The subsecond, temporal, vesicular exocytosis is ubiquitous, but difficult detecting in communication mechanisms of cells. A microelectrode array （MEA）, fabricated by MEMS technology, was applied successfully for re...The subsecond, temporal, vesicular exocytosis is ubiquitous, but difficult detecting in communication mechanisms of cells. A microelectrode array （MEA）, fabricated by MEMS technology, was applied successfully for real-time monitoring of quantal exocytosis from single pheochromocytoma （PC12） cell, The developed MEA was evaluated by dopamine （DA） using electrochemical methods and the results revealed that the sensitivity of DA was improved to 12659.24 p.A L mmol 1 cm 2. The modified MEA was used to detect in vitro vesicular exocytosis of DA from single PCI 2 cells stimulated by concentrated 100 mmol L-1 K＋ cell solution. A total of 592 spikes were measured and analyzed by three parameters and the statistical results revealed the population of each parameter was an approximate Gaussian distribution, and on average, 1.31 × 106 ± 9.25× 104 oxidizable molecules were released in each quantal exocytosis. In addition, results also indicate that a single PC12 cell probably releases the spikes with T ranging from 25.6 ms to 35.4 ms corresponding to/max ranging from 45.6 pA to 65.2 pA. The devices, including a homemade computer interface and the MEA modified with polymer film, provides a new means for further research on the neural, intercellular, communication mechanism.展开更多
A microelectrode array（MEA） is presented, which is composed of 60 independent electrodes with 59 working ones and one reference one, and they are divided into 30 pairs. Except for the reference electrode, each pair ...A microelectrode array（MEA） is presented, which is composed of 60 independent electrodes with 59 working ones and one reference one, and they are divided into 30 pairs. Except for the reference electrode, each pair consists of one stimulating electrode and one recording electrode. Supported by the peripheral circuits, four electrode states to study the bioelectrical signal of biological tissue or slice cultured in-vitro on the surface of the electrodes can be realized through each pair of electrodes. The four electrode states are stimulation, recording, stimulation and recording simultaneously, and isolation. The state of each pair of working electrodes can be arbitrarily controlled according to actual needs. The MEAs are fabricated in printed circuit board （PCB） technology. The total area of the PCB-based MEA is 49 mm × 49 mm. The impedance measurement of MEA is carried out in 0.9% sodium chloride solution at room temperature by means of 2-point measurements with an Agilent LCR meter, and the test signal for the impedance measurement is sinusoidal （AC voltage 50 mV, sweeping frequency 20 Hz to 10 kHz）. The electrode impedance is between 200 and 3 kΩ while the frequency is between 500 and 1 000 Hz. The electrode impedance magnitude is inversely proportional to the frequency. Experiments of toad sciatic nerve in-vitro stimulation and recording and signal regeneration between isolated toad sciatic nerves are carried out on the PCB-based MEA. The results show that the MEA can be used for bioelectrical signal stimulation, recording, stimulation and recording simultaneously, and isolation of biological tissues or slices in-vitro.展开更多
A neuronal signal detecting circuit and a neuronal signal stimulating circuit designed for a monolithic integrated MEA（micro-electrode array） system are described. As a basic cell of the circuits, an OPA（ operation...A neuronal signal detecting circuit and a neuronal signal stimulating circuit designed for a monolithic integrated MEA（micro-electrode array） system are described. As a basic cell of the circuits, an OPA（ operational amplifier） is designed with low power, low noise, small size and high gain. The detecting circuit has a chip area of 290 μm × 400 μm, a power dissipation of 2.02 mW, an equivalent input noise of 17.72 nV/ Hz, a gain of 60. 5 dB, and an output voltage from - 2. 48 to ＋ 2. 5 V. The stimulating circuit has a chip area of 130 μm × 290 μm, a power dissipation of 740 μW, and an output voltage from - 2. 5 to 2. 04 V. The parameters show that two circuits are suitable for a monolithic integrated MEA system. The detecting circuit and MEA have been fabricated. The test results show that the detecting circuit works well.展开更多
Neuronal connections can be detected by neuronal network discharges in hippocampal neurons cultured on multi-electrodes.However,the multi-electrode-array（MEA）has not been widely used in hippocampal slice culture stu...Neuronal connections can be detected by neuronal network discharges in hippocampal neurons cultured on multi-electrodes.However,the multi-electrode-array（MEA）has not been widely used in hippocampal slice culture studies focused on epilepsy.The present study induced spontaneous synchronous epileptiform activity using low Mg2＋artificial cerebrospinal fluid on acute hippocampal slices to record hippocampal discharges with MEA.Results showed that burst duration and average number of spikes in a burst were significantly greater in the CA3 compared with dentate gyrus and CA1 areas.In Schaffer cut-off group,CA1 area discharges disappeared,but synchronous discharges remained in the CA3 area.Moreover,synchronous discharge frequency in the Schaffer cut-off group was similar to control.However,burst duration and average number of spikes in a burst were significantly decreased compared with control（P 〈 0.05）.Results demonstrated that highest neuronal excitability occurred in the CA3 area,and synchronous discharges induced by low Mg2＋originated from the CA3 region.展开更多
