CN108853717A - A kind of method for implantation of flexibility nerve electrode and flexible nerve electrode - Google Patents
A kind of method for implantation of flexibility nerve electrode and flexible nerve electrode Download PDFInfo
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- CN108853717A CN108853717A CN201810630076.0A CN201810630076A CN108853717A CN 108853717 A CN108853717 A CN 108853717A CN 201810630076 A CN201810630076 A CN 201810630076A CN 108853717 A CN108853717 A CN 108853717A
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- flexible
- nerve electrode
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- layer
- flexibility
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- 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
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- 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
Abstract
The invention discloses a kind of flexible nerve electrode and the method for implantation of flexible nerve electrode.The flexibility nerve electrode includes flexible substrate, flexible insulating layer and conductive layer and magnetic material layer between flexible substrate and flexible insulating layer；Wherein, conductive layer includes at least one conductor wire, and conductor wire includes interconnecting lead and the record site for being located at interconnecting lead both ends and solder joint；Magnetic material layer includes multiple magnetic material parts, and magnetic material part and first part's interconnecting lead correspond；At least one through-hole is formed on flexible insulating layer, through-hole and record site correspond, and through-hole exposes corresponding record site through flexible insulating layer.Technical solution provided in an embodiment of the present invention, flexible nerve electrode have magnetism, can be implanted into cerebral cortex under the draw of magnetic field force, so that the implantation of flexible nerve electrode not will cause biggish acute injury to brain tissue.
Description
Technical field
The present embodiments relate to nerve electrode field more particularly to a kind of flexible nerve electrodes and flexible nerve electrode
Method for implantation.
Background technique
Nerve electrode is the hot issue in Neuroscience Research, is to connect neuron and external electronic device
Bridge, by nerve electrode, we can measure corticocerebral electricity physiological signal, including local field potentials and action potential,
This is of great significance for the development of brain science and the diagnosis of cerebral disease, such as epilepsy, Parkinson and Alzheimer's disease etc..
The nerve electrode haveing excellent performance needs to have following two condition：First is that implantation damage is small, rejection of the brain tissue to electrode is reduced
Reaction；Second is that spatial and temporal resolution with higher can be measured for nerve signal.
Currently, most widely used is silicon substrate rigidity nerve electrode, silicon substrate nerve electrode spatial and temporal resolution with higher, energy
The action potential of single neuron is enough recorded, still, there are larger differences with cerebral cortex for the mechanical property of silicon substrate nerve electrode
Different, it is dynamic to be easy to generate micro-shifting in brain tissue, causes biggish immune response, and it is thin in surrounding them to generate a large amount of colloids
Born of the same parents lead to electrode failure.
In view of the above-mentioned problems, it has been developed that flexible nerve electrode, mechanical property are more matched with cerebral cortex, greatly
Histogenic immunity reaction is reduced greatly, and still, current flexible nerve electrode is generally required through curing agent solidification or rigid objects
Auxiliary implantation cerebral cortex, can cause biggish acute injury to brain tissue.
Summary of the invention
The present invention provides the method for implantation of a kind of flexible nerve electrode and flexible nerve electrode, to avoid flexible neuroelectricity
The implantation of pole causes biggish acute injury to brain tissue.
In a first aspect, the embodiment of the invention provides a kind of flexible nerve electrode, the flexibility nerve electrode includes：
Flexible substrate, flexible insulating layer and conductive layer between the flexible substrate and the flexible insulating layer and
Magnetic material layer；
Wherein, the conductive layer includes at least one conductor wire, and the conductor wire includes interconnecting lead and is located at
The record site at the interconnecting lead both ends and solder joint；
The flexibility nerve electrode includes probe region, auxiliary region and bonding pad, the record site and with the note
First part's interconnecting lead of record site connection is located at the probe region, and second in addition to first part's interconnecting lead
Interconnecting lead is divided to be located at the auxiliary region, the solder joint is located at the bonding pad；
The magnetic material layer includes multiple magnetic material parts, the magnetic material part and first part's interconnecting lead
Correspond, on the stacking direction of the flexible substrate and the flexible insulating layer, the magnetic material part with it is corresponding described in
First part's interconnecting lead is stacked；
The flexible insulating layer at least covers the conductive layer and the magnetic material layer, is formed on the flexible insulating layer
There is at least one through-hole, the through-hole and the record site correspond, and the through-hole exposes through the flexible insulating layer
The corresponding record site；
The flexible substrate in the probe region includes multiple and the one-to-one strip structure of the conductor wire.
Second aspect, the embodiment of the invention also provides a kind of method for implantation of flexible nerve electrode, are applied to first party
Flexible nerve electrode described in face, it is described flexibility nerve electrode method for implantation include：
The head of fixed postanesthetic animal to be implanted；
Sphenotresia exposes the cerebral cortex on the head；
Determine the position to be implanted on the cerebral cortex；
The mobile flexible nerve electrode, makes the position to be implanted be located at conductor wire described in the flexible nerve electrode
The long line of extension on；
Magnetic field generation section part is placed in the lower jaw on the head far from the side of the flexible nerve electrode；
The mobile flexible nerve electrode is close to the head；
The probe region of the flexible nerve electrode is planted under the draw for the magnetic force that the magnetic field generation section part generates
Enter the cerebral cortex of the animal to be implanted.
