CN102335065A - Implanted retina micro-stimulation electrode chip with drug slow release function - Google Patents
Implanted retina micro-stimulation electrode chip with drug slow release function Download PDFInfo
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- CN102335065A CN102335065A CN2011102135457A CN201110213545A CN102335065A CN 102335065 A CN102335065 A CN 102335065A CN 2011102135457 A CN2011102135457 A CN 2011102135457A CN 201110213545 A CN201110213545 A CN 201110213545A CN 102335065 A CN102335065 A CN 102335065A
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Abstract
The invention provides an implanted retina micro-stimulation electrode chip with a drug slow release function, which comprises an electrode substrate and micro-electrodes, wherein all micro-electrodes are distributed on the electrode substrate in a display mode and protrude out of the surface of the electrode substrate; annular micro-grooves which are distributed adjacently and are used for drug slow release are arranged on the electrode substrate; each micro-electrode is respectively arranged at the center of a circle of each annular micro-groove; a drug slow release coating is coated on the surface of each annular micro-groove; and drugs are released to biological tissues on the surface of a micro-electrode chip through the micro-grooves on the micro-electrodes. In the invention, a micro-electrode substrate is used as a platform for carrying drugs, and a polymer carrier is used for controlling the drug slow release time, so that the drugs are released. The drugs can improve the transmission efficiency of neural electric stimulation signals on an electrode-tissue interface and can improve the control on drug slow release directionality. Strip-shaped micro-channels are also arranged on the electrode substrate and are communicated with the annular micro-grooves, and drugs to be slowly released are stored in the strip-shaped micro-channels, thus the drug storage capacity is larger and the life cycle of the drugs is prolonged.
Description
Technical field
The present invention relates to the artificial retina technical field, be specifically related to a kind of implanted retinal microstimulation electrode chip with the medicament slow release function.
Background technology
Retinitis pigmentosa (retinitis pigmentosa RP), age related maculopathy (age-related macular degeneration; Outer retina degenerative disease such as AMD); Be the main oculopathy that causes nerve blind; Still there is not effective treatment means at present, serious harm people's quality of life, and caused the huge social burden.Humayun etc. find that with histological examination the internal layer neuron of 78.14 % is still survived in because of the retinal tissue of suffering from the blind eye of RP.When Chow etc. confirm to accept electricity irritation before the retina and under the retina in animal eye, all can record visual cortex and bring out potentiometric response.These experimental results show that visual system can be activated by extraneous electricity irritation.
Artificial retina obtains external image through the miniature image acquisition system, and be translated into the retinochrome neuron can identified signal, thereby recover the blind patient's of degeneration retina sensitization function.Artificial retina mainly is applicable to the outer retina degenerative disease, like RP, AMD etc.The report of relevant artificial retina is shown in 1956 the earliest, and after reports such as Tassiker placed 1 blind person's retina with a little and flat photosensitive selenium cell, the patient had recovered light sensation in a short time.After the 90's of 20th century, because the progress of electronic technology and medical science level, artificial retina has become vision and has repaired field direction with fastest developing speed.Its ultimate principle is to utilize the prosthese of implanting that outside visual signal is converted into the signal of telecommunication, directly stimulates the retinal neuronal cell of internal layer, to replace photoreceptor cell, makes the patient produce phosphene, and so the blind patient of degeneration retina can recover vision to a certain degree.According to the implantation position of stimulating electrode chip, artificial retina is divided into top layer type artificial retina (stimulating chip to be positioned at ophthalmic retina top layer), outer stratotype artificial retina (stimulating chip between neuroepithelium of retina and retinal pigment epithelium) at first.Afterwards, for reducing, occurred again amphiblestroid indirect electrical stimulus patterns is comprised electrode chip is implanted between choroid and the sclera, or is fixed on outside the sclera to amphiblestroid damage.
