Silicon-based Microelectrode Array Research Articles

Recent Development of Neural Microelectrodes with Dual-Mode Detection

Neurons communicate through complex chemical and electrophysiological signal patterns to develop a tight information network. A physiological or pathological event cannot be explained by signal communication mode. Therefore, dual-mode electrodes can simultaneously monitor the chemical and electrophysiological signals in the brain. They have been invented as an essential tool for brain science research and brain-computer interface (BCI) to obtain more important information and capture the characteristics of the neural network. Electrochemical sensors are the most popular methods for monitoring neurochemical levels in vivo. They are combined with neural microelectrodes to record neural electrical activity. They simultaneously detect the neurochemical and electrical activity of neurons in vivo using high spatial and temporal resolutions. This paper systematically reviews the latest development of neural microelectrodes depending on electrode materials for simultaneous in vivo electrochemical sensing and electrophysiological signal recording. This includes carbon-based microelectrodes, silicon-based microelectrode arrays (MEAs), and ceramic-based MEAs, focusing on the latest progress since 2018. In addition, the structure and interface design of various types of neural microelectrodes have been comprehensively described and compared. This could be the key to simultaneously detecting electrochemical and electrophysiological signals.

Investigation of displacement of intracranial electrode induced by focused ultrasound stimulation.

Transcranial focused ultrasound (tFUS) is an emerging neuromodulation technique to modulate brain activity non-invasively with high spatial specificity and focality. Given the influence of tFUS on brain activity, combining tFUS with multi-channel intracranial electrophysiological recordings enables monitoring of the activity of large populations of neurons with high temporal resolution. However, the physical interactions between tFUS and the electrode may affect a reliable assessment of neuronal activity, which remains poorly understood. In this paper, high-frequency ultrasound (HFUS) system was developed and integrated into tFUS neuromodulation system. The performance of the HFUS-based displacement tracking and analysis was evaluated by the theoretical analysis in the literature. The effects of various pressure levels on the displacements of the silicon-based microelectrode array in ex vivo brain tissue were investigated. The developed approach was capable of tracking and measuring the motion of a solid sphere in a tissue-mimicking phantom and measured displacements were comparable to theoretical predictions. The significant changes in the averaged peak displacements of the microelectrode array in ex vivo brain were observed with a pulse duration of 200 μs and a peak-to-peak pressure from 131 kPa at a center frequency of 500 kHz compared with the values from the negative control group. The present results demonstrate the relationship between several pressure levels and displacements of the microelectrode array in ex vivo brain through the developed approach. This approach can be used to determine a vibration-free threshold of ultrasound parameters in multi-channel intracranial recordings for a reliable assessment of electrophysiological activities of living neurons.

Active Temperature Regulation and Teamed Boronate Affinity-Facilitated Microelectrode Module for Blood Glucose Detection in Physiological Environment

Physiological environment analysis is highly important to accurate detection of biological samples. In this work, a teamed boronate affinity-based molecular imprinting microelectrode module (MEM) with active temperature regulation was prepared for blood glucose detection in physiological environment. A silicon-based microelectrode array was utilized as working electrode, and arc-shaped electrodes on a printed circuit board contributed to a compact tri-electrode system. This module integrates a thermistor and a semiconductor cooler/heater, enabling active temperature regulation. Blood glucose were analyzed at physiological temperature. Physiological temperature retained primitiveness and avoided changing physicochemical properties of blood glucose. Meanwhile, constant temperature provided a constant adsorption capacity of functional materials towards glucose. Functional electrode materials, aminoferrocene-modified multi-walled carbon nanotubes (MWCNTs-AFC) and teamed boronate affinity-based molecular imprinting polymers modified multi-walled carbon nanotubes (MWCNTs-TBA-MIPs), were filled in the measurement cell to form MWCNTs-TBA-MIPs/AFC MEM. MWCNTs-TBA-MIPs/AFC MEM detected glucose in physiological environment within 10 min and possessed a wide linear range (1 ∼ 180 μM) and a low LOD (0.61 μM). With MWCNTs-TBA-MIPs/AFC MEM, blood glucose was determined selectively, eliminating the interferences from other co-existing molecules. Moreover, MWCNTs-TBA-MIPs/AFC MEM was employed to accurately measure the blood glucose in human serum, revealing its potential for biochemical detection.

An implantable multifunctional neural microprobe for simultaneous multi-analyte sensing and chemical delivery.

