Surface Electrode Array Research Articles

A Clinically Feasible Electrode Array for 3D Intraoperative Electrical Impedance Tomography-Based Surgical Margin Assessment in Robot-Assisted Radical Prostatectomy.

A novel small form factor circular electrode array was designed specifically for electrical impedance tomography (EIT) based assessment of surgical margins during robot assisted radical prostatectomy (RARP). The electrode array consists of 33 gold-plated electrodes arranged within a 9.5 mm diameter circular footprint on the end of a surgical probe that can be introduced through a standard 12 mm laparoscopic port used during RARP. The electrode array contains 8 larger, low-contact impedance outer electrodes dedicated for current drive and an internal grid of 25 smaller electrodes for simultaneous voltage measurement. Separating electrode geometry by function is designed to improve current delivery, speed, and resolution while reducing hardware requirements. Simulations demonstrated that 1 mm diameter hemispherical prostate cancer inclusions could be localized within regions of adipose and benign prostate tissue; 1.5 mm diameter inclusions were required for localization within muscle tissue. A 2.38 mm diameter aluminum rod in 0.2 S/m saline could be localized throughout the imaging domain with a position error of less than 2.5 mm for depths from the electrode array surface of up to 1.7 mm. Ex vivo tissue experiments with a bovine model demonstrate visual congruence of muscle and adipose tissue locations between the sample and reconstructed images. Simulation and experimental results indicate good detection and location of inclusions. These results suggest the proposed electrode array design can provide sufficient accuracy in the detection and localization of prostate cancer against clinically relevant background tissues for use during RARP.

Vertebrates on a Chip: Noninvasive Electrical and Optical Mapping of Whole Brain Activity Associated with Pharmacological Treatments.

Mapping brain activities is necessary for understanding brain physiology and discovering new treatments for neurological disorders. Such efforts have greatly benefited from the advancement in technologies for analyzing neural activity with improving temporal or spatial resolution. Here, we constructed a multielectrode array based brain activity mapping (BAM) system capable of stabilizing and orienting zebrafish larvae for recording electroencephalogram (EEG) like local field potential (LFP) signals and brain-wide calcium dynamics in awake zebrafish. Particularly, we designed a zebrafish trap chip that integrates with an eight-by-eight surface electrode array, so that brain electrophysiology can be noninvasively recorded in an agarose-free and anesthetic-free format with a high temporal resolution of 40 μs, matching the capability typically achieved by invasive LFP recording. Benefiting from the specially designed hybrid system, we can also conduct calcium imaging directly on immobilized awake larval zebrafish, which further supplies us with high spatial resolution brain-wide activity data. All of these innovations reconcile the limitations of sole LFP recording or calcium imaging, emphasizing a synergy of combining electrical and optical modalities within one unified device for activity mapping across a whole vertebrate brain with both improved spatial and temporal resolutions. The compatibility with in vivo drug treatment further makes it suitable for pharmacology studies based on multimodal measurement of brain-wide physiology.

A Cyto-silicon Hybrid System with On-chip Closed-loop Modulation.

We introduce a bioelectronic interface between biological electrogenic cells and a mixed-signal CMOS integrated circuit with an array of surface electrodes, where not only is the CMOS electrode array capable of electrophysiological recording and stimulation of the cells with 1,024 recording and stimulation channels, but it can also provide low-latency artificial signal pathways from cells it records to cells it stimulates. This on-chip closed-loop modulation has an intrinsic latency less than 5 μs. To demonstrate the utility of the on-chip closed loop modulation as an artificial feedback pathway between biological cells, we develop a silicon-cardiomyocyte self-sustained oscillator with a tunable frequency to which both the relevant part of the CMOS chip and cells are locked, and also a silicon-neuron interface with a silicon inhibitory connection between neuronal cells. This line of cyto-silicon hybrid system, where the boundary between biological and semiconductor systems is blurred, may find applications in prosthesis, brain-machine interface, and fundamental biology research.

Multiplexed Surface Electrode Arrays Based on Metal Oxide Thin-Film Electronics for High-Resolution Cortical Mapping.