Qualitative and quantitative analysis of trace heavy metals in aqueous environment are rapidly assuming significance along with the rapid development of industry.In this paper,gold microelectrode array(MEA)plated with...Qualitative and quantitative analysis of trace heavy metals in aqueous environment are rapidly assuming significance along with the rapid development of industry.In this paper,gold microelectrode array(MEA)plated with mercury film was used for simultaneous voltammetric detection of zinc,cadmium,lead and copper ions in water.The electrochemical behavior and the actual surface area of the MEA were investigated by cyclic voltammetry in K_(3)[Fe(CN)_(6)].Electrochemical impedance spectrum(EIS)was utilized to examine the deposition of mercury on the electrode surface.Based on anodic stripping voltammetry,mercury filmAu MEA was applied to the detection of heavy metals in artificial analyte,where good calibrate linearity was obtained for cadmium,lead and copper ions,but with zinc exhibiting poor linearity.展开更多
Conducting polymers have been studied extensively. An interesting property of the conducting polymer is that the conductivity of some polymers, such as polypyrrolc, polyaniline, poly(3-methylthiophene) etc. , is affec...Conducting polymers have been studied extensively. An interesting property of the conducting polymer is that the conductivity of some polymers, such as polypyrrolc, polyaniline, poly(3-methylthiophene) etc. , is affected by the voltage applied to them. For polypyrrole, the oxidized state is an electronic conductor and the reduced state is essentially insulating. Using this property, one can fabricate the polymer-based electronic devices. Experimental results of Pickun展开更多
Most biological tissues are supple and elastic, while current electronic devices fabricated by semiconductors and metals are usually stiff and brittle. As a result, implanted electronic devices can irritate and damage...Most biological tissues are supple and elastic, while current electronic devices fabricated by semiconductors and metals are usually stiff and brittle. As a result, implanted electronic devices can irritate and damage surrounding tissues, causing immune reaction and scarring. In this work, we develop stretchable microelectrode arrays, with the development of a novel soft lithography technology, which are designed and fabricated with a polymer/stretchable metal/polymer sandwich structure. With the great deformability of stretch, compression, bend and twisting, while preserving electrical property, this technology overcomes the fundamental mismatch of mechanical properties between biological tissues and electronic devices, and provides highly-compliant, confonnal and stretchable bio-electronic interfaces. Here we also describe the following three applications of the stretchable electrode arrays： a. monitoring intracranial electroencephalography （EEG）; b. stimulating peripheral nerves to drive muscles; c. monitoring epicardial electrocardiography （ECG）. Stretchable microelectrode arrays create a promising field in biomedical applications for its better modulus match with biological tissues and robust mechanical and electrical properties. They allow for construction of electronic integrated circuits spread over on complex and dynamic curved surfaces, providing a much friendlier bio-electronic interface for diagnosis, treatment and in- telligent bio-control.展开更多
Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Adv...Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.展开更多
Magnesium （Mg）-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg2. and the corrosion products from Mg-based biomaterials, particularly their effec...Magnesium （Mg）-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg2. and the corrosion products from Mg-based biomaterials, particularly their effects on neurons, have been little studied. Although viability tests are most commonly used, a functional evaluation is critically needed. Here, both methyl thiazolyl tetrazolium （MTT） and lactate de- hydrogenase （LDH） assays were used to test the effect of Mg2. and Mg-extract solution on neuronal viability. Microelectrode arrays （MEAs）, which provide long-term, real-time recording of extracellular electro- physiological signals of in vitro neuronal networks, were used to test for toxic effects. The minimum effective concentrations （ECmin） of Mg2. from the MTr and LDH assays were 3 mmol/L and 100 mmol/L respec- tively, while the ECmin obtained from the MEA assay was 0.1 mmol/L MEA data revealed significant loss of neuronal network activity when the culture was exposed to 25% Mg-extract solution, a concentra- tion that did not affect neuronal viability. For evaluating the biocompatibility of Mg-based biomaterials with neurons, MEA electrophysiological testing is a more precise method than basic cell-viability testing.展开更多
