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Obtaining cell concentration measurements from a culture assay by using bioimpedance is a very useful method that can be used to translate impedances to cell concentration values. The purpose of this study was to find a method to obtain the cell concentration values of a given cell culture assay in real time by using an oscillator as the measurement circuit. From a basic cell–electrode model, enhanced models of a cell culture immersed in a saline solution (culture medium) were derived. These models were used as part of a fitting routine to estimate the cell concentration in a cell culture in real time by using the oscillation frequency and amplitude delivered by the measurement circuits proposed by previous authors. Using real experimental data (the frequency and amplitude of oscillations) that were obtained by connecting the cell culture to an oscillator as the load, the fitting routine was simulated, and real-time data of the cell concentration were obtained. These results were compared to concentration data that were obtained by using traditional optical methods for counting. In addition, the error that we obtained was divided and analyzed in two parts: the first part of the experiment (when the few cells were adapting to the culture medium) and the second part of the experiment (when the cells exponentially grew until they completely covered the well). Low error values were obtained during the growth phase of the cell culture (the relevant phase); therefore, the results obtained were considered promising and show that the fitting routine is valid and that the cell concentration can be measured in real time by using an oscillator.

Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Tutor/Director: Rodríguez Trujillo, Romen, This project focuses on the development and experimentation of a microfluidic device with integrated electrodes, specifically designed to support the growth and maturation of a 3D cardiac cell matrix. The goal is to create a functional system that not only enables the cells to thrive and pump, but also facilitates the propagation of electrical stimuli, mimicking the behavior of natural cardiovascular tissue. The motivation behind this research stems from the limited regenerative capacity of adult heart tissue, particularly when it comes to cardiomyocytes. Traditional healing methods are often inadequate, necessitating heart transplants as the only definitive treatment option. To address this challenge, scientists are exploring the potential of biomaterial scaffolds to regenerate cardiovascular tissue by replacing damaged or necrotic tissue. The microfluidic device developed in this project holds great promise for researchers in the pharmaceutical field, offering a valuable tool for drug testing and disease modeling. Despite facing challenges in incorporating gold electrodes into the device, the team has successfully characterized it using an EIS machine. The design of the microelectrodes and microchannels, along with the overall functionality of the microchip, have been accomplished. While the current focus has been on a 2D layer of cells, the future objectives involve achieving a fully functional 3D matrix to fulfill the original research goals. Overall, this project aims to represent a significant step towards the advancement of regenerative medicine and the potential for innovative solutions in treating cardiovascular diseases.

Obtaining cell concentration measurements from a culture assay by using bioimpedance is a very useful method that can be used to translate impedances to cell concentration values. The purpose of this study was to find a method to obtain the cell concentration values of a given cell culture assay in real time by using an oscillator as the measurement circuit. From a basic cell–electrode model, enhanced models of a cell culture immersed in a saline solution (culture medium) were derived. These models were used as part of a fitting routine to estimate the cell concentration in a cell culture in real time by using the oscillation frequency and amplitude delivered by the measurement circuits proposed by previous authors. Using real experimental data (the frequency and amplitude of oscillations) that were obtained by connecting the cell culture to an oscillator as the load, the fitting routine was simulated, and real-time data of the cell concentration were obtained. These results were compared to concentration data that were obtained by using traditional optical methods for counting. In addition, the error that we obtained was divided and analyzed in two parts: the first part of the experiment (when the few cells were adapting to the culture medium) and the second part of the experiment (when the cells exponentially grew until they completely covered the well). Low error values were obtained during the growth phase of the cell culture (the relevant phase); therefore, the results obtained were considered promising and show that the fitting routine is valid and that the cell concentration can be measured in real time by using an oscillator.

