CN114522339A - Thin film photoelectrode oriented to neural regulation and control and preparation method and application thereof - Google Patents
Thin film photoelectrode oriented to neural regulation and control and preparation method and application thereof Download PDFInfo
- Publication number
- CN114522339A CN114522339A CN202210167262.1A CN202210167262A CN114522339A CN 114522339 A CN114522339 A CN 114522339A CN 202210167262 A CN202210167262 A CN 202210167262A CN 114522339 A CN114522339 A CN 114522339A
- Authority
- CN
- China
- Prior art keywords
- thin film
- photoelectrode
- film photoelectrode
- dopant
- monocrystalline silicon
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000010409 thin film Substances 0.000 title claims abstract description 121
- 230000033228 biological regulation Effects 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title abstract description 6
- 230000001537 neural effect Effects 0.000 title description 8
- 229910021421 monocrystalline silicon Inorganic materials 0.000 claims abstract description 42
- 239000002019 doping agent Substances 0.000 claims abstract description 39
- 239000010408 film Substances 0.000 claims abstract description 26
- 210000005036 nerve Anatomy 0.000 claims abstract description 19
- 239000000758 substrate Substances 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 18
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 17
- 229910052796 boron Inorganic materials 0.000 claims description 17
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 16
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000011574 phosphorus Substances 0.000 claims description 16
- 229910052698 phosphorus Inorganic materials 0.000 claims description 16
- 229910052710 silicon Inorganic materials 0.000 claims description 16
- 239000010703 silicon Substances 0.000 claims description 16
- 238000000137 annealing Methods 0.000 claims description 12
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 8
- 238000005530 etching Methods 0.000 claims description 7
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 230000004007 neuromodulation Effects 0.000 claims description 6
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 6
- 239000003292 glue Substances 0.000 claims description 5
- 238000005468 ion implantation Methods 0.000 claims description 5
- 239000011368 organic material Substances 0.000 claims description 5
- -1 polydimethylsiloxane Polymers 0.000 claims description 5
- 238000000206 photolithography Methods 0.000 claims description 4
- 238000001020 plasma etching Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 3
- 238000005286 illumination Methods 0.000 abstract description 11
- 210000001519 tissue Anatomy 0.000 abstract description 11
- 239000011575 calcium Substances 0.000 abstract description 9
- 230000028161 membrane depolarization Effects 0.000 abstract description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 7
- 229910052791 calcium Inorganic materials 0.000 abstract description 7
- 230000002964 excitative effect Effects 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 239000012528 membrane Substances 0.000 abstract description 4
- 210000000944 nerve tissue Anatomy 0.000 abstract description 4
- 230000000630 rising effect Effects 0.000 abstract description 4
- 230000000593 degrading effect Effects 0.000 abstract description 3
- 230000008035 nerve activity Effects 0.000 abstract description 3
- 230000000638 stimulation Effects 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 15
- 210000003710 cerebral cortex Anatomy 0.000 description 9
- 210000003594 spinal ganglia Anatomy 0.000 description 8
- 235000012431 wafers Nutrition 0.000 description 8
- 230000005684 electric field Effects 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000002102 hyperpolarization Effects 0.000 description 4
- 210000003141 lower extremity Anatomy 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 210000003497 sciatic nerve Anatomy 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000004118 muscle contraction Effects 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000003322 Coinfection Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000003479 dental cement Substances 0.000 description 1
- 210000001951 dura mater Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000019935 photoinhibition Effects 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 210000004092 somatosensory cortex Anatomy 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 229910001868 water Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
- A61N1/0526—Head electrodes
- A61N1/0529—Electrodes for brain stimulation
- A61N1/0531—Brain cortex electrodes
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B29/00—Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape
- C30B29/02—Elements
- C30B29/06—Silicon
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B31/00—Diffusion or doping processes for single crystals or homogeneous polycrystalline material with defined structure; Apparatus therefor
- C30B31/20—Doping by irradiation with electromagnetic waves or by particle radiation
- C30B31/22—Doping by irradiation with electromagnetic waves or by particle radiation by ion-implantation
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B33/00—After-treatment of single crystals or homogeneous polycrystalline material with defined structure
- C30B33/02—Heat treatment
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B33/00—After-treatment of single crystals or homogeneous polycrystalline material with defined structure
- C30B33/04—After-treatment of single crystals or homogeneous polycrystalline material with defined structure using electric or magnetic fields or particle radiation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E60/00—Enabling technologies; Technologies with a potential or indirect contribution to GHG emissions mitigation
- Y02E60/30—Hydrogen technology
- Y02E60/36—Hydrogen production from non-carbon containing sources, e.g. by water electrolysis
Abstract
The invention relates to a thin film photoelectrode for nerve regulation and control and a preparation method and application thereof. The thin film photoelectric electrode is a monocrystalline silicon thin film, and the monocrystalline silicon thin film contains a dopant. The film photoelectrode can be degraded in biological tissue environment, and the degrading elements have good biocompatibility. Under the illumination condition, the film photoelectrode can regulate and control the depolarization and the super-change membrane potential of cells cultured on the photoelectrode, and regulate and control the rising and the falling of a cell calcium signal; simultaneously, the thin film photoelectrode is attached to the surface of the nerve tissue to cause excitatory or inhibitory nerve activity. Therefore, the thin film photoelectrode can be highly applied to nerve regulation.