To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip...To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.展开更多
An automatic monitoring electronic tongue based on differential pulse stripping voltammetry (DPSV) was developed for heavy metals analysis.Simultaneous detections of trace Zn(Ⅱ),Cd(Ⅱ),Pb(Ⅱ),Cu(Ⅱ),Fe(Ⅲ) and Cr(Ⅲ)...An automatic monitoring electronic tongue based on differential pulse stripping voltammetry (DPSV) was developed for heavy metals analysis.Simultaneous detections of trace Zn(Ⅱ),Cd(Ⅱ),Pb(Ⅱ),Cu(Ⅱ),Fe(Ⅲ) and Cr(Ⅲ) in water samples were performed with three electrochemical sensors.The sensor chip combined a silicon-based Hg-coated Au microelectrode array (MEA) as the working electrode on one side with an Ag/AgCl reference electrode and a Pt counter electrode on the other side.With a computer controlled multipotentiostat,pumps and valves,the electronic tongue realized in-situ real-time detection of the six metals mentioned above at parts-per-billion level without manual operation.展开更多
The electrical excitability of neural networks is influenced by different environmental factors. Effective and simple methods are required to objectively and quantitatively evaluate the influence of such factors, incl...The electrical excitability of neural networks is influenced by different environmental factors. Effective and simple methods are required to objectively and quantitatively evaluate the influence of such factors, including variations in temperature and pharmaceutical dosage. The aim of this paper was to introduce ‘the voltage threshold measurement method＇, which is a new method using microelectrode arrays that can quantitatively evaluate the influence of different factors on the electrical excitability of neural networks. We sought to verify the feasibility and efficacy of the method by studying the effects of acetylcholine, ethanol, and temperature on hippocampal neuronal networks and hippocampal brain slices. First, we determined the voltage of the stimulation pulse signal that elicited action potentials in the two types of neural networks under normal conditions. Second, we obtained the voltage thresholds for the two types of neural networks under different concentrations of acetylcholine, ethanol, and different temperatures. Finally, we obtained the relationship between voltage threshold and the three influential factors. Our results indicated that the normal voltage thresholds of the hippocampal neuronal network and hippocampal slice preparation were 56 and 31 m V, respectively. The voltage thresholds of the two types of neural networks were inversely proportional to acetylcholine concentration, and had an exponential dependency on ethanol concentration. The curves of the voltage threshold and the temperature of the medium for the two types of neural networks were U-shaped. The hippocampal neuronal network and hippocampal slice preparations lost their excitability when the temperature of the medium decreased below 34 and 33°C or increased above 42 and 43°C, respectively. These results demonstrate that the voltage threshold measurement method is effective and simple for examining the performance/excitability of neuronal networks.展开更多
Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefront...Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefrontal cortex is essential for various cognitive and motor functions,yet high-spatiotemporal-resolution electrodes at the cellular level remain challenging to develop,which has hindered the acquisition of detailed electrophysiological data from anesthetized subjects.Here,we design a 16-channel silicon-based microelectrode array(MEA),which,after modification with platinum black nanoparticles,exhibits significantly reduced impedance(22.5 kΩ)and increased phase(−33.5°),enhancing its electrical performance and electrophysiological signal detection capabilities.Using this modified MEA,we have recorded cellular-level neural activity during the recovery process of a rhesus macaque following prolonged anesthesia.Over a 660 s period,we observed a gradual increase in the neuronal firing rate in the F7 area,along with distinctive patterns in local field potentials across different frequency bands.Notably,power in the δ and θ bands increased continuously during recovery,highlighting their potential role in the transition from anesthesia to wakefulness.Our findings provide new insights into the dynamic recovery process of cortical neurons and offer a powerful tool for high-spatiotemporal-resolution neural monitoring in nonhuman primates.展开更多