Objectives One of the main challenges posed by the surgical deep brain stimulation (DBS) procedure is the successful targeting of the structures of interest and avoidance of side effects, especially in asleep surgery. Here, intraoperative motor evoked potentials (MEPs) might serve as tool to identify the pyramidal tract. We hypothesized that intraoperative MEPs are useful to define the distance to the pyramidal tract and reduce the occurrence of postoperative capsular side effects. Materials and methods Motor potentials were evoked through both microelectrode and DBS-electrode stimulation during stereotactic DBS surgery on 25 subthalamic nuclei and 3 ventral intermediate thalamic nuclei. Internal capsule proximity was calculated for contacts on microelectrode trajectories, as well as for DBS-electrodes, and correlated with the corresponding MEP thresholds. Moreover, the predictivity of intraoperative MEP thresholds on the probability of postoperative capsular side effects was calculated. Results Intraoperative MEPs thresholds correlated significantly with internal capsule proximity, regardless of the stimulation source. Furthermore, MEPs thresholds were highly accurate to exclude the occurrence of postoperative capsular side effects. Conclusions Intraoperative MEPs provide additional targeting guidance, especially in asleep DBS surgery, where clinical value of microelectrode recordings and test stimulation may be limited. As this technique can exclude future capsular side effects, it can directly be translated into clinical practice.

Rapid screening of foodborne pathogens is of great significance to ensure food safety. A microfluidic biosensor based on immunomagnetic separation, enzyme catalysis and electrochemical impedance analysis was developed for rapid and sensitive detection of Salmonella typhimurium. First, the bacterial sample, the magnetic nanoparticles (MNPs) modified with capture antibodies, and the enzymatic probes modified with detection antibodies and glucose oxidase (GOx) were simultaneously injected into the microfluidic chip, followed by mixing and incubation to form MNP-bacteria-probe sandwich complexes. Then, glucose with high impedance was injected into the chip and catalyzed by the GOx on the complexes into hydrogen peroxide with high impedance and gluconic acid with low impedance, which was finally measured using the low-cost interdigitated microelectrode and the electrochemical impedance analyzer to determine the target bacteria. Under the optimal conditions, this biosensor could quantitatively detect Salmonella typhimurium at the concentrations from 1.6 × 102 CFU/mL to 1.6 × 106 CFU/mL in 1 h with the low detection limit of 73 CFU/mL. Besides, this biosensor was demonstrated with good feasibility for practical applications by detecting the Salmonella typhimurium spiked chicken meat samples.

International audience; High Frequency Oscillations (HFO: 80-600 Hz) and particularly Fast-Ripples (FRs: 200-600 Hz) gained increasing interest over the last decade as a biomarker of epileptogenic networks. FRs were shown to be generated by small clusters of weakly synchronized hyperexcitable neurons, the recording of which requires the use of intracerebral microelectrodes. Nonetheless, the detection of FRs recorded using classical metal microelectrodes is very challenging. This is due to their small size which increases the impedance resulting in poor signal-to-noise ratio (SNR) and distortion. Coating electrodes with Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is a promising approach that was found to reduce their impedance by several orders of magnitude. However, it is also associated with poor adhesion to metals, which severely impacts its stability for chronic usage. In this study, we compared the performances of novel carbon microelectrodes combined with PEDOT:PSS and gold electrodes with PEDOT:PSS coating to Stainless Steel electrodes for the recording and detection of in vivo FRs (mouse hippocampus, kainate model of epilepsy). Results suggest that carbon electrodes allow for better detectability of epileptiform events and, in particular FRs. Perspectives of this work include the design of clinical hybrid (micro-macro) electrodes for the pre-surgical evaluation of patients with Drug-Resistant Epilepsy (DRE) and the design of neural implants for other applications in which chronic recording over long periods of time is required. © 2023 IEEE.