Technical solution provided in an embodiment of the present invention, by the way that magnetic material is arranged in the probe region of flexible nerve electrode
Layer can move under the action of externally-applied magnetic field so that the flexible nerve electrode in probe region has magnetism and be implanted into brain skin
Layer greatly reduces flexible nerve electrode implantation to brain tissue due to no longer needing the auxiliary or curing process of rigid element
Acute injury can carry out measurement steady in a long-term to nerve signal.
Detailed description of the invention
In order to more clearly illustrate the technical scheme of the exemplary embodiment of the present invention, below to required in description embodiment
The attached drawing to be used does a simple introduction.Obviously, the attached drawing introduced is present invention a part of the embodiment to be described
Attached drawing, rather than whole attached drawings without creative efforts, may be used also for those of ordinary skill in the art
To obtain other attached drawings according to these attached drawings.
Fig. 1 is a kind of overlooking structure diagram of flexible nerve electrode provided in an embodiment of the present invention；
Fig. 2 is the schematic diagram of the section structure of the dotted line AB along Fig. 1；
Fig. 3 is the structural schematic diagram of conductive layer in Fig. 1；
Fig. 4 is the structural schematic diagram of magnetic material layer in Fig. 1；
Fig. 5 is the structural schematic diagram of another magnetic material layer provided in an embodiment of the present invention；
Fig. 6 is a kind of flow diagram of the method for implantation of flexible nerve electrode provided in an embodiment of the present invention.
Specific embodiment
The present invention is described in further detail with reference to the accompanying drawings and examples.It is understood that this place is retouched
The specific embodiment stated is used only for explaining the present invention rather than limiting the invention.It also should be noted that in order to just
In description, only some but not all contents related to the present invention are shown in the drawings.Exemplary reality is being discussed in greater detail
It should be mentioned that some exemplary embodiments are described as the processing or method described as flow chart before applying example.Although
Operations (or step) are described as the processing of sequence by flow chart, but many of these operations can be by concurrently, concurrently
Ground is implemented simultaneously.In addition, the sequence of operations can be rearranged.The processing when its operations are completed can be by
It terminates, it is also possible to have the additional step being not included in attached drawing.It is described processing can correspond to method, function, regulation,
Subroutine, subprogram etc..
Fig. 1 is a kind of overlooking structure diagram of flexible nerve electrode provided in an embodiment of the present invention.Fig. 2 is along Fig. 1
The schematic diagram of the section structure of dotted line AB.As shown in Fig. 2, flexible nerve electrode include flexible substrate 100, flexible insulating layer 400 with
And conductive layer 200 and magnetic material layer 300 between the flexible substrate 100 and the flexible insulating layer 400.Fig. 3 is
The structural schematic diagram of conductive layer in Fig. 1.As shown in figure 3, the conductive layer 200 includes at least one conductor wire 210, the conduction
Line 210 includes interconnecting lead 211 and the record site 212 and the solder joint 213 that are located at 211 both ends of interconnecting lead.After
Continue referring to Fig. 1 and Fig. 3, the flexibility nerve electrode includes probe region 10, auxiliary region 20 and bonding pad 30, the record site
212 and it is located at the probe region 10 with first part's interconnecting lead 211/1 for connect of the record site 212, removes described the
Second part interconnecting lead 211/2 except a part of interconnecting lead 211/1 is located at the auxiliary region 20, the solder joint 213
In the bonding pad 30.Fig. 4 is the structural schematic diagram of magnetic material layer in Fig. 1.As shown in figure 4, the magnetic material layer 300 wraps
Include multiple magnetic material parts 310.With continued reference to Fig. 2 and Fig. 4, the magnetic material part 310 and first part's interconnecting lead
211/1 corresponds, on the stacking direction Y of the flexible substrate 100 and the flexible insulating layer 400, the magnetic material
Portion 310 is stacked with corresponding first part's interconnecting lead 211/1.It should be noted that avoid structure from obscuring, Fig. 1
Flexible substrate 100, conductive layer 200, magnetic material layer 300 and flexible insulating layer 400 are not indicated, but in above-mentioned each structure
Same structure uses identical hatching designation into Fig. 4 with Fig. 2 in Fig. 1, can determine the position of above-mentioned each structure in Fig. 1 accordingly
It sets and shape.Referring to figs. 2 to after Fig. 4 it is found that the flexible insulating layer described in Fig. 1 at least covers the conductive layer and the magnetism
Material layer is formed at least one through-hole 410, the through-hole 410 and described one a pair of record site on the flexible insulating layer
It answers, the through-hole 410 exposes the corresponding record site through the flexible insulating layer, the flexibility in the probe region 10
Substrate 100 includes the multiple and one-to-one strip structure of the conductor wire 210.
It should be noted that it is illustrative, as shown in Figure 1, the shape of the flexible substrate 100 in auxiliary region 20 can be
The shape of bulk, the flexible substrate 100 in bonding pad 30 can be identical as the shape of multiple solder joints, the flexibility in auxiliary region 20
The size and shape of insulating layer can be identical as flexible substrate.It is understood that due to only having the structure meeting in probe region 10
Be implanted into the cerebral cortex of animal to be implanted, thus in auxiliary region 20 and bonding pad 30 flexible substrate shape and flexible insulating layer
Shape can also be the shape except structure shown in Fig. 1, but should be noted that guarantee that it is higher that flexible nerve electrode has
Reliability, i.e. the property of magnetic material layer and conductive layer is constant, and flexible insulating layer need at least cover conductive layer and magnetic material
Layer, on the other hand, to guarantee that flexible nerve electrode is integral structure, at least one film layer in flexible substrate and flexible insulating layer
It is continuous structure in auxiliary region 20 and/or bonding pad 30.