Description
Technical Field
The invention belongs to the technical field of nerve regulation and control, and particularly relates to a nerve regulation-oriented thin film photoelectrode and a preparation method and application thereof.
Background
Electrical stimulation plays an important role in biobased research, neuroscience, and disease treatment. For neuromodulation at the cellular level, electrically induced devices typically involve an active electronic circuit layout, lacking some spatial-temporal resolution. For the nerve regulation and control at the living body level, the traditional non-implanted electronic equipment (such as transcranial electrical stimulation, magnetic stimulation, ultrasonic stimulation and the like) tries to remotely intervene in the nerve living body from the physical modes of external electric field, magnetic field, ultrasound and the like, the spatial resolution is severely restricted, and the precise regulation and control on a specific area and a specific nerve nucleus are difficult. In addition, the implantable electronic product can be better close to the stimulation target point, and the stimulation efficacy is improved. However, such implantable electronic products often involve bulky power circuit configurations or require external power supplies, such as: vagus nerve stimulators, spinal cord stimulators, and the like. The space occupied by these power circuits and the wires running through the tissue can cause undesirable inflammatory reactions. In addition, non-degradable implantable electrical stimulation devices inevitably require a secondary operation to remove them after the task is completed, with the potential for secondary infection and tissue damage risks. Finally, there are two wireless energy transmission modes. The first is ultrasonic conversion electrical stimulation, which requires an ultrasonic emission source to contact the tissue surface, and the conversion efficiency is greatly influenced by the composition of different tissues; the second is radio frequency conversion electrical stimulation, and the conversion efficiency is greatly influenced by the coupling angle of the coil.
Therefore, a new neural regulation mode is urgently needed, and the excitation and inhibition orientation of the nerve is accurately regulated in real time.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a thin film photoelectrode for nerve regulation, which can be degraded in a biological tissue environment, and the degraded elements have good biocompatibility. Under the illumination condition, the film photoelectrode can regulate and control the depolarization and the super membrane potential of cells cultured on the film photoelectrode, and regulate and control the rising and the falling of a cell calcium signal; simultaneously, the thin film photoelectrode is attached to the surface of the nerve tissue to cause excitatory or inhibitory nerve activity.
To this end, the invention provides, in a first aspect, a thin film photoelectrode facing neuromodulation, which is a monocrystalline silicon thin film, and the monocrystalline silicon thin film contains a dopant thereon.
In some embodiments of the invention, the dopant is any one of phosphorus and boron; preferably, the doping amount of the dopant is (1-5) multiplied by 1014ions/cm2。
In other embodiments of the present invention, the thickness of the single crystal silicon thin film is 2 to 5 μm; and/or a resistivity of 1 to 10 Ω · cm.