Previous studies have demonstrated the electropermeabilization of cell membranes exposed to an electric field with moderate intensity (

The regeneration of the injured nerve and recovery of its function have brought attention in the medical field. Electrical stimulation (ES) can enhance the cellular biological behavior and has been widely studied in the treatment of neurological diseases. Microfluidic technology can provide a cell culture platform with the well-controlled environment. Here a novel microfluidic/microelectrode composite microdevice was developed by embedding the microelectrodes to the microfluidic platform, in which microfluidics provided a controlled cell culture platform, and ES promoted the NSCs proliferation. We performed ES on rat neural stem cells (NSCs) to observe the effect on their growth, differentiation, proliferation, and preliminary explored the ES influence on cells in vitro. The results of immunofluorescence showed that ES had no significant effect on the NSCs specific expression, and the NSCs specific expression reached 98.9% ± 0.4% after three days of ES. In addition, ES significantly promoted cell growth and the cell proliferation rate reached 49.41%. To conclude, the microfluidic/microelectrode composite microdevice can play a positive role in the nerve injury repair and fundamental research of neurological diseases.

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.

Blood–brain barrier on a chip (BBBoC) has emerged as a promising tool for high-throughput screening of central nervous system drugs. During the drug screening, it is essential to ensure high repeatability and consistency of assays in different culture units or chips with the same structures. For the assembled chip, cells are introduced into the inoculating chamber by perfusion. However, this method leads to differences between BBBoC because of the uncontrollable flow and sedimentation of the cell suspension in initial stages of cell inoculating. In this work, an inoculating-first and assembling-later method was presented to overcome the shortcoming. First, a porous membrane fixed between the PDMS brackets was made to support the cells. Then human brain microvascular endothelial cells and human astrocytes were respectively inoculated in turn onto the two sides of the porous membrane. When cells grew and occupied the porous membrane, the cell support was sandwiched between two glass substrates with microelectrodes for TEER detection. The method ensured high consistency of cell inoculating number on the porous membrane. Subsequently, a blood-brain barrier model in vitro with high trans-endothelial electrical resistance (TEER) value and expression of ZO-1 was achieved.

Detailed effects of electrode size on electrograms (EGMs) have not been systematically examined.We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode size and interelectrode spacing for gap detection and far-field reduction.This study included 8 sheep in which probes with different electrode size and interelectrode spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. Between 3 electrode sizes (0.1 mm/0.2 mm/0.5 mm) with 3 mm spacing. As indices of capability in gap detection and far-field reduction, in different electrode sizes (0.1 mm/0.2 mm/0.5 mm) and interelectrode spacing (0.1 mm/0.2 mm/0.3 mm/0.5 mm/3 mm) and the optimized electrode size and interelectrode spacing were determined. Compared between PentaRay and the optimal probe determined in study 2.Study 1 demonstrated that unipolar voltage and the duration of EGMs increased as the electrode size increased in any tissue (P.001). Bipolar EGMs had the same tendency in healthy/fat tissues, but not in lesions. Study 2 showed that significantly higher gap to lesion volume ratio and healthy to fat tissue voltage ratio were provided by a smaller electrode (0.2 mm or 0.3 mm electrode) and smaller spacing (0.1 mm spacing), but 0.3 mm electrode/0.1 mm spacing provided a larger bipolar voltage (P.05). Study 3 demonstrated that 0.3 mm electrode/0.1 mm spacing provided less deflection with more discrete EGMs (P .0001) with longer and more reproducible AF cycle length (P .0001) compared to PentaRay.Electrode size affects both unipolar and bipolar EGMs. Catheters with microelectrodes and very small interelectrode spacing may be superior in gap detection and far-field reduction. Importantly, this electrode configuration could dramatically reduce artifactual complex fractionated atrial electrograms and may open a new era for AF mapping.

The miniaturization of boron-doped diamond (BDD) electrodes is an important requirement for application to the study of electrochemical processes in living beings. In this work, we describe the fab...

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.