Microelectrode arrays(MEAs)are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format.However,they typically lack the capability to record intracellular action pot...Microelectrode arrays(MEAs)are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format.However,they typically lack the capability to record intracellular action potentials(APs).Recent studies have relied on costly fabrication of high-resolution microelectrodes combined with electroporation for intracellular recordings,but the impact of microelectrode size on micro-electroporation and the quality of intracellular signal acquisition has yet to be explored.Understanding these effects could facilitate the design of microelectrodes of various sizes to enable lower-cost manufacturing processes.In this study,we investigated the influence of microelectrode size on intracellular AP parameters and recording metrics post-micro-electroporation through simulations and experiments.We fabricated microelectrodes of different sizes using standard photolithography techniques to record cardiomyocyte APs from various culture environments with coupled micro-electroporation.Our findings indicate that larger microelectrodes generally recorded electrophysiological signals with higher amplitude and better signal-to-noise ratios,while smaller electrodes exhibited higher perforation efficiency,AP duration,and single-cell signal ratios.This work demonstrates that the micro-electroporation technique can be applied to larger microelectrodes for intracellular recordings,rather than being limited to high-resolution designs.This approach may provide new opportunities for fabricating microelectrodes using alternative low-cost manufacturing techniques for high-quality intracellular AP recordings.展开更多
Intracortical neural interfaces directly connect brain neurons with external devices to achieve high temporal resolution and spatially precise sampling of neural activity.When applied to freely moving animals,this tec...Intracortical neural interfaces directly connect brain neurons with external devices to achieve high temporal resolution and spatially precise sampling of neural activity.When applied to freely moving animals,this technology provides in-depth insight into the underlying neural mechanisms for their movement and cognition in real-world scenarios.However,the application of implanted devices in freely moving animals is limited by restrictions on their behavioral freedom and physiologic impact.In this paper,four technological directions for ideal implantable neural interface devices are analyzed:higher spatial density,improved biocompatibility,enhanced multimodal detection of electrical/neurotransmitter signals,and more effective neural modulation.Finally,we discuss how these technological developments have been applied to freely moving animals to provide better insight into neuroscience and clinical medicine.展开更多
A two-dimensional （2D） multi-channel silicon-based microelectrode array is developed for recording neural signals. Three photolithographic masks are utilized in the fabrication process. SEM images show that the micr...A two-dimensional （2D） multi-channel silicon-based microelectrode array is developed for recording neural signals. Three photolithographic masks are utilized in the fabrication process. SEM images show that the microprobe is 1.2mm long, 100μm wide,and 30μm thick,with recording sites spaced 200μm apart for good signal isolation. For the individual recording sites, the characteristics of impedance versus frequency are shown by in vitro testing. The impedance declines from 14MΩ to 1.9kΩ as the frequency changes from 0 to 10MHz. A compatible PCB （print circuit board） aids in the less troublesome implantation and stabilization of the microprobe.展开更多
基金sponsored by the NSFC (Nos. 61527815, 61471342, 31500800, 61501426)the Beijing Municipal Science & Technology Commission (No. Z141100000214002)the Major National Scientific Research Plan (No. 2014CB74465)
文摘The subsecond, temporal, vesicular exocytosis is ubiquitous, but difficult detecting in communication mechanisms of cells. A microelectrode array （MEA）, fabricated by MEMS technology, was applied successfully for real-time monitoring of quantal exocytosis from single pheochromocytoma （PC12） cell, The developed MEA was evaluated by dopamine （DA） using electrochemical methods and the results revealed that the sensitivity of DA was improved to 12659.24 p.A L mmol 1 cm 2. The modified MEA was used to detect in vitro vesicular exocytosis of DA from single PCI 2 cells stimulated by concentrated 100 mmol L-1 K＋ cell solution. A total of 592 spikes were measured and analyzed by three parameters and the statistical results revealed the population of each parameter was an approximate Gaussian distribution, and on average, 1.31 × 106 ± 9.25× 104 oxidizable molecules were released in each quantal exocytosis. In addition, results also indicate that a single PC12 cell probably releases the spikes with T ranging from 25.6 ms to 35.4 ms corresponding to/max ranging from 45.6 pA to 65.2 pA. The devices, including a homemade computer interface and the MEA modified with polymer film, provides a new means for further research on the neural, intercellular, communication mechanism.