In a second aspect, the present invention provides a method of preparing a thin film photoelectrode according to the first aspect of the present invention, comprising the steps of:
s1, doping dopant in the monocrystalline silicon layer of the top silicon wafer, and annealing to obtain doped monocrystalline silicon film;
s2, etching the doped monocrystalline silicon film to obtain a graphical doped monocrystalline silicon film with a required shape;
and S3, removing the oxide layer by adopting hydrofluoric acid to release the patterned doped monocrystalline silicon film, namely the film photoelectrode.
In some embodiments of the present invention, in step S1, a dopant is doped in the single crystal silicon layer by ion implantation.
In other embodiments of the present invention, in step S1, the annealing temperature is 900 to 950 ℃, and the annealing time is 20 to 30 minutes.
In some embodiments of the present invention, the etching is performed by photolithography and a reactive ion etching process in step S2.
In a third aspect, the present invention provides an integrated thin film photoelectrode comprising a thin film photoelectrode according to the first aspect of the present invention or a thin film photoelectrode prepared by the method of the second aspect, and a substrate.
In some embodiments of the invention, the substrate is a flexible substrate or a rigid substrate.
In other embodiments of the present invention, the material of the substrate is a degradable organic material.
A fourth aspect of the present invention provides a method for producing the integrated thin film photoelectrode according to the third aspect of the present invention, which comprises transferring the thin film photoelectrode onto a target substrate coated with a glue layer, thereby obtaining the integrated thin film photoelectrode.
In some embodiments of the invention, the thin film photoelectrode is transferred using a polydimethylsiloxane stamp.
In a fifth aspect, the present invention provides a thin film photoelectrode according to the first aspect, or a thin film photoelectrode prepared by the method of the second aspect, or an integrated thin film photoelectrode according to the third aspect, or an integrated thin film photoelectrode prepared by the method of the fourth aspect, and the thin film photoelectrode is applied to neuromodulation.
The invention has the beneficial effects that: the thin film photoelectrode for nerve regulation provided by the invention has the following advantages: (1) the thin film photoelectrode can be degraded in a biological tissue environment, and the degrading elements have good biocompatibility; (2) under the condition of illumination, the contact surface of the thin film photoelectrode and the solution can be excited by an electric field in the positive direction or the negative direction of light-induced excitation, and accordingly cations or anions in the solution are attracted; (3) under the illumination condition, the film photoelectrode can regulate and control the depolarization and the super membrane potential of cells cultured on the film and the rising and the falling of calcium signals of the cells; (4) the application of the thin film photoelectrode to the surface of nerve tissue can induce excitatory or inhibitory nerve activity.
Drawings
The invention will be further explained with reference to the drawings.
FIG. 1 is a pictorial representation of an integrated thin film photoelectrode in accordance with the present invention; fig. 1-1 shows the combination of a circular thin film photoelectrode and a flexible substrate, fig. 1-2 shows the combination of a circular thin film photoelectrode and a rigid substrate, and fig. 1-3 shows the combination of a grid-shaped thin film photoelectrode and a rigid substrate.
Fig. 2 is a flow chart of the process for preparing the integrated thin film photoelectrode of the present invention.
FIG. 3 is a schematic of the photo-electric stimulation of cultured ex vivo cells of a thin film photoelectrode.
FIG. 4 is a schematic diagram of a thin film photoelectrode applied to a nerve bundle for stimulation.
FIG. 5 is a schematic diagram of the thin film photoelectrode attached to the cerebral cortex of a mouse for stimulation.
Detailed Description
The present invention will be described in detail below.
As previously mentioned, existing electrical stimulation-based neuromodulation suffer from the following drawbacks: (1) the cellular electrical induction of the active electronic circuit lacks a certain spatio-temporal resolution; (2) non-invasive neural in vivo stimulation lacks high spatial resolution; (3) bulky, rigid implantable electrodes, as well as power supplies with connecting wires and their circuitry lack good in vivo biocompatibility; (4) the non-biodegradable electrical stimulation device has risks brought by secondary operations; (5) the wireless nerve regulation and control modes such as ultrasound, radio frequency and the like have defects in principle. The inventor of the present application has obtained a new thin film photoelectrode facing nerve regulation through research, which is a doped monocrystalline silicon thin film having degradable characteristics and good biocompatibility, so that it can be degraded in a biological tissue environment, and the degrading elements have good biocompatibility; meanwhile, the film photoelectrode can generate a light-induced positive/negative electric field, so that depolarization and hyperpolarization of light-induced cells are realized, and calcium activity in the cells is regulated; in addition, the template photoelectrode is also capable of inducing excitatory or inhibitory neural activity in vivo.