An electrochemical aptamer-based sensor was developed for glutamate, the major excitatory neurotransmitter in the central nervous system. Determining glutamic acid release and glutamic acid levels is crucial for studying signal transmission and for diagnosing pathological conditions in the brain. Glutamic acid-selective oligonucleotides were isolated from an ssDNA library using the Capture-SELEX protocol in complex medium. The selection permitted the isolation of an aptamer 1d04 with a dissociation constant of 12 µM. The aptamer sequence was further used in the development of an electrochemical aptamer sensor. For this purpose, a truncated aptamer sequence named glu1 was labelled with a ferrocene redox tag at the 3′-end and immobilized on a gold electrode surface via Au-thiol bonds. Using 6-mercapto-1-hexanol as the backfill, the sensor performance was characterized by alternating current voltammetry. The glu1 aptasensor showed a limit of detection of 0.0013 pM, a wide detection range between 0.01 pM and 1 nM, and good selectivity for glutamate in tenfold diluted human serum. With this enzyme-free aptasensor, the highly selective and sensitive detection of glutamate was demonstrated, which possesses great potential for implementation in microelectrodes and for in vitro as well as in vivo monitoring of neurotransmitter release.

Blocking electrochemistry, a subfield of nanochemistry, enables nondestructive, in situ measurement of the concentration, size, and size heterogeneity of highly dilute, nanometer-scale materials. This approach, in which the adsorptive impact of individual particles on a microelectrode prevents charge exchange with a freely diffusing electroactive redox mediator, has expanded the scope of electrochemistry to the study of redox-inert materials. A limitation, however, remains: inhomogeneous current fluxes associated with enhanced mass transfer occurring at the edges of planar microelectrodes confound the relationship between the size of the impacting particle and the signal it generates. These "edge effects" lead to the overestimation of size heterogeneity and, thus, poor sample characterization. In response, we demonstrate here the ability of catalytic current amplification (EC') to reduce this problem, an effect we term "electrocatalytic interruption". Specifically, we show that the increase in mass transport produced by a coupled chemical reaction significantly mitigates edge effects, returning estimated particle size distributions much closer to those observed using ex situ electron microscopy. In parallel, electrocatalytic interruption enhances the signal observed from individual particles, enabling the detection of particles significantly smaller than is possible via conventional blocking electrochemistry. Finite element simulations indicate that the rapid chemical kinetics created by this approach contributes to the amplification of the electronic signal to restore analytical precision and reliably detect and characterize the heterogeneity of nanoscale electro-inactive materials.

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

Cardiac reentry is a lethal arrhythmia associated with cardiac diseases. Although arrhythmias are reported to be due to localized propagation abnormalities, little is known about the mechanisms underlying the initiation and termination of reentry. This is primarily because of a lack of an appropriate experimental system in which activity pattern switches between reentry and normal beating can be investigated. In this study, we aimed to develop a culture system for measuring the spatial dynamics of reentry-like activity during its onset and termination. Rat cardiomyocytes were seeded in microelectrode arrays and purified with a glucose-free culture medium to generate a culture with a heterogeneous cell density. Reentry-like activity was recorded in purified cardiomyocytes, but not in the controls. Reentry-like activity occurred by a unidirectional conduction block after shortening of the inter-beat interval. Furthermore, reentry-like activity was terminated after propagation with a conduction delay of less than 300 ms, irrespective of whether the propagation pattern changed or not. These results indicate that a simple purification process is sufficient to induce reentry-like activity. In the future, a more detailed evaluation of spatial dynamics will contribute to the development of effective treatment methods.

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.

The objective of the study was to evaluate the impact of distractions on intracortical brain–computer interface (BCI) performance. Two individuals with tetraplegia had microelectrode arrays implant...

