CN101204603B - Embedded MENS bioelectrode and preparation technology thereof - Google Patents
Embedded MENS bioelectrode and preparation technology thereof Download PDFInfo
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- CN101204603B CN101204603B CN2007101992358A CN200710199235A CN101204603B CN 101204603 B CN101204603 B CN 101204603B CN 2007101992358 A CN2007101992358 A CN 2007101992358A CN 200710199235 A CN200710199235 A CN 200710199235A CN 101204603 B CN101204603 B CN 101204603B
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Abstract
本发明公开了一种植入式MEMS生物电极及其制备工艺，适用于临床医学中神经性疾病的康复治疗。电极采用MEMS加工技术在基底上制备图形化的刺激电极、记录电极和具有凹槽结构的电极电路引出端，通过化学气相沉积方法生长多层的防渗透绝缘层，用湿法腐蚀的方法腐蚀掉刺激电极、记录电极和电路引出端上的防渗透绝缘层，露出电极和电极引出端的金属薄膜；并结合电镀技术形成电极电路引出端的厚膜结构并实现和外接导线的可靠连接。电极的金属和绝缘层采用生物相容性很好的材料制备，在电极电路和外部导线连接后用生物聚氨酯封装刺激电极和记录电极以外的所有部分，使整个电极具有很好的生物相容性，适合长期植入人体内。
The invention discloses an implantable MEMS bioelectrode and a preparation process thereof, which are suitable for rehabilitation treatment of neurological diseases in clinical medicine. The electrode adopts MEMS processing technology to prepare patterned stimulating electrodes, recording electrodes and electrode circuit terminals with groove structure on the substrate, grows a multi-layer anti-permeation insulating layer by chemical vapor deposition, and etches it away by wet etching. The anti-penetration insulating layer on the stimulation electrode, recording electrode and circuit lead-out end exposes the metal film of the electrode and electrode lead-out end; and combines electroplating technology to form a thick film structure of the electrode circuit lead-out end and realize reliable connection with external wires. The metal and insulating layer of the electrode are made of materials with good biocompatibility. After the electrode circuit and external wires are connected, all parts other than the stimulating electrode and the recording electrode are encapsulated with biological polyurethane, so that the entire electrode has good biocompatibility. , suitable for long-term implantation in the human body.
Description
Technical field
The invention belongs to little manufacturing field, particularly a kind of MEMS bioelectrode that is suitable for implant into body and preparation method thereof, this electrode are mainly used in the chronicity implanted treatment of nervous system disease in the clinical medicine.
Background technology
In clinical medicine, for the more serious nervous system disease of treatment, as parkinsonism, optic nerve disorder, audition neurological disorder, paralysis and serious epilepsy or the like, the normal effective and efficient manner that adopts is at the long-term implant electrode in patient's brain deep by surgical operation, utilize the stimulator battery to give electrode power supply, disease sites is stimulated treat.Now the stimulating electrode of used implant into body is the millimeter ring electrode clinically, as the series of products that Medtronic Inc. produced, have 4 stimulating electrodes, its diameter is 1.26 millimeters, each electrode length is 1.5 millimeter, because its size is bigger, easily tissue is caused bigger infringement when implant into body; Power consumption is bigger, and the service life of stimulator battery is shorter relatively, and frequent replacing battery has increased patient's misery; The cost costliness, only one-sided implantation expense is about about 100,000 RMB; This product does not have recording electrode, can not accurately locate when implanting, because the brain neuron cell size is not more than 100 microns, thereby can locate because of it is oversize when adopting stimulating electrode as recording electrode and be forbidden.