In addition, to increase the record site of flexible nerve electrode, it can also be in flexible insulating layer 400 far from flexible substrate
At least one additional conductive layer is arranged in 100 side again, and sets in each additional conductive layer far from the side of flexible substrate 100
An additional flexibility insulating layer is set, the shape of each additional conductive layer is identical as conductive layer, and is directed toward flexibility absolutely along flexible substrate 100
The direction of edge layer 400, length of each additional conductive layer in probe region 10 are successively successively decreased, and each additional conductive layer is far from flexible liner
Additional vias is arranged in the record site 212 corresponded in the additional conductive layer on all additional flexibility insulating layers of 100 side of bottom.
Technical solution provided in this embodiment, by the way that magnetic material layer is arranged in the probe region of flexible nerve electrode 10
300, so that the flexible nerve electrode in probe region 10 has magnetism, it can be moved under the action of externally-applied magnetic field and be implanted into brain
Cortex greatly reduces flexible nerve electrode implantation to brain tissue due to no longer needing the auxiliary or curing process of rigid element
Acute injury, measurement steady in a long-term can be carried out to nerve signal.
Optionally, as shown in figure 3, each conductor wire 210 is flat when the quantity of at least one conductor wire 210 is greater than 1
Row setting.Such setting enables to each conductor wire 210 can be perpendicular to the region to be implanted on cerebral cortex, so that right
The each probe 101 answered can be reduced part probe 101 in implantation process because stress is inadequate by biggish magnetic field force
The occurrence probability of caused buckling phenomenon.
Preferably, as shown in Fig. 2, the magnetic material layer 300 can be located at the conductive layer 200 far from the flexible liner
The side at bottom 100.Such setting enables to conductive layer 200 to be located on smooth 100 surface of flexible substrate, can be avoided same
Record site 212 in one conductor wire 210 is with interconnecting lead 211 since the presence of film layer step is not connected firmly.
Illustratively, the material of the flexible substrate 100 can be in polyimides, Parylene and SU8 photoresist
Any one or any at least two combination.
Optionally, the Thickness of the flexible substrate 100 may range from 0.5~4um.It should be noted that flexible
The thickness of substrate 100 is too small to will lead to its mechanical property and insulation performance deficiency, and then influences each film layer on flexible nerve electrode
Formation and brain signal measurement, thickness is excessive and the integral thickness of flexible nerve electrode can be made to increase, is unfavorable for flexible refreshing
Miniature through electrode, and also result in the flexible decline of flexible nerve electrode.Specifically, the Thickness of flexible substrate 100
Range preferably from 1~3um, further preferably 2um.
Illustratively, the material of the conductive layer 200 can be any one in gold, platinum and iridium or any at least two
Combination.On the one hand above-mentioned material is convenient for preparing tiny film pattern, on the other hand have preferable electrology characteristic, be conducive to soft
The promotion of micromation and the sensitivity of nerve electrode.
Optionally, the Thickness of the conductive layer 200 may range from 20~500nm.It is led in above-mentioned value range
Electric layer 200 can reach relatively better electrical sensitivity.Specifically, the Thickness of conductive layer 200 range preferably from 50~
300nm, further preferably 100nm.
Optionally, the width value range of the interconnecting lead 211 can be 2~100um.It should be noted that mutual
In the case that even the thickness of conducting wire 211 determines, the width of interconnecting lead 211 is related to the current strength for flowing through interconnecting lead 211,
To make flexible nerve electrode have preferable signal transmission characteristics, the width of interconnecting lead 211 is preferably arranged in the present embodiment
Value range is 2~100um.Specifically, the width value range of interconnecting lead 211 is preferably 10~30um, further preferably
For 12um.
In the present embodiment, the length value range of the strip structure can be 1~15mm.It is understood that shape
At in conductive layer 200, magnetic material layer 300 and flexible insulating layer 400 in flexible substrate 100 size not more than pair
The size of flexible substrate 100 in region is answered, therefore, the length of strip structure described herein is flexible neuroelectricity in probe region 10
The length of each probe 101 of pole.Probe is the part for being implanted into animal head to be implanted, if too short will lead to note connected to it
Record site 212 can not go deep into effective coverage, it is too long but can due to flexibility characteristics increase implantation difficulty, it is contemplated that it is above-mentioned two aspect
Reason, it is 1~15mm that its length value range is preferably arranged herein.Specifically, the length value range of the strip structure
Preferably 2~5mm, further preferably 3mm.
Optionally, the width value range of the strip structure can be 5~100um.It is understood that the strip
The width of structure is the width of each probe 101 of flexible nerve electrode in probe region 10.The width of probe 101 is excessive or mistake
It is small to will increase implantation difficulty, it is therefore advantageous to setting value range be 5~100um.Specifically, the width of the strip structure
Spending value range is preferably 10~30um, further preferably 20um.
In the present embodiment, the quantity value range of the conductor wire 210 can be 1~500.In certain amount range
Interior, the quantity of conductor wire 210 is more, the record site more than 212 of flexible nerve electrode, carries out the brain area area of signal record
It is bigger, on the other hand in view of the increase of quantity will increase implantation difficulty, the quantity value of conductor wire 210 is preferably set herein
Range is 1~500.Specifically, the quantity value range of conductor wire 210 is preferably 1~16, further preferably 4.
