CN102336386A - Three-dimensional solid needle tip flexible micro-electrode array and making method thereof - Google Patents
Three-dimensional solid needle tip flexible micro-electrode array and making method thereof Download PDFInfo
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- CN102336386A CN102336386A CN2011103017335A CN201110301733A CN102336386A CN 102336386 A CN102336386 A CN 102336386A CN 2011103017335 A CN2011103017335 A CN 2011103017335A CN 201110301733 A CN201110301733 A CN 201110301733A CN 102336386 A CN102336386 A CN 102336386A
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Abstract
The invention provides a three-dimensional solid needle tip flexible micro-electrode array and a making method thereof. The micro-electrode array comprises a split insulating column array wrapped in an insulating flexible substrate, an electrode and an electricity conducting lead, wherein the head of an insulating column is in a shape of a needle tip and wrapped by the electrode, the needle tip electrode is exposed outside, the electricity conducting lead is paved along the insulating column and the insulating flexible substrate, one end of the electricity conducting lead is connected with the electrode, and the other end is exposed outside. The insulating column is of a solid structure, so that the electrode can be pierced into a stimulation part and effectively provide electric stimulation and record. In order to make the three-dimensional solid needle tip flexible micro-electrode array, silicon materials are treated by a silicon dicing-corrosion process for making the three-dimensional solid needle tip flexible micro-electrode array. The three-dimensional solid needle tip flexible micro-electrode array provided by the invention can be used for nerve electric stimulation and record and can be widely used in the fields of nerve disease treatment, nerve rehabilitation, neurobiology basic research and the like.
Description
Technical field
The present invention relates to a kind of 3D solid needle point flexible micro-electrode array and preparation method thereof, relate in particular to and utilize silicon scribing-corrosion preparation method to make 3D solid needle point flexible micro-electrode array, belong to the micromachining technology field.
Background technology
Human research to neural interface has continued to have surpassed 30 years.Neural interface; Be meant the direct connecting path of between human or animal's neural (perhaps culture of nerve cell) and external equipment, creating; Comprise nerve electrode and peripheral processes circuit part, realize electro photoluminescence and record, thereby reach the electrical activity that improves and analyze cortex nerve.Since the mid-90 in 20th century, this type of knowledge that from experiment, obtains is remarkable growth.On zooperal practical basis for many years, the early stage neural interface that is applied to human body is designed and creates, and is used to the sense of hearing, vision and the limb motion ability recovering to damage.The microelectrode array that is applied to nerve electric stimulation and record is as the tightst with nerve connections in the neural interface, and contact is part the most directly, and its performance directly affects the application and the efficient of neural interface.Good microelectrode array is the key issue in the neural interface research how to produce bio-compatibility, electro photoluminescence and record effect.
In recent years owing to have good bio-compatibility and to organizing less infringement based on the electrod-array of flexible substrate, by broad research be applied to the neural built-in type device of repairing.But based on this type of flexible substrate generally is the plane electrode array, and it is the most representative wherein to repair chip with the retina of the Y.C.Tai development of the M.S.Humayun of USC and Caltech (California Institute of Technology).At file " Flexible Parylene-based Microelectrode Technology for Intraocular Retinal Prostheses " in Proceedings of the 1st IEEE International Conference on Nano/Micro Engineered and Molecular Systems January 18-21,2006, Zhuhai; China (be applied to the flexible micro-electrode technology that the intraocular retina is repaired based on Parylene, first Nano/micron engineering and the meeting of molecular system International Year, January 18-21; 2006; Zhuhai, China) in, they are on the good parylene substrate of bio-compatibility; Prepare the plane electrode chip that is integrated with ASIC; Success is implanted on the eyeball retina, realizes that the electro photoluminescence retina passes to visual cortex to signal through optic nerve then, forms the artificial vision.This plane electrode can satisfy the requirement of bio-compatibility and the function of conductivity preferably, and weak point is that electrode can not effectively be adjacent to tissue, effect of stimulation is influenced, also just because this, has limited the application that this type of plane electrode is applied to other neural interfaces.