Therefore, the thin film photoelectrode facing nerve modulation according to the first aspect of the present invention is a single crystal silicon thin film, and the single crystal silicon thin film contains a dopant.
The monocrystalline silicon thin film has the characteristics of biodegradability and good biocompatibility. Meanwhile, the photoelectric conversion efficiency of the film photoelectrode can be improved by doping the doping agent on the monocrystalline silicon film.
In some embodiments of the invention, the dopant is any one of phosphorus and boron.
In the invention, when the dopant is phosphorus, the monocrystalline silicon is p-type; and the doping amount of the dopant is (1-5) × 1014ions/cm2Preferably 4X 1014ions/cm2(ii) a The doping energy was 75 KeV.
In the invention, when the dopant is boron, the monocrystalline silicon is n-type; and the doping amount of the dopant is (1-5) × 1014ions/cm2Preferably 4X 1014ions/cm2(ii) a The doping energy was 30 KeV.
In other embodiments of the present invention, the thickness of the single crystal silicon thin film is 2 to 5 μm; and/or a resistivity of 1 to 10 Ω · cm.
In the present invention, the crystal orientation of the single crystal silicon may be 100.
A second aspect of the present invention is directed to a method of making a thin film photoelectrode, as defined in the first aspect of the present invention, comprising the steps of:
s1, doping dopant in the monocrystalline silicon layer of the top silicon wafer, and annealing to obtain doped monocrystalline silicon film;
s2, etching the doped monocrystalline silicon film to obtain a graphical doped monocrystalline silicon film with a required shape;
and S3, removing the oxide layer by adopting hydrofluoric acid to release the patterned doped monocrystalline silicon film, namely the film photoelectrode.
In the present invention, the Silicon On Insulator (SOI) wafer comprises a single crystal silicon layer, an oxide layer and a base layer. The oxide layer is located between the monocrystalline silicon layer and the substrate layer. The oxide layer may be, for example, a silicon dioxide layer, and the base layer may be, for example, a Si substrate.
In some embodiments of the present invention, in step S1, a dopant is doped in the single crystal silicon layer by ion implantation.
In other embodiments of the present invention, in step S1, the annealing temperature is 900 to 950 ℃, and the annealing time is 20 to 30 minutes.
In the present invention, the doped dopant can be activated by annealing.
In some embodiments of the invention, the temperature of the annealing is 950 ℃ and the time of the annealing is 30 minutes.
In some embodiments of the present invention, the etching is performed by photolithography and a reactive ion etching process in step S2.
A third aspect of the invention relates to an integrated thin film photoelectrode comprising a thin film photoelectrode according to the first aspect of the invention or a thin film photoelectrode prepared by the method of the second aspect, and a substrate.
In some embodiments of the invention, the substrate is a flexible substrate or a rigid substrate.
In the invention, the thin film photoelectrode can be integrated with a flexible substrate (as shown in figure 1-1), so that the bending capability of the whole device is improved; the thin film photoelectrode can also be integrated with a hard substrate (as shown in fig. 1-2), and the hard substrate can be a cell glass slide for photoelectric regulation of cell culture. In addition, the thin film photoelectrode can be designed in a patterning mode (such as a grid shape), and then the patterned thin film photoelectrode and a hard substrate are integrated (such as shown in figures 1-3), so that the thin film photoelectrode can be used for photoelectric regulation and control of directional growth of a neural network.
In some embodiments of the invention, the material of the substrate is a degradable organic material. The degradation rate of the whole integrated device is optimized by regulating and controlling the synthesis ratio of the organic material.
A fourth aspect of the present invention is directed to a method of manufacturing the integrated thin film photoelectrode according to the third aspect of the present invention, which comprises transferring the thin film photoelectrode onto a target substrate coated with a glue layer, thereby obtaining the integrated thin film photoelectrode.
