CN106178271A

CN106178271A - Flexible nerve electrode device that LED light stimulates and electrographic recording is integrated and preparation method thereof

Info

Publication number: CN106178271A
Application number: CN201610523059.8A
Authority: CN
Inventors: 刘景全; 吉博文; 康晓洋; 王明浩; 杨斌; 陈翔; 王晓林; 杨春生
Original assignee: Shanghai Jiaotong University
Current assignee: Shanghai Jiaotong University
Priority date: 2016-07-05
Filing date: 2016-07-05
Publication date: 2016-12-07
Anticipated expiration: 2036-07-05
Also published as: CN106178271B

Abstract

The present invention provides flexible nerve electrode device that a kind of LED light stimulates and electrographic recording is integrated and preparation method thereof, described device includes photostimulation electrode and recording electrode, photostimulation electrode and recording electrode all comprise underlying polymer insulating barrier, overlayer polymer insulating barrier and centre gold circuit layer, and underlying polymer insulating barrier, overlayer polymer insulating barrier are provided with multiple hole；Draw point sequentially passes through the hole arranged on photostimulation electrode and recording electrode, it is ensured that when gluing connects photostimulation electrode, recording electrode, photostimulation electrode, recording electrode will not be subjected to displacement.Described method independently prepared photostimulation electrode and recording electrode, then bond photostimulation electrode with recording electrode.The present invention uses LED directly to contact with cerebral tissue, it is ensured that light transmission, is prevented effectively between light and recording electrode owing to record result is impacted by photoelectric effect simultaneously；Thickness of electrode is little, it is ensured that attaches cerebral cortex and has conformality；Meet acute experiment and chronic implantation experiment demand.

Description

Flexible nerve electrode device that LED light stimulates and electrographic recording is integrated and preparation method thereof

Technical field

The present invention relates to the microelectrode in a kind of biomedical engineering technology field, in particular it relates to a kind of LED light stimulates and Flexible nerve electrode device that electrographic recording is integrated and preparation method thereof.

Background technology

In in the past few decades, electricity irritation brings huge help for research brain function.In order to study complicated god Interact before having how many neurons in network, advance the further development of neuroscience, optionally activate or suppress Certain certain types of neuron becomes required, and electricity irritation cannot effectively realize this function.In recent years, light hereditism (Optogenetics) it is that neural circuit analysis brings revolutionary variation, by photosensitive protein (opsin) is introduced certain kinds , there is clear and definite action potential pattern in the cell of type so that these cells can respond with photic stimuli.

The light utilizing certain wavelength irradiates specific opsin, can be precisely controlled specific cells work on room and time Dynamic.Such as, rhodopsin channel protein 2 (ChR2) and halorhodopsin (NpHR) can be expressed in same cell simultaneously, point Blue light (473nm) and gold-tinted (590nm) is not utilized to realize depolarization and the hyperpolarization of target neuronal cell.This combination Particular target cell can accurately manipulate neuron activity.Can optionally process single neuron, measure specific nerve simultaneously The discharge time in computing interval and behavior, its time precision can reach several milliseconds.In order at utmost play these opsins' Advantage, the engineering tools for synchronizable optical transmission and electrophysiological recording are badly in need of exploitation.

In recent years, advanced micro-processing technology is used for manufacturing the optical neuron implant devices of miniaturization, to realize multiple spot, office Portion, the three-dimensional brain photostimulation of high spatial resolution.These devices are divided into two classes, a class to be laser based on different light sources, another Class is LED, and compared to currently used more LASER Light Source, LED light source has the advantage of uniqueness, including power consumption Low, illumination is stable, and rapidly, compact conformation, mechanical flexibility, spatial resolution is high, and is suitable for wireless integrated, for fully implanted for switch The system research and development of free moving animals body provides probability.Wherein, sticking type Minitype LED array in surface is at mice, rat, Mi Application on the cerebral cortex of the animals such as monkey just starts to be paid close attention to, and synchronization ECoG eeg signal acquisition is as feedback, available Characterize the photostimulation impact on cerebral neuron loop.

Through to the retrieval of prior art and contrast, Kwon K Y, Sirowatka B, Weber A et al. is at Biomedical Circuits and Systems, IEEE Transactions on, 2013,7 (5): 593-600 write articles " Opto-μ ECoG Array:A Hybrid Neural Interface with TransparentμECoG Electrode Array and Integrated LEDs for Optogenetics ", independently prepared micro-for the transparent ITO of electroneurographic signal record in literary composition Electrod-array and for the LED array of neuron photostimulation, each subarray comprise 16 passages be packaged into 2.5 × 2.5mm²Size to adapt to the bilateral hemispherical area of rat visual cortex, the surface of each transparent record electrode points assembling one Individual miniature LED chip, chip size 220 × 270 × 50 μm², peak wavelength 460nm.Preparing LED array main method is: On flexible Parylene C substrate, deposition wet etching copper are as LED conductor layer, photoresist as mask, expose needs with The metal of LED contact pads, coats low melting point scolding tin, then will be embedded in the miniature LED chip pad on PDMS mould and scolding tin Point alignment realizes laminating.The combination of two electrod-arrays is essentially relying on transparent record electrode one layer of 50 μ m-thick of back side spin coating SU-8 is as adhesive, then is bonded on recording electrode array by the LED array assembled alignment, forms gross thickness 75 μm The flexible nerve electrode that LED light stimulates and electrographic recording is integrated.The advantage of this electrode is that LED is luminous directly over transparent electrical limit Passing, the signal that lower section measuring point record obtains is LED maximum photostimulation position.But due to the introducing of SU-8 adhesive, increase Electrode integral thickness, have impact on that electrode is flexible and conformality when being attached to cerebral cortex, it addition, transparent metal oxide ITO is brittle, and life-time service can rupture and come off, and affects recording electrode performance, is not therefore suitable for being chronically implanted use.

Kassiri H, Salam M T, Der Chen F et al. is at Biomedical Circuits and Systems Conference (BioCAS), 2015IEEE, 2015:1-4 write articles " Inductively powered arbitrary- Waveform adaptive-supply electro-optical neurostimulator ", literary composition is mentioned and prepares photoelectricity one The process of body electrod-array: sputtering sedimentation 800nm thickness gold, metallic pattern on polyimides (PI) thin film that thickness is 100 μm Change and form LED plain conductor, LED is welded on gold contact point, and is adhesive in ECoG record prepared by two-layer PI with epoxy resin Between electrode.Being integrated with altogether 8 LED and 4 × 4 golden measuring points on electrode, LED luminescence is through diameter 300 μ on recording electrode The hole injection of m, electrode gross thickness reaches 1.5mm.The shortcoming of this electrode is that thickness is big, flexible poor, it is impossible to ensure electrode points with Form good contact between tissue, affect record effect.

Richner T J, Thongpang S, Brodnick S K et al. is at Journal of neural Engineering, 2014,11 (1): 016010 write " Optogenetic micro-electrocorticography for Modulating and localizing cerebral cortex activity ", at 15 μ m-thick Parylene C bases in literary composition Graphical diameter 150 μm at the end, 4 × 4 chrome gold/platinum (10/200/20nm) metal electrode points of spacing 500 μm, the most again Deposit one layer of 10 μ m-thick Parylene C, complete ECoG recording electrode and prepare, literary composition is not prepared LED array, but first with 1 The LED of peak wavelength 465nm irradiates whole recording electrode region as light source, then it is different to irradiate recording electrode with 4 LED wheel streams Region.The shortcoming of this mode is that LED light source separates with recording electrode, and light source or rocking of electrode will be unable to ensure LED light source With the relative position of recording electrode, if light source contacts is to metal electrode point, owing to photoelectric effect can be in the voltage signal of record Introduce artefact.

In sum, the method that LED light source and ECoG recording electrode combine all be there are by the above several of report at present Some problems, and document having no, report gold ball bonding method prepares LED light stimulating electrode and ECoG recording electrode combines this light Electricity bulk electrode device.