Electrode grids are used in neuroscience research and clinical practice to record electrical activity from the surface of the brain. However, existing passive electrocorticography (ECoG) technologies are unable to offer both high spatial resolution and wide cortical coverage, while ensuring a compact acquisition system. The electrode count and density are restricted by the fact that each electrode must be individually wired. This work presents an active micro-electrocorticography (µECoG) implant that tackles this limitation by incorporating metal oxide thin-film transistors (TFTs) into a flexible electrode array, allowing to address multiple electrodes through a single shared readout line. By combining the array with an incremental-ΔΣ readout integrated circuit (ROIC), the system is capable of recording from up to 256 electrodes virtually simultaneously, thanks to the implemented 16:1 time-division multiplexing scheme, offering lower noise levels than existing active µECoG arrays. Invivo validation is demonstrated acutely in mice by recording spontaneous activity and somatosensory evoked potentials over a cortical surface of ≈8×8mm2 . The proposed neural interface overcomes the wiring bottleneck limiting ECoG arrays, holding promise as a powerful tool for improved mapping of the cerebral cortex and as an enabling technology for future brain-machine interfaces.

The ultra-thin, minimally invasive surface electrode array NeuroWeb for probing neural activity

Electrophysiological recording technologies can provide valuable insights into the functioning of the central and peripheral nervous systems. Surface electrode arrays made of soft materials or implantable multi-electrode arrays with high electrode density have been widely utilized as neural probes. However, neither of these probe types can simultaneously achieve minimal invasiveness and robust neural signal detection. Here, we present an ultra-thin, minimally invasive neural probe (the “NeuroWeb”) consisting of hexagonal boron nitride and graphene, which leverages the strengths of both surface electrode array and implantable multi-electrode array. The NeuroWeb open lattice structure with a total thickness of 100 nm demonstrates high flexibility and strong adhesion, establishing a conformal and tight interface with the uneven mouse brain surface. In vivo electrophysiological recordings show that NeuroWeb detects stable single-unit activity of neurons with high signal-to-noise ratios. Furthermore, we investigate neural interactions between the somatosensory cortex and the cerebellum using transparent dual NeuroWebs and optical stimulation, and measure the times of neural signal transmission between the brain regions depending on the pathway. Therefore, NeuroWeb can be expected to pave the way for understanding complex brain networks with optical and electrophysiological mapping of the brain.

Characterization of Benchtop-Fabricated Arrays of Nanowrinkled Surface Electrodes as a Nitric Oxide Electrochemical Sensor.

In this work, we present an accessible benchtop fabrication technique to obtain a planar array of gold nanowrinkled surface electrodes (ANSE) for the construction of electrochemical cells, specifically to monitor soluble biomarkers of interest in cell culture environments. We present a complete characterization of the array and its response as an electrochemical cell. To validate our sensor, we evaluated the device sensitivity to detect nitric oxide (NO), an important molecule produced by endothelial cells as a response to environmental signals such as mechanics and growth factors. While testing measurements of nitric oxide in aqueous solutions with isotonic salt concentrations, we evidenced the influence of the environmental conditions for such electrochemical measurements, showing that the aqueous medium, usually not accounted for, significantly impacts the outcome. Finally, we present the application of the electrochemical sensor for the detection of nitric oxide released from stimulated endothelial cells as a proof of concept.

High Density Body Surface Potential Mapping with Conducting Polymer-Eutectogel Electrode Arrays for ECG imaging.

Electrocardiography imaging (ECGi) is a non-invasive inverse reconstruction procedure which employs body surface potential maps (BSPM) obtained from surface electrode array measurements to improve the spatial resolution and interpretability of conventional electrocardiography (ECG) for the diagnosis of cardiac dysfunction. ECGi currently lacks precision, which has prevented its adoption in clinical setups. The introduction of high-density electrode arrays could increase ECGi reconstruction accuracy but is not attempted before due to manufacturing and processing limitations. Advances in multiple fields have now enabled the implementation of such arrays which poses questions on optimal array design parameters for ECGi. In this work, a novel conducting polymer electrode manufacturing process on flexible substrates is proposed to achieve high-density, mm-sized, conformable, long-term, and easily attachable electrode arrays for BSPM with parameters optimally selected for ECGi applications. Temporal, spectral, and correlation analysis are performed on a prototype array demonstrating the validity of the chosen parameters and the feasibility of high-density BSPM, paving the way for ECGi devices fit for clinical application.