In some embodiments of the invention, the subbing layer may be an SU-8 subbing layer. The thin film photoelectrode and the target substrate can be firmly integrated through the glue layer.
In some embodiments of the invention, the thin film photoelectrode is transferred using a Polydimethylsiloxane (PDMS) stamp.
In the present invention, a complete flow chart of the method for manufacturing the integrated thin film photoelectrode is shown in fig. 2.
A fifth aspect of the present invention relates to a thin film photoelectrode according to the first aspect of the present invention, or a thin film photoelectrode prepared by the method according to the second aspect, or an integrated thin film photoelectrode according to the third aspect, or an integrated thin film photoelectrode prepared by the method according to the fourth aspect, for use in neuromodulation.
The invention develops a simple, light and flexible implantable thin film photoelectrode facing the directions of biological basic research, neuroscience and disease treatment. The thin film photoelectrode is utilized to regulate and control nerve tissues in a remote light control mode, and the flexibility is high. Under the condition of illumination, the photoinduced electric field of the thin film photoelectrode can regulate and control the neural activity of isolated cells, nerve bundles and superficial tissues, has wide applicability, and simultaneously, the positive and negative properties of the photoinduced electric field can selectively regulate and control excitatory or inhibitory neural activity. The film photoelectrode is constructed by biodegradable monocrystalline silicon materials, integrates degradable organic materials to control the degradation rate of the whole device, and has plasticity for realizing short-term or long-term photoelectric stimulation in a living body.
Examples
In order that the present invention may be more readily understood, the following detailed description will proceed with reference being made to examples, which are intended to be illustrative only and are not intended to limit the scope of the invention. The starting materials or components used in the present invention may be commercially or conventionally prepared unless otherwise specified.
Example 1: preparation of thin film photoelectrode
Doping a single crystal silicon layer (crystal orientation 100, resistivity 1-10 Ω · cm, thickness 2 μm) of an insulating top silicon wafer (SOI) with boron (dose 4X 10) by ion implantation14ions/cm2Energy 30keV) to form boron-doped siliconA silicon wafer of (2); doping a single crystal silicon layer (crystal orientation 100, resistivity 1-10 Ω · cm, thickness 2 μm) of an insulating top silicon wafer (SOI) with phosphorus (4 × 10) by ion implantation14ions/cm275keV), a silicon wafer doped with phosphorus is constructed. The wafers were separately cleaned and annealed at 950 c for 30 minutes to activate the dopants. By photolithography and reactive ion etching (power 100W, gas SiF)6Flow rate of 150sccm, gas pressure of 90mTorr, etching rate of 20nm/s) to obtain a patterned doped monocrystalline silicon thin film of a desired shape. Sample at H2O:H2O2:NH4After cleaning in 5:1:1(10 minutes, 80 ℃), the silicon oxide layer was removed in hydrofluoric acid (49% HF, ACS) to release a patterned doped monocrystalline silicon film of a desired shape, and a thin-film photoelectrode in which the dopant was boron and a thin-film photoelectrode in which the dopant was phosphorus were obtained, respectively.
Example 2: preparation of integrated thin film photoelectrode
The boron doped thin film photoelectrode and the phosphorus doped thin film photoelectrode prepared in example 1 were transferred onto flexible, transparent polyethylene terephthalate (PET, thickness-25 μm) thin film substrates, respectively, using a polydimethylsiloxane (PDMS, Dow Corning Sylgard 184kit,1:10 weight ratio) stamp and a thermal release tape (No.3198, Semiconductor Equipment Corp.). Before transfer, a 5 μm thick epoxy (SU8-3005) was spin coated on the substrate as a glue layer. After the transfer, the plate was dried at 110 ℃ for 30 minutes. And finally, cleaning the substrate by using acetone, isopropanol and deionized water to respectively obtain an integrated thin film photoelectrode with boron as a dopant and an integrated thin film photoelectrode with phosphorus as a dopant.