Summary of the invention

For defect of the prior art, the present invention provides the flexible neuroelectricity that a kind of LED light stimulates and electrographic recording is integrated Pole device and preparation method thereof, photostimulation electrode utilizes gold wire ball welding method that miniature LED bare chip is connected to flexible substrates metal On pad, then through the adhesives filled in openings on photostimulation electrode, it is achieved and the bonding of recording electrode, reach photostimulation and electrographic recording one The purpose of body.

According to an aspect of the present invention, it is provided that the flexible nerve electrode device that a kind of LED light stimulates and electrographic recording is integrated, institute The electrode device stated includes photostimulation electrode and recording electrode, wherein:

Described photostimulation electrode package is containing photostimulation electrode under-layer polymer insulation layer, the insulation of photostimulation electrode overlayer polymer Gold circuit layer in the middle of layer and photostimulation electrode, at photostimulation electrode under-layer polymer insulation layer, photostimulation electrode overlayer polymer Insulating barrier is provided with multiple hole, this some holes is respectively used to miniature LED bare chip printing opacity, through draw point, gluing with fixing photostimulation Electrode with recording electrode relative to position；Miniature LED bare chip utilizes gold wire ball welding method to be connected to gold circuit in the middle of photostimulation electrode On layer；

Described recording electrode comprises recording electrode underlying polymer insulating barrier, recording electrode overlayer polymer insulating barrier and note In the middle of record electrode, gold circuit layer, also sets on recording electrode underlying polymer insulating barrier, recording electrode overlayer polymer insulating barrier There is multiple hole, these hole sites and described photostimulation electrode under-layer polymer insulation layer, the insulation of photostimulation electrode overlayer polymer Hole site on layer is corresponding, is respectively used to miniature LED bare chip printing opacity, through draw point location photostimulation electrode and recording electrode； Recording electrode exposes the one of recording electrode point and faces down and attach thin piece of elastomeric polymer；

Draw point sequentially passes through photostimulation electrode overlayer polymer insulating barrier, photostimulation electrode under-layer polymer insulation layer, note The hole arranged on record electrode overlayer polymer insulating barrier, recording electrode underlying polymer insulating barrier, and penetrate polymer thin block In, thus ensure that when gluing connects photostimulation electrode, recording electrode, photostimulation electrode, recording electrode will not be subjected to displacement.

Preferably, in described photostimulation electrode: insulate in photostimulation electrode under-layer polymer insulation layer and overlayer polymer Have the slot of location overlap, circular hole and square opening on layer, be respectively intended to ensure miniature LED bare chip printing opacity, through steel Pin fixes photostimulation electrode with recording electrode relative to position with gluing.

It is highly preferred that the slot on photostimulation electrode overlayer polymer insulating barrier is arranged over groove, recessed at this Groove is coated with daub so that miniature LED bare chip is fixed on photostimulation electrode.

It is highly preferred that also have circular port, in exposing below circular port on photostimulation electrode overlayer polymer insulating barrier Between gold circuit layer as gold circuit layer pad, the cathode and anode pad of miniature LED bare chip and gold circuit layer pad pass through gold wire ball Weldering connects, and smears electrocondution slurry and guarantee conducting on gold circuit layer pad；Miniature LED bare chip, spun gold and gold circuit layer pad Encapsulated by glue.

Preferably, in described recording electrode: on recording electrode underlying polymer insulating barrier and overlayer polymer insulating barrier Having slot and the circular hole of location overlap, slot is used for miniature LED bare chip printing opacity；Circular hole is for fixed through draw point Position photostimulation electrode and recording electrode.

It is highly preferred that also have circular port on recording electrode overlayer polymer insulating barrier, circular port exposes middle gold electricity Road floor is as recording electrode point；

Recording electrode exposes the one of recording electrode point and faces down and attach polymer thin block, and photostimulation electrode exposes gold circuit The one of layer pad faces up, and draw point passes the symmetrical circular hole of same position on photostimulation electrode and recording electrode and penetrates polymer Thin piece, the square opening gluing on photostimulation electrode realizes the connection of photostimulation electrode and recording electrode and fixes.

Preferably, described photostimulation electrode under-layer polymer insulation layer and photostimulation electrode overlayer polymer insulating barrier, Non-photosensitivity type all selected by described recording electrode underlying polymer insulating barrier and the material of recording electrode overlayer polymer insulating barrier Or photosensitive polyimide, or water white Parylene.

Preferably, described photostimulation electrode under-layer polymer insulation layer and photostimulation electrode overlayer polymer insulating barrier, The thickness range of recording electrode underlying polymer insulating barrier and recording electrode overlayer polymer insulating barrier is 2～25 microns.

Preferably, described photostimulation electrode overlayer polymer insulating barrier, photostimulation electrode under-layer polymer insulation layer, note Record electrode overlayer polymer insulating barrier, recording electrode underlying polymer insulating barrier shape profile are identical, and photostimulation electrode, note The size for the hole through draw point having on record electrode is identical.

According to a further aspect in the invention, it is provided that the flexible nerve electrode device that a kind of LED light stimulates and electrographic recording is integrated Preparation method, described method independently prepared photostimulation electrode and recording electrode, then photostimulation electrode is glued with recording electrode Close.

Preferably, described preparation photostimulation electrode, comprise the steps:

S1.1: make photostimulation electrode under-layer polymer insulation layer

On the silicon chip of deposition sacrificial metal layer, spin coating or deposition one layer of polymeric thin film, through graphically obtaining photostimulation Electrode under-layer polymer insulation layer, has multiple equidistant rectangle on photostimulation electrode under-layer polymer insulation layer Hole, multiple symmetrical circular holes and multiple square opening, wherein: multiple equidistant slots ensure that miniature LED bare chip luminescence passes through, Multiple symmetrical circular holes are for through draw point, and multiple square openings fix photostimulation electrode with recording electrode relative to position for gluing；

S1.2: make gold circuit layer in the middle of photostimulation electrode

Sputtering layer of metal adhesion layer and one layer of gold, spin coating positive photoresist as mask, through front baking, exposes, develops And after bake, use ion beam etching or wet etching, obtain gold circuit layer in the middle of patterned photostimulation electrode；

S1.3: make photostimulation electrode overlayer polymer insulating barrier

In the middle of the photostimulation electrode of S1.2 on gold circuit layer, use the operation identical with S1.1, make and obtain graphically Photostimulation electrode overlayer polymer insulating barrier, at the same position with the photostimulation electrode under-layer polymer insulation layer of S1.1 Have the multiple equidistant slot of same shape, symmetrical circular hole and a square opening, and have and organize circular port, under circular port more Photostimulation electrode middle gold circuit layer exposes as gold circuit layer pad in side；

S1.4: make groove

Spin on polymers glue is the most graphical, at the slot of the photostimulation electrode overlayer polymer insulating layer of S1.3 Around form groove；

Miniature LED bare chip fixed by S1.5: gluing

It is stained with water white transparency glue by fine needle and spreads upon in groove, single miniature LED bare chip is picked up, miniature LED naked core The cathode and anode gold solder dish of sheet is placed in groove upward, presses lightly on miniature LED bare chip top, to guarantee miniature LED naked core Sheet position level, water white transparency glue contacts with miniature LED bare chip surrounding and does not spills over the miniature LED bare chip top of covering completely Portion, treats that water white transparency adhesive curing completes single miniature LED bare chip and fixes, and remaining miniature LED bare chip in like manner operates；

S1.6: gold wire ball welding method connects miniature LED bare chip and gold circuit layer pad

Size according to miniature LED bare chip cathode and anode gold solder dish on gold wire bonder, selects the gold of suitable diameter Silk, connects below cathode and anode pad and the corresponding photostimulation electrode overlayer polymer insulating barrier circular port of miniature LED bare chip The golden circuit layer pad exposed, underlying polymer insulating barrier is flexible substrate, spun gold cannot with gold the firm connection of circuit layer pad, Only the second bonding point of spun gold is pressed in gently on gold circuit layer pad；

S1.7: smear electrocondution slurry and ensure conducting

Gold circuit layer pad smears a small amount of electrocondution slurry with glass capillary, it is ensured that spun gold and gold circuit layer pad jail By connecting；

S1.8: gluing encapsulates

Encapsulation is realized with fine needle gluing, it is ensured that photostimulation above miniature LED bare chip, gold circuit layer pad and spun gold After electrode release, miniature LED bare chip does not falls out, and gold thread is solid and reliable, and electrocondution slurry does not reacts simultaneously；

S1.9: release photostimulation electrode

By electrochemical corrosion or dilute Acids eat metals sacrifice layer, complete the release of photostimulation electrode.