Optionally, the spacing value range when quantity of the conductor wire 210 is greater than 1, between the adjacent strip structure
It can be 20~1000um.It should be noted that the spacing of the adjacent strip structure be between adjacent probe 101 between
Away from the too small signal section repetition for being likely to result in adjacent probe 101 and detecting of the spacing leads to the waste of resource, spacing mistake
The big implantation process that can be unfavorable for again using magneticaction, comprehensively considers above-mentioned two aspects reason, the present embodiment is preferably arranged
The value range of the spacing is 20~1000um.Specifically, the spacing value range between the adjacent strip structure is preferred
For 200~600um, further preferably 500um.
Illustratively, adhesion layer can be set between the flexible substrate 100 and the conductive layer 200.Adhesion layer energy
Enough increase the adhesion strength of conductive layer 200 on substrate, conductive layer 200 is avoided to remove in the use process of flexible nerve electrode.
Optionally, the material of the adhesion layer can be chromium or titanium.
Optionally, the Thickness of the adhesion layer may range from 5~60nm.Adhesion layer is excessively thin, and to be unable to reach increase viscous
The Thickness model of adhesion layer is preferably arranged in the effect of attached power, the blocked up integral thickness that will increase flexible nerve electrode herein
It encloses for 5~60nm.Specifically, the Thickness of adhesion layer ranges preferably from 5~15nm, further preferably 5nm.
Optionally, the shape in the record site 212 can be circle.Such setting enables to record site 212
Size it is larger relative to interconnecting lead, increase record site 212 and brain neuroblastoma contact area.It is understood that
In the other embodiments of the present embodiment, record site 212 can also be other shapes, and the present embodiment does not do specific limit to this
It is fixed.
Preferably, the diameter value range in the record site 212 can be 5~30um.It is undersized to record site 212
It is smaller with the contact area of brain neuroblastoma to will lead to it, so that its electrochemical impedance is larger and is unfavorable for brain signal measurement, it is excessive
The spatial resolution that flexible nerve electrode carries out signal measurement can be reduced, and the implantation difficulty of probe 101 increases, it is contemplated that above-mentioned
Problem, the diameter value range of preferably setting record microdot is 5~30um herein.Specifically, the diameter in record site 212 takes
Value ranges preferably from 5~20um, further preferably 10um.
Optionally, the material of the magnetic material layer 300 can for any one in FeNi, FePt and CoPt or it is any extremely
Few two kinds of combination.So that the probe 101 for being located at flexible nerve electrode in probe region 10 has preferable magnetism, convenient for soft
The implantation of nerve electrode.
Optionally, the Thickness of the magnetic material layer 300 may range from 0.5~4um.Magnetic material layer 300
Thickness is excessively thin will lead to magnetic material layer 300 magnetism it is not high, integral thickness that is blocked up and will increase flexible nerve electrode to
Reduce the flexibility of flexible nerve electrode, therefore, herein the Thickness range of preferably setting magnetic material layer 300 be 0.5~
4um.Specifically, the Thickness of magnetic material layer 300 ranges preferably from 1.5~3um, further preferably 2.5um.
Optionally, the magnetic material layer 300 can be formed by electroplating technology.Specifically, being adopted in the electroplating technology
Temperature value range can be 20~70 DEG C, preferably 30~50 DEG C, further preferably 45 DEG C；Electroplating time value model
Enclosing can be 1~15min, preferably 3~7min, further preferably 5min；Current density value range can for 50~
600A/m2, preferably 150~500A/m2, further preferably 350A/m2.
It is understood that magnetic material layer 300 can also pass through other works in the other embodiments of the present embodiment
Skill is formed, and the present embodiment is not specifically limited in this embodiment.
Illustratively, the width value range of the magnetic material part 310 can be 2~90um.To guarantee magnetic material
Layer 300 has preferable magnetism, and not will increase the overall dimensions of probe 101, and magnetic material part is preferably arranged in the present embodiment
310 width value range is 2~90um.Specifically, the width value range of magnetic material part 310 is preferably 5~20um, into
One step is preferably 10um.
Optionally, the magnetic material part 310 can be for strip or including at least two along 210 side of extension of conductor wire
To the discrete sub-portion 311 of arrangement.Magnetic material part 310 is used for so that flexible nerve electrode is located at the probe 101 in probe region 10
It with magnetism, therefore also can may include at least two discrete sub-portions arranged along 210 extending direction of conductor wire for strip
311, specifically, magnetic material part 310 is strip in Fig. 4.Fig. 5 is another magnetic material layer provided in an embodiment of the present invention
Structural schematic diagram.As shown in figure 5, magnetic material part 310 includes multiple discrete sub-portions along the arrangement of 210 extending direction of conductor wire
311.It should be noted that magnetic material part 310 is correspondingly arranged with the first interconnecting lead, it, will since width is relatively small
It is set as including multiple discrete sub-portions 311 along the arrangement of 210 extending direction of conductor wire relative to other division mode techniques
Difficulty is lower.
Illustratively, the material of the flexible insulating layer 400 can be polyimides, Parylene and SU8 photoresist
In any one or any at least two combination.
Optionally, the Thickness of the flexible insulating layer 400 may range from 0.5~4um.Thickness is too small to will lead to it
Mechanical property and insulation performance are insufficient, and then influence implantation process and brain signal measurement, and thickness is excessive and will increase flexible mind
Integral thickness through electrode, is unfavorable for the micromation of flexible nerve electrode, and also results in flexible nerve electrode flexibility decline, examines
Consider the above problem, the Thickness range that flexible insulating layer 400 is preferably arranged in the present embodiment is 0.5~4um.Specifically,
The Thickness of flexible insulating layer 400 ranges preferably from 1~3um, further preferably 2um.