Along with the development of MEMS technology, making microelectrode with micro-processing technology becomes possibility.Domestic and international many scholars have proposed different microelectrode structure and manufacture method thereof.Prepared the neuromechanism of Si base probe as people such as K.D.Wise [Proceedings of the IEEE.92 (2004) 76-96], this Si base probe-type nerve electrode has higher intensity, but its edge shape is too sharp, only the stimulation of suitable short-term or human body cortex use, can cause tissue injury when implanting the brain deep tissue, use is implanted in uncomfortable syncerebrum deep for a long time; People [Sensors and ActuatorsB.83 (2002) 8-14] such as Thomas Stieglitz have made the implantation micro-electrode having of flexible substrates, flexible basic implantation micro-electrode having is fit to the brain deep and implants, damage to tissue is little, but because its intensity is very low, is unfavorable for operating operation; In addition, adopt the connected mode of molten weld metal between the lead of millimeter ring electrode of Medtronic Inc. and connection pulse stimulater, this mode obviously is not suitable for the connection between membrane electrode and the lead.
Summary of the invention
At existing millimeter electrode and existing defective of microelectrode or deficiency, the objective of the invention is to, provide a kind of and be base material, be electrode material that preparation possesses the implanted MEMS bioelectrode of stimulating electrode and recording electrode simultaneously with Si or glass with platinum or platinumiridio.This MEMS bioelectrode can write down respectively and stimulate, and is suitable for the long-term implantation in brain deep.Its preparation method adopts and carries out the preparation of the electrode material membrane of good biocompatibility based on the spatter film forming technology of microelectronic processing technique on photoetching and the formed figure of etching, on Si substrate between the electrode or the substrate of glass and telegraph circuit on the good impermeable insulant of multilamellar of the sedimentary organism compatibility, when the exit of telegraph circuit forms thick-film technique, realize being connected of external wire and thick film in conjunction with electroplating technology, with biological polyurethane material the All Ranges outside stimulating electrode and the recording electrode is encapsulated then.Resulting MEMS bioelectrode can be used as the rehabilitation of the behavior disorder that nervous system disease causes, and can be used as the stimulation/recording electrode of long-term implant into body.
Improvements of the present invention are to adopt micro-processing technology to make to have the single face of stimulating electrode and recording electrode or the strip shaped electric poles of bilateral structure simultaneously, and the platinum of employing good biocompatibility or platinumiridio are (as PtIr
10) be electrode material, electrode film thickness is nanoscale, the recording electrode size is less than 20 microns, about 500 microns of stimulating electrode size; Adopt body silicon etching process and thin film to thicken technology in telegraph circuit exit position and have the thick film of micron order thickness as the platings making of etc.ing, realization external wire and telegraph circuit thick film is connected when preparing thick film; All good multilayer material of the circuit of stimulation/recording electrode and substrate insulating properties, anti-permeability and biocompatibility such as SiO
2/ Si
3N
4/ SiO
2Shelter, utilization has certain flexible bioabsorbable polymer material such as polyurethane is packaged near cylindrical with it.
For achieving the above object, the present invention takes following technical solution:
A kind of implanted MEMS bioelectrode, comprise a substrate, in substrate, deposit stimulating electrode, recording electrode and the impermeable insulating barrier of insulating barrier, shaping, it is characterized in that, the metal level of the telegraph circuit exit that described stimulating electrode, recording electrode are made of telegraph circuit that is shaped in the substrate and a plurality of grooves that form at substrate one end respectively is connected, and also is coated with impermeable insulating barrier on outer all body structure surfaces of stimulating electrode, recording electrode and telegraph circuit exit.
The preparation method of above-mentioned implanted MEMS bioelectrode is characterized in that may further comprise the steps:
Step 1 at first adopts the method for photoetching, wet etching to form a plurality of grooves, forming circuit exit in substrate;
Step 2, with the method for LPCVD at substrate and the groove surfaces layer insulating of growing;
Step 3, the method that adopts metal sputtering deposition or evaporation of metal to deposit and peel off is made the figure that forms stimulating electrode and recording electrode, telegraph circuit and telegraph circuit exit in substrate;
Step 4 is with the good impermeable insulating barrier of the method growth multi-layer biological compatibility of PECVD;
Step 5, the method for employing photoetching and wet etching etches away the lip-deep impermeable insulating barrier of circuit exit of stimulating electrode, recording electrode and electrode, exposes stimulating electrode, recording electrode and circuit exit;
Step 6, electroplate at the circuit exit, external wire one end that will connect is placed in the groove of circuit exit after peeling insulating barrier off, only circuit exit and external wire are inserted in the electroplate liquid then, with the other end of external wire as galvanized working electrode, peel growing metal on the external wire of insulating barrier off, filling up the groove of circuit exit until metal.