A multifunctional chemical neural probe fabrication process exploiting PDMS thin-film transfer to incorporate a microfluidic channel onto a silicon-based microelectrode array (MEA) platform, and enzyme microstamping to provide multi-analyte detection is described. The Si/PDMS hybrid chemtrode, modified with a nano-based on-probe IrOx reference electrode, was validated in brain phantoms and in rat brain.

A silicon-based microelectrode array with a microdrive for monitoring brainstem regions of freely moving rats

Objective. Exploring neural activity behind synchronization and time locking in brain circuits is one of the most important tasks in neuroscience. Our goal was to design and characterize a microelectrode array (MEA) system specifically for obtaining in vivo extracellular recordings from three deep-brain areas of freely moving rats, simultaneously. The target areas, the deep mesencephalic reticular-, pedunculopontine tegmental-and pontine reticular nuclei are related to the regulation of sleep-wake cycles. Approach. The three targeted nuclei are collinear, therefore a single-shank MEA was designed in order to contact them. The silicon-based device was equipped with 3 × 4 recording sites, located according to the geometry of the brain regions. Furthermore, a microdrive was developed to allow fine actuation and post-implantation relocation of the probe. The probe was attached to a rigid printed circuit board, which was fastened to the microdrive. A flexible cable was designed in order to provide not only electronic connection between the probe and the amplifier system, but sufficient freedom for the movements of the probe as well. Main results. The microdrive was stable enough to allow precise electrode targeting into the tissue via a single track. The microelectrodes on the probe were suitable for recording neural activity from the three targeted brainstem areas. Significance. The system offers a robust solution to provide long-term interface between an array of precisely defined microelectrodes and deep-brain areas of a behaving rodent. The microdrive allowed us to fine-tune the probe location and easily scan through the regions of interest.

Durability of high surface area platinum deposits on microelectrode arrays for acute neural recordings

The durability of high surface area platinum electrodes during acute intracerebral measurements was investigated. Electrode sites with extremely rough surfaces were realized using electrochemical deposition of platinum onto silicon-based microelectrode arrays from a lead-free platinizing solution. The close to 1000-fold increase in effective surface area lowered impedance, its absolute value at 1kHz became about 7 and 18% of the original Pt electrodes in vitro and in vivo, respectively. 24-channel probes were subjected to 12 recording sessions, during which they were implanted into the cerebrum of rats. Our results showed that although on the average the effective surface area of the platinized sites decreased, it remained more than two orders of magnitude higher than the average effective surface area of the original, sputtered thin-film platinum electrodes. Sites with electrochemical deposits proved to be superior, e.g. they provided less thermal and 50Hz noise, even after 12 penetrations into the intact rat brain.

A compact neural recording interface based on silicon microelectrode

A prototype of hybrid neural recording interface has been developed for extracellular neural recording. It consists of a silicon-based plane microelectrode array and a CMOS low noise neural amplifier chip. The neural amplifier chip is designed and implemented in 0.18 μm N-well CMOS 1P6M technology. The area of the neural preamplifier is only 0.042 mm2 with a gain of 48.3 dB. The input equivalent noise is 4.73 μVrms within pass bands of 4 kHz. To avoid cable tethering for high dense multichannel neural recording interface and make it compact, flip-chip bonding is used to integrate the preamplifier chip and the microelectrode together. The hybrid device measures 3 mm×5.5 mm×330 μm, which is convenient for implant or in-vivo neural recording. The hybrid device was testified in in-vivo experiment. Neural signals were recorded from hippocampus region of anesthetized Sprague Dawley rats successfully.

An implantable wireless neural interface for recording cortical circuit dynamics in moving primates

Objective. Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims and those living with severe neuromotor disease. Such systems must be chronically safe, durable and effective. Approach. We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based microelectrode array via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1 Hz to 7.8 kHz, 200× gain) and multiplexed by a custom application specific integrated circuit, digitized and then packaged for transmission. The neural data (24 Mbps) were transmitted by a wireless data link carried on a frequency-shift-key-modulated signal at 3.2 and 3.8 GHz to a receiver 1 m away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7 h continuous operation between recharge via an inductive transcutaneous wireless power link at 2 MHz. Main results. Device verification and early validation were performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance. We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight into how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions and will advance brain research.