In addition, also in nerve stimulation and record, be widely used based on the three-diemsnional electrode array of rigid substrate, its three-dimensional needlepoint can penetrate tissue effectively; Galvanism and record are provided, and " Utah " electrod-array (UTAH MEA) of the Richard Normann of Univ Utah USA research and development for example is like document " Neuronal ensemble control of prosthetic devices by a human with tetraplegia " Vol 442|13July 2006; Nature is (to quadriplegia patient's nerve control prosthetic device; 442 13 phases of volume, in July, 2006, nature) report; It develops 96 electrode dot-matrix arrays based on silicon substrate; Be named as BrainGate, be applied to the intrusive mood brain-computer interface, have and successfully implant cortex and make the patient control the case of mechanical arm; Can accomplish tasks such as mechanical arm control, computer cursor control through the motion intention, the zone of corresponding arm of the motor cortex that goes back to before its implant is arranged in and hand.With BrainGate is the Cybernetics company of main product, runs after fame with Cybernetics Neurostream Technologies Inc. and goes on the market in the US stock market, and aim is the development that promotes practical human brain-computer interface technology, worldwide sells its product.But because the relation of rigid substrate, electrode must be in a fixed position in strictness, and the damage of tissue is also caused on the out-of-flatness surface of can not effectively fitting easily.The rigid substrate area can not be too big, limited the scale of electrod-array.In addition, the silicon needle point also needs the conductivity function except making support structure, and the electrode self-resistance that obtains can be very big than metal electric, and antijamming capability dies down.
So, based on the improvement of flexible substrate and three-dimensional needlepoint constantly the someone propose.People's invention disclosed patent (Chinese patent publication number CN101172184 such as the Li Gang of Shanghai micro-system institute of the Chinese Academy of Sciences; Denomination of invention " a kind of three-dimensional flexible nervus and preparation method ") in a kind of three-dimensional flexible nervus and preparation method thereof has been proposed; This microelectrode utilizes flexible polymer as base material; Through the annular patterns design of metal seed layer, carry out laddering plating, formation has the electrode site structure of slick and sly three-dimensional protruding features.But slick and sly convexity can not make electric field assemble in the tip, and the more important thing is and can't effectively penetrate tissue, is difficult to reach the optimal stimulus effect.Grand (the Chinese patent publication number CN101398614 in an invention disclosed patent once of the Li Zhi of Beijing University; Denomination of invention " a kind of preparation method of the three-dimensional needlepoint electrode array based on the Parylene Parylene ") proposed to utilize the silicon 3 D pinpoint array to prepare three-dimensional needlepoint electrode array based on Parylene (Parylene) flexible substrate; This electrod-array is a kind of Parylene-metal level-Parylene three-decker that is similar to sandwich structure, implant surgery under the retina that can be used for repairing to artificial retina.Yet this flexible substrate array is hollow needle point, can not penetrate tissue, is to limit the main cause of this arrayed applications in other nerve stimulations and record.
Summary of the invention
The technical problem that the present invention will solve provides a kind of 3D solid needle point flexible micro-electrode array, and this microelectrode array is the entity pinpoint array, can penetrate stimulation location, and electro photoluminescence and record effectively are provided.
Another technical problem that will solve of the present invention provides a kind of 3D solid needle point flexible micro-electrode array making method; Its method can be made the entity pinpoint array, can penetrate stimulation location, and electro photoluminescence and record effectively are provided; And cost is low; Can accomplish that the needle point height is big, pattern also can be controlled relatively evenly by etching process, and yield rate is high.
Technical scheme of the present invention is: a kind of 3D solid needle point flexible micro-electrode array comprises: the flexible substrate 1 of insulation, insulated column 2, needle electrode 3, conductive lead wire 4 wherein are wrapped in discrete insulated column 2 arrays in the flexible substrate 1 of insulation; Discrete insulated column 2 insulated column heads are tip-like; By needle electrode 3 parcels, needlepoint electrode is exposed outside, and conductive lead wire 4 is laid along the flexible substrate 1 of insulated column 2 and insulation; One end links to each other with needle electrode 3, and an other end is exposed outside.