Preferably, described prepare recording electrode, comprise the steps:

Described prepare recording electrode, comprise the steps:

S2.1: make recording electrode underlying polymer insulating barrier

On the silicon chip of deposition sacrificial metal layer, spin coating or deposition one layer of polymeric thin film, through graphically obtaining record electricity Pole underlying polymer insulating barrier, recording electrode underlying polymer insulating layer has multiple equidistant slot, multiple right Claim circular hole, wherein: multiple equidistant slots ensure that miniature LED bare chip luminescence passes through, multiple symmetrical circular holes for through Draw point；

S2.2: make gold circuit layer in the middle of recording electrode

Sputtering layer of metal adhesion layer and one layer of gold, spin coating positive photoresist as mask, through front baking, exposes, develops And after bake, use ion beam etching or wet etching, obtain gold circuit layer in the middle of patterned recording electrode；

S2.3: make recording electrode overlayer polymer insulating barrier

In the middle of the recording electrode of S2.2 on gold circuit layer, the operation identical with S2.1, making is used to obtain patterned Recording electrode overlayer polymer insulating barrier, with the recording electrode underlying polymer insulating barrier same position of S2.1 at have identical The equidistant slot of shape, symmetrical circular hole, and have multiple circular port, circular port exposes gold circuit in the middle of recording electrode Layer is as recording electrode point；

S2.4: RR release record electrode

By electrochemical corrosion or dilute Acids eat metals sacrifice layer, complete the release of recording electrode.

Preferably, described photostimulation electrode and recording electrode are bonded, comprise the steps:

S3.1: preparation surfacing, resilient polymer thin block, expose recording electrode the one of recording electrode point and face Under, entirely it is attached on polymer thin block；

S3.2: photostimulation electrode is exposed the one of gold circuit layer pad and faces up, with draw point through photostimulation electrode and note Record the symmetrical circular hole at same position on electrode, and penetrate in polymer thin block, press lightly on photostimulation electrode and recording electrode Ensure that contact is smooth；

S3.3: in the square opening position of photostimulation electrode, gluing fixes photostimulation electrode with recording electrode relative to position, The flexible nerve electrode device that described LED light stimulates and electrographic recording is integrated is i.e. obtained after adhesive curing.

Preferably, in S1.1, S1.3 and S2.1, S2.3:

Described photostimulation electrode under-layer polymer insulation layer and photostimulation electrode overlayer polymer insulating barrier, described note The material of record electrode under-layer polymer insulation layer and recording electrode overlayer polymer insulating barrier all selects non-photosensitivity type or Photosensitive Polyimides (Polyimide), or water white Parylene (Parylene C), thickness range is 2～25 microns；As Durimide7500 series of light sensitive type polyimides divides three kinds of models: Durimide7505, Durimide 7510 and Durimide 7520, after solidification, monolayer film thickness is respectively 2～5 microns, 4～15 microns and 11～25 microns and more than, select as required With different model and thickness.

Preferably, in S1.1, S1.3 and S2.1, S2.3；

Described photostimulation electrode overlayer polymer insulating barrier, photostimulation electrode under-layer polymer insulation layer, recording electrode Overlayer polymer insulating barrier, recording electrode underlying polymer insulating barrier shape profile are identical, and photostimulation electrode, recording electrode On the size for 2 symmetrical circular holes through draw point that has identical.

Preferably, in S1.1, S1.3 and S2.1, S2.3:

The length and width size of 3 described equidistant slots determines according to the size of miniature LED bare chip, and Its size is bigger than the bottom-emission face size of miniature LED bare chip, so that miniature LED bare chip is placed in position, slot hole Time upper, the bottom-emission face of miniature LED bare chip contacts with the silicon chip of deposition sacrificial metal layer, ensures miniature LED naked core simultaneously The surrounding of sheet and slot hole wall have gap.

Preferably, in S1.2 and S2.2:

The material selection titanium of described metal adhesion layers, chromium, titanium-tungsten, its thickness is 10～100 nanometers；Metal adhesion Layer is for being respectively increased the knot between gold and photostimulation electrode under-layer polymer insulation layer, recording electrode underlying polymer insulating barrier Make a concerted effort；

The thickness of described gold is 200～500 nanometers.

Preferably, in S1.4:

The material selection SU-8 photoresist of described groove or polyimides glue, need and overlayer polymer insulating barrier has relatively Good adhesion；

The wall thickness of described groove is 5～50 microns, and the interior hole size of groove is according to miniature LED bare chip cathode and anode gold The size of pad place plane determines, thickness is according to the height of miniature LED bare chip and photostimulation electrode overlayer polymer The difference of insulating barrier and photostimulation electrode under-layer polymer insulation layer sum determines；

Described groove is used for laying miniature LED bare chip and gluing, to ensure the consistent of miniature LED bare chip position Property.

Preferably, in S1.5:

Described water white transparency glue needs control rubber quality when spreading upon groove, it is ensured that place miniature LED naked core with tweezers transfer Sheet after pressing lightly on, part glue is extruded to the rectangular of miniature LED bare chip and photostimulation electrode overlayer polymer insulating barrier At gap between shape hole wall, between miniature LED bare chip and groove, between miniature LED bare chip and groove upper surface, thus carry High-adhesive-strength, it is to avoid during follow-up gold ball bonding, miniature LED bare chip band is got up by spun gold；The painting of water white transparency glue does not adhere to miniature On the cathode and anode pad of LED bare chip, it is to avoid affect gold thread ball bonding quality；

Described water white transparency glue selects high temperature resistant instant drying adhesive, or high temperature resistant ultraviolet cured adhesive (UV glue), as having ready conditions Point gum machine can be used, it is ensured that dispensing amount and the uniformity putting glue position.

It is highly preferred that described miniature LED bare chip selects TR2227 or the TR2432 series of Cree company, or according to reality Border needs to select the LED product of other companies or model；

Instant drying adhesive LOCTITE498 or ultraviolet cured adhesive (UV glue) TOKOTITE-G15 selected by described water white transparency glue Model or other suitable type, for bearing thermal station temperature higher during gold ball bonding.

Preferably, in S1.6 and S1.7:

Described golden circuit layer pad size is more than 100 microns, in order to gold ball bonding is placed the second bonding point and smears Electrocondution slurry；Spun gold is pressed in the photostimulation electrode on gold circuit layer pad, below gold circuit layer pad by gold wire bonder chopper Underlying polymer insulating barrier can absorb ultrasonic energy, and spun gold blocks at the second bonding point tail end impression；If the second bonding point Spun gold tilt, utilize chopper press lightly on spun gold end make spun gold deformation press close to gold circuit layer pad, repaste and smear electrocondution slurry, Ensure spun gold and the connection of gold circuit layer pad；

Described electrocondution slurry selects conductive silver paste, aluminium paste, copper slurry, nickel slurry.

Preferably, in S1.8, epoxide-resin glue, or organic silica gel, or polyurethane adhesive are selected in described encapsulation；Wherein: ring After epoxy resins solidification, hardness is high；Organic silica gel and polyurethane adhesive are flexible after solidifying, less on the impact of electrode flexibility.

Preferably, in S3.1, described polymer thin block selects polydimethylsiloxane (PDMS), polyolefin elastomer (POE), vinyl-vinyl acetate copolymer (EVA), ethylene propylene diene rubber (EPDM), polymer thin block size is more than described electricity Pole device size, and the surface smooth cleaning of guarantee.