Focused Epicranial Brain Stimulation by Spatial Sculpting of Pulsed Electric Fields Using High Density Electrode Arrays.

Transcranial electrical neuromodulation of the central nervous system is used as a non-invasive method to induce neural and behavioral responses, yet targeted non-invasive electrical stimulation of the brain with high spatial resolution remains elusive. This work demonstrates a focused, steerable, high-density epicranial current stimulation (HD-ECS) approach to evoke neural activity. Custom-designed high-density (HD) flexible surface electrode arrays are employed to apply high-resolution pulsed electric currents through skull to achieve localized stimulation of the intact mouse brain. The stimulation pattern is steered in real time without physical movement of the electrodes. Steerability and focality are validated at the behavioral, physiological, and cellular levels using motor evoked potentials (MEPs), intracortical recording, and c-fos immunostaining. Whisker movement is also demonstrated to further corroborate the selectivity and steerability. Safety characterization confirmed no significant tissue damage following repetitive stimulation. This method can be used to design novel therapeutics and implement next-generation brain interfaces.

Stretchable Surface Electrode Arrays Using an Alginate/PEDOT:PSS-Based Conductive Hydrogel for Conformal Brain Interfacing.

An electrocorticogram (ECoG) is the electrical activity obtainable from the cerebral cortex and an informative source with considerable potential for future advanced applications in various brain-interfacing technologies. Considerable effort has been devoted to developing biocompatible, conformal, soft, and conductive interfacial materials for bridging devices and brain tissue; however, the implementation of brain-adaptive materials with optimized electrical and mechanical characteristics remains challenging. Herein, we present surface electrode arrays using the soft tough ionic conductive hydrogel (STICH). The newly proposed STICH features brain-adaptive softness with Young's modulus of ~9.46 kPa, which is sufficient to form a conformal interface with the cortex. Additionally, the STICH has high toughness of ~36.85 kJ/mm3, highlighting its robustness for maintaining the solid structure during interfacing with wet brain tissue. The stretchable metal electrodes with a wavy pattern printed on the elastomer were coated with the STICH as an interfacial layer, resulting in an improvement of the impedance from 60 kΩ to 10 kΩ at 1 kHz after coating. Acute in vivo experiments for ECoG monitoring were performed in anesthetized rodents, thereby successfully realizing conformal interfacing to the animal's cortex and the sensitive recording of electrical activity using the STICH-coated electrodes, which exhibited a higher visual-evoked potential (VEP) amplitude than that of the control device.

A flexible adhesive surface electrode array capable of cervical electroneurography during a sequential autonomic stress challenge

This study introduces a flexible, adhesive-integrated electrode array that was developed to enable non-invasive monitoring of cervical nerve activity. The device uses silver-silver chloride as the electrode material of choice and combines it with an electrode array consisting of a customized biopotential data acquisition unit and integrated graphical user interface (GUI) for visualization of real-time monitoring. Preliminary testing demonstrated this electrode design can achieve a high signal to noise ratio during cervical neural recordings. To demonstrate the capability of the surface electrodes to detect changes in cervical neuronal activity, the cold-pressor test (CPT) and a timed respiratory challenge were employed as stressors to the autonomic nervous system. This sensor system recording, a new technique, was termed Cervical Electroneurography (CEN). By applying a custom spike sorting algorithm to the electrode measurements, neural activity was classified in two ways: (1) pre-to-post CPT, and (2) during a timed respiratory challenge. Unique to this work: (1) rostral to caudal channel position-specific (cephalad to caudal) firing patterns and (2) cross challenge biotype-specific change in average CEN firing, were observed with both CPT and the timed respiratory challenge. Future work is planned to develop an ambulatory CEN recording device that could provide immediate notification of autonomic nervous system activity changes that might indicate autonomic dysregulation in healthy subjects and clinical disease states.