Said insulated column 2 is a solid construction.
Said insulated column 2 is silicon posts.
Said needle electrode 3 is made up of Metal Cr/Au with conductive lead wire 4, and Au is on the Cr upper strata.
The Metal Cr of said needle electrode (3) and conductive lead wire (4)/Au thickness is: 15nm/150nm.
The said needle point height 400um that states needle electrode (3).
Technical scheme of the present invention also has: 3D solid needle point flexible micro-electrode array making method may further comprise the steps:
Step 1: cleaning silicon chip, LPCVD (chemical vapor deposition) SiO
2/ Si
3N
4
Step 2: silicon chip back side photoetching for the first time forms back-etching SiO
2/ Si
3N
4Figure;
Step 3: silicon chip back side dry etching SiO
2/ Si
3N
4, form silicon chip back side TMAH etching mask;
Step 4: silicon chip back side TMAH (TMAH) corrodes silicon, forms the silicon groove, is used to corrode the release of back silicon;
Step 5: silicon chip photoetching for the second time, the silicon chip dual surface lithography is at the positive etching SiO that forms of silicon chip
2/ Si
3N
4Figure, form positive TMAH etching mask; Back side dry etching Si
3N
4, wet etching is removed back side SiO then
2, so that the silicon bonding face is smooth;
Step 6: on sheet glass, do photoetching for the third time, splash-proofing sputtering metal Cr/Au, acetone ultrasonic the peeling off of removing photoresist made the metal connecting line figure;
Step 7: the silicon chip back side and glass front are aimed at anode linkage;
Step 8: with the positive SiO of silicon chip
2/ Si
3N
4Be mask, corrosion obtains discrete silicon post array, and the while is isotropic etch glass also, has formed the side direction undercutting groove under metal connecting line and the silicon post;
Step 9: the silicon post arranged in arrays metal electrode in the silicon chip front, metal electrode links to each other with metal connecting line on the sheet glass;
Step 10: deposit ground floor Parylene, and graphical etching Parylene, expose needlepoint electrode;
Step 11:HF wet etching glass, releasing structure because the side direction undercutting groove under metal connecting line and the silicon post is filled by Parylene, discharges so metal connecting line and silicon post also are wrapped in by Parylene;
Step 12: deposit Parylene in the back side obtains the 3D solid needle point microelectrode array of final flexible substrate.
Silicon caustic solution in the said step 8 may further comprise the steps:
Step 1: front dry etching SiO
2/ Si
3N
4, forming the scribe line mark, the positive scribing of silicon chip forms silicon post array;
Step 2: with SiO
2/ Si
3N
4Be mask, TMAH corrosion silicon post, silicon post sidewall is the plane; The silicon post inwardly dwindles, and the top forms the salient angle that is made up of silicon post sidewall plane for the salient angle corrosion of band convex corner compensation mask; In this process; The TMAH corrosion is the silicon groove to the back side, makes the silicon of silicon groove separate release, obtains discrete silicon post array;
Step 3: continue SiO
2/ Si
3N
4Be mask, HNA (mixed liquor of hydrofluoric acid, nitric acid, glacial acetic acid) isotropic etch silicon makes the silicon top form needle point, and mask comes off after forming needle point; While is isotropic etch glass also, has formed the side direction undercutting groove under metal connecting line and the silicon post.
Layout metal electrode method in the said step 9; May further comprise the steps: front splash-proofing sputtering metal Cr/Au, the silicon needle point is wrapped up by metal, because the existence of side direction undercutting groove; Metal on silicon needle point, the metal connecting line in the sputter and the metal separation on the glass substrate are opened, and have accomplished the graphical of metal.
Of the present invention have an effect to be: adopt above silicon scribing-corrosion to form silicon post array, cost is low, and the silicon pinpoint array height that finally obtains is determined by silicon wafer thickness, can accomplish that the needle point height is big, and pattern also can be controlled relatively evenly by etching process.
