CN101006953A - Artificial retina neural flexible microelectrode array chips and processing method thereof - Google Patents
Artificial retina neural flexible microelectrode array chips and processing method thereof Download PDFInfo
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- CN101006953A CN101006953A CN 200710036558 CN200710036558A CN101006953A CN 101006953 A CN101006953 A CN 101006953A CN 200710036558 CN200710036558 CN 200710036558 CN 200710036558 A CN200710036558 A CN 200710036558A CN 101006953 A CN101006953 A CN 101006953A
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Abstract
The invention discloses a flexible array micro-electrode chip of artificial retinal nerve and making method, which comprises the following steps: adopting poly-p-xylene as flexible base; making several micro-electrode sensitive elements; synthesizing micro-electrode array and micro-cable lead, lead contact and switching interface; constituting the product.
Description
Technical field
The present invention relates to a kind of artificial retina neural flexible array micro-electrode chip and manufacture method thereof, be subjected to producing after the electricity irritation principle design micro-electrode chip of visual signal according to sclera in the vitreous body of eye or optic nerve, the employing micro-electromechanical processing technology is prepared from, the key technology that relates to artificial retina belongs to biomedical engineering and MEMS (MEMS) crossing domain.
Background technology
Artificial retina neural flexible array micro-electrode chip be a kind of be substrate with the flexible material, the surface has the metal material microelectrode unit of a plurality of arrays, in the implantable, dock with optic nerve, the transmitting telecommunication breath, thus stimulate optic nerve to reach a kind of nerve microelectrode chip that recovers visual performance.Traditional microelectrode is mainly used in neuroelectricity physiological Study and functional nerve electric stimulation clinically at present.By nerve microelectrode, can carry out electricity irritation to N﹠M, and record is from the signal of telecommunication of sensor or motor fiber.Artificial retina neural flexible array micro-electrode chip belongs to a kind of of nerve microelectrode, bringing into play important function as the artificial retina neural flexible array micro-electrode chip of substrate aspect retina reparation and the retina prosthese with flexible material or silicon (Si) material, this method principle is: after accepting ambient light information by the implant prosthese, convert bioelectrical signals to, stimulate and activation retinal neuronal cell and connection network thereof, import the signal of telecommunication into the brain visual center through optic nerve then.For being lost by the photoreceptor due to retinitis pigmentosa (RP) and the age-related macular degeneration (AMD), the alternative amphiblestroid partial function of this device makes eye blind or that be on the brink of to lose one's sight regain the useful vision of part.
The research of nerve microelectrode starts from the 1950's and rests on initial stage for a long time.Along with the development of little power technology and Ophthalimic microsurgery, the research that plays the artificial vision field nineties has just had significant progress.Wherein, the preparation of optic nerve interface becomes a big emphasis and a difficult point.Though the material of intraocular implant has better biocompatibility, place ophthalmic for a long time, a series of current active that produced are still the problem that attracts people's attention to influence, the implant long-time stability within the eye of local and whole retinal tissue.
Usually nerve microelectrode generally adopts flexible polymer as backing material, this class nerve microelectrode is as the excellent tools that detects and write down nerve signal, especially as amphiblestroid restoration, be used for treating age-related macular degeneration (AMD) and retinitis pigmentosa (RP), great value and application prospect are arranged.
At present flexible nervus mainly adopts two kinds of materials as substrate: polyimides (Polyimide) and Parylene (Parylene).By the biocompatibility test experiments, prove that polyimides and tissue have the good compatibility, after the implantation, have good stability.But the relative Parylene of polyimides, in dielectric constant, dielectric loss, water absorption, and exist certain limitation (Choong Jae Lee on the performances such as tensile strength and yang type modulus, Seung Jae Oh, Jong Keun Song, Sung June Kim, Neural signal recording using microelectrode arrays fabricated on liquid crystalpolymer material, Materials Science and Engineering C 24 (2004) 265-268).People wish to find the flexible base material that a kind of impedance is low, Phase delay is little, mechanical property is excellent, to reduce the hot injury that nervous tissue is caused to greatest extent in the stimulating electrical signal process.The flexible electrode chip that with Parylene is substrate has better performance, by this micro-electrode array stimulus of direct current retina, i.e. and retina chip technology, the potentiality that produce desirable vision are bigger.Implant is seemingly most promising under the retina, because meet normal vision mechanism most, does not need too much external encode program.Present research institution mainly contains the Alan Chow research group of Univ Chicago USA and the EberhartZrenner research group of German Tubingen university.
