CN101138663A - Fabrication method of biological microelectrode array based on flexible substrate - Google Patents

Abstract

The invention relates to a preparation method of a biological microelectrode array based on a flexible substrate, which adopts secondary photolithography and electroforming technology, and sequentially coats polydimethylsiloxane sacrificial layer and polyimide acid on the substrate surface, Thermal curing forms a polyimide flexible substrate, and prepares metal circuits on the flexible substrate by sputtering, photolithography and electroforming processes, then etches the metal base film, coats polyimide acid, photolithography and etch polyimide Imino acid, electroformed metal electrodes, thermally cured to form polyimide, and the prepared biomicroelectrode array based on polyimide flexible substrate was peeled off from polydimethylsiloxane. The electrodes are located at both ends of the metal circuit, and the electrode array is arranged according to the application requirements. One end of the electrode is connected to the biological tissue, and the other end is connected to the stimulator or measuring instrument. The metal circuit at the bottom of the electrode connects the electrodes on both sides. The biological microelectrode array manufactured by the invention has the advantages of high yield, controllable electrode position, small impedance, biocompatibility and the like.

Description

Fabrication method of biological microelectrode array based on flexible substrate

technical field

The invention relates to a method for preparing a biological microelectrode array based on a flexible substrate. The prepared biological microelectrode array is used for artificial retina, brain stimulation and measurement electrodes, etc., and belongs to the field of biomedical engineering.

Background technique

Implantable bioelectrodes are mainly used for brain stimulation and brain current measurement. They can be used in the treatment of epilepsy or Parkinson's disease, and can also be used in cochlear implants or artificial retinas, so that the blind can see images and the deaf can hear sounds. The development of bioelectrode preparation technology will greatly improve and enhance people's living standards. Bioelectrodes require flexibility, biocompatibility, and low impedance, and the electrodes can be arranged according to needs. A. Hung introduced a flexible substrate biological microelectrode array preparation method in Microtechnologies in Medicine & Biology 2nd Annual InternationalIEEE-EMB Special Topic Conference on 2-4May 2002: 76-79, which uses a double-layer polyimide process , the electrode is prepared by electroforming process, but the biological microelectrode array prepared by this method is not insulated from each other, and short circuit will occur in use. N.MacCarthy in Sensors and Actuators A, 2006, 132: 296-301, used laser to release the flexible substrate biological microelectrode array from the substrate. The microelectrode array prepared by this process did not undergo a second electroforming, and its electrode was low The package plane is 8 μm, the impedance is large, and a large stimulation current is required. The release of the microelectrode array requires photosensitive polyimide and laser equipment. DCRodger used photoresist as a sacrificial layer in Nano/Micro Engineered and Molecular System, 2006.NEMS 06.1st IEEEInternational Conference on Jan.2006: 743-746, and prepared flexible substrate biological microelectrode arrays on parylene , the microelectrode array prepared by this process is not electroformed for the second time, and its electrodes are lower than the packaging plane, the impedance is large, and a large stimulation current is required. For the release of devices based on polyimide on flexible substrates, Tayfun Akin et al. reported in Transactions on biomedical engineering, 1999, 46: 471-480 that Ti was used as a sacrificial layer, and finally 20% HF and 80% Go Ionized water corrodes the sacrificial layer to release the device; Xiao Suyan and others used SiO ₂ as the sacrificial layer in "Optical Precision Engineering", 2005, 13: 674-680, and spin-coated a layer of photoresist on the device surface before releasing to protect the Pt resistor and Au electrodes, and then use a 1:1 volume ratio of HF (49%) and HCl (36%) mixture to etch the sacrificial layer. Metal or _SiO2 is used as the sacrificial layer, and the corrosion solution used is toxic and is not conducive to the biocompatibility of the device.

It has become a major trend in biomedical engineering to prepare bioelectrode arrays with excellent biocompatibility and electrical parameters by using Micro Electro Mechanical Systems (MEMS) processing technology.

Contents of the invention

The purpose of the present invention is to address the deficiencies of the prior art, to provide a method for preparing a biological microelectrode array based on a flexible substrate, which has the advantages of simple process, high yield, electrode positions can be arranged as required, low impedance, biocompatibility, etc. advantage.