Optionally, the material of the flexible substrate 100 and the flexible insulating layer 400 can be identical.Such setting makes
It obtains and only needs in the preparation process of flexible nerve electrode using same flexible material, main technologic parameters only need to design once
, reached the beneficial effect of simplified flexible nerve electrode preparation process.
The following are three kinds of specific design schemes of each structural parameters in flexible nerve electrode provided in an embodiment of the present invention：
Scheme 1, flexible substrate material be polyimides, with a thickness of 2um；The flexible substrate of strip structure in probe region
Length is 3mm, width 20um；Spacing in probe region between the flexible substrate of adjacent strip structure is 500um；
The quantity of conductor wire is 4；The material of conductive layer is gold, with a thickness of 100um；The length of conductor wire is in probe region
3um, the width of interconnecting lead are 12um；The material of adhesion layer is chromium, with a thickness of 5nm；
The shape for recording site is circle, a diameter of 10um；
Solder joint is rectangle, a length of 1000um, width 200um, and adjacent pad spacing is 500um；
The material of flexible insulating layer is polyimides, with a thickness of 2um；The flexible insulation of a conductor wire is covered in probe region
The length of layer is 3um, width 20um, corresponds to each record site thereon and is provided with through-hole；Flexible insulating layer does not cover weldering
Point.
Scheme 2, flexible substrate material be polyimides, with a thickness of 2um；The flexible substrate of strip structure in probe region
Length is 2mm, width 20um；Spacing in probe region between the flexible substrate of adjacent strip structure is 200um；
The quantity of conductor wire is 8；The material of conductive layer is gold, with a thickness of 100um；The length of conductor wire is in probe region
2um, the width of interconnecting lead are 12um；The material of adhesion layer is chromium, with a thickness of 5nm；
The shape for recording site is circle, a diameter of 10um；
Solder joint is rectangle, a length of 1000um, width 200um, and adjacent pad spacing is 200um；
The material of flexible insulating layer is polyimides, with a thickness of 2um；The flexible insulation of a conductor wire is covered in probe region
The length of layer is 2um, width 20um, corresponds to each record site thereon and is provided with through-hole；Flexible insulating layer does not cover weldering
Point.
Scheme 3, flexible substrate material be polyimides, with a thickness of 2um；The flexible substrate of strip structure in probe region
Length is 1.5mm, width 20um；Spacing in probe region between the flexible substrate of adjacent strip structure is 150um；
The quantity of conductor wire is 16；The material of conductive layer is gold, with a thickness of 100um；The length of conductor wire is in probe region
1.5um, the width of interconnecting lead are 12um；The material of adhesion layer is chromium, with a thickness of 5nm；
The shape for recording site is circle, a diameter of 10um；
Solder joint is rectangle, a length of 1000um, width 200um, and adjacent pad spacing is 150um；
The material of flexible insulating layer is polyimides, with a thickness of 2um；The flexible insulation of a conductor wire is covered in probe region
The length of layer is 1.5um, width 20um, corresponds to each record site thereon and is provided with through-hole；Flexible insulating layer does not cover
Solder joint.
The following are a kind of preparation process of flexible nerve electrode provided in an embodiment of the present invention：
The preparation of step 11, sacrificial layer (material of sacrificial layer is Al)
1) Wafer Cleaning：The silicon wafer that diameter is four cun is placed in clean culture dish, successively with acetone, isopropyl alcohol and water
It is cleaned by ultrasonic 10min (power 30W), silicon wafer is placed on 105 DEG C of hot plates after being dried with nitrogen and heats 3min, removes steam, temperature
Degree, which is cooled to room temperature, cleans 3min (power 100W) with oxygen plasma.
2) spin coating：Clean silicon wafer is placed in sol evenning machine sucker center to fix, sets sol evenning machine parameter (500rpm 5s
Plus 2000rpm 60s), the S1813 photoresist of 4mL is added dropwise at silicon wafer center with dropper, starts spin coating.
3) front baking：The silicon wafer that spin coating is terminated is placed on 115 DEG C of hot plates, is dried 3min, is then lifted down and be down to room temperature.
4) it exposes：Use double-sided alignment contact ultraviolet photolithographic machine (model：MA6), chromium exposure mask corresponding to installing Al layers
Version, silicon wafer is put on the workbench of litho machine, is arranged exposure parameter (time for exposure 65s, mode Vac, gap 40um), is opened
Begin to expose.
5) develop：Appropriate S1813 developer solution is poured into clean culture dish, then silicon wafer puts in, and appropriateness shakes silicon
Piece, developing time 1min with water go to clean up and with being dried with nitrogen after development.
6) residue glue is removed：With oxygen plasma cleaning silicon chip 1min (power 50W).
7) Al is deposited：Use magnetron sputtering coating system (model：Lab-18), depositing Al layer, thickness 100nm.
8) Al is removed：Proper amount of acetone is poured into clean culture dish, then silicon wafer puts in, and is heated on 80 DEG C of hot plates
1 hour, the Al stripped down is all blown off using dropper；Then it is cleaned up respectively with acetone, isopropanol, water, uses nitrogen
Drying, is put on 105 DEG C of hot plates and dries 3min, removes steam.
The preparation of step 12, flexible substrate (material of flexible substrate is polyimides)
1) surface clean：With oxygen plasma cleaning silicon chip 3min (power 100W).