Excessive aeration in wastewater treatment plants (WWTPs) will lead to energy waste. A large number of studies have shown that the control of low dissolved oxygen (DO) operation in WWTPs not only achieves considerable wastewater treatment effects, but also reduces energy waste. In this study, the transfer regulation of substrates and oxygen inside activated sludge flocs was measured under different equipment conditions (particle size of flocs, wastewater quality and sludge retention time of the treatment system) by using a microelectrode. A diffusion–reaction model based on the Monod kinetic model and Fick’s first law of diffusion was established by considering both the internal diffusion resistance and the diffusion rate of oxygen and substrates inside the activated sludge flocs, and the critical DO (DOc) was calculated by MATLAB software. The results showed that the attenuation of DO concentration in activated sludge flocs increased slightly with the increasing particle size, but it decreased with increasing external DO concentration. A critical DO as low as 0.3 mg/L could be achieved in flocs with low DO concentrations. This study provides strong support to carry out effective and feasible process design and process optimization. In addition, it can further guide WWTPs to achieve energy savings and consumption under stable operation.

Microelectrode recording (MER) or microelectrode signals recording of local field potentials by means of subthalamic-nuclei deep brain stimulation is highly successful for construing or deducing Parkinson disease (PD) signal analysis acquiescent to elucidation are fetching ever more germane. These signals are supposed to emulate STN neurons action-potential movement and, these potential frequency modulations are coupled to spiking-events. The method uses auto regression stochastic (random nature) model machine learning approach and, other standard techniques as of system identification field. A usual conventional local field potential implication involves computing spectral-densities, i.e., power (P S Ds) of these signals—waveforms, that confines power on different frequencies. But, P S D s is second-order statistics might not confine non trivial temporal-dependencies which subsist in unprocessed data. Hence, we suggest L F Ps technique which is valuable in support of relating or unfolding distinctive plus sole features of temporal-dependencies in L F P waveforms. This technique is derived as of auto-regression (A R) modeling originating as of the systems plus control theory in fastidious systems-identification. We have distinctively, built A R models of L F P movement activity plus inferred, and also verified statistically major differentiations in temporal-dependencies among damaged tissues of nuclei plus protective areas in Parkinson`s receiving innocuous microelectrodes via deep brain stimulator (D BS). Differentiations in spectral-densities of field-waveforms amid the two conglomerates were not statistically-significant. Keywords: Microelectrode recording (MER), Parkinson disease (PD).

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.

A fundamental limitation of the implantable brain-machine interfaces (BMI) is the wiring requirements for power transfer and signal transmission. Existing microelectrode technologies can only record from localized sections of the brain and require implantation of invasive electrodes through cranial surgeries. Here, we introduce a system-on-a-nanoparticle probe, a Neurophotonic Solution-dispersible Wireless Activity Reporter for Massively Multiplexed Measurements (Neuro-SWARM3), enabling remote detection of in vivo bioelectric signals. Neuro-SWARM3 offers five fundamental advancements simultaneously: (1) it enables use of infrared light within the biologically transparent near infrared (NIR-II, 1000–1700 nm) window for direct read-out through the skull, (2) it circumvents invasive surgical operations since no wiring or power supply is needed for the wireless (electro-plasmonic) excitation and remote detection, (3) due to its diminutive dimensions ( in vivo measurements that are not restricted by electrode dimensions, physical wiring, and electronic bandwidth limitations, (5) by being much smaller than the critical dimensions that trigger glial cell response ( $\sim 12~\mu \text{m}$ ), it offers a long term operation capability. As we show below, NeuroSWARM3 provides high signal to shot noise ratio (SSNR $\sim 10^{3}$ ) wireless recording capability from single neurons due to its enhanced scattering cross-section ( $\sim 10^{4}$ nm $^{2}$ ) and field-sensitivity (up to ~40%).