Foldable three dimensional neural electrode arrays for simultaneous brain interfacing of cortical surface and intracortical multilayers

Challenges in the understanding of three-dimensional (3D) brain networks by simultaneously recording both surface and intracortical areas of brain signals remain due to the difficulties of constructing mechanical design and spatial limitations of the implanted sites. Here, we present a foldable and flexible 3D neural prosthetic that facilitates the 3D mapping of complex neural circuits with high spatiotemporal dynamics from the intracortical to cortical region. This device is the tool to map the 3D neural transmission through sophisticatedly designed four flexible penetrating shanks and surface electrode arrays in one integrated system. We demonstrate the potential possibilities of identifying correlations of neural activities from the intracortical area to cortical regions through continuous monitoring of electrophysiological signals. We also exploited the structural properties of the device to record synchronized signals of single spikes evoked by unidirectional total whisker stimulation. This platform offers opportunities to clarify unpredictable 3D neural pathways and provides a next-generation neural interface.

Differences between vastus medialis and lateralis excitation onsets are dependent on the relative distance of surface electrodes placement from the innervation zone location

Conflictual results between the onset of vastus medialis (VM) and vastus lateralis (VL) excitation may arise from methodological aspects related to the detection of surface electromyograms. In this study we used an array of surface electrodes to assess the effect of detection site, relative to the muscle innervation zone, on the difference between VM and VL excitation onsets. Ten healthy males performed moderate isometric knee extension at 40 % of their maximal voluntary isometric contraction. After the actual VM-VL onset was defined (estimated when action potentials were generated at the neuromuscular junctions of both muscles), we calculated the largest bias that the detection site may introduce in the VM-VL onset estimation. We also assessed whether the location often considered for positioning bipolar electrodes on each muscle leads to VM-VL onset estimations comparable to the actual VM-VL onset. Our main results revealed that a maximum absolute bias of 20.48 ms may be introduced in VM-VL onset estimations due to the electrodes’ detection site. In addition, mean differences of ∼ 12 ms in VM-VL onset estimations were attributable to largest possible discrepancies in the paired position of channels with respect to the innervation zone for VL and VM. When considering the classical location for positioning the bipolar electrodes over these muscles, differences error was subtle (∼3.4 ms) when compared with the actual VM-VL onset. Nonetheless, when accounting for the effect of relative differences in electrode position between muscles is not possible, our results suggest that a systematic absolute error of ∼ 12 ms should be considered in future studies regarding VM-VL onset estimations, suggesting that onset differences lower than that might not be clinically relevant.

Bagged tree ensemble modelling with feature selection for isometric EMG-based force estimation

EMG-based force estimation is crucial in applications, such as control of powered prosthetic and rehabilitation devices. Most previous studies focus on intra-subject force modelling. However, a generalized EMG-force estimation model, which is capable of estimating force across users, is needed for surgical and rehabilitation robotics. In this study, EMG signals are recorded from the long head and short head of the biceps brachii, and brachioradialis using 3 linear surface electrode arrays, during isometric elbow flexions, at different joint angles and forearm postures, while recording the induced force at the wrist. The recorded EMGs are pre-processed and segmented, and 336 time and frequency domain features are extracted from 21 EMG channels. We explore developing a model that can perform well across subjects, where Bagged Tree Ensemble (BTE) models are used to learn the non-linear, complex relationships between the EMG and force data. The BTE models are compared with several machine learning approaches. The BTE model performs best, giving an average normalized mean squared error (%NMSE) of 5.65±16.24%. To reduce the dimensionality of the feature space and improve force estimation performance, a novel feature selection technique, called modified sequential feature selection (MSFS) is implemented and compared to other commonly used feature selection methods. Results show that the MSFS algorithm outperformed other methods tested, significantly reducing the force estimation error. We also found that there was no effect of forearm posture and joint angle on force modelling accuracy, permitting the development of an isometric force estimation model generalized across participants and arm positions.

Oddball-irrelevant visual stimuli cross-modally attenuate auditory mismatch negativity in rats.