Example 3: photoelectric regulation of in vitro cultured cells
The thin film photoelectrode with boron as dopant and the thin film photoelectrode with phosphorus as dopant prepared in example 1 were used to culture rat Dorsal Root Ganglion (DRG) neurons, respectively, and the electrophysiological properties of the light-induced cells were studied using whole cell patch recordings (as shown in fig. 3). The holding potential was maintained at-65 mV and changes in cell membrane potential below the threshold were recorded at different illumination intensities.
The results show that sustained illumination (for 5s) on a thin film photoelectrode with boron as the dopant increases the membrane potential of the cell, leading to cell depolarization. In contrast, similar lighting conditions on a thin film photoelectrode where the dopant is phosphorus lowers the cell membrane potential, resulting in cell hyperpolarization.
In addition, rat Dorsal Root Ganglion (DRG) neurons cultured on thin film photoelectrodes with boron as dopant and phosphorus as dopant were subjected to dynamic calcium (Ca)2+) And (7) imaging.
The results show that intracellular Ca was recorded2+Fluorescence shows that changes in cell activity are associated with depolarization and hyperpolarization. Fluorescence enhancement under light for rat Dorsal Root Ganglion (DRG) neurons cultured on a thin film photoelectrode with boron as the dopant. In contrast, photostimulation of rat Dorsal Root Ganglion (DRG) neurons cultured on a thin film photoelectrode with a phosphorous dopant reduced calcium fluorescence, indicating that cellular activity was inhibited.
And (4) conclusion: under illumination, the photoinduced electric field of the thin film photoelectrode acts on dorsal root nerve cells to selectively regulate depolarization or hyperpolarization of cell membrane potential and rising or falling of calcium signals.
Example 4: photoelectric modulation on nerve bundles
Wild type mice (C57BL/6, 6 weeks old) were used. During surgery, animals were anesthetized with 2% isoflurane balanced oxygen, and the sciatic nerve was exposed by uncovering the surrounding connective tissue without damaging the muscle. The integrated thin film photoelectrode doped with boron and the integrated thin film photoelectrode doped with phosphorus prepared in example 2 were respectively wrapped on the exposed sciatic nerves of different mice, and the silicon surface of the integrated thin film photoelectrode was decorated with a thin layer of gold nanoparticles to reduce silicon/tissue impedance and enhance the effectiveness of photoelectric stimulation. A laser beam (635nm) was remotely incident on the silicon surface of the integrated thin film photoelectrode (as shown in figure 4) and the recording electrode was inserted into the relevant location of the hindlimb muscle and the muscle contraction conducted by the nerve was recorded.
The results show that illumination of the silicon surface of the integrated thin film photoelectrode with boron as the dopant induces Complex Muscle Action Potentials (CMAPs) and leads to hind limb lifting. This behavior can be explained by the fact that the optically-activated thin-film photoelectrode, with boron as the dopant, induces more positive charge in the nerve fibers, causing cell depolarization and triggering CMAPs and hind limb lifting. In contrast, when light irradiates the silicon surface of the integrated thin film photoelectrode with phosphorus as a dopant, the generated nerve negative charges can block the transmission of positive charge signals from the near end to the far end, and the CMAPs are inhibited.
And (4) conclusion: the change of the muscle contraction of the hind limb can be regulated and controlled by the action of the photoelectric field of the thin film photoelectrode on the sciatic nerve.
Example 5: photoelectric regulation on superficial nervous tissue
Wild type mice (C57BL/6, 23 months) were deeply anesthetized with sodium pentobarbital (80-100mg/kg) and placed in a stereotactic frame. A skin incision was made on the cerebral cortex to expose the skull. The stainless steel set screw with the spade tip was secured to the skull with dental cement and hardened for at least 30 minutes. Screws are then installed into the optical post for holding the mouse head for surgery. A hole with a diameter of about 3mm is drilled in the motor cortex and the somatosensory cortex by a dental drill, and then the dura mater is peeled off to expose the cortex completely. During the experiment, 0.9% saline was applied to the exposed cortical areas to prevent dehydration. The integrated thin film photoelectrode doped with boron and the integrated thin film photoelectrode doped with phosphorus prepared in example 2 were respectively attached to the cerebral cortex exposed to different mice, a laser beam (473nm) was incident on the silicon surface of the integrated thin film photoelectrode (as shown in fig. 5), and a multichannel recording electrode was inserted into the tissue just below the thin film photoelectrode to record the neural activity inside the cerebral cortex.