Accomplished the graphical of metal as 3D solid needle point flexible micro-electrode array making method.Avoid the metal patternization photoetching of high step, effectively improved yield rate;
Description of drawings
Fig. 1 is a kind of 3D solid needle point of the present invention flexible micro-electrode array structure sketch map.
Accompanying drawing indicates: 1 flexible substrate 1 for insulation; 2 is insulated column; 3 is needle electrode 3; 4 is conductive lead wire 4.
The specific embodiment
Below in conjunction with the description of drawings and the specific embodiment the present invention is further specified.
Fig. 1 shows the 3D solid needle point microelectrode array of flexible substrate material based on insulation with the stereogram mode, comprises discrete insulated column 2, electrode 3, conductive lead wire 4 in the flexible substrate 1 that is wrapped in insulation, and wherein insulated column 2 heads are tip-like; By electrode 3 parcels; Needlepoint electrode 3 exposes outside, and conductive lead wire 4 is laid along the flexible substrate 1 of insulated column 2 and insulation, and an end links to each other with electrode 3; An other end is exposed outside, and said insulated column 2 is a solid construction.Conductive lead wire 4 has guaranteed the reliability of electrode by double-insulated flexible substrate 1 insulation and protection; Electrode 3 places include the needle point shape head of the insulated column 2 of three-dimensional convexity, and needle point can penetrate tissue, effectively carries out electro photoluminescence and record; The flexible substrate 1 of whole insulation can be used flexible Parylene, the out-of-flatness surface of effectively fitting, and electrode 3, conductive lead wire 4 are Cr/Au; It is little to tissue injury to implant the back, and the bio-compatibility of all material is well, wherein excellent with real Parylene and the Au bio-compatibility that contacts of tissue; The needle point silicon materials are only as mechanical part; Not as electrical conductivity component, make that the electrode self-resistance is little, antijamming capability strengthens.
3D solid needle point flexible micro-electrode array making method may further comprise the steps:
LPCVD SiO on the thick N of 400um (100) silicon chip
2/ Si
3N
4, 100nm/100nm; Back side photoetching for the first time, back side dry etching SiO
2/ Si
3N
4, as mask, back side TMAH corrosion silicon 30um forms the silicon groove, is used for the release of scribing-corrosion back silicon;
Photoetching for the second time, dual surface lithography, front dry etching SiO
2/ Si
3N
4100nm/100nm forms the scribe line mark, also forms positive TMAH etching mask simultaneously; Back side dry etching Si
3N
4100nm, wet etching is removed back side SiO then
2, so that the silicon bonding face is smooth;
On sheet glass, do photoetching for the third time, wet etching glass 100nm, splash-proofing sputtering metal Cr/Au 15nm, 150nm, acetone ultrasonic the peeling off of removing photoresist made the metal connecting line figure;
The silicon chip back side and glass front are aimed at anode linkage, the groove gap of 30um make groove silicon not with the glass bonding on;
The positive scribing of silicon chip, the surplus 50um of silicon chip does not draw and wears, and forms silicon post array;
With SiO2/Si3N4 is mask, TMAH corrosion silicon post, and silicon post sidewall does<110>Face, corrosion rate is higher, the silicon post inwardly dwindles, the top is the salient angle corrosion of band convex corner compensation mask, form by<111>The salient angle that constitutes is about 54.7 degree; In this process, the TMAH corrosion is the silicon groove to the back side, makes the silicon of silicon groove separate release, obtains discrete silicon pinpoint array; Continue SiO
2/ Si
3N
4Be mask, HNA isotropic etch silicon makes the silicon top form needle point, needle point height 400um, and mask comes off after forming needle point; While is isotropic etch glass also, has formed the side direction undercutting groove under metal connecting line and the silicon post;
Front splash-proofing sputtering metal Cr/Au 15nm/150nm, the silicon needle point is wrapped up by metal, because the existence of side direction undercutting groove, metal on silicon needle point, the metal connecting line in the sputter and the metal separation on the glass substrate are opened, and have accomplished the graphical of metal;
Deposit ground floor Parylene 10um, and graphical etching Parylene expose needlepoint electrode;
HF wet etching glass, releasing structure because the side direction undercutting groove under metal connecting line and the silicon post is filled by Parylene, discharges so metal connecting line and silicon post also are wrapped in by Parylene; Deposit Parylene in the back side obtains the 3D solid pinpoint array of final flexible substrate.