基金The National Natural Science Foundation of China(No. 61076118, 90307013, 90707005)the Natural Science Foundation of Jiangsu Province (No. BK2008032)Special Foundation and Open Foundation of the State Key Laboratory of Bioelectronics of Southeast University
文摘A microelectrode array（MEA） is presented, which is composed of 60 independent electrodes with 59 working ones and one reference one, and they are divided into 30 pairs. Except for the reference electrode, each pair consists of one stimulating electrode and one recording electrode. Supported by the peripheral circuits, four electrode states to study the bioelectrical signal of biological tissue or slice cultured in-vitro on the surface of the electrodes can be realized through each pair of electrodes. The four electrode states are stimulation, recording, stimulation and recording simultaneously, and isolation. The state of each pair of working electrodes can be arbitrarily controlled according to actual needs. The MEAs are fabricated in printed circuit board （PCB） technology. The total area of the PCB-based MEA is 49 mm × 49 mm. The impedance measurement of MEA is carried out in 0.9% sodium chloride solution at room temperature by means of 2-point measurements with an Agilent LCR meter, and the test signal for the impedance measurement is sinusoidal （AC voltage 50 mV, sweeping frequency 20 Hz to 10 kHz）. The electrode impedance is between 200 and 3 kΩ while the frequency is between 500 and 1 000 Hz. The electrode impedance magnitude is inversely proportional to the frequency. Experiments of toad sciatic nerve in-vitro stimulation and recording and signal regeneration between isolated toad sciatic nerves are carried out on the PCB-based MEA. The results show that the MEA can be used for bioelectrical signal stimulation, recording, stimulation and recording simultaneously, and isolation of biological tissues or slices in-vitro.
基金The National Natural Science Foundation of China (No.90307013,90707005)the Natural Science Foundation of Jiangsu Province(No. BK2008032)Open Foundation of State Key Laboratory of Bio-Electronics of Southeast University
文摘A neuronal signal detecting circuit and a neuronal signal stimulating circuit designed for a monolithic integrated MEA（micro-electrode array） system are described. As a basic cell of the circuits, an OPA（ operational amplifier） is designed with low power, low noise, small size and high gain. The detecting circuit has a chip area of 290 μm × 400 μm, a power dissipation of 2.02 mW, an equivalent input noise of 17.72 nV/ Hz, a gain of 60. 5 dB, and an output voltage from - 2. 48 to ＋ 2. 5 V. The stimulating circuit has a chip area of 130 μm × 290 μm, a power dissipation of 740 μW, and an output voltage from - 2. 5 to 2. 04 V. The parameters show that two circuits are suitable for a monolithic integrated MEA system. The detecting circuit and MEA have been fabricated. The test results show that the detecting circuit works well.
文摘Neuronal connections can be detected by neuronal network discharges in hippocampal neurons cultured on multi-electrodes.However,the multi-electrode-array（MEA）has not been widely used in hippocampal slice culture studies focused on epilepsy.The present study induced spontaneous synchronous epileptiform activity using low Mg2＋artificial cerebrospinal fluid on acute hippocampal slices to record hippocampal discharges with MEA.Results showed that burst duration and average number of spikes in a burst were significantly greater in the CA3 compared with dentate gyrus and CA1 areas.In Schaffer cut-off group,CA1 area discharges disappeared,but synchronous discharges remained in the CA3 area.Moreover,synchronous discharge frequency in the Schaffer cut-off group was similar to control.However,burst duration and average number of spikes in a burst were significantly decreased compared with control（P 〈 0.05）.Results demonstrated that highest neuronal excitability occurred in the CA3 area,and synchronous discharges induced by low Mg2＋originated from the CA3 region.