2) spin coating：Silicon wafer is placed in sol evenning machine sucker center to fix, sets sol evenning machine parameter (500rpm5s plus
2000rpm 60s), 15% polyimides of 4mL is added dropwise at silicon wafer center with dropper, starts spin coating.
3) it dries：The silicon wafer that spin coating is terminated, which is put on 120 DEG C of hot plates, dries 10min, then puts 200 DEG C of vacuum ovens into
In dry 2 hours, furnace cooling.
The preparation of step 13, conductive layer (material of conductive layer is Au)：
1) surface clean：It is put on 105 DEG C of hot plates and is dried with being dried with nitrogen with acetone, isopropanol, water cleaning silicon chip respectively
3min removes steam, and temperature, which is cooled to room temperature, cleans 1min (power 50W) with oxygen plasma.
2) spin coating：Silicon wafer is placed in sol evenning machine sucker center to fix, sets sol evenning machine parameter (500rpm5s plus
2000rpm 60s), the S1813 photoresist of 4mL is added dropwise at silicon wafer center with dropper, starts spin coating.
3) front baking：The silicon wafer that spin coating is terminated is placed on 115 DEG C of hot plates, is dried 3min, is then lifted down and be down to room temperature.
4) it exposes：Use double-sided alignment contact ultraviolet photolithographic machine (model：MA6), chromium exposure mask corresponding to installing Au layers
Version, silicon wafer is put on the workbench of litho machine, is arranged exposure parameter (time for exposure 65s, mode Vac, gap 40um), is opened
Begin to expose.
5) develop：Appropriate S1813 developer solution is poured into clean culture dish, then silicon wafer puts in, and appropriateness shakes silicon
Piece, developing time 1min are washed with water clean and with being dried with nitrogen after development.
6) residue glue is removed：With oxygen plasma cleaning silicon chip 1min (power 50W).
7) Au is deposited：Use electron beam evaporation deposition system (model：OHMIKER-50B), deposition of adhesion layers of chrome, thickness
Then 5nm deposits Au layers, thickness 100nm.
8) Au is removed：Proper amount of acetone is poured into clean culture dish, then silicon wafer puts in, and is heated on 80 DEG C of hot plates
1 hour, the Au stripped down is all blown off using dropper；Then it is cleaned up respectively with acetone, isopropanol, water, uses nitrogen
Drying, is put on 105 DEG C of hot plates and dries 3min, removes steam.
Step 14, magnetic coating (material of magnetic coating is FeNi)：
1) surface clean：With oxygen plasma cleaning silicon chip 1min (power 50W).
2) spin coating：Silicon wafer is placed in sol evenning machine sucker center to fix, sets sol evenning machine parameter (500rpm5s plus
2000rpm 60s), the S1813 photoresist of 4mL is added dropwise at silicon wafer center with dropper, starts spin coating.
3) front baking：The silicon wafer that spin coating is terminated is placed on 115 DEG C of hot plates, is dried 3min, is then lifted down and be down to room temperature.
4) it exposes：Use double-sided alignment contact ultraviolet photolithographic machine (model：MA6), chromium corresponding to installing FeNi layers is covered
Film version, silicon wafer is put on the workbench of litho machine, is arranged exposure parameter (time for exposure 65s, mode Vac, gap 40um),
Start to expose.
5) develop：Appropriate S1813 developer solution is poured into clean culture dish, then silicon wafer puts in, and appropriateness shakes silicon
Piece, developing time 1min are washed with water clean and with being dried with nitrogen after development.
6) residue glue is removed：With oxygen plasma cleaning silicon chip 1min (power 50W).
7) FeNi is electroplated：Use electrochemical workstation (model：Gamry Reference 3000) it is electroplated, control electricity
Plating temperature is 45 DEG C, electroplating time 5min, and current density is 350A/m2 etc..After plating, with deionized water silicon wafer table
The plating solution in face cleans up, and with being dried with nitrogen
8) S1813 template is removed：Proper amount of acetone is poured into clean culture dish, then silicon wafer puts in, and impregnates 5min
After take out, cleaned up respectively with isopropyl alcohol and water, with being dried with nitrogen, be put on 105 DEG C of hot plates and dry 3min, remove steam.
Step 15, flexible insulating layer (material of flexible insulating layer is polyimides)
1) spin coating：Silicon wafer is placed in sol evenning machine sucker center to fix, sets sol evenning machine parameter (500rpm5s plus
2000rpm 60s), 15% polyimides of 4mL is added dropwise at silicon wafer center with dropper, starts spin coating.
2) it dries：The silicon wafer that spin coating is terminated, which is put on 120 DEG C of hot plates, dries 10min, then puts 200 DEG C of vacuum ovens into
In dry 2 hours, furnace cooling.
Step 16, flexible nerve electrode it is graphical
1) surface clean：Use reactive plasma etching machine (model：ETCHLAB-200), silicon wafer is put into etching machine
Cavity in, vacuumize, etch 10s (power 200W).
2) spin coating：Silicon wafer is placed in sol evenning machine sucker center to fix, sets sol evenning machine parameter (500rpm5s plus
2000rpm 60s), the AZ4620 photoresist of 4mL is added dropwise at silicon wafer center with dropper, starts spin coating.
3) front baking：The silicon wafer that spin coating is terminated is placed on 120 DEG C of hot plates, is dried 5min, is then lifted down and be down to room temperature.
4) it exposes：Use double-sided alignment contact ultraviolet photolithographic machine (model：MA6), graphical corresponding Cr is installed to cover
Film version, silicon wafer is put on the workbench of litho machine, is arranged exposure parameter (time for exposure 180s, mode Vac, gap 40um),
Start to expose.
