An in vitro microelectrode array chip and its preparation method

Abstract

The invention discloses an in vitro microelectrode array chip and a preparation method thereof, the preparation method comprising cleaning and drying an insulating substrate; printing a microelectrode array on the surface of the insulating substrate using 3D printing technology; forming an insulating layer on the microelectrode array, then etching the insulating layer by photolithography and plasma etching to expose the microelectrodes; and modifying nanomaterials on the surface of the microelectrodes by an electrochemical method. The preparation method can prepare an in vitro microelectrode array chip efficiently and at a low cost.

Description

Technical Field

[0001] The invention relates to the field of micro-processing of biosensors, and in particular to an in vitro microelectrode array chip and a preparation method thereof. Background Art

[0002] MEMS stands for Micro Electromechanical System, which is a high-tech electronic mechanical device developed on the basis of microelectronics technology (semiconductor manufacturing technology) and is made by integrating lithography, corrosion, thin film, LIGA, silicon micromachining, non-silicon micromachining and precision machining technologies. MEMS micro-nano processing technology is the key to the realization of MEMS device manufacturing.

[0003] MEMS micro-nano processing technology refers to the design, processing, assembly, integration and application technology of parts with millimeter, micron and nanometer scales, as well as components or systems composed of these parts. It can achieve smaller scale and higher precision processing, which can significantly improve the functional density and performance of processed products, and is conducive to promoting high-quality development in high-tech fields such as optoelectronics, high-end manufacturing and biomedicine.

[0004] Micro-nano 3D printing is a new type of micro-nano processing technology that manufactures micro-nano structures based on the principle of additive manufacturing. Its working principles mainly include methods such as photocuring, electron beam and laser beam. During the printing process, the required micro-nano structure model is first created through computer-aided design software, and then it is formed layer by layer through photocuring, electron beam or laser beam, and finally the manufacture of micro-nano objects is completed.

[0005] In the field of micro-nano processing, 3D printing technology has shown significant technical advantages over traditional MEMS micro-nano processing technology in the preparation of in vitro microelectrode arrays, especially in terms of cost-effectiveness and customizability.

[0006] First, from a cost-effectiveness perspective, 3D printing technology can significantly reduce the startup costs of small and medium-volume customized MEMS devices. Traditional MEMS production costs are high. If traditional semiconductor technology is used to manufacture a MEMS product, the cost is around hundreds of thousands of dollars, and the production cycle usually takes several months or even longer. 3D printing technology is not only low-cost, but also greatly shortens the production time.

[0007] Secondly, in terms of customization, 3D printing technology provides unprecedented design and layout flexibility, and the height and position of each shank, as well as their respective electrical wiring, can be individually customized with minimal resources and time. This flexibility enables 3D printing technology to support the possibility of a variety of biomedical devices, especially in the design and manufacture of microelectrode arrays, which can record electrical signals throughout the brain in a targeted and large-scale manner.

[0008] In summary, 3D printing technology has lower costs and higher levels of customization when preparing in vitro microelectrode arrays compared to MEMS micro-nano processing technology, which gives 3D printing technology a significant technical advantage in the field of micro-nano processing. Summary of the invention

[0009] The invention provides a method for preparing an in vitro microelectrode array chip. The method can prepare the in vitro microelectrode array chip efficiently and at a low cost.

[0010] The present invention provides a method for preparing an in vitro microelectrode array chip, comprising:

[0011] S1. Clean and dry the insulation base;

[0012] S2, printing a microelectrode array on the surface of the insulating substrate using 3D printing technology;

[0013] S3, forming an insulating layer on the microelectrode array, and then etching the insulating layer by photolithography and plasma etching to expose the microelectrodes;

[0014] S4. Modify nanomaterials on the surface of microelectrodes by electrochemical methods.

[0015] Preferably, the insulating layer is formed on the microelectrode array using 3D printing technology.

[0016] Preferably, the insulating substrate is made of a hard transparent insulating material, and the hard transparent insulating material includes quartz glass, polyvinyl chloride or polycarbonate.

[0017] Preferably, the insulating base has a side length of 25 mm to 80 mm and a thickness of 1 mm to 2 mm.

[0018] Preferably, the material of the microelectrode array is a conductive film material, and the conductive film material is a metal, a metal compound or a conductive polymer.

[0019] Preferably, the material of the conductive film is gold, platinum or titanium nitride, and the conductive polymer is polyacetylene, polypyrrole, polythiophene or polyaniline.

[0020] Preferably, the microelectrode array comprises 9 to 512 microelectrodes, the diameter of the microelectrodes is 1 um to 100 um, and the spacing between the microelectrodes is 5 um to 200 um.

[0021] Preferably, the insulating layer is made of silicon dioxide, silicon nitride, silicon oxynitride, SU8, polyimide or polyparaxylene.

[0022] Preferably, the nanomaterial is a conductive polymer, a carbon nanotube, nano-gold or nano-platinum.

[0023] The present invention also provides a method for preparing the in vitro microelectrode array chip, comprising an insulating substrate, a microelectrode array on the insulating substrate, and an insulating layer and nanomaterials on the microelectrode array.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The present invention utilizes 3D technology to prepare microelectrode arrays and wires on the surface of an insulating substrate, thereby solving the problem of high cost and long time of existing MEMS micro-nano processing, and improving preparation accuracy, saving time, and saving costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative labor.

[0027] Figure 1 A schematic diagram of an in vitro microelectrode array microelectrode provided in a specific embodiment of the present invention;

[0028] Figure 2 A longitudinal cross-sectional view of an in vitro microelectrode array provided in a specific embodiment of the present invention;

[0029] Figure 3 The present invention provides a flowchart of the preparation of an in vitro microelectrode array in an embodiment.