The result shows that illumination irradiates the silicon surface of the integrated thin film photoelectrode with boron as a dopant to induce cerebral cortex to generate a photoelectric activation excitation signal; in contrast, light is irradiated on the silicon surface of the integrated thin film photoelectrode with the dopant of phosphorus to induce the cerebral cortex to generate a photoinhibition signal.
And (4) conclusion: under illumination, the photoinduced electric field of the thin film photoelectrode acts on the cerebral cortex to regulate the activity degree of nerves inside the cerebral cortex.
It should be noted that the above-mentioned embodiments are only for explaining the present invention, and do not constitute any limitation to the present invention. The present invention has been described with reference to exemplary embodiments, but the words which have been used herein are words of description and illustration, rather than words of limitation. The invention can be modified, as prescribed, within the scope of the claims and without departing from the scope and spirit of the invention. Although the invention has been described herein with reference to particular means, materials and embodiments, the invention is not intended to be limited to the particulars disclosed herein, but rather extends to all other methods and applications having the same functionality.
Claims (10)
1. The thin film photoelectrode facing the nerve regulation is a monocrystalline silicon thin film, and a dopant is contained on the monocrystalline silicon thin film.
2. The thin film photoelectrode of claim 1 wherein said dopant is any one of phosphorus and boron; preferably, the doping amount of the dopant is (1-5) multiplied by 1014ions/cm2。
3. The thin film photoelectrode of claim 1 or 2, wherein the thickness of the single crystal silicon thin film is 2 to 5 μm; and/or a resistivity of 1 to 10 Ω · cm.
4. A method of making a thin film photoelectrode according to any one of claims 1 to 3 comprising the steps of:
s1, doping dopant in the monocrystalline silicon layer of the top silicon wafer, and annealing to obtain doped monocrystalline silicon film;
s2, etching the doped monocrystalline silicon film to obtain a graphical doped monocrystalline silicon film with a required shape;
and S3, removing the oxide layer by adopting hydrofluoric acid to release the patterned doped monocrystalline silicon film, namely the film photoelectrode.
5. The method of claim 4, wherein in step S1, the single crystal silicon layer is doped with a dopant by ion implantation; and/or
The annealing temperature is 900-950 ℃, and the annealing time is 20-30 minutes.
6. The method according to claim 4 or 5, wherein in step S2, the etching is performed by photolithography and reactive ion etching processes.
7. An integrated thin film photoelectrode comprising a thin film photoelectrode according to any one of claims 1 to 3 or a thin film photoelectrode prepared by the method of any one of claims 4 to 6, and a substrate.
8. The integrated thin film photoelectrode of claim 7 wherein said substrate is a flexible substrate or a rigid substrate; and/or
The substrate is made of degradable organic materials.
9. A method of producing the integrated thin film photoelectrode of claim 7 or 8, comprising transferring the thin film photoelectrode onto a target substrate coated with a glue layer, thereby obtaining the integrated thin film photoelectrode; preferably, the thin film photoelectrode is transferred using a polydimethylsiloxane stamp.