The present invention compared with prior art, its technical characterstic that brings is: utilize the microelectrode of microelectronic processing technique preparation, have stimulating electrode and recording electrode simultaneously, accurate positioning; Overall dimensions is less, avoids the damage to organizing when surgery is implanted as far as possible; Production cost is low, greatly reduces the expense that surgical operation is implanted; Utilize body silicon etching process and thick film technology as thicker telegraph circuit exits of preparation such as plating, simultaneously external wire directly is connected in the groove of telegraph circuit exit, can realize the reliable connection between electrode and the lead, help realizing the chronicity implantation use of electrode.
Description of drawings
Fig. 1～Fig. 8 is preparation technology's schematic flow sheet of implanted MEMS bioelectrode of the present invention.
Wherein:
Fig. 1 is photoetching and etching technics sketch map;
Fig. 2 is the LPCVD process schematic representation;
Fig. 3 is photoetching process and metal deposition process sketch map for the second time;
Fig. 4 is the stripping technology sketch map;
Fig. 4-a is the appearance profile diagram of Fig. 4;
Fig. 5 is the pecvd process sketch map;
Fig. 6 is photoetching process and etching technics sketch map for the third time;
Fig. 7 is the scribing process sketch map;
Fig. 8 is for electroplating sketch map;
Fig. 9 is the overall structure figure of implanted MEMS bioelectrode of the present invention;
Fig. 9-a is that A-A among Fig. 9 is to view.
Label among the figure is represented respectively: 1, substrate, 2, impermeable insulating barrier, 3, stimulating electrode, 4, recording electrode, 5, the circuit exit, 6, photoresist for the first time, 7, as the groove of circuit exit 6,8, insulating barrier, 9, photoresist for the second time, 10, metal level, 11, telegraph circuit, 12, the scribing position, 13, external wire, 14, electroplate and to use power supply, 15, electroplating solution, 16, auxiliary electrode.
The present invention is described in further detail below in conjunction with drawings and Examples.
The specific embodiment
The implanted MEMS bioelectrode of the present invention's preparation, comprise a substrate 1, the stimulating electrode 3, recording electrode 4 and the impermeable insulating barrier 2 that in substrate 1, deposit insulating barrier 8, are shaped, stimulating electrode 3 is connected with the electrode leads to client 5 that a plurality of grooves 7 that form at substrate 1 one ends constitute by the telegraph circuit 11 that is provided with in the substrate 1 with recording electrode 4, be coated with metal level 10 on the electrode leads to client 5, also be coated with impermeable insulating barrier 2 on all surface outside stimulating electrode 3, recording electrode 4 and the telegraph circuit exit 5.
The material of substrate 1 is Si, glass etc. not; The material of impermeable insulating barrier 2 adopts SiO
2/ Si
3N
4/ SiO
2Deng having the saturating insulating biological multilayer film of good barrier; Stimulating electrode 3 is of a size of micron order, and about about 500 microns, material is that biocompatibility is good as platinum or platinumiridio etc., and it is fixed that the quantity of stimulating electrode 3 can be come by needs, and present embodiment adopts 3 stimulating electrodes; The size of recording electrode 4 is less than 20 microns, and material is that biocompatibility is good as titanium/platinum or titanium/platinumiridio etc., and it is fixed that its quantity is also come by needs, and present embodiment adopts 4 recording electrodes; The quantity of circuit exit 5 is by the total quantity decision of stimulating electrode 3 and recording electrode 4, the circuit exit 5 of present embodiment always has 7, the material of circuit exit 5 and stimulating electrode, recording electrode are identical, as titanium/platinum or titanium/platinumiridio etc., be connected conducting with stimulating electrode 3 and recording electrode 4 respectively by the telegraph circuit 11 that covers under the impermeable insulating barrier 2, its size is decided by the conductor size that connects stimulator, and its size should be than conductor size about 20 microns～50 microns; The material of the photoresist 9 of photoresist 6 and photoetching for the second time adopts photoresist commonly used to get final product for the first time; The material of impermeable insulating barrier is selected SiO
2The material of metal level 10 selects biocompatibility well as titanium/platinum or titanium/platinumiridio etc.