In addition, be that the artificial retina neural flexible array micro-electrode chip of substrate has following some advantage again: (1) excellent biological compatibility and biological stability with Parylene; (2) film thickness controllability, minimum thickness can reach 500A; (3) ultra-thin property can cover the surface of all exposures of object; (4) miniature sealability; (5) excellent in chemical performance, the ability of moistureproof moist and block electrons.Through USP (Certificateof Compliance, USP Biological Test.North American Science Associates, Incorporated, Northwood, Ohio) Pyatyi plastics system and ISO-10993 prove that in this test aspect several of cytotoxicity, sensitization, intradermoreaction, acute system toxicity and blood compatibility Parylene has comprehensively performance reliably.As the processing substrate, both for design with make a kind of flexible package system and cleared away obstacle, the implantation for this artificial retina neural flexible array micro-electrode chip provides convenience again with it.Increased the success rate of implanting greatly.
At present, the most research of Chinese scholars mainly concentrates on the polyimides (Polyimide), then mostly concentrate on the test analysis (Wu Liqun of material property about the report of Parylene, the Parylene conformal coat, the electric mechanical engineering, 2004 the 20th the 6th phases of volume, 51-53), it relates to application also mainly is coating, wrap articles, and the applied research that relates to flexible optic nerve film seldom.
Summary of the invention
The objective of the invention is to deficiency at the prior art existence, a kind of artificial retina neural flexible array micro-electrode chip and manufacture method thereof are proposed, the micro-electrode chip of preparation has the characteristics of mechanical property excellence, stable work in work, can be used for substituting amphiblestroid partial function, make blind or frequency domain blind eye regain the useful vision of part, and can reduce the hot injury who in the stimulating electrical signal process nervous tissue is caused.
For realizing this purpose, the present invention is substrate with the Parylene, adopt the MEMS processing technique, on this flexible base material, prepare microelectrode array, and microelectrode array and metal lead wire layer, lead contact, cable tail, converting interface etc. partly constituted a retina chip conglomerate, and can be used for implanting ophthalmic, dock with optic nerve, the transmitting telecommunication breath, thus stimulate optic nerve to reach the recovery visual performance.
The present invention is directed to the amphiblestroid organizational structure of human body, consider that from implanting space and nerve stimulation two aspects the artificial retina neural flexible array micro-electrode chip of design is made of array, metal lead wire layer, lead contact, cable tail, converting interface five parts that flexible substrates, the responsive unit of microelectrode constitute.Flexible base material is Parylene, size: long 3000～4000 μ m, wide 1000 μ m, high 5～10 μ m.On the flexible substrates, become microelectrode array by the responsive identical permutation of several microelectrodes, the metal lead wire layer that the responsive unit of each microelectrode draws is connected to lead contact, is connected to converting interface via cable tail at last.
The responsive unit of microelectrode is made of the Ti/Pt composite material, and diameter is 50 μ m～200 μ m, and Ti/Pt thickness is 10～50nm/300～500nm; The responsive unit of microelectrode is 16～64, and the spacing between the responsive unit of microelectrode is 50 μ m～200 μ m.Cable tail adopts metal Pt or Au material, and responsive first number is corresponding has 16～64 with microelectrode, external coated insulant, and to both sides or extend all around, live width is 5 μ m～50 μ m.
Wherein the preparation of flexible substrates is a key issue, its whether good success rate that directly determines subsequent technique, and the overall performance of artificial retina neural flexible array micro-electrode chip.So the thickness of substrate can not be too thick (the RIE etch period is of a specified duration excessively, easily cause Parylene aging), can not too thin (can't support electrode, and curl easily).
The artificial retina neural flexible array of the present invention micro-electrode chip manufacture method comprises following concrete steps:
1, deposit layer of even Parylene on the Si sheet in any crystal orientation, the flexible substrates of formation support electrode, flexible substrates thickness is 5～20 μ m;
2, spin coating photoresist on flexible substrates, thickness is 5 μ m, obtains the mask layer pattern behind the photoetching development;
3, sputter thickness is the metal A l of 300nm～500nm on the mask layer pattern, uses lift-off (peeling off) technology then, obtains the metal mask layer;
4, the metal mask layer is carried out reactive ion etching (PIE) in oxygen atmosphere, remove unwanted Parylene, obtain base patterns;
5, wet etching, adopting concentration is 2% HCl solution, 20～40 ℃ of following etchings 10～20 minutes, removes the mask layer metal A l on the base patterns;
6, continue the spin coating photoresist, thickness is 5 μ m, behind the exposure imaging, obtains the microelectrode array figure;
7, on the microelectrode array figure that obtains splash-proofing sputtering metal Ti/Pt layer as the responsive first material of microelectrode, Ti/Pt thickness is 10～50nm/300～500nm, then utilize lift-off technology, obtain the Si base microelectrode array that the responsive unit of microelectrode constitutes, the responsive unit of each microelectrode all has the metal lead wire layer of drawing to be connected to lead contact.Then Si base microelectrode array being placed concentration is 1%～2% HF solution, soaks 2～3 minutes, cleans the back and from the Si sheet microelectrode array is stripped down, and obtains the bare chip of artificial retina neural flexible array microelectrode;
8, by bond technology cable tail is connected with the chip converting interface with lead contact, adopts the Parylene thin-film material that bare chip is encapsulated then, only that the responsive unit of microelectrode is exposed, obtain artificial retina neural flexible array micro-electrode chip.