Preferably, in S3.3, described fixing photostimulation electrode selects epoxide-resin glue with recording electrode relative to position, or Organic silica gel, or polyurethane adhesive.

Compared with prior art, the present invention has a following beneficial effect:

Photostimulation electrode and recording electrode technique prepared by the present invention are general, can be according to mice or rat difference cortical region The neuron distribution different pattern device of preparation；By perforate on the insulating layer, LED luminescence direct irradiation cerebral tissue, it is ensured that thoroughly Photosensitiveness, is prevented effectively between light and metal recording electrode owing to record result is impacted by photoelectric effect simultaneously；By micro Process The flexible electrode obtained and commercialization miniature LED bare chip are connected by the gold wire ball welding method of mature and reliable, reduce photoelectric integral Electrode integral thickness, improves the electrode conformality when brain cortex surface attaches.

Accompanying drawing explanation

By the detailed description non-limiting example made with reference to the following drawings of reading, the further feature of the present invention, Purpose and advantage will become more apparent upon:

Fig. 1 is the overall structure explosive view of one embodiment of the invention；

The photostimulation electrode process flow chart of Fig. 2-be one embodiment of the invention；

Fig. 3 is the recording electrode process chart of one embodiment of the invention；

Fig. 4 is the adhesion technique flow chart of one embodiment of the invention, is respectively adopted graphics and is shown；

In Fig. 5 a, b be respectively one embodiment of the invention bonding after photostimulation electrode one on the side with recording electrode side Schematic three dimensional views upwards and partial enlarged drawing；

In Fig. 6 a, b be respectively one embodiment of the invention bonding after miniature LED bare chip luminescence signal on photostimulation electrode Scheme the miniature LED bare chip with dominant wavelength 470nm and the relative intensity curve chart of ChR2 photosensitive protein sensitivity optical band；

Fig. 7 is the electrode device fundamental diagram of one embodiment of the invention；

In Fig. 1: draw point 1, epoxide-resin glue 2, epoxide-resin glue 3, conductive silver paste 4, spun gold 5, high temperature resistant instant drying adhesive 6, recessed Groove 7, miniature LED bare chip 8, photostimulation electrode top layer polyimide insulative layer 9, photostimulation electrode intermediate metal layer 10, polished bard Sharp electrode under-layer polyimide insulative layer 11, recording electrode bottom polyimide insulative layer 12, recording electrode intermediate metal layer 13, Recording electrode top layer polyimide insulative layer 14, elastomeric polymer thin piece 15.

Detailed description of the invention

Below in conjunction with specific embodiment, the present invention is described in detail.Following example will assist in the technology of this area Personnel are further appreciated by the present invention, but limit the present invention the most in any form.It should be pointed out that, the ordinary skill to this area For personnel, without departing from the inventive concept of the premise, it is also possible to make some deformation and improvement.These broadly fall into the present invention Protection domain.

As it is shown in figure 1, the flexible nerve electrode device that a kind of LED light stimulates and electrographic recording is integrated, including photostimulation electrode And recording electrode, wherein:

In section Example of the present invention, described photostimulation electrode under-layer polymer insulation layer and photostimulation electrode top layer The material of polymer insulation layer, described recording electrode underlying polymer insulating barrier and recording electrode overlayer polymer insulating barrier is equal Select non-photosensitivity type or photosensitive polyimide (Polyimide), or water white Parylene (Parylene C), thick Degree scope is 2～25 microns；As Durimide7500 series of light sensitive type polyimides divide three kinds of model: Durimide7505, Durimide 7510 and Durimide 7520, after solidification, monolayer film thickness is respectively 2～5 microns, 4～15 microns and 11～ 25 microns and more than, select different model and thickness as required.

The number in described hole and shape can be set according to actual needs, for the purpose of realizing its function, in part In embodiment:

Have on photostimulation electrode under-layer polymer insulation layer 3 equidistant slots, 2 symmetrical circular holes and 4 square openings, wherein: 3 equidistant slots ensure that miniature LED bare chip luminescences pass through, 2 symmetrical circular holes for through Draw point, 4 square openings fix photostimulation electrode with recording electrode relative to position for gluing.Corresponding, recording electrode bottom gathers Compound insulating layer has 3 equidistant slots, 2 symmetrical circular holes, wherein: 3 equidistant slots ensure micro- The bare chip luminescence of type LED passes through, and 2 symmetrical circular holes are for through draw point.

Described photostimulation electrode overlayer polymer insulating barrier, photostimulation electrode under-layer polymer insulation layer, recording electrode Overlayer polymer insulating barrier, recording electrode underlying polymer insulating barrier shape profile are identical, and photostimulation electrode, recording electrode On the size for 2 symmetrical circular holes through draw point that has identical；

In section Example of the present invention, the material selection titanium of described metal adhesion layers, chromium, titanium-tungsten, its thickness It is 10～100 nanometers；Metal adhesion layers is used for being respectively increased at the bottom of gold and photostimulation electrode under-layer polymer insulation layer, recording electrode Adhesion between one polymer insulating barrier；

The thickness of described gold is 200～500 nanometers.

In section Example of the present invention, the material selection SU-8 photoresist of described groove or polyimides glue, need It is well bonded with overlayer polymer insulating barrier；

Based on described above of the present invention, the detailed description of specific embodiment given below.

Embodiment 1

As it is shown in figure 1, the present embodiment provides the flexible nerve electrode device that a kind of LED light stimulates and electrographic recording is integrated, by Photostimulation electrode and recording electrode composition；

Described photostimulation electrode, comprises: photostimulation electrode top layer polyimide insulative layer 9, photostimulation electrode intermetallic metal Layer 10, photostimulation electrode under-layer polyimide insulative layer 11, wherein: at photostimulation electrode top layer polyimide insulative layer 9, polished bard Swash and have the slot of location overlap, circular port and square opening above electrode under-layer polyimide insulative layer 11, be respectively intended to Ensure miniature LED bare chip 8 printing opacity, fix photostimulation electrode and recording electrode phase para-position through draw point 1 and painting epoxide-resin glue 2 Put；Slot in photostimulation electrode top layer polyimide insulative layer 9 is arranged over rectangular recess 7, miniature LED naked core The cathode and anode gold solder dish of sheet 8 is placed in groove 7 upward, and smears high temperature resistant instant drying adhesive 6 in groove 7 to ensure miniature LED Bare chip 8 is fixed firmly on photostimulation electrode；One end of photostimulation electrode intermediate metal layer 10 is provided with circular pad, the other end Being provided with four road oblong pads, wherein a road is connected as the negative electrode gold solder dish of omnibus circuit with all miniature LED bare chips 8； Cathode and anode pad and and the photostimulation electrode intermediate metal layer one of correspondence of miniature LED bare chip 8 is connected by spun gold 5 ball bonding End circular pad, and smear in circular pad conductive silver paste 4 make spun gold 5 and the firm connection of circular pad and guarantee conducting； Finally encapsulate miniature LED bare chip 8, spun gold 5 and circular pad with epoxide-resin glue 3；

Described recording electrode, comprises: recording electrode bottom polyimide insulative layer 12, recording electrode intermediate metal layer 13, Recording electrode top layer polyimide insulative layer 14, wherein: recording electrode bottom polyimide insulative layer 12, recording electrode top layer are poly- Have slot and the circular port of location overlap above acid imide insulating barrier 14, and with the photostimulation electrode top of photostimulation electrode Slot in layer polyimide insulative layer 9, photostimulation electrode under-layer polyimide insulative layer 11 and circular port location overlap, It is used for ensureing miniature LED bare chip 8 printing opacity respectively and positioning photostimulation electrode and recording electrode through draw point 1；Final at polished bard Swash the square opening in electrode top layer polyimide insulative layer 9, photostimulation electrode under-layer polyimide insulative layer 11 and be coated with epoxy resin Glue 2, it is achieved the connection of photostimulation electrode and recording electrode is fixed.

In the present embodiment, described photostimulation electrode intermediate metal layer 10 is used for powering to miniature LED bare chip 8, its forward Voltage is 2.7～3.4V.