Its preparation technology comprises the combination of following technology: photoetching and etching technics (accompanying drawing 1), LPCVD technology (accompanying drawing 2), photoetching process and metal deposition process (accompanying drawing 3), stripping technology (accompanying drawing 4 and accompanying drawing 4-a), pecvd process (accompanying drawing 5), photoetching process and etching technics (accompanying drawing 6), scribing process (accompanying drawing 7), electroplating technology (accompanying drawing 8) for the third time for the second time.
In the present embodiment, for the groove of the circuit exit 5 that obtains being exposed to lateral electrode so that carry out follow-up electroplating technology, when design layout, with 2 MEMS electrode pattern designs together, scratch from the scribing position 12 between two MEMS electrodes during scribing, can obtain required electrode structure, as shown in Figure 7.The circuit 11 under stimulating electrode 3, recording electrode 4, impermeable insulating barrier are sheltered and the metal level of telegraph circuit exit 5 all are the good conductive material of biocompatibility, can be materials such as platinum or platinumiridio; Impermeable insulating barrier 2 can be multiwalled SiO
2/ Si
3N
4/ SiO
2Deng material; The quantity of the circuit exit 5 of stimulating electrode 2, recording electrode 3 and electrode can be determined according to real needs; Present embodiment is a single-sided structure, also can be bilateral structure, can constitute other various embodiments thus.
The specific implementation process of present embodiment is as follows:
(1) in substrate 1, applies photoresist 6 for the first time, carry out photolithographic exposure after the preceding baking, in developer solution, after the dissolving, obtained the figure of the circuit exit 5 of electrode by the zone of illumination (in the perhaps negative glue not by the zone of illumination) in the positive glue in the exposure back substrate 1; With the substrate 1 in the resulting photoresist figure of etching method etching, in substrate 1, etch about 100 microns dark grooves 7, the structure of this groove 7 is as the circuit exit 5 of back.Remove photoresist 6 for the first time after the etching.Substrate 1 can be commercially available Si sheet or glass disc, the optional commercially available photoresist commonly used of photoresist, etching method can select as dry etching or wet etching.
(2) LPCVD even growth SiO on substrate 1 and groove 7 surfaces
2Insulating barrier 8, thickness are about 500 nanometers.SiO
2Layer has the effect that stops impurity to be invaded, and is a kind of very good electrically insulating material, and chemical property is highly stable, is again a kind of biocompatibility material preferably simultaneously, can be used as the spacer medium or the dielectric material of telegraph circuit.
(3) photoetching for the second time and depositing metal films 10.Resist coating 9 for the second time, the figure of the groove 7 of expose, develop after the preceding baking stimulating electrode 3, recording electrode 4, telegraph circuit 11 and circuit exit 5 is then by sputtering technology depositing metallic films 10.
In little processing, the microelectrode material selects as gold, titanium, platinum and alloy thereof.Gold is the good electrode material of a kind of electric conductivity, and its little processing characteristics is also relatively good, but its biocompatibility is relatively poor; Titanium and alloy thereof are the good materials of a kind of biocompatibility, but as electrode material, its impedance is bigger; Platinum and alloy thereof not only biocompatibility are fine, and its impedance is less, and have good corrosion resistance, as PtIr10 alloy etc.All metal materials are all selected platinum or platinum alloy preparation for use in the MEMS electrode of the present invention.For increasing the adhesion of metal and substrate, adopt titanium/platinum or titanium/platinumiridio multiple layer metal layer, titanium film thickness is about 10～30 nanometers, and the thickness of platinum or platinumiridio film is about 200～400 nanometers.