Microelectrodes are widely used for neural signal analysis because they can record high-resolution signals. In general, the smaller the size of the microelectrode for obtaining a high-resolution signal, the higher the impedance and noise value of the electrodes. Therefore, to improve the signal-to-noise ratio (SNR) of neural signals, it is important to develop microelectrodes with low impedance and noise. In this research, an Au hierarchical nanostructure (AHN) was deposited to improve the electrochemical surface area (ECSA) of a microelectrode. Au nanostructures on different scales were deposited on the electrode surface in a hierarchical structure using an electrochemical deposition method. The AHN-modified microelectrode exhibited an average of 80% improvement in impedance compared to a bare microelectrode. Through electrochemical impedance spectroscopy analysis and impedance equivalent circuit modeling, the increase in the ECSA due to the AHN was confirmed. After evaluating the cell cytotoxicity of the AHN-modified microelectrode through an in vitro test, neural signals from rats were obtained in in vivo experiments. The AHN-modified microelectrode exhibited an approximate 9.79 dB improvement in SNR compared to the bare microelectrode. This surface modification technology is a post-treatment strategy used for existing fabricated electrodes, so it can be applied to microelectrode arrays and nerve electrodes made from various structures and materials.

Multichannel electrophysiological sensors and stimulators—particularly those used to study the nervous system—are usually based on monolithic microelectrode arrays. However, the architecture of such arrays limits flexibility in electrode placement and scaling to a large number of nodes, especially across non-contiguous locations. Here we report wirelessly networked and powered electronic microchips that can autonomously perform neural sensing and electrical microstimulation. The microchips, which we term neurograins, have an ~1 GHz electromagnetic transcutaneous link to an external telecom hub, providing bidirectional communication and control at the individual device level. To illustrate the potential of the approach, we show that 48 neurograins can be individually addressed on a rat cortical surface and used for the acute recording of neural activity. Theoretical calculations and experimental measurements show that the link configuration could potentially be scaled to 770 neurograins using a customized time-division multiple access protocol. Wirelessly powered microchips, which have an ~1 GHz electromagnetic transcutaneous link to an external telecom hub, can be used for multichannel in vivo neural sensing, stimulation and data acquisition.

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 one of the significant intracellular signaling molecules, hydrogen peroxide (H2O2) regulates some vital biological processes. However, it remains a challenge to develop noninvasive electrodes that can be used for sensing trace H2O2 at the cellular level. Here, we evaluated a high-performance solid-state electrochemiluminescence (ECL) H2O2 sensor based on MIL-88B(Fe) nanocrystal-anchored Ti microwires. Semiconducting TiO2 nanotubes (TiNTs) vertically grown around a Ti wire via an anodization technique act as an intrinsic ECL luminophore. By integrating with MIL-88B(Fe), the synergistic effect of the TiO2 luminophore and the remarkable peroxidase-like activity of MIL-88B(Fe) enable the resulting H2O2 sensor an ultrahigh sensitivity featuring a minimum detection limit of 0.1 nM (S/N = 3), long-term stability, high durativity, and wide-range linear response to a concentration of up to 10 mM. To demonstrate the concept of a MIL-88B(Fe)@TiO2 microelectrode for single-cell sensing, the electrode was used to detect intracellular H2O2 in a single cell. Moreover, benefiting from the heterojunction of MIL-88B(Fe)/TiO2, the microelectrode was found to exhibit excellent photocatalytic activity in the visible-light range, that is, the sensor surface can be self-cleaning after a short visible-light treatment. These advanced sensor characteristics involving easy reusability reveal that the MIL-88B(Fe)@TiO2 microelectrode is a new platform for cytosensing. This study provides a new strategy to design semiconductor materials with arbitrary shape and size, allowing for profound applications in biomedical and clinical analysis.

Electrophysiological research on neural networks and their activity focuses on the recording and analysis of large data sets that include information of thousands of neurons. CMOS microelectrode arrays (MEAs) feature thousands of electrodes at a spatial resolution on the scale of single cells and are, therefore, ideal tools to support neural-network research. Moreover, they offer high spatio-temporal resolution and signal-to-noise ratio (SNR) to capture all features and subcellular-resolution details of neuronal signaling. Here, we present a dual-mode (DM) MEA, which enables simultaneous: 1) full-frame readout from all electrodes and 2) high-SNR readout from an arbitrarily selectable subset of electrodes. The DM-MEA includes 19 584 electrodes, 19 584 full-frame recording channels with noise levels of 10.4 $\mu \text{V}~_{\text {rms}}$ in the action potential (AP) frequency band (300 Hz–5 kHz), 246 low-noise recording channels with noise levels of 3.0 $\mu \text{V}~_{\text {rms}}$ in the AP band and eight stimulation units. The capacity to simultaneously perform full-frame and high-SNR recordings endows the presented DM-MEA with great flexibility for various applications in neuroscience and pharmacology.