In the present embodiment, it is 470 nano blue lights that described miniature LED bare chip 8 sends dominant wavelength, and brightness increases with forward current Adding and increase, concrete brightness can come according to the temperature rise that the light intensity of Cortical Neurons signal granting needs and cerebral tissue can be born Determine.

In the present embodiment, described draw point 1 sequentially passes through photostimulation electrode top layer polyimide insulative layer 9, photostimulation electrode Bottom polyimide insulative layer 11, recording electrode bottom polyimide insulative layer 12, recording electrode top layer polyimide insulative layer The circular port of location overlap arranged on 14, and penetrate in elastomeric polymer thin piece 15, thus ensure to be coated with epoxide-resin glue 2 even During connecing photostimulation electrode, recording electrode, photostimulation electrode, recording electrode will not be subjected to displacement.

Embodiment 2

As shown in figs 2-4, the present embodiment provides the flexible nerve electrode device that a kind of LED light stimulates and electrographic recording is integrated Preparation method, including:

One, the preparation of photostimulation electrode sequentially includes the following steps:

1) as shown in a in Fig. 2, sputtering or one layer 500 microns thick aluminum conducts of thermal evaporation deposition on 500 microns of thick silicon chips Sacrifice layer；

2) as shown in b in Fig. 2, one layer of photosensitive polyimide Durimide 7510 of spin coating, through front baking, expose, develop And solidification, making and obtain patterned photostimulation electrode under-layer polyimide insulative layer, its thickness is 10 microns；At photostimulation electricity Having three slots above the bottom polyimide insulative layer of pole, it is micro-that the size of three slots is 210 microns × 260 Rice, centre-to-centre spacing are 500 microns；Two circular ports, two circles are had on photostimulation electrode under-layer polyimide insulative layer The diameter in hole be 300 microns, centre-to-centre spacing be 1.5 millimeters；Four are had on photostimulation electrode under-layer polyimide insulative layer Individual square opening, the size of four square openings is 300 microns × 300 microns, centre-to-centre spacing is 1.5 millimeters；

3) as shown in c in Fig. 2, sputtering one layer of titanium and one layer of gold, thickness is respectively 30 nanometers and 300 nanometers, spin coating 5 microns Thick positive photoresist AZ4620, through front baking, photoetching, development and after bake, uses wet etching to obtain patterned photostimulation electricity Pole intermediate metal layer；There are three groups of circular pad one end of photostimulation electrode intermediate metal layer, and often group includes two circles, two circles Diameter is 200 microns；The other end of photostimulation electrode intermediate metal layer has four road oblong pads, and wherein a road is as public Circuit is for connecting the negative electrode gold solder dish of all miniature LED bare chips；

4) as shown in d in Fig. 2, making and obtain patterned photostimulation electrode top layer polyimide insulative layer, thickness is 10 Micron, is having slot of a size, circular port at photostimulation electrode under-layer polyimide insulative layer same position And square hole, directly over the circular pad of photostimulation electrode intermediate metal layer, have three groups of circular ports simultaneously, often group includes two Circle, two diameter of a circles be 160 microns, spacing be 730 microns；

5) as shown in e in Fig. 2, the SU-8 glue that spin coating 30 microns is thick, through front baking, expose, develop and after bake, in photostimulation The surface placing the slot of miniature LED bare chip is needed to form three width in electrode top layer polyimide insulative layer equal Be the rectangular recess of 30 microns, rectangular recess inside dimension be 240 microns × 290 microns, centre-to-centre spacing be 500 microns；

6) as shown in f in Fig. 2, it is stained with water white high temperature resistant instant drying adhesive by fine needle and spreads upon in rectangular recess, as Have ready conditions and point gum machine can be used to replace；

7) as shown in g in Fig. 2, being picked up by single miniature LED bare chip with tweezers, its cathode and anode gold solder dish is placed upward In rectangular recess, press lightly on miniature LED bare chip top to guarantee miniature LED bare chip position level, high temperature resistant wink Dry glue contacts with miniature LED bare chip surrounding and does not spills over covering top completely, waits high temperature resistant instant drying adhesive to solidify and fixes；Its In: the model of miniature LED bare chip is the TR2227 of Cree company, a size of 220 × 270 × 50 microns；Miniature LED bare chip A diameter of 80 microns of cathode and anode gold solder dish, spacing be 135 microns；

8) as shown in h in Fig. 2, gold wire bonder use the spun gold of diameter 25 microns connect miniature LED bare chip Cathode and anode gold solder dish and the circular pad of corresponding photostimulation electrode intermediate metal layer one end, due to underlying polymer insulating barrier For flexible substrate, spun gold cannot connection firm with circular pad, the most only the second bonding point of spun gold is pressed in gently circular weldering On dish；

9) as shown in i in Fig. 2, circular pad smears a small amount of conductive silver paste with glass capillary, it is ensured that spun gold and circle The firm connection of shape pad, ensures that conductive silver paste is in the range of the circular pad of diameter 160 microns as far as possible；

10) as shown in j in Fig. 2, above miniature LED bare chip, circular pad and spun gold, transparent ring is smeared by fine needle Epoxy resins glue with realize encapsulation, it is ensured that photostimulation electrode release after miniature LED bare chip do not come off, gold thread solid and reliable, with Time conductive silver paste will not react；

11) as shown in k in Fig. 2, corrode aluminum sacrificial layer by electrochemical corrosion or dilute hydrochloric acid, complete photostimulation electrode and release Put, wherein:

Use electrochemical erosion method, in high concentration NaCl solution, photostimulation electrode can be put into electrolytic cell anode, electricity Pressure 0.7～1.0V, corrosion aluminum sacrificial layer is to photostimulation electrode Automatic-falling；

Use dilute hydrochloric acid etch, can be according to concentrated hydrochloric acid: deionized water=1:4 corrosion aluminum sacrificial layer is to photostimulation electrode Automatic-falling.

Two, the preparation of recording electrode sequentially includes the following steps:

1) as shown in a in Fig. 3, sputtering or one layer 500 microns thick aluminum conducts of thermal evaporation deposition on 500 microns of thick silicon chips Sacrifice layer；

2) as shown in b in Fig. 3, one layer of photosensitive polyimide Durimide 7510 of spin coating, through front baking, expose, develop And solidification, making and obtain patterned recording electrode bottom polyimide insulative layer, its thickness is 15 microns；At the bottom of recording electrode Strata acid imide insulating layer has three slots, the size of three slots be 190 microns × 240 microns, Centre-to-centre spacing is 500 microns；Two circular ports are had, two circular ports straight on recording electrode bottom polyimide insulative layer Footpath be 300 microns, spacing be 1.5 millimeters, slot and the position of circular port in recording electrode bottom polyimide insulative layer Put and the slot in photostimulation electrode top layer polyimide insulative layer, photostimulation electrode under-layer polyimide insulative layer and circle Hole is identical；

3) as shown in c in Fig. 3, sputtering one layer of titanium and one layer of gold, thickness is respectively 30 nanometers and 300 nanometers, spin coating 5 microns Thick positive photoresist AZ4620, through front baking, photoetching, development and after bake, uses wet etching to obtain patterned recording electrode Intermediate metal layer, there are four circular gold measuring points, the diameter of four circular gold measuring points in one end of recording electrode intermediate metal layer Be 150 microns, centre-to-centre spacing be 500 microns；

4) as shown in d in Fig. 3, making and obtain patterned recording electrode top layer polyimide insulative layer, its thickness is 5 micro- Rice, is having slot of a size and circular port at recording electrode bottom polyimide insulative layer same position, with Time have the concentric circular of a diameter of 100 microns in the surface of the circular gold measuring point of recording electrode intermediate metal layer；

5) as shown in e in Fig. 3, corrode aluminum sacrificial layer by electrochemical corrosion or dilute hydrochloric acid, complete recording electrode release, Method for releasing is with (11) in step one.