Artificial retina neural flexible array micro-electrode chip involved in the present invention, adopted Parylene to do the flexible electrode substrate, it has the characteristic that impedance is low, Phase delay is little, mechanical property is excellent, can reduce the hot injury that nervous tissue is caused in the stimulating electrical signal process to greatest extent.Place ophthalmic for a long time, by this artificial retina neural flexible array micro-electrode chip stimulus of direct current retina, the potentiality that produce desirable vision are bigger, and long-time stability are good.
Description of drawings
Fig. 1 is the artificial retina neural flexible array of a present invention micro-electrode chip structure chart.
Among Fig. 1,1 is flexible substrates, and 2 is the responsive unit of microelectrode, and 3 is the metal lead wire layer, and 4 is lead contact, and 5 is cable tail, and 6 is converting interface.
Fig. 2 is the process chart of the artificial retina neural flexible array of the present invention micro-electrode chip manufacture method.
The Si base microelectrode array of the different size that Fig. 3 prepares simultaneously for the inventive method.
Fig. 4 is a microelectrode array structure among Fig. 3.
The specific embodiment
Below in conjunction with accompanying drawing technical scheme of the present invention is described in detail.
The artificial retina neural flexible array micro-electrode chip structure of the present invention's design is made of flexible substrates 1, the responsive unit 2 of microelectrode, metal lead wire layer 3, lead contact 4, cable tail 5 and converting interface 6 as shown in Figure 1.On the flexible substrates 1, be arranged in microelectrode array by several by the responsive unit 2 of microelectrode that the Ti/Pt composite material constitutes, the responsive unit of each microelectrode 2 metal lead wire layers 3 of drawing are connected to lead contact 4, are connected to converting interface 6 via cable tail 5 at last.
The material of flexible substrates 1 is Parylene, size: long 3000～4000 μ m, wide 1000 μ m, high 5～10 μ m; On the flexible substrates 1, responsive unit 2 is arranged in microelectrode array by several microelectrodes, and the responsive unit of microelectrode 2 is made of the Ti/Pt composite material, and diameter is 50 μ m～200 μ m, and Ti/Pt thickness is 10～50nm/300～500nm; The responsive unit 2 of microelectrode in the microelectrode array is 16～64, and the spacing between the responsive unit 2 of microelectrode is 50 μ m～200 μ m; Metal lead wire layer 3 adopts metal Pt or Au material, has 16～64 with the responsive unit of microelectrode 2 is corresponding one by one, external coated insulant, and to both sides or extend all around, live width is 5 μ m～50 μ m.Lead contact 4 is connected with converting interface 6 by cable tail 5.
Fig. 2 is the flow chart of the artificial retina neural flexible array of the present invention micro-electrode chip manufacture method, and concrete implementation step is as follows:
1, deposit one deck Parylene is as flexible substrates on the Si sheet in any crystal orientation, and shown in Fig. 2 a, the thickness of flexible substrates is 5～20 μ m (equipment: SCS PDS 2060PC, pressure: 2～18mTorr, temperature :-20～50 ℃).
2, spin coating photoresist on flexible substrates, thickness are 5 μ m (Fig. 2 b); Obtain mask layer pattern (Fig. 2 c) behind the photoetching development.
3, on the mask layer pattern sputter thickness be 300nm～500nm metal A l (Fig. 2 d) (equipment: A-SPC-350, pressure: 100mTorr, 40～60 ℃ of temperature, the time: 4～7min), use lift-off technology then, obtain metal mask layer (Fig. 2 e).
4, the metal mask layer is carried out reactive ion etching (RIE) in oxygen atmosphere, remove unwanted Parylene, obtain base patterns (Fig. 2 f) (equipment: Alcatel Nextral 100, pressure: 120mTorr, temperature: 20 ℃, gas concentration: 24sccm).
5, wet etching, adopting concentration is 2% HCl solution, 20～40 ℃ of following etchings 10～20 minutes, removes the mask layer metal A l (Fig. 2 g) on the base patterns.
6, continue the spin coating photoresist, thickness is 5 μ m (Fig. 2 h), behind the exposure imaging, obtains microelectrode array figure (Fig. 2 i).