Design and Implementation Challenges of Microelectrode Arrays: A Review

The emerging field of neuroprosthetics is focused on design and implementation of neural prostheses to restore some of the lost neural functions. Remarkable progress has been reported at most bioelectronic levels—particularly the various brain-machine interfaces (BMIs)—but the electrode-tissue contacts (ETCs) remain one of the major obstacles. The success of these BMIs relies on electrodes which are in contact with the neural tissue. Biological response to chronic implantation of Microelectrode arrays (MEAs) is an essential factor in determining a successful electrode design. By altering the material compositions and geometries of the arrays, fabrication techniques of MEAs insuring these ETCs try to obtain consistent recording signals from small groups of neurons without losing microstimulation capabilities, while maintaining low-impedance pathways for charge injection, high-charge transfer, and high-spatial resolution in recent years. So far, none of these attempts have led to a major breakthrough. Clearly, much work still needs to be done to accept a standard model of MEAs for clinical purposes. In this paper, we review different microfabrication techniques of MEAs with their advantages and drawbacks, and comment on various coating materials to enhance electrode performance. Then, we propose high-density, three-dimensional (3D), silicon-based MEAs using micromachining methods. The geometries that will be used include arrays of penetrating variable-height probes.

In vivo validation of custom-designed silicon-based microelectrode arrays for long-term neural recording and stimulation.

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays' insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays' recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation.

Silicon-based microelectrode arrays for stimulation and signal recording of in vitro cultured neurons

Microelectrode arrays (MEAs) for stimulation and signal recording of in vitro cultured neurons are presented. Each MEA is composed of 60 independent electrodes with 59 working ones and one reference one. These electrodes are divided into 30 pairs. Through each pair of electrodes, four independent states can be realized to define the accessing modes of neurons cultured on the surface of the electrodes. A total MEA covers an area of 10 mm×10 mm. MEAs are fabricated in a silicon-based semiconductor process. An implemented MEA is bonded on a specially designed printed-circuit-board (PCB) and surrounded by a culture chamber. An impedance measurement has been made to verify the electrical characteristics of MEAs. The surface was modified to enhance the biocompatibility. A series of PC12 cells culture experiments validates the effectiveness of the modification. An extracellular signal recording experiment with acetylcholine (Ach) as a stimulant has been carried out, and the results show the feasibility of MEAs for extracellular action potential recording. Extracellular electrical stimulation and recording experiments have been carried out too. They indicate that MEAs can be used for extracellular stimulation, recording, simultaneous stimulation and recording, and isolation of PC12 cells network cultured in vitro.

High channel count electrode system to investigate thalamocortical interactions

A novel silicon-based microelectrode array with one- and two-dimensional variants was developed in the framework of the EU-funded research project NeuroProbes. The electrode array comprises complementary-metal-oxide-semiconductor based integrated circuitry to implement the concept of electronic depth control which is used to select up to 32 recording sites from more than 1000 possible electrode channels integrated on four slender probe shafts. The electrode array was tested in acute experiments performed simultaneously in cortex and thalamus of the rat brain. In both brain regions good quality local field potential and multiunit activity was recorded during the tests.

Development of silicon-based microelectrode array

This paper introduces in details a kind of silicon-based microelectrode array. MEMS (micro-electromechanical system) technology is used in the fabrication of the microelectrode array, which is designed to perform signal recording and electrical stimulation for nerves in neural engineering. A simple fabrication process is developed. An improved model of microelectrodes is brought forward and successfully validated by the excellent match between circuit simulations and electrical measurements, including both magnitude and phase of microelectrode impedance. Compared with the simple one that is usually used, the improved model is believed to be an advance and more accurate. This modeling helps to improve the design of microelectrodes and understand the behavior of interface between electrode and cell. Furthermore, the microelectrode is proved to be a feasible tool for researches in neural engineering by successfully recording neural activities of sciatic nerve of a bullfrog.

Electrokinetic Alignment of Polymer Microspheres for Biomedical Applications

AbstractOne of the applications of clinical proteomics is the development of protein sensor platform technologies for rapid bedside detection of disease biomarkers. Multiplexed protein biomarker analysis is a new way to predict the disease earlier and monitor its progress with more specificity and accuracy. We present here the development of a prototype electrical protein biomarker detection system. It comprises of a silicon based microelectrode array also known as the sensor chip. Polystyrene beads act as the carriers or transportation agents for the proteins and provide surface area for immobilizing protein receptors (antibodies) on the surface of the sensor chip. Polystyrene “microbridge” structures are patterned on the surface of the sensor chip, such that they form conductive paths between the selected electrodes. This is achieved by the electrokinetic assembly of the antibody functionalized polystyrene beads. The electrical assembly is achieved using dielectrophoresis. The “microbridge” structures couple signals arising due to the antibody-antigen binding event that occurs when the test sample is flowed on to the sensor platform. We demonstrate the functioning of this device in the detection for an inflammation marker, namely, C-reactive protein at microgram/ml sensitivity.