Three, the bonding of photostimulation electrode and recording electrode is according to the following steps:

1) as shown in a in Fig. 4, thin piece of the polydimethylsiloxane (PDMS) of preparation surfacing, its a size of 2 cm x 4 centimetres, thickness be 5 millimeters, recording electrode is exposed the circular gold measuring point of electrode points (i.e. in above-mentioned steps two 3)) one side Down, entirely it is attached on thin piece of polydimethylsiloxane (PDMS)；

2) as shown in b in Fig. 4, photostimulation electrode is exposed facing up of gold circuit layer pad, and with diameter 0.3 millimeter Draw point through two symmetrical circular holes at photostimulation electrode and recording electrode same position, penetrate polydimethylsiloxane (PDMS), in thin piece, press lightly on photostimulation electrode and contact smooth with recording electrode with guarantee；

3) as shown in c in Fig. 4, in four square opening positions of photostimulation electrode, smear a small amount of epoxide-resin glue and fix Photostimulation electrode with recording electrode relative to position；

4) as shown in d in Fig. 4, after waiting that epoxide-resin glue is dry, draw point is extracted, by whole electrode from polydimethylsiloxane (PDMS) take off on thin piece, have the circular gold record of miniature LED bare chip and recording electrode point (i.e. in above-mentioned steps two 3) Point) one end be bonded together, photostimulation electrode, the recording electrode other end oblong pad independently separately, can give respectively Miniature LED chip is powered and gathers nerve signal.

As shown in a, b in Fig. 5, it is photostimulation electrode one schematic three dimensional views drawn game on the side after the present embodiment bonding respectively Portion's enlarged drawing, recording electrode one schematic three dimensional views on the side and partial enlarged drawing, can be clear and intuitive from schematic three dimensional views Finding out the whole electrode outward appearance prepared, it is 2 that partial enlarged drawing illustrates its apparent size being attached to cerebral cortex one end × 2 millimeters, meet and on mice or rat cerebral cortex, select specific region and attach use；It addition, in miniature LED bare chip The heart away from for 500 microns, the circular gold measuring point of recording electrode point (i.e. in above-mentioned steps two 3)) a diameter of 100 microns, centre-to-centre spacing It it is 500 microns, it is also possible to according to practical stimulation and record needs, change miniature LED bare chip centre-to-centre spacing, recording electrode point size With centre-to-centre spacing, miniature LED bare chip and recording electrode point relative to position, and miniature LED bare chip and recording electrode are counted out.

As shown in a, b in Fig. 6, it is miniature LED bare chip luminescence signal on photostimulation electrode after the present embodiment bonds respectively Scheme the miniature LED bare chip with dominant wavelength 470nm and the relative intensity curve chart of ChR2 photosensitive protein sensitivity optical band, miniature Peak wavelength and the ChR2 photosensitive protein sensitivity peak wavelength of LED bare chip are close, and relative intensity curve has overlap, illustrates micro- The light that type LED bare chip sends meets initiation ChR2 photosensitive protein ion channel and opens, produces the wavelength required for electric pulse.

As it is shown in fig. 7, be the present embodiment integrated LED photostimulation and electrographic flexible nerve electrode device operation principle Figure, whole electrode is directly against being attached to rat cerebral cortex surface, by miniature LED bare chip powering arrays, miniature LED naked core The blue light that the sheet back side sends shines directly into the brain region needing to stimulate by slot, induces ChR2 gene transfected Or rat neuronal cell produces electric pulse, and by the recording electrode synchronous acquisition signal of telecommunication.

The present embodiment uses the gold wire ball welding method of mature and reliable to connect the miniature LED bare chip meeting stimulation neuron yardstick With photostimulation electrode and recording electrode, photostimulation electrode and recording electrode use has good flexibility and intensity, high temperature resistant, good The polyimide material of biocompatibility, effectively combines micro-processing technology, and technique is simple；Light can hinder without other materials Gear shines directly into the region needing to stimulate, and effect of stimulation is good, dependable performance；Photostimulation electrode and the combination of recording electrode, form Make the nerve electrode of photostimulation-electrographic recording one, provide a kind of new type nerve electrode tool for brain science research.

Embodiment 3

The present embodiment provides the flexible nerve electrode device that a kind of LED light similar to Example 1 stimulates and electrographic recording is integrated The preparation method of part, including:

1) on 500 microns of thick silicon chips the aluminum of one layer of 1.0 millimeters thick of thermal evaporation as sacrifice layer；

2) one layer of photosensitive polyimide Durimide 7505 of spin coating, through front baking, exposes, develops and solidifies, be made to To patterned photostimulation electrode under-layer polymer insulation layer 11, its thickness is 5 microns；Exhausted at photostimulation electrode under-layer polymer Having 3 slots above edge layer 11, the size of slot is 190 microns × 270 microns, centre-to-centre spacing is 700 microns；? Have 2 circular ports above photostimulation electrode under-layer polymer insulation layer 11, a diameter of 200 microns of circular port, centre-to-centre spacing be 1.5 millimeter；Having 4 square openings on photostimulation electrode under-layer polymer insulation layer 11, the size of square opening is 300 microns × 300 microns, centre-to-centre spacing be 1.5 millimeters；

3) one layer of chromium of sputtering and one layer of gold, thickness is respectively 20 nanometers and 300 nanometers；10 microns of thick positive photoresists of spin coating AZ4620；Through front baking, photoetching, development and after bake, ion beam etching is used to obtain patterned photostimulation electrode intermetallic metal Layer 10；One end of photostimulation electrode intermediate metal layer 10 is provided with three groups of circular pad, and often group includes two circles, and circular diameter is 250 Micron；The other end of photostimulation electrode intermediate metal layer 10 is provided with four road oblong pads, and wherein a road is as omnibus circuit, uses In connecting all miniature LED bare chip 8 negative electrode gold solder dishes；

4) make obtain patterned photostimulation electrode top layer polyimide insulative layer 9, its thickness is 5 microns, with light Slot of a size, circular port and square hole is had at stimulating electrode bottom polyimide insulative layer 11 same position, with Time directly over the circular pad of photostimulation electrode intermediate metal layer 10, have three groups of circular ports, often group includes 2 circles, circle straight Footpath is 200 microns, spacing is 800 microns；

5) the SU-8 glue that spin coating 100 microns is thick, through front baking, exposes, develops and after bake, at photostimulation electrode top layer polyamides Needing to place the surface of the slot of miniature LED bare chip 8 on imines insulating barrier 9, forming width is 20 microns rectangular Connected in star 7, rectangular recess 7 inside dimension is 260 microns × 340 microns, and 3 groove center are away from for 700 microns；

6) it is stained with high temperature resistant ultraviolet cured adhesive (UV glue) by fine needle and spreads upon in groove 7, a glue can be used as having ready conditions Machine replaces；

7) being picked up by single miniature LED bare chip 8 with tweezers, its cathode and anode gold solder dish is placed in groove 7, gently upward Light press miniature LED bare chip 8 top, makes high temperature resistant ultraviolet light polymerization adhesive curing with ultraviolet curing light irradiation glue bearing areas, Wherein: miniature LED bare chip 8 model is the TR2432 of Cree company, a size of 240 × 320 × 115 microns；Cathode and anode gold solder A diameter of 90 microns of dish, spacing be 135 microns；

8) spun gold 5 of diameter 25 microns is used to connect the cathode and anode gold solder of miniature LED bare chip 8 on gold wire bonder Dish and the circular pad of corresponding photostimulation electrode intermediate metal layer 10 one end, be only pressed in gently by the second bonding point of spun gold 5 In circular pad；

9) in circular pad, a small amount of conductive silver paste 4 is smeared with glass capillary, it is ensured that spun gold 5 and the firm company of circular pad Connect, ensure that conductive silver paste 4 is in the range of the circular pad of diameter 200 microns as far as possible；

10) above miniature LED bare chip 8, circular pad and spun gold 5, transparent organic silicon glue is smeared by fine needle, it is achieved Encapsulation；

11) by electrochemical corrosion or dilute hydrochloric acid corrosion aluminum sacrificial layer, the release of photostimulation electrode is completed.