基金This work has been supported by grants from the National Basic Research Program of China(973 program),Grant No.2009CB320303.
文摘Qualitative and quantitative analysis of trace heavy metals in aqueous environment are rapidly assuming significance along with the rapid development of industry.In this paper,gold microelectrode array(MEA)plated with mercury film was used for simultaneous voltammetric detection of zinc,cadmium,lead and copper ions in water.The electrochemical behavior and the actual surface area of the MEA were investigated by cyclic voltammetry in K_(3)[Fe(CN)_(6)].Electrochemical impedance spectrum(EIS)was utilized to examine the deposition of mercury on the electrode surface.Based on anodic stripping voltammetry,mercury filmAu MEA was applied to the detection of heavy metals in artificial analyte,where good calibrate linearity was obtained for cadmium,lead and copper ions,but with zinc exhibiting poor linearity.
基金Supported by the National Natural Science Foundation of China
文摘Conducting polymers have been studied extensively. An interesting property of the conducting polymer is that the conductivity of some polymers, such as polypyrrolc, polyaniline, poly(3-methylthiophene) etc. , is affected by the voltage applied to them. For polypyrrole, the oxidized state is an electronic conductor and the reduced state is essentially insulating. Using this property, one can fabricate the polymer-based electronic devices. Experimental results of Pickun
基金National Natural Science Foundation of China (No. 61102042)Youth Innovation Foundation of Chinese Academy of SciencesShenzhen"Peacock Plan"to Z.Y.
文摘Most biological tissues are supple and elastic, while current electronic devices fabricated by semiconductors and metals are usually stiff and brittle. As a result, implanted electronic devices can irritate and damage surrounding tissues, causing immune reaction and scarring. In this work, we develop stretchable microelectrode arrays, with the development of a novel soft lithography technology, which are designed and fabricated with a polymer/stretchable metal/polymer sandwich structure. With the great deformability of stretch, compression, bend and twisting, while preserving electrical property, this technology overcomes the fundamental mismatch of mechanical properties between biological tissues and electronic devices, and provides highly-compliant, confonnal and stretchable bio-electronic interfaces. Here we also describe the following three applications of the stretchable electrode arrays： a. monitoring intracranial electroencephalography （EEG）; b. stimulating peripheral nerves to drive muscles; c. monitoring epicardial electrocardiography （ECG）. Stretchable microelectrode arrays create a promising field in biomedical applications for its better modulus match with biological tissues and robust mechanical and electrical properties. They allow for construction of electronic integrated circuits spread over on complex and dynamic curved surfaces, providing a much friendlier bio-electronic interface for diagnosis, treatment and in- telligent bio-control.
基金supported by the National Natural Science Foundation of China(Nos.T2293730,T2293731,62121003,61960206012,61973292,62171434,61975206,and 61971400)the National Key Research and Development Program of China(Nos.2022YFC2402501 and 2022YFB3205602)+1 种基金the Major Program of Scientific and Technical Innovation 2030(No.2021ZD02016030)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.GJJSTD20210004).
文摘Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.
基金supported by the National Basic Research Program of China (973 Program,No.2012CB619102)the National Natural Science Foundation of China (Nos.31070847 and 31370956)+3 种基金the National Science and Technology Support Program (No.2012BAI18B01)the Strategic New Industry Development Special Foundation of Shenzhen,China (No.JCYJ20130402172114948)the Guangdong Provincial Department of Science and Technology,China (No.2011B050400011)NIH NIGMS COBRE (No.NIH P20GM103444)
文摘Magnesium （Mg）-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg2. and the corrosion products from Mg-based biomaterials, particularly their effects on neurons, have been little studied. Although viability tests are most commonly used, a functional evaluation is critically needed. Here, both methyl thiazolyl tetrazolium （MTT） and lactate de- hydrogenase （LDH） assays were used to test the effect of Mg2. and Mg-extract solution on neuronal viability. Microelectrode arrays （MEAs）, which provide long-term, real-time recording of extracellular electro- physiological signals of in vitro neuronal networks, were used to test for toxic effects. The minimum effective concentrations （ECmin） of Mg2. from the MTr and LDH assays were 3 mmol/L and 100 mmol/L respec- tively, while the ECmin obtained from the MEA assay was 0.1 mmol/L MEA data revealed significant loss of neuronal network activity when the culture was exposed to 25% Mg-extract solution, a concentra- tion that did not affect neuronal viability. For evaluating the biocompatibility of Mg-based biomaterials with neurons, MEA electrophysiological testing is a more precise method than basic cell-viability testing.
