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 s...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,conformal 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 intelligent bio-control.展开更多
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—par...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.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
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
可编程约瑟夫森电压基准(programmable Josephson voltage standard,PJVS)通过生成阶梯波构建交流量子电压,其产生量子电压台阶过程中,会伴生过渡过程,导致电压台阶两端数据的准确性较低。常见的数据处理方法是将过渡过程的数据剔除,仅...可编程约瑟夫森电压基准(programmable Josephson voltage standard,PJVS)通过生成阶梯波构建交流量子电压,其产生量子电压台阶过程中,会伴生过渡过程,导致电压台阶两端数据的准确性较低。常见的数据处理方法是将过渡过程的数据剔除,仅利用量子电压台阶上平稳区的数据,实现交流量子电压量值的复现。针对常用的3σ(σ为数据标准差)准则、片段采样方法等数据筛选准则,该文提出一种由量子电压台阶中心双向延拓并最小化A类测量不确定度的平稳区与过渡区判据,通过自动识别量子电压台阶的平稳区与过渡区,提升PJVS电压阶梯波复现交流电压量值的准确性。实验结果表明:该文提出的数据平稳区与过渡区的判据具有较高的鲁棒性和交流电压复现准确性,在2.5 kHz范围内,可使量子电压阶梯波信号复现交流电压幅值的偏差和A类测量不确定度均优于2.5×10-6。研究成果可有效提升量子电压阶梯波信号的测算准确性。展开更多
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
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,conformal 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 intelligent bio-control.
文摘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.
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
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.
文摘可编程约瑟夫森电压基准(programmable Josephson voltage standard,PJVS)通过生成阶梯波构建交流量子电压,其产生量子电压台阶过程中,会伴生过渡过程,导致电压台阶两端数据的准确性较低。常见的数据处理方法是将过渡过程的数据剔除,仅利用量子电压台阶上平稳区的数据,实现交流量子电压量值的复现。针对常用的3σ(σ为数据标准差)准则、片段采样方法等数据筛选准则,该文提出一种由量子电压台阶中心双向延拓并最小化A类测量不确定度的平稳区与过渡区判据,通过自动识别量子电压台阶的平稳区与过渡区,提升PJVS电压阶梯波复现交流电压量值的准确性。实验结果表明:该文提出的数据平稳区与过渡区的判据具有较高的鲁棒性和交流电压复现准确性,在2.5 kHz范围内,可使量子电压阶梯波信号复现交流电压幅值的偏差和A类测量不确定度均优于2.5×10-6。研究成果可有效提升量子电压阶梯波信号的测算准确性。
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
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.