Chinese patent number is 200610025215.4 to disclose " a kind of implantable sheet type optic nerve micro stimulating electrode " in biomedical engineering technology field, comprising: electrode basement, microelectrode, electrode lead, lead-in wire substrate, lead-in wire interface and bunch of cables.Microelectrode is distributed on the electrode basement and protrudes in the surface of electrode basement, and it is right to form microelectrode by two or more microelectrodes in the horizontal direction, the microelectrode of being formed between in vertical direction space stagger; The electrode lead connects microelectrode and lead-in wire interface, and walking is at the surface or the interlayer of electrode basement; The lead-in wire substrate directly links to each other with electrode basement; The lead-in wire interface is distributed in the surface of lead-in wire substrate; Bunch of cables is made up of the cable that connects lead-in wire interface and external equipment.The present invention can stimulate optic nerve fiber effectively, and optic nerve fiber is transmitted to visual cortex with the stimulating current that stimulator produces, and makes visual cortex produce the excitement that produces behind the similar photostimulation retina, thereby produces phosphene, and can write down the current potential of optic nerve fiber.In addition, multinomial patent is mentioned the release method of medicine, like 101940802 patented inventions " stent for controlled drug release ", medicine is used to suppress intimal thickening; 101757718 patented inventions " method for preparing of implanted magnetic control drug microchip ", drug release are to be utilized on the medicine to cover four ferric oxide nanometer particles, thus through pulse to medicine fix a point, regularly, quantitative release; CN200710039131 has announced a kind of " sandwich type medical releasing film and preparation method thereof ", realizes that the hysteresis of medicine discharges, and lag time is controlled.CN200610021508 provides a kind of " having biological material film of loose structure and preparation method thereof ", is used to prevent postoperative tissue adhesion etc.
Yet along with going deep into of research, electricity irritation retina recovery technique runs into many difficult problems gradually, and one of them subject matter one is that after a period of time that implants, microelectrode array can't effectively be worked.Experimental analysis learns that one of reason is the therapeutic effect that glial cell parcel degree all influences retina electrostimulation to some extent.
Summary of the invention:
The deficiency that implants and effectively to work after a period of time to microelectrode array; The technical problem that the present invention solves is; After the artificial retina microelectrode that overcomes the traditional electrical stimulation mode implants, because of oligodendrocyte, microglia parcel cause microelectrode can't the normal electrical stimulating neural tissue.The present invention designs a kind of implanted microstimulation electrode with the medicament slow release function to overcome the above problems.The implanted microstimulation electrode of this band medicament slow release function; Can be when applying electric stimulation pulse; Medicament slow release layer through the inner little raceway groove of microelectrode and little flute surfaces discharges certain chemical substance; Suppress microglia and the oligodendrocyte parcel to microelectrode, enhancing signal is in the transmission at electrode tissue interface.
The present invention realizes through following technical scheme: the implanted retinal microstimulation electrode chip of band medicament slow release function comprises: electrode basement, microelectrode, electrode lead, lead-in wire substrate, lead-in wire interface and lead-in wire bundle; Each microelectrode is distributed on the electrode basement with display and protrudes in the surface of electrode basement; It is characterized in that; The top layer of said electrode basement is provided with the little groove of the annular that is used for medicament slow release of adjacent distributions, and each microelectrode is located at the center of circle of the little groove of annular respectively; The surfaces coated of the little groove of this annular is covered with medicament controlled-release coating, and this medicine discharges in the biological tissue of microelectrode to the electrode chip surface through little groove.
Further; The internal layer of said electrode basement also is provided with the little raceway groove of bar shaped; The little raceway groove of bar shaped is positioned at the lower floor of the little groove adjacent regions of two annulars, and the little raceway groove of this bar shaped is surperficial invisible electrode chip, and the little raceway groove of said bar shaped is communicated with the little groove of annular through micropore.
The present invention has following beneficial effect:
1. among the present invention; Carry medicine with the micro-electrode chip substrate as platform; Through the polymer carrier control medicament slow release time; Make drug release, weaken the parcel to micro-electrode chip such as microglia and oligodendrocyte, improve the transmission efficiency of nerve electric stimulation signal at the electrode tissue interface thereby reach.
2. the present invention is provided with the little groove of the annular that is used for medicament slow release of adjacent distributions on the top layer of electrode basement; The surfaces coated of the little groove of this annular is covered with medicament controlled-release coating; This medicine is discharged into the surperficial biological tissue of electrode chip through little groove, and this design can improve the control of medicament slow release directivity greatly.
3. also be provided with the little raceway groove of bar shaped at the internal layer of electrode basement and be communicated with, can make the medicine storage capacity bigger, prolong its life cycle with the little groove of annular.
