its medium. The advantage of this DEP microelectrode is the capability of isolating EVs using a droplet of 1 μL placed onto the microelectrode within 30 s and 20 V peak-to-peak (Vp-p) of alternating current (AC). The method used in the characterization of sample are dynamic light scattering (DLS) and transmission electron microscopy (TEM); both prove the heterogeneity of EVs’ population and the EVs appear to be spherical with size ranging from 40 to 200 nm. The experimental results from this preliminary experiment show that the DEP microelectrode was able to manipulate EVs as evidenced by the negative dielectrophoresis (NDEP) fluorescent images. Further investigation of grid analysis conducted shows the consistency of the theory and the results presented. Corrected Total Cell Fluorescence (CTCF) values from the grid analysis concluded that the EVs were manipulated to the center of region of interest, (ROI). Therefore, this DEP technique suggests a rapid strategy for EVs isolation from its medium in small quantity while maintaining accuracy and cost-effectivity.

This paper introduces the versatile of an electrokinetic technique by using the non-uniform electric field for dielectrophoresis (DEP) application. This technique is defined as electromicrofluidics. The potential application for portable and real time detection method of Enterococcus faecium (EF), Staphylococcus aureus (SA), Klebsiella pneumoniae (KP), Acinetobacter baumannii (AB), Pseudomonas aeruginosa (PA) and Enterobacter aerogenes (EA), which are the (ESKAPE) bacteria. The MATLAB analytical modelling was used in simulating the polarisation factor and velocities of bacteria based on Clausius-Mossotti factor (CMF). The validation of CMF simulation through the DEP experimental can be quantified based on the response of alternating current (AC) voltage applied using 6 voltage peak to peak (Vp-p) to their input frequencies from 100 to 15000 kHz. The droplet method was deployed to place properly 0.2 μL of sample onto DEP microelectrode. The velocities and crossover frequency (fxo) ranges of bacteria were determined through bacteria trajectory in specific time interval monitored by microscope attached with eyepiece camera. The applied range of input frequencies from 100 to 15000 kHz at 6 Vp-p for each bacteria were successfully identified the unique ranges of frequencies response for detection application. The advantages of this works are selective with rapid capability for multidrug resistant (MDR) bacteria detection application.

Real-world bioelectronics applications, including drug delivery systems, biosensing, and electrical modulation of tissues and organs, largely require biointerfaces at the macroscopic level. However, traditional macroscale bioelectronic electrodes usually exhibit invasive or power-inefficient architectures, inability to form uniform and subcellular interfaces, or faradaic reactions at electrode surfaces. Here, we develop a micelle-enabled self-assembly approach for a binder-free and carbon-based monolithic device, aimed at large-scale bioelectronic interfaces. The device incorporates a multiscale porous material architecture, an interdigitated microelectrode layout, and a supercapacitor-like performance. In cell training processes, we use the device to modulate the contraction rate of primary cardiomyocytes at the subcellular level to target frequency in vitro. We also achieve capacitive control of the electrophysiology in isolated hearts, retinal tissues, and sciatic nerves, as well as bioelectronic cardiac sensing. Our results support the exploration of device platforms already used in energy research to identify new opportunities in bioelectronics.

The persistent use of pesticides in the agriculture field remains a serious issue related to public health. In the present work, molecularly imprinted polymer thin films were developed using electropolymerization of pyrrole (py) onto gold microelectrodes followed by electrodeposition for the selective detection of chlorpyrifos (CPF). The molecularly imprinted polymer (MIP) was synthesized by the electrochemical deposition method, which allowed in-line transfer of MIP on gold microelectrodes without using any additional adhering agents. Various parameters such as pH, monomer ratio, scan rate, and deposition cycle were optimized for sensor fabrication. The sensor was characterized at every stage of fabrication using various spectroscopic, microscopic, and electrochemical techniques. The sensor requires only 2 μL of the analyte and its linear detection range was found to be 1 μM to 1 fM. The developed sensor’s limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.93 and 2.82 fM, respectively, with a sensitivity of 3.98 (μA/(μM)/ mm2. The sensor’s shelf life was tested for 70 days. The applicability of the sensor in detecting CPF in fruit and vegetable samples was also assessed out with recovery % between 91 and 97% (RSD < 5%). The developed sensor possesses a huge commercial potential for on-field monitoring of pesticides.