基金sponsored by the National Natural Science Foundation of China (Grant Nos.61960206012,62121003,T2293731,62171434,61975206,61971400,and 61973292)the National Key Research and Development Program of China (Grant Nos.2022YFB3205602 and 2022YFC2402501)+1 种基金Major Program of Scientific and Technical Innovation 2030 (Grant No.2021ZD02016030)the Scientific Instrument Developing Project of the Chinese Academy of Sciences (Grant No.GJJSTD20210004).
文摘To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.
文摘An automatic monitoring electronic tongue based on differential pulse stripping voltammetry (DPSV) was developed for heavy metals analysis.Simultaneous detections of trace Zn(Ⅱ),Cd(Ⅱ),Pb(Ⅱ),Cu(Ⅱ),Fe(Ⅲ) and Cr(Ⅲ) in water samples were performed with three electrochemical sensors.The sensor chip combined a silicon-based Hg-coated Au microelectrode array (MEA) as the working electrode on one side with an Ag/AgCl reference electrode and a Pt counter electrode on the other side.With a computer controlled multipotentiostat,pumps and valves,the electronic tongue realized in-situ real-time detection of the six metals mentioned above at parts-per-billion level without manual operation.
基金supported by the National Natural Sciences Foundation of China,No.61534003,61076118the Innovation Foundation for State Key Laboratory of the Ministry of Science and Technology,China,No.2016-2018a grant from the Open Projects of Key Laboratory of Child Development and Learning of the Ministry of Education of China,No.CDLS201205
文摘The electrical excitability of neural networks is influenced by different environmental factors. Effective and simple methods are required to objectively and quantitatively evaluate the influence of such factors, including variations in temperature and pharmaceutical dosage. The aim of this paper was to introduce ‘the voltage threshold measurement method＇, which is a new method using microelectrode arrays that can quantitatively evaluate the influence of different factors on the electrical excitability of neural networks. We sought to verify the feasibility and efficacy of the method by studying the effects of acetylcholine, ethanol, and temperature on hippocampal neuronal networks and hippocampal brain slices. First, we determined the voltage of the stimulation pulse signal that elicited action potentials in the two types of neural networks under normal conditions. Second, we obtained the voltage thresholds for the two types of neural networks under different concentrations of acetylcholine, ethanol, and different temperatures. Finally, we obtained the relationship between voltage threshold and the three influential factors. Our results indicated that the normal voltage thresholds of the hippocampal neuronal network and hippocampal slice preparation were 56 and 31 m V, respectively. The voltage thresholds of the two types of neural networks were inversely proportional to acetylcholine concentration, and had an exponential dependency on ethanol concentration. The curves of the voltage threshold and the temperature of the medium for the two types of neural networks were U-shaped. The hippocampal neuronal network and hippocampal slice preparations lost their excitability when the temperature of the medium decreased below 34 and 33°C or increased above 42 and 43°C, respectively. These results demonstrate that the voltage threshold measurement method is effective and simple for examining the performance/excitability of neuronal networks.
基金sponsored by the National Key R&D Program of China(Grant Nos.2022YFC2402500 and 2022YFB3205602)the National Natural Science Foundation of China(Grant Nos.62121003,T2293730,T2293731,62333020,62171434,62471291)+2 种基金the Major Program of Scientific and Technical Innovation 2030(Grant No.2021ZD02016030)the Joint Foundation Program of the Chinese Academy of Sciences(Grant No.8091A170201)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(Grant No.PTYQ2024BJ0009).
