Microelectrode array chip for multi-parameter detection of nerve cells and preparation method thereof

Abstract

The invention discloses a microelectrode array chip for multi-parameter detection of nerve cells and a preparation method thereof, relating to a sensor technology. The chip consists of seven parts including an insulating base, a microelectrode array, counter electrodes, reference electrodes, electrode leads, contacts, a superficial insulating layer and a modification material, wherein the electrodes are prepared by using a micro-electro-mechanical system (MEMS) process, and a specific nano-composite material and enzymes are modified at fixed points on the surfaces of the electrodes. The nerve cells are cultivated on the surfaces of modified working electrodes, and by combining the counter electrodes and the reference electrodes, the microelectrode array chip can be used for detecting electrophysiological signals of the nerve cells and electrochemical signals of neurotransmitters such as dopamine, acetyl choline and the like in real time at the same time, and has a function of applying electrical stimulation to the nerve cells. The microelectrode array chip integrates functions, modifies a material at fixed points, is convenient to use, and is suitable for culturing the nerve cells and making related research on multi-parameter detection of the nerve cells in laboratories.

Description

technical field [0001] The invention relates to the field of micro-processing technology and nano-modification of biosensors, and relates to a micro-electrode array chip for multi-parameter detection of nerve cells and a preparation method thereof. Background technique [0002] Traditional methods for detecting electrophysiological signals of nerve cells are basically patch clamp, voltage clamp, etc. Usually, only a few channels of data can be obtained, and the electrode positioning is difficult and the operation is cumbersome. Cells die in a short period of time, which largely limits the detection of cell electrophysiology and electrochemical aspects; extracellular signal detection methods can achieve non-destructive, long-term measurement, with the micro-electromechanical system (MEMS) processing technology The development of extracellular microelectrode arrays (microelectrode, MEA) provides a long-term non-destructive monitoring of cell electrophysiological activities, th...

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Problems solved by technology

[0002] Traditional methods for detecting electrophysiological signals of nerve cells are basically patch clamp, voltage clamp, etc. Usually, only a few channels of data can be obtained, and the electrode positioning is difficult and the operation is cumbersome. Cells die in a short period of time, which largely limits the detection of cell electrophysiology and electrochemical aspects; extracellular signal detection methods can achieve non-destructive, long-term measurement, with the micro-electromechanical system (MEMS) processing technology The development of extracellular microelectrode arrays (microelectrode, MEA) provides a long-term non-destructive monitoring of cell electrophysiological activities, through high-throughput channels, the electrical activity data of dozens or even hundreds of cells can be transmitted, and can Localized to a single cell to realize real-time detection of changes in membrane potential under external electrical stimulation and drug action

Some microelectrode array chips made of various materials and processes have appeared at home and abroad, which can realize the simultaneous detection of the electrophysiological activities of group nerve cells. However, the microelectrode arrays used before have no integrated electrochemical detection of neurotransmitters. The main reason is that bare electrodes cannot detect the concentration of neurotransmitters in biological tissues, and there is no reliable method for modifying enzymes on the surface of microelectrodes, so it is even more impossible to specifically detect a certain neurotransmitter.

At present, large electrodes or in vitro microdialysis are mostly used to detect neurotransmitters, which has poor real-time detection and low sensitivity.

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