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.

Digital Microfluidics is an emerging technology for automating laboratory procedures in biochemistry. With more and more complex biochemical protocols getting mapped to biochip devices and microfluidics receiving a wide adoption, it is becoming indispensable to develop automated tools and synthesis platforms that can enable a smooth transformation from complex cumbersome benchtop laboratory procedures to biochip execution. Given an informal/semi-formal assay description and a target microfluidic grid architecture on which the assay has to be implemented, a synthesis tool typically translates the high-level assay operations to low-level actuation sequences that can drive the assay realization on the grid. With more and more complex biochemical assay protocols being taken up for synthesis and biochips supporting a wider variety of operations (e.g., MicroElectrode Dot Arrays (MEDAs)), the task of assay synthesis is getting intricately complex. Errors in the synthesized assay descriptions may have undesirable consequences in assay operations, leading to unacceptable outcomes after execution on the biochips. In this work, we focus on the challenge of examining the correctness of synthesized protocol descriptions, before they are taken up for realization on a microfluidic biochip. In particular, we take up a protocol description synthesized for a MEDA biochip and adopt a formal analysis method to derive correctness proofs or a violation thereof, pointing to the exact operation in the erroneous translation. We present experimental results on a few bioassay protocols and show the utility of our framework for verifiable protocol synthesis.

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.

Zinc (Zn(II)) is a divalent cation involved in regulating intracellular signal transduction and gene expression through transcription factor activity, and can act as a metal neurotransmitter by modulating synaptic activity and neuronal plasticity. Previous research has demonstrated spatial heterogeneity of Zn(II) in the brain, has estimated extracellular concentrations of Zn(II) across various brain regions, and has measured rapid intracellular changes in Zn(II) concentration during glutamate flux. Despite this work, quantification of rapid extracellular Zn(II) release from neurons, on a millisecond time scale, in real time has remained difficult with existing technologies. Here, we have developed an electrochemical waveform, called the "extended sawhorse waveform (ESW)," for fast-scan cyclic voltammetry detection at carbon-fiber microelectrodes which enabled rapid and stable Zn(II) monitoring over time. This waveform was developed to overcome existing challenges in monitoring metallotransmitters stably over time electrochemically by introducing a brief cleaning step to facilitate rapid cleaning of the electrode surface in between scans. The ESW scans from 0.5 V down to -1.0 V, up to 1.45 V for 3 ms (cleaning step), and back to 0.5 V at a scan rate of 400 V/s. Repeated introductions of Zn(II) at the electrode using a traditional waveform cause plating which ultimately deteriorates the sensitivity over time; however, using the ESW, significant improvements in stability were observed. Overall, we provide a unique approach to monitor and quantitate rapid Zn(II) signaling in the brain at carbon electrodes which will impact our ability to advance fundamental knowledge of Zn(II) involvement in extracellular signaling pathways in the brain.

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.

Objective of Study: To compare cuff electrodes, microelectrodes (those commonly used in clinical microneurography), and longitudinal intrafascicular electrodes (LIFE) (commonly used in pre-clinical studies) on their ability to 1) measure electrically evoked compound action potentials (ECAPs) and spontaneous activity on the cervical vagus nerve and 2) measure sensory evoked (by stroking) and transcutaneous electrical stimulation (TES) ECAP on the great auricular nerve. See full pre-registration in attached PDF file.