2) one layer of photosensitive polyimide Durimide 7505 of spin coating, through front baking, exposes, develops and solidifies, be made to To patterned recording electrode bottom polyimide insulative layer 12, its thickness is 3 microns；Exhausted at recording electrode bottom polyimides The above of edge layer 12 has 3 slots, and the size of slot is 140 microns × 220 microns, centre-to-centre spacing is 700 microns； Having 2 circular ports on recording electrode bottom polyimide insulative layer 12, the diameter of circular port 200 microns, spacing are 1.5 Millimeter；Rectangular on slot in recording electrode bottom polyimide insulative layer 12 and circular port position and photostimulation electrode Shape hole is identical with circular port；

3) one layer of titanium-tungsten of sputtering and one layer of gold, thickness is respectively 20 nanometers and 300 nanometers；5 microns of thick positivities of spin coating Photoresist AZ4620, through front baking, photoetching, development and after bake, uses ion beam etching to obtain in the middle of patterned recording electrode Metal level 13, there are 4 circular gold measuring points, a diameter of the 250 of circular gold measuring point in one end of recording electrode intermediate metal layer 13 Micron, centre-to-centre spacing are 700 microns；

4) make obtain patterned recording electrode top layer polyimide insulative layer 14, its thickness is 3 microns, and with note Slot of a size and circular port is had, simultaneously at record at record electrode under-layer polyimide insulative layer 12 same position The concentric circular of a diameter of 200 microns is had directly over the circular gold measuring point of gold circuit layer 13 in the middle of electrode；

5) by electrochemical corrosion or dilute hydrochloric acid corrosion aluminum sacrificial layer, recording electrode release is completed.

Three, photostimulation electrode and the bonding of recording electrode:

The adhesion process of photostimulation electrode and recording electrode is with described in embodiment 1.

The present invention can carry out surface modification to the electrode points of recording electrode further after prepared by electrode, reduces Impedance, improves signal to noise ratio, such as ultrasonic electroplating platinum black, plating yttrium oxide or plating PEDOT/ graphene oxide etc., this partial content To describe in detail the most in the present invention.

The present invention two class technology for preparing electrode is general, and LED directly contacts with cerebral tissue, it is ensured that light transmission, effectively keeps away simultaneously Exempt between light and recording electrode owing to record result is impacted by photoelectric effect；Thickness of electrode is little, it is ensured that attach cerebral cortex There is conformality；Meet acute experiment and chronic implantation experiment demand, be suitable for brain science research.

Above the specific embodiment of the present invention is described.It is to be appreciated that the invention is not limited in above-mentioned Particular implementation, those skilled in the art can make various deformation or amendment within the scope of the claims, this not shadow Ring the flesh and blood of the present invention.

Claims

1. a LED light stimulates the flexible nerve electrode device integrated with electrographic recording, it is characterised in that described device includes polished bard Swash electrode and recording electrode, wherein:

Described photostimulation electrode package containing photostimulation electrode under-layer polymer insulation layer, photostimulation electrode overlayer polymer insulating barrier and Gold circuit layer in the middle of photostimulation electrode, in photostimulation electrode under-layer polymer insulation layer, the insulation of photostimulation electrode overlayer polymer Layer is provided with multiple hole, this some holes is respectively used to miniature LED bare chip printing opacity, through draw point, gluing with fixing photostimulation electrode With recording electrode relative to position；Miniature LED bare chip utilizes gold wire ball welding method to be connected on photostimulation electrode middle gold circuit layer；

Described recording electrode comprises recording electrode underlying polymer insulating barrier, recording electrode overlayer polymer insulating barrier and record electricity In the middle of extremely, gold circuit layer, also is provided with many on recording electrode underlying polymer insulating barrier, recording electrode overlayer polymer insulating barrier On individual hole, these hole sites and described photostimulation electrode under-layer polymer insulation layer, photostimulation electrode overlayer polymer insulating barrier Hole site corresponding, be respectively used to miniature LED bare chip printing opacity, through draw point location photostimulation electrode and recording electrode；Record Electrode exposes the one of recording electrode point and faces down and attach thin piece of elastomeric polymer；

Draw point sequentially passes through photostimulation electrode overlayer polymer insulating barrier, photostimulation electrode under-layer polymer insulation layer, record electricity The hole arranged on pole overlayer polymer insulating barrier, recording electrode underlying polymer insulating barrier, and penetrate in polymer thin block, from And ensure that, when gluing connects photostimulation electrode, recording electrode, photostimulation electrode, recording electrode will not be subjected to displacement.

The flexible nerve electrode device that LED light the most according to claim 1 stimulates and electrographic recording is integrated, it is characterised in that In described photostimulation electrode: have location overlap in photostimulation electrode under-layer polymer insulation layer and overlayer polymer insulating barrier Slot, circular hole and square opening, be respectively intended to ensure miniature LED bare chip printing opacity, fix polished bard through draw point and gluing Swash electrode with recording electrode relative to position.

The flexible nerve electrode device that LED light the most according to claim 2 stimulates and electrographic recording is integrated, it is characterised in that Slot on photostimulation electrode overlayer polymer insulating barrier is arranged over groove, is coated with daub so that miniature at this groove LED bare chip is fixed on photostimulation electrode.

The flexible nerve electrode device that LED light the most according to claim 2 stimulates and electrographic recording is integrated, it is characterised in that Photostimulation electrode overlayer polymer insulating barrier also has circular port, exposes middle gold circuit layer below circular port as gold electricity Road floor pad, the cathode and anode pad of miniature LED bare chip and gold circuit layer pad are connected by gold ball bonding, at gold circuit layer Smear electrocondution slurry on pad and guarantee conducting；Miniature LED bare chip, spun gold and gold circuit layer pad are encapsulated by glue.

The flexible nerve electrode device that LED light the most according to claim 1 stimulates and electrographic recording is integrated, it is characterised in that In described recording electrode: have the length of location overlap on recording electrode underlying polymer insulating barrier and overlayer polymer insulating barrier Square opening and circular hole, slot is used for miniature LED bare chip printing opacity, and circular hole is for through draw point location photostimulation electrode and note Record electrode.

The flexible nerve electrode device that LED light the most according to claim 5 stimulates and electrographic recording is integrated, it is characterised in that Also having circular port on recording electrode overlayer polymer insulating barrier, circular port exposes middle gold circuit layer as recording electrode Point；

Recording electrode exposes the one of recording electrode point and faces down and attach polymer thin block, and photostimulation electrode exposes gold circuit layer weldering The one of dish faces up, and draw point passes the symmetrical circular hole of same position on photostimulation electrode and recording electrode and penetrates polymer thin Block, the square opening gluing on photostimulation electrode realizes the connection of photostimulation electrode and recording electrode and fixes.

7. stimulating the flexible nerve electrode device integrated with electrographic recording according to the LED light described in any one of claim 1-6, it is special Levy and be, described photostimulation electrode under-layer polymer insulation layer and photostimulation electrode overlayer polymer insulating barrier, described note The material of record electrode under-layer polymer insulation layer and recording electrode overlayer polymer insulating barrier all selects non-photosensitivity type or Photosensitive Polyimides, or water white Parylene；

Described photostimulation electrode under-layer polymer insulation layer and photostimulation electrode overlayer polymer insulating barrier, recording electrode bottom The thickness range of polymer insulation layer and recording electrode overlayer polymer insulating barrier is 2～25 microns.

8. stimulating the flexible nerve electrode device integrated with electrographic recording according to the LED light described in any one of claim 1-6, it is special Levy and be, described photostimulation electrode overlayer polymer insulating barrier, photostimulation electrode under-layer polymer insulation layer, recording electrode top One polymer insulating barrier, recording electrode underlying polymer insulating barrier shape profile are identical, and on photostimulation electrode, recording electrode The size for the hole through draw point having is identical.