[0030] Among them, 1 is an insulating substrate, 2 is a microelectrode array, 21 is a microelectrode, 22 is a wire; 3 is an insulating layer; 4 is a nanomaterial; DETAILED DESCRIPTION

[0031] In conjunction with the accompanying drawings, the in vitro microelectrode array chip and the preparation method thereof provided by the present invention are described in detail.

[0032] A specific embodiment of the present invention provides an in vitro microelectrode array chip, such as Figure 1 As shown, it includes an insulating substrate 1, a microelectrode array 2 located on the insulating substrate 1, an insulating layer 3 and a nanomaterial 4 located on the microelectrode array 2, as shown in FIG. Figure 2 As shown, the microelectrode array 2 includes a circular microelectrode 21 and a wire 22 made of a conductive film material. The nanomaterial 4 is located at the site of the circular microelectrode of the microelectrode array. The surface of the microelectrode of the microelectrode array 2 is modified with a nanocomposite material for detecting neural electrophysiological signals, and all lead surfaces are covered with an insulating layer.

[0033] The material used for the insulating base is quartz glass, and the side length of the insulating base is 50 mm and the thickness is 1.5 mm.

[0034] The conductive film material of the microelectrodes, leads and contacts is PEDOT:PSS with a thickness of 1um.

[0035] The insulating layer material covering the surface of the lead is SiO2 / Si3N4 / SiO2.

[0036] The present invention is used for the preparation method of in vitro microelectrode array chip, such as Figure 3 As shown, the following steps are included:

[0037] a) Use boiling concentrated sulfuric acid solution to wash the glass sheet for 15-20 minutes, using its strong oxidizing property to remove the organic or inorganic impurities remaining on the substrate;

[0038] b) A PEDOT:PSS conductor layer including detection sites, conduction and contacts is printed on the substrate surface using aerosol jet 3D printing.

[0039] c) printing a layer of SU8 material on the wire using aerosol jet 3D printing;

[0040] The method for point-modifying the surface of an in vitro microelectrode array chip with MWCNTs / PEDOT:PSS nanocomposite material of the present invention comprises the following steps:

[0041] a) Wash the microelectrode array chip in deionized water and dry the chip surface with a nitrogen gun.

[0042] b) Clean the chip surface by oxygen plasma etching with a power of 100 W, an oxygen flow rate of 30 L / min, and a time of 90 s.

[0043] c) Place the microelectrode site to be modified in PBS solution and activate the electrode surface using chronoamperometry at a voltage of -2 V for 20 seconds.

[0044] d) Prepare 4 ml of 0.1 M PSS and 2 mg / ml MWCNT suspension and disperse by ultrasonic for 30 minutes.

[0045] e) 20 mM EDOT was measured and dropped into 4 ml of the dispersion, and ultrasonic dispersion was continued for 30 minutes. 2 ml of the dispersion after ultrasonication was extracted and dropped into the microelectrode array.

[0046] f) The cyclic voltammetry method used for electrodeposition was carried out in a three-electrode system, in which the counter electrode was a platinum wire and the reference electrode was Ag / AgCl. The voltage range was 0-0.95V, the scan rate was 100mV / s, and the number of scans was 3-5.

Claims

1. A method for preparing an in vitro microelectrode array chip, characterized in that: include: S1. Clean and dry the insulation base; S2, printing a microelectrode array on the surface of the insulating substrate using 3D printing technology; S3, forming an insulating layer on the conductive layer, and then etching the insulating layer by photolithography and plasma etching to expose the microelectrodes, or forming an insulating layer on the wires of the microelectrode array by 3D printing technology to expose the microelectrodes; S4. Modify nanomaterials on the surface of microelectrodes by electrochemical methods.

2. The method for preparing an in vitro microelectrode array chip according to claim 1, characterized in that: The insulating substrate is made of a hard transparent insulating material, and the hard transparent insulating material includes quartz glass, polyvinyl chloride or polycarbonate.

3. The method for preparing an in vitro microelectrode array chip according to claim 1, characterized in that: The insulating base has a side length of 25 mm to 80 mm and a thickness of 1 mm to 2 mm.

4. The method for preparing an in vitro microelectrode array chip according to claim 1, characterized in that: The material of the microelectrode array is a conductive film material, and the conductive film material is a metal, a metal compound or a conductive polymer.

5. The method for preparing an in vitro microelectrode array chip according to claim 4, characterized in that: The material of the conductive film is gold, platinum or titanium nitride, and the conductive polymer is polyacetylene, polypyrrole, polythiophene or polyaniline.

6. The method for preparing an in vitro microelectrode array chip according to claim 1, characterized in that: The microelectrode array comprises 9 to 512 microelectrodes, the diameter of the microelectrodes is 1 um to 100 um, and the spacing between the microelectrodes is 5 um to 200 um.

7. The method for preparing an in vitro microelectrode array chip according to claim 1, characterized in that: The insulating layer is made of silicon dioxide, silicon nitride, silicon oxynitride, SU8, polyimide or polyparaxylene.

8. The method for preparing an in vitro microelectrode array chip according to claim 1, characterized in that: The nano material is a conductive polymer, a carbon nanotube, nano gold or nano platinum.

9. An in vitro microelectrode array chip prepared by the method for preparing an in vitro microelectrode array chip according to claims 1-8, characterized in that: The invention comprises an insulating substrate, a microelectrode array located on the insulating substrate, and an insulating layer and nanomaterials located on the microelectrode array.

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