5) develop：Appropriate AZ4620 developer solution is poured into clean culture dish, then silicon wafer puts in, and appropriateness shakes silicon
Piece, developing time 10min are washed with water clean and with being dried with nitrogen after development.
6) reactive ion etching：Use reactive plasma etching machine (model：ETCHLAB-200), silicon wafer is put into quarter
It in the cavity of erosion machine, vacuumizes, etches 7.5min (power 200W).
7) AZ4620 residue glue is removed：Proper amount of acetone is poured into clean culture dish, then silicon wafer puts in, and impregnates 5min
After take out, cleaned up respectively with isopropyl alcohol and water, with being dried with nitrogen, be put on 105 DEG C of hot plates and dry 3min, remove steam.
Step 17, solder joint connection
1) scribing：Along silicon wafer crystal orientation, entire silicon wafer is divided into discrete electrode with silicon knife.
2) soft arranging wire is pressed：Soft arranging wire spacing is 0.5mm, appropriately sized ACF is adhesive at solder joint, soft arranging wire and solder joint
Alignment, 120 DEG C of hot pressing 1min.
3) it encapsulates：Solder joint and soft arranging wire junction are encapsulated with AB glue, 60 DEG C are dried in vacuo 2 hours.
4) Al sacrificial layer is discharged：The electrode that encapsulation finishes is immersed into the FeCl3 solution of 0.5mol/L, by Al sacrificial layer
It etches away, so that the probe region of flexible nerve electrode is detached from silicon wafer substrate.
5) extra silicon wafer is crossed out：The extra silicon wafer below the internal probe of probe region is crossed out using silicon knife, is then turned in water
It moves on to and is paved on the glass slide of isopropanol, to isopropanol natural air drying, flexible nerve electrode, which is just prepared, to be finished.
Fig. 6 is a kind of flow diagram of the method for implantation of flexible nerve electrode provided in an embodiment of the present invention.Flexible mind
Method for implantation through electrode is applied to flexible nerve electrode described in any embodiment of that present invention.As shown in fig. 6, flexible neuroelectricity
The method for implantation of pole specifically includes as follows：
Step 1, the head for fixing postanesthetic animal to be implanted.
Step 2, sphenotresia expose the cerebral cortex on the head.
Step 3 determines position to be implanted on the cerebral cortex.
Step 4, the mobile flexible nerve electrode, are located at the position to be implanted described in the flexible nerve electrode
On the long line of the extension of conductor wire.
Magnetic field generation section part is placed in the lower jaw on the head far from the side of the flexible nerve electrode by step 5.
Illustratively, magnetic field generation section part can be permanent magnet.It is understood that magnetic field generation section part can also be it
He can produce the component in magnetic field, and the present embodiment is not specifically limited in this embodiment.
Step 6, the mobile flexible nerve electrode are close to the head.
The traction work of step 7, the magnetic force for generating the probe region of the flexible nerve electrode in the magnetic field generation section part
With the cerebral cortex of the lower implantation animal to be implanted.
The following are a kind of specific implementation process of the method for implantation of flexible nerve electrode provided in an embodiment of the present invention：
Step 21, Preoperative Method
It gets out C57 mouse, stereotaxic apparatus, surgical operation microscope, cold light source, scale, isoflurane, penta bar of ratio in advance
It is appropriate sodium, 1mL syringe, physiological saline, chlorotetracycline eye ointment, Iodophor, elbow scissors, straight peen scissors, tip tweezers, clean-cloth, clean
Net paper, gauze, permanent magnet, the flexible nerve electrode for connecting rear end, cranium brill, cotton swab etc..
Step 22, anesthesia
The mouse being in a good state of health is taken, is weighed, according to the injection volume of the criterion calculation yellow Jackets of 0.01mL/g, is used
Yellow Jackets anaesthetize mouse.
Step 23, surgical procedure
1) it after mouse deep anaesthesia, is fixed on stereotaxic apparatus, dips in Iodophor with cotton swab and disappear in mouse head wiping
Poison simultaneously cuts off head hair.
2) mouse scalp is stitched with scissors in and is cut off, expose skull, sphenotresia exposes cerebral cortex and chooses hard brain
Film adjusts the underface that stereotaxic apparatus makes brain area to be implanted be in flexible nerve electrode.
6) permanent magnet is placed on mouse lower jaw in the following, the flexible nerve electrode for connecting rear end is fixed on Naoliqing capsule
On the electrode stem of instrument, slowly downwards close to Cerebral Cortex, when flexible nerve electrode is close enough apart from Cerebral Cortex,
The form that flexible nerve electrode is controlled by slowly moving permanent magnet is allowed to holding and the perpendicular relationship of cortical surface, in magnetic
Under the auxiliary implantation power that field provides, flexible nerve electrode is slowly implanted into cortex.
7) rear end of flexible nerve electrode and 128 channel Electrophysiologies record system are connected, carries out neural letter
Number record (including local field potentials and action potential).
Note that the above is only a better embodiment of the present invention and the applied technical principle.It will be appreciated by those skilled in the art that
The invention is not limited to the specific embodiments described herein, be able to carry out for a person skilled in the art it is various it is apparent variation,
It readjusts and substitutes without departing from protection scope of the present invention.Therefore, although being carried out by above embodiments to the present invention
It is described in further detail, but the present invention is not limited to the above embodiments only, without departing from the inventive concept, also
It may include more other equivalent embodiments, and the scope of the invention is determined by the scope of the appended claims.