The goal of this project is to demonstrate the capability of a surface-based microelectrode interface with neural ganglia. Experiments have been performed in both feline dorsal root ganglia (DRG) and Aplysia californica buccal ganglia.

The goal of this project is to demonstrate a long-term interface with dorsal root ganglia and the bladder for monitoring and controlling lower urinary tract function. Data within this project are part of a manuscript published at the Journal of Neural Engineering. DOI: 10.1088/1741-2552/aa6801. http://iopscience.iop.org/article/10.1088/1741-2552/aa6801

Corals are globally important calcifiers that exhibit complex responses to anthropogenic warming and acidification. Although coral calcification is supported by high seawater pH, photosynthesis by the algal symbionts of zooxanthellate corals can be promoted by elevated pCO2. To investigate the mechanisms underlying corals’ complex responses to global change, three species of tropical zooxanthellate corals (Stylophora pistillata, Pocillopora damicornis, and Seriatopora hystrix) and one species of asymbiotic cold-water coral (Desmophyllum pertusum, syn. Lophelia pertusa) were cultured under a range of ocean acidification and warming scenarios. Under control temperatures, all tropical species exhibited increased calcification rates in response to increasing pCO2. However, the tropical species’ response to increasing pCO2 flattened when they lost symbionts (i.e., bleached) under the high-temperature treatments—suggesting that the loss of symbionts neutralized the benefit of increased pCO2 on calcification rate. Notably, the cold-water species that lacks symbionts exhibited a negative calcification response to increasing pCO2, although this negative response was partially ameliorated under elevated temperature. All four species elevated their calcifying fluid pH relative to seawater pH under all pCO2 treatments, and the magnitude of this offset (Δ[H+]) increased with increasing pCO2. Furthermore, calcifying fluid pH decreased along with symbiont abundance under thermal stress for the one species in which calcifying fluid pH was measured under both temperature treatments. This observation suggests a mechanistic link between photosymbiont loss (‘bleaching’) and impairment of zooxanthellate corals’ ability to elevate calcifying fluid pH in support of calcification under heat stress. This study supports the assertion that thermally induced loss of photosymbionts impairs tropical zooxanthellate corals’ ability to cope with CO2-induced ocean acidification.

Nowadays, bioelectronic devices are evolving from rigid to flexible materials and substrates, among which thermally-drawn-fiber-based bioelectronics represent promising technologies thanks to their inherent flexibility and seamless integration of multi-functionalities. However, electrochemical sensing within fibers remains a poorly explored area, as it imposes new demands for material properties—both the electrochemical sensitivity and the thermomechanical compatibility with the fiber drawing process. Here, we designed and fabricated microelectrode fibers made of carbon nanotube (CNT)-based hybrid nanocomposites and further evaluated their detailed electrochemical sensing performances. Carbon-black-impregnated polyethylene (CB-CPE) was chosen as the base material, into which CNT was loaded homogeneously in a concentration range of 3.8 to 10 wt%. First, electrical impedance characterization of CNT nanocomposites showed a remarkable decrease of the resistance with the increase in CNT loading ratio, suggesting that CNTs notably increased the effective electrical current pathways inside the composites. In addition, the proof-of-principle performance of fiber-based microelectrodes was characterized for the detection of ferrocenemethanol (FcMeOH) and dopamine (DA), exhibiting an ultra-high sensitivity. Additionally, we further examined the long-term stability of such composite-based electrode in exposure to the aqueous environment, mimicking the in vivo or in vitro settings. Later, we functionalized the surface of the microelectrode fiber with ion-sensitive membranes (ISM) for the selective sensing of Na+ ions. The miniature fiber-based electrochemical sensor developed here holds great potential for standalone point-of-care sensing applications. In the future, taking full advantage of the thermal drawing process, the electrical, optical, chemical, and electrochemical modalities can be all integrated together within a thin strand of fiber. This single fiber can be useful for fundamental multi-mechanistic studies for biological applications and the weaved fibers can be further applied for daily health monitoring as functional textiles.