Microelectrode array device and special device for cell manipulation and electrophysiological signal detection

Abstract

The invention discloses a microelectrode array device and a special device for cell manipulation and electrophysiological signal detection. The microelectrode array device consists of a chip unit, a printed circuit board and a bottomless cultivation cavity, wherein the chip unit is arranged on the printed circuit board by pressure welding and is embedded into the cultivation cavity; the cultivation cavity is in seal connection with the printed circuit board; the chip unit comprises a substrate, a lower metal layer, an insulation layer, an upper metal layer and a passivation layer in turn frombottom to top; the lower metal layer is provided with at least one measuring electrode and a contact conductor and a bonding pad corresponding to the measuring electrode; the upper metal layer is provided with at least four positioning electrodes and contact conductors and bonding pads corresponding to the positioning electrodes; each of all measuring electrodes and positioning electrodes of the chip unit is led out by a separate contact conductor; one contact conductor is connected with one bonding pad; and each electrode can be applied with a signal or be detected independently.

Description

technical field [0001] The invention relates to a micro-electrode array device and a special device for cell operation and electrophysiological signal detection. Background technique [0002] Microelectrode array chip (microelectrode array, MEA) refers to the general term for microdevices that can detect nerve electrophysiological signals or neurotransmitters in multiple channels at the nerve cell, tissue or system level in real time. The earliest planar microelectrode array chip was created by Thomas in 1972. reported by et al., for recording the electrical activity of cardiomyocytes cultured in vitro. [0003] As mentioned above, the microelectrode array chip was first developed for the purpose of studying the characteristics and mechanism of nervous system activity. In 1949, Lilly first used the multi-tube combination microelectrode insertion method perfused with electrolyte to study the relationship between primate behavior and neuron discharge; then the microelectrode ...

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Problems solved by technology

[0004] This kind of microelectrode array chip faces a problem: the nerve cells cultured in vitro are not accurately positioned on the electrodes, resulting in poor adhesion or distance between the cells and the electrodes, and the electrical stimulation and electrical signal detection may occur in different cells. on different parts

However, in addition to the need to effectively bind active biomolecules to the substrate, this method is difficult to achieve precise alignment between the neural network and the microelectrode array, and the modified chip cannot be reused.

[0005] In recent years, people began to try to use microelectrodes to generate dielectric force to locate nerve cells: Heida et al. Collect nerve cells through negative dielectric force; the group led by Ozkan (Prasad S. et al., J NeurosciMethods, 135(1-2): 79-88, 2004) uses 16 microelectrode array chips to directly generate positive The dielectric force is used to adsorb nerve cells, but pushing the cells to the area of ​​strong electric field will cause irreversible damage to the cells

In 2008, Pan et al. (Pan L. et al., J Neurosci Methods, 170:123-129, 2008) disclosed a microelectrode array that automatically positions cells and detects electrophysiological signals, which uses a double-layer wiring process, Measuring electrodes are arranged on the lower metal layer, and an 8*8 positioning electrode array is arranged on the upper metal layer. They divide the positioning electrodes on the chip into two groups according to the different signals applied, and connect the two groups of electrodes respectively. After being drawn together, cells are enriched by means of negative dielectric force, but this method can only form a single fixed cell network, and can only complete cell positioning and detect this single function

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