Above content is to combine concrete preferred implementation to the further explain that the present invention did, and comprises material and forms of corrosions such as being not limited to Parylene, silicon, Cr/Au, can not assert that practical implementation of the present invention is confined to these explanations.For the those of ordinary skill of technical field under the present invention, under the prerequisite that does not break away from the present invention's design, can also make some simple deduction or replace, all should be regarded as belonging to protection scope of the present invention.
Claims (10)
1. 3D solid needle point flexible micro-electrode array; The flexible substrate (1), insulated column (2), needle electrode (3), the conductive lead wire (4) that comprise insulation; It is characterized in that: wherein be wrapped in discrete insulated column (2) array in the flexible substrate (1) of insulation, discrete insulated column (2) insulated column head is tip-like, is wrapped up by needle electrode (3); Needlepoint electrode is exposed outside; Conductive lead wire (4) is laid along the flexible substrate (1) of insulated column (2) and insulation, and an end links to each other with needle electrode (3), and an other end is exposed outside.
2. a kind of 3D solid needle point flexible micro-electrode array according to claim 1, it is characterized in that: said insulated column (2) is a solid construction.
3. a kind of 3D solid needle point flexible micro-electrode array according to claim 1, it is characterized in that: the flexible substrate of said insulation (1) material is a Parylene.
4. a kind of 3D solid needle point flexible micro-electrode array according to claim 1, it is characterized in that: said insulated column (2) is the silicon post.
5. according to the described a kind of 3D solid needle point flexible micro-electrode array of one of claim 1 to 4, it is characterized in that: said needle electrode (3) and conductive lead wire (4) are made up of Metal Cr/Au, and Au is on the Cr upper strata.
6. a kind of 3D solid needle point flexible micro-electrode array according to claim 4, it is characterized in that: the Metal Cr/Au thickness of said needle electrode (3) and conductive lead wire (4) is: 15nm/150nm.
7. a kind of 3D solid needle point flexible micro-electrode array according to claim 4 is characterized in that: the said needle point height 400um that states needle electrode (3).
8. a 3D solid needle point flexible micro-electrode array making method as claimed in claim 1 is characterized in that, may further comprise the steps:
Step 1: cleaning silicon chip, chemical vapor deposition SiO
2/ Si
3N
4
Step 2: silicon chip back side photoetching for the first time forms back-etching SiO
2/ Si
3N
4Figure;
Step 3: silicon chip back side dry etching SiO
2/ Si
3N
4, form silicon chip back side TMAH etching mask;
Step 4: silicon chip back side TMAH corrosion silicon, form the silicon groove, be used to corrode the release of back silicon;
Step 5: silicon chip photoetching for the second time, the silicon chip dual surface lithography is at the positive etching SiO that forms of silicon chip
2/ Si
3N
4Figure, form front TMAH etching mask; Back side dry etching Si
3N
4, wet etching is removed back side SiO then
2, so that the silicon bonding face is smooth;
Step 6: on sheet glass, do photoetching for the third time, splash-proofing sputtering metal Cr/Au, acetone ultrasonic the peeling off of removing photoresist made the metal connecting line figure;
Step 7: the silicon chip back side and glass front are aimed at anode linkage;
Step 8: with the positive SiO of silicon chip
2/ Si
3N
4Be mask, corrosion obtains discrete silicon post array, and the while is isotropic etch glass also, has formed the side direction undercutting groove under metal connecting line and the silicon post;
Step 9: the silicon post arranged in arrays metal electrode in the silicon chip front, metal electrode links to each other with metal connecting line on the sheet glass;
Step 10: deposit ground floor Parylene, and graphical etching Parylene, expose needlepoint electrode;
Step 11:HF wet etching glass, releasing structure because the side direction undercutting groove under metal connecting line and the silicon post is filled by Parylene, discharges so metal connecting line and silicon post also are wrapped in by Parylene;
Step 12: deposit Parylene in the back side obtains the 3D solid needle point microelectrode array of final flexible substrate.