4. this medicament controlled-release coating adopts the polymer carrier with retardation; Can make medicine present stable release; Keep valid density in the stable vitreous body; Reach inhibition microglia and oligodendrocyte to the parcel of micro-electrode chip, enough strengthen the affinity to microelectrode such as microglia and oligodendrocyte, improve the transmission efficiency of nerve electric stimulation signal at the electrode tissue interface.Said medicament controlled-release coating adopts the polymer coating, can guarantee certain drugs rate of release and persistent period.
Description of drawings
Fig. 1 is the microelectrode array structural representation of micro-electrode chip of the present invention;
Fig. 2 is the cross sectional representation of micro-electrode chip of the present invention at microelectrode array;
Fig. 3 is the microelectrode array and the lead-in wire interface structure sketch map of micro-electrode chip of the present invention.
Wherein, 1-electrode basement, the substrate that goes between of 2-microelectrode, the little groove of 3-annular, the little raceway groove of 4-bar shaped, 5-micropore, 6-electrode lead, 7-, the 8-interface that goes between, the 9-bundle that goes between.
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The specific embodiment
Below in conjunction with accompanying drawing and specific embodiment the present invention is described further.
As shown in figures 1 and 3, a kind of implanted retinal microstimulation electrode chip with the medicament slow release function comprises electrode basement 1, microelectrode 2, electrode lead 6, lead-in wire substrate 7, lead-in wire interface 8 and lead-in wire bundle 9; Each microelectrode is distributed in the top layer of electrode basement with display and protrudes in the surface of electrode basement, and said electrode basement 1 is provided with the little groove 3 of the annular that is used for medicament slow release of adjacent distributions, and each microelectrode 2 is located at the center of circle of the little groove 3 of annular respectively; The surfaces coated of the little groove 3 of this annular is covered with medicament controlled-release coating, and this medicine discharges to the biological tissue that the electrode chip surface touches at microelectrode through little groove 3.The radius of said microelectrode 2 is about 50～100 microns, and is high 50～100 microns, and microelectrode is spatially pressed array distribution, and 4 * 4 ..., 10 * 10 all can, microelectrode is about 1000 microns of lateral separation and longitudinal separation, its material is a gold (Au).Said electrode basement 5 is a rectangle, and length is 2～5 millimeters, by the materials processing generation of pliability and good biocompatibility.Said lead-in wire substrate 7 is generated by the materials processing of pliability and good biocompatibility, and directly links to each other with said electrode basement 1,2～5 millimeters of the length of lead-in wire substrate 7, and wide is 1～2.5 millimeter.Said lead-in wire bundle will be tied up bunchy from the lead-in wire of each interface that goes between, and the diameter of lead-in wire is 50 microns, draw described microstimulation electrod-array.The lead-in wire bundle is described microstimulation electrode chip and the stimulator of outside or the connection cord bundle of recorder.
Referring to Fig. 2; For the internal layer that strengthens the said electrode basement 1 of storage medication amount also is provided with the little raceway groove 4 of bar shaped; The little raceway groove 4 of this bar shaped is invisible on the electrode top layer; The little raceway groove 4 of bar shaped is positioned at the bottom of little groove 3 adjacent regions of two annulars, and the little groove 3 of said annular is communicated with the little raceway groove 4 of bar shaped through micropore 5.
The present invention provides a kind of micro-electrode chip with little raceway groove and medicament controlled-release coating; Its medicament controlled-release coating is to carry medicine in the microelectrode substrate as platform; Through the polymer carrier control medicament slow release time; Make drug release, suppress oligodendrocyte and the parcel of microglia to implantation micro-electrode having thereby reach, raising nerve electric stimulation signal is in the transmission efficiency at electrode tissue interface.This medicament controlled-release coating adopts the polymer coating, can guarantee certain drugs rate of release and persistent period.Be mixed with the polymer carrier in the described medicament controlled-release coating, the part by weight of this polymer carrier and medication coat is 3:1～10:1.And described medicament controlled-release coating is a resveratrol, medicament controlled-release coating be distributed as 0.01～0.1mg/cm2.