(4) peel off photoresist 9 and the metal level (lift-off) on it for the second time.Dissolving photoresist 9 second time in photoresist solvent peels off photoresist 9 and the metal level (lift-off) on it for the second time, obtains the metal layer image of stimulating electrode 3, recording electrode 4, telegraph circuit 11 and circuit exit 5.
(5) PECVD generates impermeable insulating barrier 2.For avoiding the conducting between conducting, telegraph circuit and the external world between the different electrodes, adopt the insulating barrier of certain material to shelter SiO between the circuit 11 of electrode
2Be the insulating film material of using always, but in human body during life-time service, the Na+ ion in the biotic environment facilitate penetration of SiO
2Thin film, the insulating properties of destruction film; Si
3N
4Density of film is bigger, and is strong to the ionic blocking capability of Na+, can adopt the multi-layer film structure such as the SiO of good biocompatibility
2/ Si
3N
4/ SiO
2Wait impermeable and insulation, its gross thickness is about about 1 micron.
(6) photoetching for the third time and etching technics.The method of employing photoetching and wet etching etches away the impermeable insulating barrier 2 on stimulating electrode 3, recording electrode 4 and the circuit exit 5, exposes the metallic film of the circuit exit 5 of stimulating electrode 3, recording electrode 4 and electrode.
(7) scribing.From the centrage between two MEMS electrodes is that scratch scribing position 12, can obtain the structure at side exposed electrode circuit exit 5 grooves.
(8) electroplate.The external wire 13 that will connect is as PtIr
10Alloy one end is peeled insulating barrier off and is placed in the metal groove of corresponding electrode circuit exit 5, only the circuit exit 5 and the external wire of electrode are inserted in the electroplate liquid 15 then, the other end with the external wire 13 that will connect is galvanized working electrode, peel growing metal platinum on the end face of insulating barrier off at external wire 13, fill up the groove of circuit exit 5 until platinum, directly external wire 13 is connected in the metal level of groove, realizes that external wire 13 is connected with the reliable of groove metal.
In microelectronics processing, the thin film upper conductor draw general employing ultrasonic wire bonding or ultrasonic heat pressure welding point method, mainly be applicable to being connected of soft metal class thin film that fusing points such as gold, copper and aluminum are relatively low and lead.Metallic film material of the present invention is platinum or platinumiridio, its fusing point very high (pure platinum is about 1772 ℃, and gold is about 1063 ℃), and hardness is very high, adopts pressure welding can't realize being connected of platinum and platinum film; And pressure welding weld strength very low (having only several gram forces), in the time of can not satisfying the electrode surgery and implant to the requirement of lead bonding strength.Adopt the mode of melting to connect nano level metal thin film and lead, the thermal source of melting will destroy metallic film, causes the circuit can not conducting.The present invention adopts the bulk silicon technological etching to form dark groove, bond deposition and electroplating technology, and the metal platinum that plating is separated out is constantly assembled growth until filling up groove on external wire 13, can realize reliable connection.
Claims (7)
1. implanted MEMS bioelectrode, comprise a substrate (1), in substrate (1), deposit insulating barrier (8), the stimulating electrode (3) and recording electrode (4) and the impermeable insulating barrier (2) that are shaped, it is characterized in that, described stimulating electrode (3), recording electrode (4) is gone up the telegraph circuit (11) that is provided with by substrate (1) respectively and is connected with the electrode leads to client (5) that a plurality of grooves (7) that form at substrate (1) one end constitutes, be coated with metal level (10) on the electrode leads to client (5), be coated with impermeable insulating barrier (2) on all structures outside stimulating electrode (3) and recording electrode (4) and the telegraph circuit exit (5).
2. implanted MEMS bioelectrode as claimed in claim 1 is characterized in that, described metal level (10) is titanium/platinum or titanium/platinumiridio film.
3. implanted MEMS bioelectrode as claimed in claim 1 is characterized in that described impermeable insulating barrier (2) is by SiO
2Thin film and Si
3N
4Film combinations constitutes.