9. 3D solid needle point flexible micro-electrode array making method as claimed in claim 8, it is characterized in that: the silicon caustic solution in the said step 8 may further comprise the steps:
Step 1: front dry etching SiO
2/ Si
3N
4, forming the scribe line mark, the positive scribing of silicon chip forms silicon post array;
Step 2: with SiO
2/ Si
3N
4Be mask, TMAH corrosion silicon post, silicon post sidewall is the plane; The silicon post inwardly dwindles, and the top forms the salient angle that is made up of silicon post sidewall plane for the salient angle corrosion of band convex corner compensation mask; In this process; The TMAH corrosion is the silicon groove to the back side, makes the silicon of silicon groove separate release, obtains discrete silicon post array;
Step 3: continue SiO
2/ Si
3N
4Be mask, the mixed liquor isotropic etch silicon of hydrofluoric acid, nitric acid, glacial acetic acid makes the silicon top form needle point, and mask comes off after forming needle point; While is isotropic etch glass also, has formed the side direction undercutting groove under metal connecting line and the silicon post.
10. one kind like claim 8 or 9 described 3D solid needle point flexible micro-electrode array making methods; It is characterized in that: the layout metal electrode method in the said step 9; May further comprise the steps: front splash-proofing sputtering metal Cr/Au, the silicon needle point is wrapped up by metal, because the existence of side direction undercutting groove; Metal on silicon needle point, the metal connecting line in the sputter and the metal separation on the glass substrate are opened, and have accomplished the graphical of metal.
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| CN106865491A (en) * | 2015-12-14 | 2017-06-20 | 国网智能电网研究院 | A kind of nano-electrode array and preparation method thereof |
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| CN107661571A (en) * | 2017-05-19 | 2018-02-06 | 山东大学 | Sandwich construction flexibility artificial hearing Neural stimulation electrodes and preparation method |
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| CN112717273A (en) * | 2020-12-30 | 2021-04-30 | 上海交通大学 | Nerve electrical stimulation electrode with micro-columnar structure and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102670193A (en) * | 2012-05-09 | 2012-09-19 | 中国科学院上海技术物理研究所 | Hybrid three-dimensional neuron probe array |
| CN102755691A (en) * | 2012-06-19 | 2012-10-31 | 吉林大学 | Medical high-sensitivity micro needle array electrode |
| CN106865491A (en) * | 2015-12-14 | 2017-06-20 | 国网智能电网研究院 | A kind of nano-electrode array and preparation method thereof |
| CN106865491B (en) * | 2015-12-14 | 2019-07-19 | 国网智能电网研究院 | A kind of nano-electrode array and preparation method thereof |
| CN107224666A (en) * | 2017-05-15 | 2017-10-03 | 杭州暖芯迦电子科技有限公司 | A kind of Neural stimulation electrodes and its manufacture method |
| CN107224666B (en) * | 2017-05-15 | 2023-03-24 | 杭州暖芯迦电子科技有限公司 | Nerve stimulation electrode and manufacturing method thereof |
| CN107661571A (en) * | 2017-05-19 | 2018-02-06 | 山东大学 | Sandwich construction flexibility artificial hearing Neural stimulation electrodes and preparation method |
| CN107661571B (en) * | 2017-05-19 | 2024-01-30 | 山东大学 | Flexible auditory nerve stimulating electrode array with multilayer structure |
| CN112631425A (en) * | 2020-12-21 | 2021-04-09 | 上海交通大学 | Microneedle array type brain-computer interface device and preparation method thereof |
| CN112631425B (en) * | 2020-12-21 | 2022-03-22 | 上海交通大学 | Microneedle array type brain-computer interface device and preparation method thereof |
| CN112717273A (en) * | 2020-12-30 | 2021-04-30 | 上海交通大学 | Nerve electrical stimulation electrode with micro-columnar structure and preparation method thereof |
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