Voltammetric characterisation of silicon-based microelectrode arrays and their application to mercury-free stripping voltammetry of copper ions

This paper describes the electrochemical characterisation of a range of gold and platinum microelectrode arrays (MEAs) fabricated by standard photolithographic methods. The inter-electrode spacing, geometry, numbers and dimensions of the electrodes in the arrays were found to influence the voltammetric behaviours obtained. Excellent correlation was found between experimental data and theoretical predictions employing published models of microelectrode behaviour. Gold MEAs were evaluated for their applicability to copper determination in a soil extract sample, where agreement was found between the standard analytical method and a method based on underpotential deposition—anodic stripping voltammetry (UPD-ASV) at the MEAs, offering a mercury-free alternative for copper sensing.

Development of a chipscale integrated microelectrode/microelectronic device for brain implantable neuroengineering applications

An ultralow power analog CMOS chip and a silicon based microelectrode array have been fully integrated to a microminiaturized "neuroport" for brain implantable neuroengineering applications. The CMOS integrated circuit (IC) includes preamplifier and multiplexing circuitry, and a hybrid flip-chip bonding technique was developed to fabricate a functional, encapsulated microminiaturized neuroprobe device. Our neuroport has been evaluated using various methods, including pseudospike detection and local excitation measurement, and showed suitable characteristics for recording neural activities. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, suggesting that the new neuroport can form a prime platform for the development of a microminiaturized neural interface to the brain in a single implantable unit. An alternative power delivery scheme using photovoltaic power converter, and an encapsulation strategy for chronic implantation are also discussed.

A Microelectrode/Microelectronic Hybrid Device for Brain Implantable Neuroprosthesis Applications

We have designed, fabricated, and characterized a microminiaturized "neuroport" for brain implantable neuroprosthesis applications, using an analog CMOS integrated circuit and a silicon based microelectrode array. An ultra-low power, low-noise CMOS preamplifier array with integral multiplexing was designed to accommodate stringent thermal and electrophysiological requirements for implantation in the brain, and a hybrid integration approach was developed to fabricate a functional microminiaturized neuroprobe device. Measurements showed that our fully scalable 16-channel CMOS amplifier chip had an average gain of 44 dB, bandwidth from 10 Hz to 7.3 kHz, and an equivalent input noise of approximately 9 microVrms with an average power consumption per preamplifier of 52 microW, which is consistent with simulation results. As a proof-of-concept demonstration, we have measured local field potentials from thalamocortical brain slices of rats, showing oscillatory behavior with an amplitude about 0.5 mV and a period ranging 80-120 ms. The results suggest that the hybrid integrated neuroport can form a prime platform for the development of a next level microminiaturized neural interface to the brain in a single implantable unit.

Optimization of passivation layers for corrosion protection of silicon-based microelectrode arrays

The protectivity of passivation layers decides on the lifetime of silicon-based sensor chips in liquid and corrosive media. In this study the barrier effect of different organic (spin-coated) and inorganic (PECVD) thin films in brine was investigated using a microelectrode array as a microsensor model. The corrosion resistance of the microelectrode array was optimized by using buried conducting tracks and duplex (SiO 2/Si 3N 4) or triplex (SiO 2/Si 3N 4/SiO 2) layers instead of inorganic monolayers. The failure mechanisms were investigated with respect to physical and mechanical effects, and corrosive attack.

A silicon-based microelectrode array for chemical analysis

A silicon-based microelectrode array consisting of various electrode shapes and sizes has been developed. This model sensor array allows a systematic study of three important aspects of electrochemical sensing: the influence of the electrode geometries and the passivation materials on corrosion effects and kinetics, the application of thin gold film electrodes for the trace analysis of heavy metals, and the galvanic modification of single microelectrodes.

Microfabricated Ultramicroelectrode Arrays: Developments, Advances, and Applications in Environmental Analysis

The wider availability of microlithographic techniques for the fabrication of electrochemical devices has led to a significant increase in the development of microfabricated arrays of microelectrodes and their use in a wide variety of analytical problems. The major microfabrication steps and the capabilities and limitations of this microsensor technology are reviewed in this article. Several examples are summarized to illustrate the breadth of work with silicon-based microelectrode arrays, with special emphasis on their use for environmental analysis in a range of diverse settings including remote electroanalysis on Mars.