7, on the microelectrode array figure that obtains splash-proofing sputtering metal Ti/Pt layer as the material of the responsive unit of microelectrode, Ti/Pt thickness is 10～50nm/300～500nm (Fig. 2 j), (equipment: Comptech 2440-C, pressure 100mTorr, temperature: 60～100 ℃, the time: 40～60min); Utilize lift-off technology again, obtain the Si base microelectrode array (Fig. 2 k) that constitutes by the responsive unit of microelectrode.It is 1%～2% HF solution that Si base microelectrode array is placed concentration, soaked 2～3 minutes, the microelectrode array that cleans the back and from the Si sheet will be with Parylene substrate strips down, and finally obtains artificial retina neural flexible array microelectrode nude chip (Figure 21).
The sketch map of the Si base microelectrode array of the different size that Fig. 3 prepares simultaneously for the inventive method.Fig. 4 is a microelectrode array structure among Fig. 3, and the responsive unit 2 of each microelectrode all has the metal lead wire layer 3 of drawing to be connected to lead contact 4.
8, by bond technology cable tail 5 is connected with chip converting interface 6 with lead contact 4 at last, adopt the parylene film material that bare chip is encapsulated then, only the responsive unit 2 of microelectrode is exposed, obtain artificial retina neural flexible array micro-electrode chip.
Claims (3)
1, a kind of artificial retina neural flexible array micro-electrode chip is characterized in that being made of flexible substrates (1), the responsive unit of microelectrode (2), metal lead wire layer (3), lead contact (4), cable tail (5) and converting interface (6); The material of described flexible substrates (1) is a Parylene, on the flexible substrates (1), be arranged in microelectrode array by several by the responsive unit of microelectrode (2) that the Ti/Pt composite material constitutes, the metal lead wire layer (3) that the responsive unit of each microelectrode (2) draws is connected to lead contact (4), is connected to converting interface (6) via cable tail (5) at last.
2,, it is characterized in that long 3000～4000 μ m of described flexible substrates (1), wide 1000 μ m, high 5～10 μ m according to the artificial retina neural flexible array micro-electrode chip of claim 1; The responsive unit of described microelectrode (2) is 16～64, and diameter is 50 μ m～200 μ m, and the thickness of (2) the material Ti/Pt of the responsive unit of microelectrode is 10～50nm/300～500nm, and the spacing between the responsive unit of microelectrode (2) is 50 μ m～200 μ m; Described metal lead wire layer (3) adopts metal Pt or Au material, external coated insulant, and live width is 5 μ m～50 μ m.
3, the manufacture method of a kind of claim 1 or 2 artificial retina neural flexible array micro-electrode chip is characterized in that comprising the steps:
1) on the Si sheet in any crystal orientation deposit one deck Parylene as flexible substrates (1), flexible substrates (1)
Thickness is 5～20 μ m;
2) go up the spin coating photoresist in flexible substrates (1), thickness is 5 μ m, obtains the mask layer pattern behind the photoetching development;
3) sputter thickness is the metal A l of 300nm～500nm on the mask layer pattern, uses stripping technology then, obtains the metal mask layer;
4) the metal mask layer is carried out reactive ion etching in oxygen atmosphere, remove unwanted Parylene, obtain base patterns;
5) wet etching, adopting concentration is 2% HCl solution, 20～40 ℃ of following etchings 10～20 minutes, removes the mask layer metal A l on the base patterns;
6) continue the spin coating photoresist, thickness is 5 μ m, behind the exposure imaging, obtains the microelectrode array figure;
7) on the microelectrode array figure that obtains splash-proofing sputtering metal Ti/Pt layer as the material of the responsive unit of microelectrode (2), Ti/Pt thickness is 10～50nm300～500nm, utilize stripping technology again, the Si base microelectrode array that acquisition is made of the responsive unit of microelectrode (2), the responsive unit of each microelectrode (2) all has the metal lead wire layer (3) of drawing to be connected to lead contact (4); Then Si base microelectrode array being placed concentration is 1%～2% HF solution, soaks 2～3 minutes, cleans the back and from the Si sheet microelectrode array is stripped down, and obtains the bare chip of artificial retina neural flexible array microelectrode;
8) by bond technology cable tail (5) is connected with chip converting interface (6) with lead contact (4), adopt the parylene film material that bare chip is encapsulated then, only that the responsive unit of microelectrode (2) is exposed, obtain artificial retina neural flexible array micro-electrode chip.
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| CN101172184B (en) * | 2007-10-10 | 2010-09-01 | 中国科学院上海微系统与信息技术研究所 | Three-dimensional flexible nervus and preparation method |
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