In order to achieve this purpose, the present invention adopts secondary photolithography and electroforming process to coat polydimethylsiloxane (PDMS: Polydimethylsiloxane) sacrificial layer and polyimide acid successively on the surface of glass or silicon wafer substrate, Thermal curing forms a polyimide flexible substrate, and prepares metal circuits on the flexible substrate by sputtering, photolithography and electroforming processes, then etches the metal base film, coats polyimide acid, photolithography and etch polyimide Amino acid, electroformed metal electrodes, the electrodes are located at both ends of the metal circuit, and the electrode array is arranged according to the application requirements. One end of the electrode is connected to the biological tissue, and the other end is connected to the stimulator or measuring instrument. The metal circuit at the bottom of the electrode connects the two sides The electrodes are connected, and finally the polyimide is thermally cured, and the prepared biomicroelectrode array based on the polyimide flexible substrate is peeled off from the polydimethylsiloxane.

Method of the present invention realizes through following steps:

1. Use glass or silicon wafers as the substrate, wash the substrate with deionized water, and dry it; then coat the surface of the substrate with a 100-500 μm sacrificial layer of polydimethylsiloxane, and then coat it with polydimethylsiloxane Coating 20-100 μm thick polyimide acid on the alkane, heat curing to form polyimide flexible substrate.

2. Sputter a 50-150nm Cr/Cu metal base film on the surface of the flexible polyimide substrate, then photolithography, electroform gold or copper, and prepare a metal circuit with a height of 1-10 μm and a line width of 5-100 μm.

3. Remove the photoresist, remove the Cr/Cu metal base film at the bottom, coat polyimide acid with a thickness of 1-5μm, then photolithography, etch polyimide acid, electroform gold, and finally heat-cure to form The polyimide film is used to prepare a biological electrode array with a height of 1-5 μm and a diameter of 5-200 μm.

4. Peel off the prepared biological microelectrode array based on the flexible substrate from the polydimethylsiloxane.

The advantages of the biological microelectrode array based on the flexible substrate manufactured by the present invention are: (1) the process is simple, the yield is high, and only the secondary photolithography electroforming process is used; (2) the position of the electrodes is controllable and can be arranged according to application requirements Electrode array; (3) This preparation method adopts the method of encapsulation first and then electroforming, and the electrode height is higher than the encapsulation plane, which has small impedance; (4) Biocompatible materials such as polyimide and gold and platinum are used, Good biocompatibility.

Description of drawings

Fig. 1 is a schematic diagram of the structure of a biological microelectrode array based on a flexible substrate provided by the present invention.

In Fig. 1, 3 is polyimide (PI), 4 is a metal base film, 5 is a metal circuit, and 6 is an electrode.

Fig. 2 is the fabrication process of the biological microelectrode array based on the flexible substrate of the present invention.

In Fig. 2, 1 is a substrate, 2 is polydimethylsiloxane (PDMS), 3 is polyimide (PI), 4 is a metal base film, 5 is a metal circuit, and 6 is an electrode.

Detailed ways

The technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. The following examples are not intended to limit the present invention.

The biological microelectrode array structure based on the flexible substrate provided by the present invention is shown in Figure 1. The flexible substrate uses polyimide 3, and a metal base film 4 is sputtered on the surface of the polyimide, and a metal circuit 5 is arranged on the metal base film 4. , the electrodes 6 are located at both ends of the metal circuit 5, and the electrode arrays are arranged according to application requirements.

The process flow of the method of the present invention is shown in Figure 2, step 1: coating polydimethylsiloxane 2 and polyimide acid successively on the substrate 1, thermal curing forms flexible base polyimide 3; 2: sputtering metal base film 4 on the surface of flexible substrate polyimide 3, photolithography, electroforming metal circuit 5; step 3: removing photoresist and metal base film, coating polyimide acid, photolithography, Etch polyimide acid, electroform metal electrode 6, and heat-cure to form polyimide; Step 4: Peel off the prepared biological microelectrode array from polydimethylsiloxane 2 to obtain a flexible substrate biological Microelectrode array samples.

Example 1

Structural parameters of biological microelectrode array: glass substrate, polydimethylsiloxane thickness 100 μm, polyimide thickness 50 μm, gold circuit height 2 μm, gold electrode height 5 μm.

(1) Preparation of flexible substrate

A glass sheet with a thickness of 2 mm was used as the substrate 1, and the substrate was firstly treated by ultrasonic cleaning with acetone, alcohol and deionized water, and dried in a vacuum oven at 180° C. for 3 hours. Then spin-coat polydimethylsiloxane 2 with a thickness of 100 μm on the substrate at a speed of 1000 rpm, and cure at 80° C. for 2 hours, then spin-coat polyimide acid with a thickness of 50 μm at a speed of 1000 rpm. The flexible base polyimide 3 is formed by thermal curing using a stepwise heating method (from 80° C. to 120° C. to 180° C. to 280° C.).

(2) Fabrication of metal metal circuits

First, sputter 50nm Cr/Cu metal base film 4 on the surface of flexible substrate polyimide 3, spin-coat positive resist AZ4620 with a thickness of 4 μm, and expose it with MA6 photolithography machine of Karl Suss Company in Germany. The exposure time is 40 seconds, and the developing time is 40 seconds. The gold circuit 5 with a thickness of 2 μm and a width of 20-100 μm was electroformed for 40 seconds, the current density was 4.4 mA/cm ² , and the electroforming time was 6 minutes.

(3) Fabrication of metal electrodes

Expose for 5 minutes under a 5.5mW/cm ² exposure machine, and then develop in a developer for 10 minutes to remove the photoresist. The Cr/Cu metal base film 4 on the surface of the polyimide was removed by argon plasma etching, the etching power was 20kW, the gas flow rate was 40sccm, and the etching time was 5 minutes. Then apply 5 μm thick polyimide acid at a rotational speed of 4000 rpm, spin-coat 5 μm thick positive resist AZ4620 on the polyimide acid, exposure time is 50 seconds, development time is 60 seconds, and the polyimide acid is etched with a developer. imidic acid, the etching time is 5 minutes, the photoresist is removed with acetone, and then a 5 μm thick gold electrode 6 is electroformed, the current density is 4.4mA/cm ² , the electroforming time is 15 minutes, and the step temperature method (from 80°C--120°C--180°C--280°C) heat curing to form a polyimide layer film.

(4) Stripping

The prepared biological microelectrode array based on the flexible substrate was peeled off from the polydimethylsiloxane.

Example 2

Structural parameters of biological microelectrode array: glass substrate, polydimethylsiloxane thickness 300 μm, polyimide thickness 20 μm, gold circuit height 1 μm, gold electrode height 3 μm.

(1) Preparation of flexible substrate

A glass sheet with a thickness of 2 mm was used as the substrate 1, and the substrate was firstly treated by ultrasonic cleaning with acetone, alcohol and deionized water, and dried in a vacuum oven at 180° C. for 3 hours. Then spin-coat polydimethylsiloxane 2 with a thickness of 300 μm on the substrate at a speed of 700 rpm, and cure at 90° C. for 2 hours, then spin-coat polyimide acid with a thickness of 20 μm at a speed of 2000 rpm. The flexible base polyimide 3 is formed by thermal curing by a stepwise heating method (from 80° C. to 120° C. to 180° C. to 280° C.).

(2) Fabrication of metal circuits

First, sputter 100nm Cr/Cu metal base film 4 on the surface of flexible substrate polyimide 3, spin-coat 2 μm thick positive resist AZ4620, and use MA6 photolithography machine of German Karl Suss company to expose, the exposure time is 30 seconds, and the developing time The gold circuit 5 with a thickness of 1 μm and a width of 20-100 μm was electroformed for 30 seconds, the current density was 4.4 mA/cm ² , and the electroforming time was 3 minutes.

(3) Fabrication of metal electrodes

Expose for 5 minutes under a 5.5mW/cm ² exposure machine, and then develop in a developer for 10 minutes to remove the photoresist. The Cr/Cu metal base film 4 on the polyimide surface was removed by argon plasma etching, with an etching power of 20 kW, a gas flow rate of 40 sccm, and an etching time of 10 minutes. Then apply a 3 μm thick polyimide acid at a speed of 4500 rpm, spin coat a 4 μm thick positive resist on the polyimide acid, expose for 50 seconds, develop for 40 seconds, and etch the polyimide with a developer. Imino acid, etching time is 3 minutes, remove photoresist with acetone, and then electroform gold electrode 6 with a thickness of 3 μm, current density is 4.4 mA/cm ² , electroforming time is 9 minutes. The polyimide film is formed by thermal curing by step-wise heating method (from 80°C to 120°C to 180°C to 280°C).

(4) Stripping

The prepared biological microelectrode array based on the flexible substrate was peeled off from the polydimethylsiloxane.

Example 3

Structural parameters of biological microelectrode array: glass substrate, polydimethylsiloxane thickness 500 μm, polyimide thickness 100 μm, copper circuit height 10 μm, gold electrode height 1 μm.

(1) Preparation of flexible substrate

A glass sheet with a thickness of 2 mm was used as the substrate 1, and the substrate was firstly treated by ultrasonic cleaning with acetone, alcohol and deionized water, and dried in a vacuum oven at 180° C. for 3 hours. Then spin-coat polydimethylsiloxane 2 with a thickness of 500 μm on the substrate at a speed of 500 rpm, and cure at 90° C. for 3 hours, then spin-coat polyimide acid with a thickness of 100 μm at a speed of 500 rpm. The flexible base polyimide 3 is formed by thermal curing by a stepwise heating method (from 80° C. to 120° C. to 180° C. to 280° C.).

(2) Fabrication of metal circuits

First, sputter 150nm Cr/Cu metal base film 4 on the surface of flexible substrate polyimide 3, spin-coat positive resist AZ4620 with a thickness of 12 μm, and use MA6 photolithography machine of German Karl Suss company to expose, the exposure time is 120 seconds, and the developing time The copper circuit 5 with a thickness of 10 μm and a width of 20-100 μm was electroformed for 120 seconds, the current density was 4.4 mA/cm ² , and the electroforming time was 30 minutes.

(3) Fabrication of metal electrodes

Expose for 5 minutes under a 5.5mW/cm ² exposure machine, and then develop in a developer for 10 minutes to remove the photoresist. The Cr/Cu metal bottom film 4 on the surface of the polyimide was removed by argon plasma etching, the etching power was 20kW, the gas flow rate was 40sccm, and the etching time was 15 minutes. Then coat 1 μm thick polyimide acid at a rotational speed of 6000 rpm, spin-coat 2 μm thick positive resist on the polyimide acid, exposure time is 30 seconds, development time is 40 seconds, and the polyimide acid is etched with developer. Imino acid, the etching time is 1 minute, the photoresist is removed with acetone, and then a 1 μm thick gold electrode 6 is electroformed, the current density is 4.4 mA/cm ² , and the electroforming time is 3 minutes. The polyimide layer film is formed by thermal curing using a stepwise heating method (from 80°C to 120°C to 180°C to 280°C).

(4) Stripping

The prepared biological microelectrode array based on the flexible substrate was peeled off from the polydimethylsiloxane.

Claims (2)

1. biological microelectrode array based on flexible substrates, comprise flexible substrates, metallic circuit (5) and electrode (6), it is characterized in that described flexible substrates is polyimides (3), at polyimide surface splash-proofing sputtering metal counterdie (4), metal counterdie (4) is gone up preparation metallic circuit (5), electrode (6) is positioned at the two ends of metallic circuit (5), and according to the application requirements electrod-array of arranging.

2. the preparation method based on the biological microelectrode array of flexible substrates of a claim 1 is characterized in that comprising the steps:

1) adopting glass or silicon chip is substrate, uses the washed with de-ionized water substrate, oven dry; Apply 100-500 μ m sacrifice layer polydimethylsiloxane at substrate surface then, apply the thick polyimide acid of 20-100 μ m again on polydimethylsiloxane, heat cure forms the polyimides flexible substrates;

2) at the Cr/Cu metal counterdie of flexible substrates polyimide surface sputter 50-150nm, photoetching then, electroforming gold or copper prepare the highly metallic circuit of 1-10 μ m, live width 5-100 μ m;

3) remove photoresist, remove the Cr/Cu metal counterdie of bottom, apply the thick polyimide acid of 1-5 μ m, photoetching then, etching polyimide acid, electroforming gold, last heat cure forms the polyimides tunic, prepares the biologic electrode array of height 1-5 μ m, diameter 5-200 μ m;

The biological microelectrode array based on the polyimides flexible substrates that 4) will prepare strips down from polydimethylsiloxane.