4. implanted MEMS bioelectrode as claimed in claim 1 is characterized in that, the surface of described stimulating electrode (3) and recording electrode (4) is lower than impermeable insulating barrier (2),
5. the preparation technology of the described implanted MEMS of claim 1 bioelectrode is characterized in that may further comprise the steps:
Step 1 at first adopts the method for photoetching, wet etching to go up formation a plurality of grooves (7), forming circuit exit (5) in substrate (1);
Step 2, with the method for LPCVD at the region surface of substrate (1) and groove (7) layer insulating (8) of growing;
Step 3, the method that adopts metal sputtering deposition or evaporation of metal to deposit and peel off goes up in substrate (1) makes the figure that forms stimulating electrode (3) and recording electrode (4), telegraph circuit (11) and telegraph circuit exit (5);
Step 4 is with the good impermeable insulating barrier (2) of the method growth multi-layer biological compatibility of PECVD;
Step 5, the method for employing photoetching and wet etching etches away the lip-deep impermeable insulating barrier of circuit exit (5) (2) of stimulating electrode (3), recording electrode (4) and electrode, exposes stimulating electrode (3), recording electrode (4) and circuit exit (5);
Step 6, circuit exit (5) is electroplated, external wire (13) one ends that will connect are placed in the groove (7) of circuit exit (5) after peeling insulating barrier off, only circuit exit (5) and external wire (13) are inserted in the electroplate liquid then, with the other end of external wire (13) as galvanized working electrode, peel upward growing metal of the external wire of insulating barrier (13) off, filling up the groove (7) of circuit exit (5) until metal.
6. technology as claimed in claim 5 is characterized in that, the material of described insulating barrier (8) is SiO
2
7. technology as claimed in claim 5 is characterized in that, the metal material that described plating is adopted is platinum or platinumiridio.
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|---|---|---|---|---|
| CN101502699B (en) * | 2009-03-09 | 2011-06-01 | 西安交通大学 | An implantable bioelectrode and its manufacturing method |
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| CN103239800A (en) * | 2013-04-22 | 2013-08-14 | 中国科学院苏州生物医学工程技术研究所 | Flexible multi-channel deep brain stimulation three-dimension electrode based on micromachining technology |
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| CN105232058B (en) * | 2015-11-12 | 2019-03-01 | 三诺生物传感股份有限公司 | A kind of flexibility implant electrode |
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| CN107301958B (en) * | 2017-06-07 | 2025-02-14 | 杭州暖芯迦电子科技有限公司 | Wire bonding device and bonding method for implantable microelectronic products |
| CN107647865B (en) * | 2017-09-20 | 2020-08-21 | 国家纳米科学中心 | A kind of flexible biological electrode and its preparation method and application |
| CN107585735B (en) * | 2017-09-22 | 2019-10-29 | 上海交通大学 | A kind of artificial cochlea electrode and preparation method thereof |
| CN110408981A (en) * | 2019-09-11 | 2019-11-05 | 河南理工大学 | An electroplating connection device for micro wires |
| CN111134831A (en) * | 2019-12-31 | 2020-05-12 | 上海交通大学 | Meander-wire-based flexible MEMS stretchable sensor and its fabrication method |
| CN112023131B (en) * | 2020-08-28 | 2023-08-18 | 杭州未名信科科技有限公司 | Electroosmosis driving module, implanted electroosmosis micropump device and electric extraction method |
| CN113038724A (en) * | 2021-03-02 | 2021-06-25 | 微智医疗器械有限公司 | Manufacturing method of circuit board, circuit board and electronic equipment |
| CN113855034A (en) * | 2021-09-10 | 2021-12-31 | 北京大学 | Microneedle electrode and preparation method thereof |
| CN113797441A (en) * | 2021-10-14 | 2021-12-17 | 杭州电子科技大学温州研究院有限公司 | Brain deep stimulation electrode based on MEMS technology |
| CN116077829B (en) * | 2023-01-18 | 2023-12-15 | 微智医疗器械有限公司 | Implant device, electro-stimulator, and electrode plating method |
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