9. the system of the flexible nerve electrode device that the LED light described in an any one of claim 1-8 stimulates and electrographic recording is integrated Preparation Method, it is characterised in that described method independently prepared photostimulation electrode and recording electrode, then by photostimulation electrode and record Electrode adhesion.

A kind of LED light the most according to claim 9 stimulates the flexible nerve electrode device integrated with electrographic recording and preparation thereof Method, it is characterised in that described preparation photostimulation electrode, comprises the steps:

S1.1: make photostimulation electrode under-layer polymer insulation layer

On the silicon chip of deposition sacrificial metal layer, spin coating or deposition one layer of polymeric thin film, through graphically obtaining photostimulation electrode Underlying polymer insulating barrier, has multiple equidistant slot, many on photostimulation electrode under-layer polymer insulation layer Individual symmetrical circular hole and multiple square opening, wherein: multiple equidistant slots ensure that miniature LED bare chip luminescence passes through, multiple Symmetrical circular hole is for through draw point, and multiple square openings fix photostimulation electrode with recording electrode relative to position for gluing；

S1.2: make gold circuit layer in the middle of photostimulation electrode

Sputtering layer of metal adhesion layer and one layer of gold, spin coating positive photoresist as mask, through front baking, expose, develop and after Dry, use ion beam etching or wet etching, obtain gold circuit layer in the middle of patterned photostimulation electrode；

S1.3: make photostimulation electrode overlayer polymer insulating barrier

In the middle of the photostimulation electrode of S1.2 on gold circuit layer, use the operation identical with S1.1, make and obtain patterned light Stimulating electrode overlayer polymer insulating barrier, has at the same position with the photostimulation electrode under-layer polymer insulation layer of S1.1 The multiple equidistant slot of same shape, symmetrical circular hole and square opening, and have and organize circular port more, dew below circular port Go out photostimulation electrode middle gold circuit layer as gold circuit layer pad；

S1.4: make groove

Spin on polymers glue is the most graphical, around the slot of the photostimulation electrode overlayer polymer insulating layer of S1.3 Form groove；

Miniature LED bare chip fixed by S1.5: gluing

It is stained with water white transparency glue by fine needle and spreads upon in groove, single miniature LED bare chip is picked up, miniature LED bare chip Cathode and anode gold solder dish is placed in groove upward, presses lightly on miniature LED bare chip top, to guarantee miniature LED bare chip position Putting level, water white transparency glue contacts with miniature LED bare chip surrounding and does not spills over the miniature LED bare chip top of covering completely, treats Water white transparency adhesive curing completes single miniature LED bare chip and fixes, and remaining miniature LED bare chip in like manner operates；

Size according to miniature LED bare chip cathode and anode gold solder dish on gold wire bonder, selects the spun gold of suitable diameter, even Connect and expose below the cathode and anode pad of miniature LED bare chip and the photostimulation electrode overlayer polymer insulating barrier circular port of correspondence Golden circuit layer pad, underlying polymer insulating barrier is flexible substrate, spun gold cannot with gold the firm connection of circuit layer pad, only will Second bonding point of spun gold is pressed on gold circuit layer pad gently；

S1.7: smear electrocondution slurry and ensure conducting

Gold circuit layer pad smears a small amount of electrocondution slurry with glass capillary, it is ensured that spun gold and the gold firm company of circuit layer pad Connect；

S1.8: gluing encapsulates

Encapsulation is realized with fine needle gluing, it is ensured that photostimulation electrode above miniature LED bare chip, gold circuit layer pad and spun gold After release, miniature LED bare chip does not falls out, and gold thread is solid and reliable, and electrocondution slurry does not reacts simultaneously；

S1.9: release photostimulation electrode

11. a kind of LED light according to claim 9 stimulate the flexible nerve electrode device integrated with electrographic recording and preparation thereof Method, it is characterised in that described prepare recording electrode, comprises the steps:

S2.1: make recording electrode underlying polymer insulating barrier

On the silicon chip of deposition sacrificial metal layer, spin coating or deposition one layer of polymeric thin film, through graphically obtaining at the bottom of recording electrode One polymer insulating barrier, recording electrode underlying polymer insulating layer has multiple equidistant slot, multiple symmetrical circle Hole, wherein: multiple equidistant slots ensure that miniature LED bare chip luminescence passes through, multiple symmetrical circular holes are for through draw point；

S2.2: make gold circuit layer in the middle of recording electrode

Sputtering layer of metal adhesion layer and one layer of gold, spin coating positive photoresist as mask, through front baking, expose, develop and after Dry, use ion beam etching or wet etching, obtain gold circuit layer in the middle of patterned recording electrode；

S2.3: make recording electrode overlayer polymer insulating barrier

In the middle of the recording electrode of S2.2 on gold circuit layer, use the operation identical with S2.1, make and obtain patterned record Electrode overlayer polymer insulating barrier, is having same shape at the recording electrode underlying polymer insulating barrier same position of S2.1 Equidistant slot, symmetrical circular hole, and have multiple circular port, circular port exposes gold circuit layer in the middle of recording electrode and makees For recording electrode point；

S2.4: RR release record electrode

12. a kind of LED light according to claim 10 stimulate the flexible nerve electrode device integrated with electrographic recording and system thereof Preparation Method, it is characterised in that described photostimulation electrode and recording electrode bonded, comprises the steps:

S3.1: preparation surfacing, resilient polymer thin block, expose recording electrode the one of recording electrode point and face down, Entirely it is attached on polymer thin block；

S3.2: photostimulation electrode exposes the one of gold circuit layer pad and faces up, with draw point through photostimulation electrode and record electricity Extremely go up the symmetrical circular hole at same position, and penetrate in polymer thin block, press lightly on photostimulation electrode and recording electrode ensures Contact smooth；

S3.3: in the square opening position of photostimulation electrode, gluing fixes photostimulation electrode with recording electrode relative to position, treats glue The flexible nerve electrode device that described LED light stimulates and electrographic recording is integrated is i.e. obtained after solidification.

The preparation side of the flexible nerve electrode device that 13. a kind of LED light according to claim 8 stimulate and electrographic recording is integrated Method, it is characterised in that in S1.2 and S2.2:

The material selection titanium of described metal adhesion layers, chromium, titanium-tungsten, its thickness is 10～100 nanometers；Metal adhesion layers is used In the combination being respectively increased between gold and photostimulation electrode under-layer polymer insulation layer, recording electrode underlying polymer insulating barrier Power；

The thickness of described gold is 200～500 nanometers.

The preparation side of the flexible nerve electrode device that 14. a kind of LED light according to claim 8 stimulate and electrographic recording is integrated Method, it is characterised in that in S1.4:

The material selection SU-8 photoresist of described groove or polyimides glue；

The wall thickness of described groove is 5～50 microns, and the interior hole size of groove is according to miniature LED bare chip cathode and anode gold solder dish The size of place plane determines, thickness insulate with photostimulation electrode overlayer polymer according to the height of miniature LED bare chip The difference of layer and photostimulation electrode under-layer polymer insulation layer sum determines；

Described groove is used for laying miniature LED bare chip and gluing, to ensure the concordance of miniature LED bare chip position.

The preparation side of the flexible nerve electrode device that 15. a kind of LED light according to claim 8 stimulate and electrographic recording is integrated Method, it is characterised in that in S1.5:

Described water white transparency glue needs control rubber quality when spreading upon groove, it is ensured that place miniature LED bare chip also with tweezers transfer After pressing lightly on, part glue is extruded to miniature LED bare chip and the slot of photostimulation electrode overlayer polymer insulating barrier At gap between wall, between miniature LED bare chip and groove, between miniature LED bare chip and groove upper surface, thus improve viscous Connect intensity, it is to avoid during follow-up gold ball bonding, miniature LED bare chip band is got up by spun gold；It is naked that water white transparency glue does not adhere to miniature LED On the cathode and anode pad of chip, it is to avoid affect gold thread ball bonding quality；

Described water white transparency glue selects high temperature resistant instant drying adhesive or high temperature resistant ultraviolet cured adhesive, uses point gum machine to ensure some glue Amount and the uniformity of some glue position.