To elaborate the recent theory of prediction models of the brain in light of actual neural activities, it is important to investigate the cross-modal interactions in the context of prediction construction. To this end, in this study, we assessed whether cross-modal disturbances would result in the attenuation of mismatch negativity in anesthetized animal models. A surface electrode array recorded neural activities from the visual and auditory cortices of rats under isoflurane anesthesia, during an auditory oddball paradigm over the course of three audiovisual sequences. In the audiovisual sequences, the visual stimuli were simultaneously presented with the first, second, or third standard before the deviants. The interrupting visual stimuli decrease the amplitude of mismatch negativity in the auditory and visual cortices. In addition, the correlation coefficients between the amplitude of middle-latency potential for the interrupting visual stimuli and the amplitude of mismatch negativity to the following auditory deviant stimuli were smaller when the visual stimuli were presented alongside the third standards from the deviants. Such attenuation in mismatch negativity has been often associated with a top-down mechanism and the present anesthesia selectively attenuates top-down transmission. Taken together, our study's findings indicate that the cross-modal disturbances on prediction and deviation detection may also be mediated by bottom-up mechanisms, as well as previously reported top-down mechanisms.

Materials for Implantable Surface Electrode Arrays: Current Status and Future Directions.

Surface electrode arrays are mainly fabricated from rigid or elastic materials, and precisely manipulated ductile metal films, which offer limited stretchability. However, the living tissues to which they are applied are nonlinear viscoelastic materials, which can undergo significant mechanical deformation in dynamic biological environments. Further, the same arrays and compositions are often repurposed for vastly different tissues rather than optimizing the materials and mechanical properties of the implant for the target application. By first characterizing the desired biological environment, and then designing a technology for a particular organ, surface electrode arrays may be more conformable, and offer better interfaces to tissues while causing less damage. Here, the various materials used in each component of a surface electrode array are first reviewed, and then electrically active implants in three specific biological systems, the nervous system, the muscular system, and skin, are described. Finally, the fabrication of next-generation surface arrays that overcome current limitations is discussed.

Raising the stakes for cortical visual prostheses.

In this issue of the JCI, the dream of restoring useful vision to blind individuals with neurotechnology moves one step closer to realization. Fernández et al. implanted an electrode array with 96 penetrating electrodes in the visual cortex of a blind patient who had been without light perception for 16 years due to optic neuropathy. Remarkably, the patient was able to perceive visual patterns created by passing current through array electrodes. The use of a penetrating electrode array meant that action potentials from single neurons could be recorded to study the neural response to stimulation. Compared with electrodes resting on the cortical surface, penetrating electrodes require one-tenth the current to create a visual percept. However, patterned electrical stimulation often fails to produce the expected percept for penetrating and surface electrode arrays, highlighting the need for further research to untangle the relationship between stimulus and perception.

Low-Cost Platform for Multiplexed Electrochemical Melting Curve Analysis.

Detection and identification of single nucleotide polymorphisms (SNPs) have garnered increasing interest in the past decade, finding potential application in detection of antibiotic resistance, advanced forensic science, as well as clinical diagnostics and prognostics, moving toward the realization of personalized medicine. Many different techniques have been developed for genotyping SNPs, and ideally these techniques should be rapid, easy-to-use, cost-effective, flexible, scalable, easily automated, and requiring minimal end-user intervention. While high-resolution melting curve analysis has been widely used for the detection of SNPs, fluorescence detection does not meet many of the desired requirements, and electrochemical detection is an attractive alternative due to its high sensitivity, simplicity, cost-effectiveness, and compatibility with microfabrication. Herein, we describe the multiplexed electrochemical melting curve analysis of duplex surfaces tethered to electrodes of an array. In this approach, thiolated probes designed to hybridize to a DNA sequence containing the SNP to be interrogated are immobilized on gold electrodes. Asymmetric PCR using a ferrocene-labeled forward primer is used to generate this single-stranded redox-labeled PCR amplicon. Following hybridization with the probe immobilized on the electrode surface, the electrode array is exposed to a controlled ramping of temperature, with concomitant constant washing of the electrode array surface while simultaneously carrying out voltammetric measurements. The optimum position of the site complementary to the SNP site in the immobilized probe to achieve maximum differentiation in melting temperature between wild-type and single base mismatch, thus facilitating allelic discrimination, was determined and applied to the detection of a cardiomyopathy associated SNP.