Claims (14)
1. a kind of flexibility nerve electrode, which is characterized in that including：
Flexible substrate, flexible insulating layer and conductive layer and magnetism between the flexible substrate and the flexible insulating layer
Material layer；
Wherein, the conductive layer includes at least one conductor wire, and the conductor wire includes interconnecting lead and is located at described
The record site at interconnecting lead both ends and solder joint；
The flexibility nerve electrode includes probe region, auxiliary region and bonding pad, the record site and with the record position
First part's interconnecting lead of point connection is located at the probe region, and the second part in addition to first part's interconnecting lead is mutual
Even conducting wire is located at the auxiliary region, and the solder joint is located at the bonding pad；
The magnetic material layer includes multiple magnetic material parts, and the magnetic material part and first part's interconnecting lead are one by one
It is corresponding, on the stacking direction of the flexible substrate and the flexible insulating layer, the magnetic material part and corresponding described first
Part interconnecting lead is stacked；
The flexible insulating layer at least covers the conductive layer and the magnetic material layer, be formed on the flexible insulating layer to
A few through-hole, the through-hole and the record site correspond, and the through-hole exposes through the flexible insulating layer to be corresponded to
The record site；
The flexible substrate in the probe region includes multiple and the one-to-one strip structure of the conductor wire.
2. flexibility nerve electrode according to claim 1, which is characterized in that the material of the flexible substrate is that polyamides is sub-
Any one in amine, Parylene and SU8 photoresist or any at least two combination；
The Thickness range of the flexible substrate is 0.5~4um.
3. flexibility nerve electrode according to claim 1, which is characterized in that the material of the flexible insulating layer is that polyamides is sub-
Any one in amine, Parylene and SU8 photoresist or any at least two combination；
The Thickness range of the flexible insulating layer is 0.5~4um.
4. flexibility nerve electrode according to claim 1, which is characterized in that the material of the conductive layer is gold, platinum and iridium
In any one or any at least two combination；
The Thickness range of the conductive layer is 20~500nm.
5. flexibility nerve electrode according to claim 1, which is characterized in that when the quantity of the conductor wire is greater than 1, each institute
State parallel conductive line setting；
The quantity value range of the conductor wire is 1~500.
6. flexibility nerve electrode according to claim 1, which is characterized in that the width value range of the interconnecting lead is
2~100um.
7. flexibility nerve electrode according to claim 1, which is characterized in that between the flexible substrate and the conductive layer
It is provided with adhesion layer；
The material of the adhesion layer is chromium or titanium；
The Thickness range of the adhesion layer is 5~60nm.
8. flexibility nerve electrode according to claim 1, which is characterized in that the magnetic material layer is located at the conductive layer
Side far from the flexible substrate；
The magnetic material layer is formed by electroplating technology；
The material of the magnetic material layer is the combination of any one in FeNi, FePt and CoPt or any at least two；
The Thickness range of the magnetic material layer is 0.5~4um.
9. flexibility nerve electrode according to claim 8, which is characterized in that the temperature value used in the electroplating technology
Range is 20~70 DEG C, and electroplating time value range is 1~15min, and current density value range is 50~600A/m2。
10. flexibility nerve electrode according to claim 1, which is characterized in that the width value model of the magnetic material part
It encloses for 2~90um；
The magnetic material part is strip or the discrete sub-portion arranged including at least two along the conductor wire extending direction.
11. flexibility nerve electrode according to claim 1, which is characterized in that the length value range of the strip structure
For 1~15mm；
The width value range of the strip structure is 5~100um；
When the quantity of the strip structure is greater than 1, the spacing value range between the adjacent strip structure is 20~1000um.
12. flexibility nerve electrode according to claim 1, which is characterized in that the shape in the record site is circle；
The diameter value range in the record site is 5~30um.
13. a kind of method for implantation of flexibility nerve electrode is applied to the described in any item flexible nerve electrodes of claim 1-12,
It is characterised in that it includes：
The head of animal to be implanted after fixed anesthesia；
Sphenotresia exposes the cerebral cortex on the head；
Determine the position to be implanted on the cerebral cortex；
The mobile flexible nerve electrode, makes the position to be implanted be located at prolonging for conductor wire described in the flexible nerve electrode
It extends on line；
Magnetic field generation section part is placed in the lower jaw on the head far from the side of the flexible nerve electrode；
The mobile flexible nerve electrode is close to the head；
The probe region of the flexible nerve electrode is implanted into institute under the draw for the magnetic force that the magnetic field generation section part generates
State the cerebral cortex of animal to be implanted.
14. the method for implantation of flexibility nerve electrode according to claim 13, which is characterized in that the magnetic field generation section part
For permanent magnet or electromagnetic coil.
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| CN111698802A (en) * | 2020-06-28 | 2020-09-22 | 苏州捷迪纳米科技有限公司 | Flexible electrode and surface heater with same |
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| CN111450411A (en) * | 2020-04-09 | 2020-07-28 | 国家纳米科学中心 | Composite nerve electrode and preparation method thereof |
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| CN112244850A (en) * | 2020-09-29 | 2021-01-22 | 中国科学院上海微系统与信息技术研究所 | Intracranial deep electrode recording device and preparation method and system thereof |
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| CN112641448A (en) * | 2020-12-18 | 2021-04-13 | 浙江大学 | Flexible magnetic compatible implanted electroencephalogram electrode array and preparation method thereof |
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