This is with the manufacture method of the micro-electrode chip of little raceway groove and medicament controlled-release coating: with the polyimides is the multi-layer sheet of backing material; Adopt the manufacturing of FPC technology, on multi-layer sheet, punch, as stimulating electrode; And on stimulating electrode electrogilding; At three-layer routing, lead-in wire is connected to the lead-in wire interface then, finally is connected with extraneous multichannel stimulator.On the mechanical layer of the second layer, etch the little raceway groove of bar shaped.Be layered on polyimides on first laminate of microstimulation electrode array chip, remove microelectrode 2 polyurethane-imide film ring on every side, between the Kapton and first laminate, form the circular ring type hollow out, promptly form annular little groove structure.Between ground floor machinery plate and second layer machinery plate, punch, form micropore 5, make the little groove 3 of annular through UNICOM between micropore 5 and the little raceway groove 4 of bar shaped.
Electrode basement 1 has certain pliability and excellent biological compatibility, is the part of implanting between amphiblestroid pigment epithelium cell and the neuroepithelium, and interior is square, and the length of side is (2～5) millimeter, and the corner of four 90 degree becomes 1/4 circle.The radius of said microelectrode 2 is about 50～100 microns, and is high 50～100 microns, and microelectrode is spatially pressed array distribution, and 4 * 4 ..., 10 * 10 all can, microelectrode is about 1000 microns of lateral separation and longitudinal separation, its material is a gold (Au).Said lead-in wire substrate 7 is generated by the materials processing of pliability and good biocompatibility, and directly links to each other with said electrode basement 1, length (2～5) millimeter of lead-in wire substrate 7, and wide is (1～2.5) millimeter.The micro-electrode chip interlayer is furnished with contact conductor and is connected with electrode lead 6, and this section lead-in wire is thicker than electrode lead, helps reducing resistance, about 50～100 microns of width, and contact conductor adopts gold (Au).Lead-in wire interface 8 is interfaces of said stimulating electrode chip lead and bunch of cables, is arranged in the lead-in wire substrate 7, is about rectangle.
The above embodiment of the present invention only be for explanation the present invention did for example, and be not to be qualification to embodiment of the present invention.For the those of ordinary skill in affiliated field, on the basis of above-mentioned explanation, can also make other multi-form variation and changes.Here can't give exhaustive to all embodiments.Everyly belong to the row that conspicuous variation that technical scheme of the present invention amplifies out or change still are in protection scope of the present invention.
Claims (6)
1. the implanted retinal microstimulation electrode chip of band medicament slow release function comprises: electrode basement (1), microelectrode (2), electrode lead (6), lead-in wire substrate (7), lead-in wire interface (8) and lead-in wire bundle (9); Each microelectrode is distributed on the electrode basement with display and protrudes in the surface of electrode basement; It is characterized in that the upper surface of said electrode basement (1) is provided with the little groove of the annular that is used for medicament slow release (3) of adjacent distributions, each microelectrode (2) is located at the middle part of the little groove of annular (3) respectively; The surfaces coated of the little groove of this annular (3) is covered with medicament controlled-release coating, and this medicine discharges in the biological tissue of microelectrode to the electrode chip surface through little groove (3).
2. the implanted retinal microstimulation electrode chip of band medicament slow release function according to claim 1; It is characterized in that; The internal layer of said electrode basement (1) also is provided with the little raceway groove of bar shaped (4); The little raceway groove of this bar shaped (4) is invisible at electrode surface, and the little raceway groove of this bar shaped (4) is positioned at the lower floor of the little groove of two annulars (3) adjacent regions, and the little groove of said annular (3) is communicated with the little raceway groove of bar shaped (4) through micropore (5).
3. the implanted retinal microstimulation electrode chip of band medicament slow release function according to claim 1 is characterized in that the radius of said microelectrode (2) is about 50～100 microns; High 50～100 microns, microelectrode is spatially pressed array distribution, 4 * 4; 10 * 10 all can, microelectrode is about 1000 microns of lateral separation and longitudinal separation, its material is a gold (Au); Said electrode basement (5) is a rectangle, and length is 2～5 millimeters, by the materials processing generation of pliability and good biocompatibility.
4. the implanted retinal microstimulation electrode chip of band medicament slow release function according to claim 1; It is characterized in that; Said lead-in wire substrate (7) is generated by the materials processing of pliability and good biocompatibility; And directly link to each other with said electrode basement (1), 2～5 millimeters of the length of lead-in wire substrate (7), wide is 1～2.5 millimeter.