Evaluating the Ability of Congenital Upper Extremity Amputees to Control a Multi-Degree of Freedom Myoelectric Prosthesis

To determine whether children and adults with unilateral congenital upper limb amputation can control myoelectric prostheses with multiple degrees of freedom (DOF) using pattern recognition (PR) technology. Seven participants (age 9-62 years) with unilateral congenital transradial amputation were tested on both their residual and sound side limbs to determine proficiency in controlling a virtual prosthesis using electromyographic signals captured by an array of surface electrodes that were processed using PR technology. Proficiency was measured through a virtual environment game called the target achievement control test, in which the testing protocol asked participants to match increasingly complex prosthesis postures with 1,2, and 3 DOF. All the participants successfully created a PR calibration at 1, 2, and 3 DOF with their residual limb during testing, and no differences in calibration accuracy were observed when comparing the residual versus sound upper limbs. No differences were noted in the mean completion rate on the target achievement control test between the residual and sound limbs. Participants with a congenital upper limb amputation achieved PR control calibration of multi-DOF prostheses with proficiency and quality results of PR calibration that were comparable to those of their sound limb. This capability was observed in children as well as in adults. This demonstrates the potential for children and adults with a unilateral congenital transradial amputation to benefit from myoelectric prostheses with PR control. The results from this study highlight the potential for patients in this population to benefit from myoelectric prostheses with PR control. Persons with unilateral congenital upper limb amputations can be considered for provision of this technology andenrollment in future research activities.

Selective electrical stimulation with current-field modulation

Abstract Selective electrical stimulation using a multielectrode array is a promising technique that can potentially bring electrical stimulation treatment modalities a step forward. A microcontroller-controlled electrical stimulator system delivering a single pulse was designed, suitable for current-field modulation. The goal is to make electrical stimulation with surface electrodes more specific. A graphical user interface (GUI) was developed to control stimulation parameters and current-field within a multi-electrode array wirelessly. The stimulator generates arbitrary biphasic waveforms with a 5-bit resolution and high temporal precision (<10 μs) and was demonstrated to stimulate posterior lumbar root fibers in transcutaneous spinal cord stimulation (tSCS) treatment selectively. Current-field modulation throughout a sixteen-electrode array was achieved. The system has the goal to improve control of stimulation conditions in electrophysiological studies and time-dependent and site-specific stimulation patterns for neuromodulation applications. A novel feature is the current-field modulation ability of the stimulator for surface electrode arrays.

Neurophysiological Factors Affecting Muscle Innervation Zone Estimation Using Surface EMG: A Simulation Study.

Surface electromyography (EMG) recorded by a linear or 2-dimensional electrode array can be used to estimate the location of muscle innervation zones (IZ). There are various neurophysiological factors that may influence surface EMG and thus potentially compromise muscle IZ estimation. The objective of this study was to evaluate how surface-EMG-based IZ estimation might be affected by different factors, including varying degrees of motor unit (MU) synchronization in the case of single or double IZs. The study was performed by implementing a model simulating surface EMG activity. Three different MU synchronization conditions were simulated, namely no synchronization, medium level synchronization, and complete synchronization analog to M wave. Surface EMG signals recorded by a 2-dimensional electrode array were simulated from a muscle with single and double IZs, respectively. For each situation, the IZ was estimated from surface EMG and compared with the one used in the model for performance evaluation. For the muscle with only one IZ, the estimated IZ location from surface EMG was consistent with the one used in the model for all the three MU synchronization conditions. For the muscle with double IZs, at least one IZ was appropriately estimated from interference surface EMG when there was no MU synchronization. However, the estimated IZ was different from either of the two IZ locations used in the model for the other two MU synchronization conditions. For muscles with a single IZ, MU synchronization has little effect on IZ estimation from electrode array surface EMG. However, caution is required for multiple IZ muscles since MU synchronization might lead to false IZ estimation.