文摘Anesthesia plays a crucial role in regulating physiological states during medical procedures,but its effects on neural activity remain incompletely understood,particularly at the prefrontal cortical level.The prefrontal cortex is essential for various cognitive and motor functions,yet high-spatiotemporal-resolution electrodes at the cellular level remain challenging to develop,which has hindered the acquisition of detailed electrophysiological data from anesthetized subjects.Here,we design a 16-channel silicon-based microelectrode array(MEA),which,after modification with platinum black nanoparticles,exhibits significantly reduced impedance(22.5 kΩ)and increased phase(−33.5°),enhancing its electrical performance and electrophysiological signal detection capabilities.Using this modified MEA,we have recorded cellular-level neural activity during the recovery process of a rhesus macaque following prolonged anesthesia.Over a 660 s period,we observed a gradual increase in the neuronal firing rate in the F7 area,along with distinctive patterns in local field potentials across different frequency bands.Notably,power in the δ and θ bands increased continuously during recovery,highlighting their potential role in the transition from anesthesia to wakefulness.Our findings provide new insights into the dynamic recovery process of cortical neurons and offer a powerful tool for high-spatiotemporal-resolution neural monitoring in nonhuman primates.
基金financial support from the National Natural Science Foundation of China(Grant No.T2225010,32171399,32171456,62105380)Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515111139)+4 种基金Science and Technology Program of Guangzhou,China(Grant No.2024B03J0121,2024B03J1284)Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.24xkjc011)the Independent Fund of the State Key Laboratory of Optoelectronic Materials and Technologies(Sun Yat-sen University)under grant No.OEMT-2022-ZRC-04Central Nervous System Drug Key Laboratory of Sichuan Province(Grant No.230036-01SZ)Fund of Key Laboratory of Advanced Materials of Ministry of Education(No.Advmat-2416).
文摘Microelectrode arrays(MEAs)are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format.However,they typically lack the capability to record intracellular action potentials(APs).Recent studies have relied on costly fabrication of high-resolution microelectrodes combined with electroporation for intracellular recordings,but the impact of microelectrode size on micro-electroporation and the quality of intracellular signal acquisition has yet to be explored.Understanding these effects could facilitate the design of microelectrodes of various sizes to enable lower-cost manufacturing processes.In this study,we investigated the influence of microelectrode size on intracellular AP parameters and recording metrics post-micro-electroporation through simulations and experiments.We fabricated microelectrodes of different sizes using standard photolithography techniques to record cardiomyocyte APs from various culture environments with coupled micro-electroporation.Our findings indicate that larger microelectrodes generally recorded electrophysiological signals with higher amplitude and better signal-to-noise ratios,while smaller electrodes exhibited higher perforation efficiency,AP duration,and single-cell signal ratios.This work demonstrates that the micro-electroporation technique can be applied to larger microelectrodes for intracellular recordings,rather than being limited to high-resolution designs.This approach may provide new opportunities for fabricating microelectrodes using alternative low-cost manufacturing techniques for high-quality intracellular AP recordings.
基金sponsored by the National Natural Science Foundation of China(62121003,T2293730,T2293731,61960206012,62333020,and 62171434)the National Key Research and Development Program of China(2022YFC2402501 and 2022YFB3205602)the Major Program of Scientific and Technical Innovation 2030(2021ZD02016030)。
文摘Intracortical neural interfaces directly connect brain neurons with external devices to achieve high temporal resolution and spatially precise sampling of neural activity.When applied to freely moving animals,this technology provides in-depth insight into the underlying neural mechanisms for their movement and cognition in real-world scenarios.However,the application of implanted devices in freely moving animals is limited by restrictions on their behavioral freedom and physiologic impact.In this paper,four technological directions for ideal implantable neural interface devices are analyzed:higher spatial density,improved biocompatibility,enhanced multimodal detection of electrical/neurotransmitter signals,and more effective neural modulation.Finally,we discuss how these technological developments have been applied to freely moving animals to provide better insight into neuroscience and clinical medicine.
文摘A two-dimensional （2D） multi-channel silicon-based microelectrode array is developed for recording neural signals. Three photolithographic masks are utilized in the fabrication process. SEM images show that the microprobe is 1.2mm long, 100μm wide,and 30μm thick,with recording sites spaced 200μm apart for good signal isolation. For the individual recording sites, the characteristics of impedance versus frequency are shown by in vitro testing. The impedance declines from 14MΩ to 1.9kΩ as the frequency changes from 0 to 10MHz. A compatible PCB （print circuit board） aids in the less troublesome implantation and stabilization of the microprobe.