10. Use of a thin film photoelectrode according to any one of claims 1 to 3, or a thin film photoelectrode prepared by a method according to any one of claims 4 to 6, or an integrated thin film photoelectrode according to claim 7 or 8, or an integrated thin film photoelectrode prepared by a method according to claim 9 for neuromodulation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210167262.1A CN114522339A (en) | 2022-02-23 | 2022-02-23 | Thin film photoelectrode oriented to neural regulation and control and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210167262.1A CN114522339A (en) | 2022-02-23 | 2022-02-23 | Thin film photoelectrode oriented to neural regulation and control and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114522339A true CN114522339A (en) | 2022-05-24 |
Family
ID=81625798
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210167262.1A Pending CN114522339A (en) | 2022-02-23 | 2022-02-23 | Thin film photoelectrode oriented to neural regulation and control and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114522339A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101912666A (en) * | 2010-08-18 | 2010-12-15 | 中国科学院上海微系统与信息技术研究所 | PDMS-based flexible implanted neural microelectrode and manufacturing method |
| CN102496421A (en) * | 2011-12-12 | 2012-06-13 | 兰州大学 | Method for preparing large-area flexible conductive film |
| US20130008495A1 (en) * | 2011-07-07 | 2013-01-10 | Massachusetts Institute Of Technology | Methods and Apparatus for Ultrathin Catalyst Layer for Photoelectrode |
| CN111939472A (en) * | 2020-08-10 | 2020-11-17 | 中国科学院上海微系统与信息技术研究所 | Intracranial stimulation recording system and preparation method thereof |
| CN111938626A (en) * | 2020-08-10 | 2020-11-17 | 中国科学院上海微系统与信息技术研究所 | Flexible implantable nerve photoelectric electrode and preparation method thereof |
-
2022
- 2022-02-23 CN CN202210167262.1A patent/CN114522339A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101912666A (en) * | 2010-08-18 | 2010-12-15 | 中国科学院上海微系统与信息技术研究所 | PDMS-based flexible implanted neural microelectrode and manufacturing method |
| US20130008495A1 (en) * | 2011-07-07 | 2013-01-10 | Massachusetts Institute Of Technology | Methods and Apparatus for Ultrathin Catalyst Layer for Photoelectrode |
| CN102496421A (en) * | 2011-12-12 | 2012-06-13 | 兰州大学 | Method for preparing large-area flexible conductive film |
| CN111939472A (en) * | 2020-08-10 | 2020-11-17 | 中国科学院上海微系统与信息技术研究所 | Intracranial stimulation recording system and preparation method thereof |
| CN111938626A (en) * | 2020-08-10 | 2020-11-17 | 中国科学院上海微系统与信息技术研究所 | Flexible implantable nerve photoelectric electrode and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6829498B2 (en) | Device for creating a neural interface and method for making same | |
| US9656061B2 (en) | Virtual electrodes for high-density electrode arrays | |
| CN100344960C (en) | Apparatus for irritating animal cell and recording its physiological signal and its production and using method | |
| CN102289148B (en) | Embedded micro-pinpoint electrode and manufacturing method thereof | |
| US10136825B2 (en) | Long-term implantable silicon carbide neural interface device using the electrical field effect | |
| Mercer et al. | Photolithographic fabrication and physiological performance of microelectrode arrays for neural stimulation | |
| CN1973918B (en) | Cluster stimulating micro electrode array capable of being implanted into nerve system of human body | |
| CN101284159B (en) | Metal fibril electrode array producing method for optic nerve stimulation | |
| CN114522339A (en) | Thin film photoelectrode oriented to neural regulation and control and preparation method and application thereof | |
| CN112717273B (en) | Nerve electric stimulation electrode with micro-columnar structure and preparation method thereof | |
| KR101168939B1 (en) | Neural device having via hole connection and using at least one nano-wire | |
| AU2015252156B2 (en) | Transmodiolar Electrode Array and a Manufacturing Method | |
| Adams et al. | Development of flexible arrays for in vivo neuronal recording and stimulation | |
| Khan et al. | A miniaturized, wirelessly-powered, reflector-coupled single channel opto neurostimulator | |
| CN114795230B (en) | Implanted wireless nerve sensor for recording brain electrical signals | |
| Oh et al. | Neural interface with a silicon neural probe in the advancement of microtechnology | |
| van der Puije et al. | Cylindrical cochlear electrode array for use in humans | |
| Rousseau et al. | Soft 3D retinal implants with diamond electrode a way for focal stimulation | |
| Puttaswamy et al. | High density nanowire electrodes for intracortical microstimulation | |
| Wilfinger | Fabrication of full soft diamond implants for functional rehabilitation | |
| Yue | Opto-Magneto-Electrical Nanoactuators for Wireless Cell Stimulation | |
| Walloch et al. | Electrical stimulation of the inner ear | |
| White et al. | Thin film electrodes for an artificial ear | |
| CN116247127A (en) | Photoelectric device, manufacturing method thereof and implantable device | |
| KR101398416B1 (en) | Implantable Magnetic Stimulation System |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |