CN100431487C

CN100431487C - Processing method of three-dimensional implantable microelectrode array

Info

Publication number: CN100431487C
Application number: CNB2007100368371A
Authority: CN
Inventors: 李刚; 程建功; 姚源; 周洪波; 孙晓娜; 赵建龙
Original assignee: Shanghai Institute of Microsystem and Information Technology of CAS
Current assignee: Shanghai Institute of Microsystem and Information Technology of CAS
Priority date: 2007-01-25
Filing date: 2007-01-25
Publication date: 2008-11-12
Anticipated expiration: 2027-01-25
Also published as: CN101006920A

Abstract

The invention discloses a making method of three-dimensional plant-typed micro-electrode array, which is characterized by the following: adopting metal yarn as electrode material directly; inserting metal yarn into fine flute of mould base; locating to break metal yarn through micro-fine pipe on the mould base by chemical erosion; forming point at breaking part; casting polydimethylsiloxane on the mould base; utilizing polymerized PDMS to form chassis support part to chuck metal yarn; stripping PDMS with metal yarn out of mould base; bombarding through oxygen ion to overlap and bond together; assembling three-dimensional micro-electrode array.

Description

A kind of manufacture method of three-dimensional implantable microelectrode array

Technical field

The present invention relates to a kind of manufacture method of three-dimensional implantable microelectrode array, can be applicable to fields such as neuropathy treatment and rehabilitation and neurobiology basic research.

Background technology

Neural engineering system is that order is previous very active and develop research field rapidly, and such as brain-computer interface, problems such as nerve prosthesis receive increasing concern.Microelectrode has become the important tool of aspects such as disclosing nervous system working mechanism, treatment sacred disease and neural rehabilitation.No matter be brain-computer interface or nerve prosthesis, usually all be that electrode is implanted in animal or the patient's body, load signal of telecommunication excitation or suppress neural activity by electrode to realize functional electric stimulation (functional electrical stimulation, FES), perhaps utilizing microelectrode that neural activity is converted to the signal of telecommunication goes on record and analyzes and researches.Different according to effective object and application target, so far people have researched and developed out the implantation micro-electrode having of various ways successively, the three dimensional needle of its middle-high density, the ordered arrangement electrod-array that declines has special advantages, in its implantable nerve tract, directly contact with neural axon, performance record and stimulatory function well especially stimulate dark cortex and write down significantly, and the high density of electrode can guarantee good selective stimulating or record.Present modal three dimensional needle declines, and to be based on silicon materials be the substrate processing and fabricating to electrod-array, such as people [P.K.Campbell such as the Normann of U.S. Utah university, K.E.Jones, R.J.Huber, et al. " A Silicon-Based; Three-Dimensional Neural Interface:Manufacturing Processes for an Intracortical Electrode Array; " IEEE Trans.Biomed.Eng.1991,38 (8): 758-68.] and people such as the Wise [Q.Bai of Michigan university, K.D.Wise, D.J.Anderson. " A High-Yield Microassembly Structure forThree-Dimensional Microelectrode Arrays; " IEEE Trans.Biomed.Eng.2000,47 (3): 281-289.] three dimensional needle of the Zhi Zuoing electrod-array that declines, wherein Utah type electrode commercialization, usually this class is that the three dimensional needle of the substrate electrod-array course of processing that declines is very complicated with silicon materials, expensive, make that the type microelectrode is difficult to extensively promote and use, vast neuroelectricity physiological science man and medical worker also are difficult to benefit from it, and have greatly limited the research steps of brain-computer interface and nerve prosthesis aspect.

Summary of the invention

The manufacture method that the purpose of this invention is to provide a kind of cheapness, easy three-dimensional implantable microelectrode array, reduce cost of manufacture, shorten the process-cycle, promote the extensive use of three-dimensional implantable microelectrode array, for neural rehabilitation and neurobiology research lay the foundation.

The manufacture method of a kind of three-dimensional implantable microelectrode array provided by the invention, it is characterized in that described three-dimensional implantable microelectrode array directly adopts commercial tinsel as electrode material, make the base support part of clamping tinsel microelectrode by simple fine process, and finally form the density three-dimensional microelectrode array of practicability by the synergetic bonding technology of multilamellar.Directly adopt tinsel as electrode material, both guaranteed implantation process counter electrode material stiffness and flexible requirement, the complexity of having avoided micro fabrication directly to make the high-aspect-ratio 3-D solid structure again.

Particularly, at first utilize fine machining method on glass or silicon chip, to process minute groove and cavity body structure, make the mould substrate; Then, will embed that (diameter wiry is between 10 microns to 500 microns, and too thin tinsel obtains difficulty, and is difficult to guarantee to implant rigidity in the mould wafer pockets as the tinsel of electrode; Wire diameter greatly then causes bigger implantation damage easily, loses the implantation micro-electrode having meaning), and be fixed with adhesive glue at mould substrate two ends; Spin coating photoresist on the mould substrate of fixing metal silk is made little groove and cavity by photoetching development; The removable cover plate of applying one deck on the mould substrate, the groove that photoresist is made on the mould substrate forms the microchannel of sealing, add electrolyte in the microchannel, utilize the method for electrochemical corrosion that all tinsels are disconnected from the microchannel corrosion, section part will taper off to a point this moment; Remove cover plate and electrolyte, spin coating polydimethylsiloxane (PDMS) on the mould substrate, and heat and make it polymerization; Afterwards, the entire die substrate is immersed in the acetone, remove photoresist; After the cleaning, clamping PDMS layer wiry is stripped down from the mould substrate, and excise unwanted PDMS part; Multilamellar clamping PDMS layer wiry is utilized the oxygen plasma bombardment, and stack is bonded together and constitutes three-dimensional micro-electrode array (PDMS layer structure level number is between 2 layers to 20 layers, and too much the number of plies will cause the electrode volume excessive, lose practical value) again; Carry out insulation processing by sputter, evaporation or submerged mode on three-dimensional micro-electrode array exposed metal silk surface, the microelectrode insulating layer material can be silicon dioxide, silicon nitride, polyimides, polydimethylsiloxane or Parylene etc., and thickness of insulating layer is between 0.001 micron to 1 micron; Remove the most advanced and sophisticated insulating barrier of microelectrode tinsel by chemical attack or electric spark mode, finishing three-dimensional micro-electrode array makes, finally make between the three-dimensional micro-electrode array adjacent electrode body of rod spacing between 100 microns to 1 millimeter, insert the difficulty of operation when spacing is crossed the young pathbreaker and caused implanting between the electrode body of rod, spacing is crossed senior general and is caused the electrode volume big, loses the microelectrode meaning.

Three-dimensional implantable microelectrode array manufacture method provided by the invention is compared based on the three-dimensional implantable microelectrode array manufacture method of silicon materials with present routine, it is simple to have process, with low cost, the characteristics that fabrication cycle is short, help promoting the extensive use of three-dimensional implantable microelectrode array, thereby promote the progress of neural rehabilitation and neurobiology research.

Description of drawings

Fig. 1 makes the glass mold substrate structure sketch map that three-dimensional micro-electrode array is processed for the embodiment of the invention

Fig. 2 embeds in the glass mold substrate fine groove and fixed sketch map for tungsten filament

The structural representation of Fig. 3 after for spin coating photoresist and photoetching on the glass mold substrate of fixing tungsten filament

Fig. 4 is the sketch map of electrochemical corrosion tungsten filament with accurate fracture tungsten filament and formation pointed tip

Fig. 5 is base support partly the sketch map of spin coating PDMS to make the clamping tungsten filament electrode on the glass mold substrate

Fig. 6 handles the PDMS base support part-structure sketch map of four tungsten filament electrodes of monolithic clamping of back formation for separation cuts

Fig. 7 is the three-dimensional micro-electrode array sketch map that forms behind the PDMS base support part bonding of four clamping tungsten filament electrodes

Fig. 8 carries out the sketch map that insulating coating is handled in the polyimides glue for the three-dimensional micro-electrode array exposed parts immerses

Fig. 9 utilizes electric spark to remove three-dimensional micro-electrode array eletrode tip SI semi-insulation coating to make the operation chart of electrode stimulating point or measuring point

The specific embodiment

Embodiment 1

Is the manufacture method that example further specifies three-dimensional implantable microelectrode array of the present invention below in conjunction with accompanying drawing with the flow process based on tungsten filament electrode material and glass mold substrate making three-dimensional micro-electrode array.

1, at first glass substrate was placed acetone, ethanol respectively each ultrasonic 10 minutes, and, place dense H then with washed with de-ionized water ₂SO ₄In boiled 15 minutes, deionized water rinsing is clean, nitrogen dries up, 200 ℃ of baking oven baking the affected part after applying some drugs 30 minutes.

2, at ready glass substrate surface spin coating AZ 4620 photoresists (3000 rev/mins of rotating speeds), and place 80 ℃ of baking ovens to carry out soft baking in 30 minutes, expose then, develop, obtain the figure of required etch mask layer, the good glass substrate that will develop at last places the hard baking of 130 ℃ of baking ovens 1 hour.

3, the glass substrate that will finish after the hard baking places BOE (Buffered Oxide Etch, BOE) about 2 hours of etching (constantly stirring with magnetic stirring apparatus in the etching process) in the glass erosion liquid, form required fine groove (wide about 120 microns, dark about 100 microns) and microcavity body structure (as shown in Figure 1).

4, the tungsten filament 2 with 100 microns of diameters embeds in the groove of glass mold substrate 1, and fixes (as shown in Figure 2) at mould substrate two ends with epoxide-resin glue 3;

5, spin coating photoresist 4 (about 100 microns of thickness) on the glass mold substrate of fixing tungsten filament, and photoetching development is made little groove 5 and cavity body structure 6 (as shown in Figure 3);

6, PDMS sheet 7 correspondence positions with a slice surfacing punch, fit in as cover plate and to utilize photoresist to make on the glass mold substrate of little groove structure to form the sealing microchannel, and in microchannel, inject 1MNaOH by micropore, insert a platinum electrode 8 in the microcavity, and tungsten filament exposed parts and platinum electrode 8 connect constant voltage dc source positive pole and negative pole by lead 9 respectively, load the 10V unidirectional current and carry out electrochemical corrosion (as shown in Figure 4);

7, after the corrosion of all tungsten filaments disconnects, remove NaOH solution and PDMS sheet 7, and nitrogen dries up, the liquid PDMS precursor of spin coating then, and place 80 ℃ of baking ovens to make it to solidify to form PDMS layer 10 (not) as Fig. 5 institute;

8, the PDMS with the clamping tungsten filament strips down, and utilizes blade to cut apart and excise unwanted PDMS part, forms the cellular construction (as shown in Figure 6) of a slice PDMS base support part 11 clampings one row's high density tungsten filament 2;

9, the PDMS layer with above-mentioned four clamping tungsten filaments utilizes the oxygen plasma bombardment, and stack is bonded together and constitutes three-dimensional micro-electrode array 12 again, and the rear end links to each other (as shown in Figure 7) with the peripheral signal of telecommunication by commercial joint 13;

10, three-dimensional micro-electrode array tungsten filament exposed parts is immersed in the polyimides glue 14, and take out, leave standstill and be placed on the curing (as shown in Figure 8) of carrying out tungsten filament surface polyimides glue in the baking oven in 30 minutes;

11, after electrode surface is finished insulating barrier 15 processing, remove the most advanced and sophisticated insulating barrier of microelectrode tinsel, form conduction stimulation point or measuring point 16, finish three-dimensional micro-electrode array and make (as shown in Figure 9) by the electric spark mode.

Claims

1, a kind of manufacture method of three-dimensional implantable microelectrode array, this method comprises:

1. utilize wet method or plasma etching to make glass or silicon mould substrate with fine groove and fine structure;

2. tinsel is embedded in the groove of mould substrate, two ends are fixed with adhesive glue;

3. spin coating photoresist on the mould substrate of fixing metal silk, and photoetching development is made little groove and cavity;

4. the removable cover plate of applying one deck on the mould substrate, the groove that photoresist is made on the mould substrate forms the microchannel of sealing, adds electrolyte in the microchannel, utilizes the method for electrochemical corrosion that all tinsels are disconnected from the microchannel corrosion;

5. remove cover plate and electrolyte, and on the mould substrate spin coating polydimethylsiloxane, the polymerization of heating;

6. remove photoresist with acetone, and clamping polydimethylsiloxane layer wiry is peeled off from the mould substrate;

7. excise the polydimethylsiloxane redundance, and multilamellar clamping polydimethylsiloxane layer wiry is utilized the oxygen plasma bombardment, the formation three-dimensional micro-electrode array that is bonded together again superposes;

8. carry out insulation processing by sputter, evaporation or submerged mode on three-dimensional micro-electrode array exposed metal silk surface;

9. remove the most advanced and sophisticated insulating barrier of microelectrode tinsel by chemical attack or electric spark mode, finish three-dimensional micro-electrode array and make.

2, the manufacture method of three-dimensional implantable microelectrode array according to claim 1 is characterized in that: described microelectrode tinsel material is tungsten, rustless steel, gold, silver, platinum or iridium.

3, the manufacture method of three-dimensional implantable microelectrode array according to claim 1 and 2 is characterized in that described microelectrode diameter wiry is between 10 microns to 500 microns.

4, the manufacture method of three-dimensional implantable microelectrode array according to claim 1 is characterized in that: described microelectrode is except that the tip, and all the other are insulated the thickness of material covering between 0.001～1 micron.

5, according to the manufacture method of claim 1 or 4 described three-dimensional implantable microelectrode arrays, it is characterized in that: described microelectrode insulating layer material is silicon dioxide, silicon nitride, polyimides, polydimethylsiloxane or Parylene.

6, the manufacture method of three-dimensional implantable microelectrode array according to claim 1 is characterized in that: the spacing between the described microelectrode adjacent electrode bar is between 100 microns to 1 millimeter.

7, the manufacture method of three-dimensional implantable microelectrode array according to claim 1 is characterized in that: described microelectrode array is to be made of 2 to 20 layers of clamping polydimethylsiloxane stack wiry bonding.