5. the implanted retinal microstimulation electrode chip of band medicament slow release function according to claim 1 is characterized in that, is mixed with the polymer carrier in the said medicament controlled-release coating, and the part by weight of this polymer carrier and medication coat is 3:1～10:1.
6. the implanted retinal microstimulation electrode chip of band medicament slow release function according to claim 5 is characterized in that said medicament controlled-release coating is a resveratrol, medicament controlled-release coating be distributed as 0.01～0.1mg/cm2.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104013491A (en) * | 2014-05-23 | 2014-09-03 | 浙江诺尔康神经电子科技股份有限公司 | Foldable minimally-invasive artificial retina microelectrode array |
| CN104352303A (en) * | 2014-10-30 | 2015-02-18 | 北京大学 | Equipment and method for forming artificial vision by electrical stimulation |
| CN106236377A (en) * | 2016-09-12 | 2016-12-21 | 北京大学 | SCNS is utilized to form the equipment of artificial vision |
| CN109171643A (en) * | 2018-06-17 | 2019-01-11 | 南京仁康医院有限公司 | A kind of MX-P neuron resuscitation therapy children's Neurological disease technology |
| CN112120695A (en) * | 2020-09-29 | 2020-12-25 | 中国科学院上海微系统与信息技术研究所 | Deep flexible brain electrode combined with drug delivery channel and preparation method thereof |
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| EP4117718A4 (en) * | 2020-03-09 | 2024-05-08 | Univ Houston System | Inflammatory bowel disease stem cells, agents which target ibd stem cells, and uses related thereto |
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| CN1820799A (en) * | 2006-03-30 | 2006-08-23 | 上海交通大学 | Implantable sheet type optic nerve micro stimulating electrode |
| CN101006953A (en) * | 2007-01-18 | 2007-08-01 | 上海交通大学 | Artificial retina neural flexible microelectrode array chips and processing method thereof |
| US20070293749A1 (en) * | 2006-06-19 | 2007-12-20 | Zhou Dao M | Electrode with increased stability and method of manufacturing the same |
| US20080319493A1 (en) * | 2007-06-21 | 2008-12-25 | Dao Min Zhou | Biocompatible electroplated interconnection bonding method and electronics package suitable for implantation |
| US20090210055A1 (en) * | 2008-02-19 | 2009-08-20 | Industrial Technology Research Institute | Artificial optic nerve network module, artificial retina chip module, and method for fabricating the same |
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- 2011-07-28 CN CN 201110213545 patent/CN102335065B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1820799A (en) * | 2006-03-30 | 2006-08-23 | 上海交通大学 | Implantable sheet type optic nerve micro stimulating electrode |
| US20070293749A1 (en) * | 2006-06-19 | 2007-12-20 | Zhou Dao M | Electrode with increased stability and method of manufacturing the same |
| CN101006953A (en) * | 2007-01-18 | 2007-08-01 | 上海交通大学 | Artificial retina neural flexible microelectrode array chips and processing method thereof |
| US20080319493A1 (en) * | 2007-06-21 | 2008-12-25 | Dao Min Zhou | Biocompatible electroplated interconnection bonding method and electronics package suitable for implantation |
| US20090210055A1 (en) * | 2008-02-19 | 2009-08-20 | Industrial Technology Research Institute | Artificial optic nerve network module, artificial retina chip module, and method for fabricating the same |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104013491A (en) * | 2014-05-23 | 2014-09-03 | 浙江诺尔康神经电子科技股份有限公司 | Foldable minimally-invasive artificial retina microelectrode array |
| CN104352303A (en) * | 2014-10-30 | 2015-02-18 | 北京大学 | Equipment and method for forming artificial vision by electrical stimulation |
| CN106236377A (en) * | 2016-09-12 | 2016-12-21 | 北京大学 | SCNS is utilized to form the equipment of artificial vision |
| CN109171643A (en) * | 2018-06-17 | 2019-01-11 | 南京仁康医院有限公司 | A kind of MX-P neuron resuscitation therapy children's Neurological disease technology |
| CN112120695A (en) * | 2020-09-29 | 2020-12-25 | 中国科学院上海微系统与信息技术研究所 | Deep flexible brain electrode combined with drug delivery channel and preparation method thereof |
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