CN111956220A - Bidirectional cortical brain electrode preparation method and bidirectional cortical brain electrode prepared by same - Google Patents

Bidirectional cortical brain electrode preparation method and bidirectional cortical brain electrode prepared by same Download PDF

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CN111956220A
CN111956220A CN202010857959.2A CN202010857959A CN111956220A CN 111956220 A CN111956220 A CN 111956220A CN 202010857959 A CN202010857959 A CN 202010857959A CN 111956220 A CN111956220 A CN 111956220A
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preparing
electrode
cortical brain
fibroin
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CN111956220B (en
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陶虎
梁佶智
周志涛
魏晓玲
郑发明
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Shanghai Institute of Microsystem and Information Technology of CAS
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Shanghai Institute of Microsystem and Information Technology of CAS
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    • G03PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03FPHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
    • G03F1/00Originals for photomechanical production of textured or patterned surfaces, e.g., masks, photo-masks, reticles; Mask blanks or pellicles therefor; Containers specially adapted therefor; Preparation thereof
    • GPHYSICS
    • G03PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
    • G03FPHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
    • G03F7/00Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
    • G03F7/20Exposure; Apparatus therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/12Manufacturing methods specially adapted for producing sensors for in-vivo measurements
    • A61B2562/125Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes

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Abstract

The invention discloses a bidirectional cortical brain electrode and a preparation method thereof. The preparation method of the bidirectional cortical brain electrode comprises the following steps: s1: preparing a polymeric substrate layer; s2: preparing a polymer packaging layer; s3: preparing a fibroin functional layer; s4: preparing an aluminum mask layer; s5: preparing a grid structure; s6: preparing electrode sites and connection sites; s7: preparing a fibroin drug release carrier; s8: preparing bidirectional cortical brain electrodes. The invention can avoid the position overlapping of the fibroin drug release carrier and the electrode site, so that the drug stimulation effect can not interfere the acquisition of the cortex electroencephalogram signal; the invention is beneficial to researching the space-time distribution characteristic of the drug acting on the cerebral cortex connecting network and evaluating the disease intervention treatment effect of the drug in situ; the invention can dynamically collect the cortical electroencephalogram signal and timely and controllably perform the drug intervention treatment of the related brain diseases.

Description

Bidirectional cortical brain electrode preparation method and bidirectional cortical brain electrode prepared by same
Technical Field
The invention relates to the technical field of neuroscience, in particular to a bidirectional cortical brain electrode and a preparation method thereof.
Background
In recent years, with the introduction of 'brain planning' worldwide, electroencephalogram signal acquisition becomes more and more important. At present, by virtue of the development of flexible electronics and the development of related advanced biomaterials, electroencephalogram signal acquisition and monitoring with a flexible nerve electrode as a main tool is an important and basic research platform for researching cerebral cortical nerve connection pathways and higher cognitive functions, and is also a powerful tool for diagnosing, monitoring and early warning, regulating and treating various neurological diseases (such as epilepsy, alzheimer disease, parkinson disease, depression and the like).
The nerve electrodes can be classified into three types, namely non-invasive, minimally invasive and invasive according to the degree of trauma to a study object when in use. The signal-to-noise ratio of the noninvasive neural electrode electroencephalogram signal is poor due to skull obstruction attenuation, and the noninvasive neural electrode electroencephalogram signal is more suitable for development and application of noninvasive brain-computer interfaces and early warning monitoring of brain related diseases. The minimally invasive nerve electrode is implanted into deep nuclei in the brain through a surgical operation or a surgical robot, and is difficult to be used for exploring conducting paths of neuron discharge in different brain areas due to the limitation of spatial distribution. Cortical brain electrodes, while requiring surgical craniotomy, minimize surgical risk through the use of ultra-thin flexible electrode substrates and mechanically biocompatible materials.
In an in vivo animal model experiment requiring a surgical craniotomy, the bidirectional cortical electroencephalograph combined with drug stimulation can effectively evaluate the effect of cell type-specific in vitro culture biomolecules and drugs on brain tissue. By means of cortical electroencephalogram data with abundant time domain, frequency domain and spatial distribution, electroencephalogram propagation effects and structural connection of cortical brain networks under normal conditions and drug intervention can be researched. In the clinical field of neurosurgery, cortical electroencephalogram monitoring is a key technology for preoperatively positioning epileptogenic focus of an epileptic patient and determining an operative treatment scheme. Compared with the traditional intravenous injection and blood circulation administration methods, the release of medicines (such as phenobarbital, lamotrigine, adenosine and the like) in the brain is faster, the effect is better, the treatment of the epilepsy is very favorable, and the bidirectional cortical electroencephalogram electrode combined with medicine stimulation is favorable for realizing the diagnosis and treatment of the epilepsy and dynamically monitoring the treatment process.
However, the existing bidirectional cortical electroencephalograph electrode combined with drug stimulation still has many defects, including that the positions of a drug release layer and an electrode site may overlap, so that the drug stimulation interferes with the acquisition of cortical electroencephalograph signals; the shape and the position of the drug release layer can not be designed according to the actual use requirement; when the medicine is used, the medicine is usually firstly administered, and then the cortex electroencephalogram signal is acquired, and because the medicine release speed is high, the cortex electroencephalogram electrode cannot acquire the cortex electroencephalogram signal at the first time of medicine release, and the medicine intervention treatment of related brain diseases can not be timely and controllably performed while the cortex electroencephalogram signal is dynamically acquired.
Disclosure of Invention
The invention aims to provide a method for preparing a bidirectional cortical brain electrode and the bidirectional cortical brain electrode prepared by the method, so as to overcome the defects in the prior art.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the invention provides a preparation method of a bidirectional cortical brain electrode, which comprises the following steps:
s1: preparing a polymeric substrate layer;
s2: preparing a polymer packaging layer;
s3: preparing a fibroin functional layer;
s4: preparing an aluminum mask layer;
s5: preparing a grid structure;
s6: preparing electrode sites and connection sites;
s7: preparing a fibroin drug release carrier;
s8: preparing bidirectional cortical brain electrodes.
Preferably, the step S1 includes:
s11: providing a substrate, and growing a sacrificial layer on the substrate;
s12: and forming a polymer substrate layer on the surface of the sacrificial layer.
Preferably, the step S2 includes:
s21: growing an electrode material layer on the surface of the polymer base layer;
s22: and forming a polymer packaging layer on the surface of the electrode material layer.
Preferably, the step S3 includes:
and spinning and coating a fibroin solution on the polymer packaging layer to prepare the fibroin functional layer.
Preferably, the step S4 includes:
and sputtering and depositing a layer of aluminum on the surface of the fibroin functional layer, and preparing an aluminum mask layer by first photoetching and patterning.
Preferably, the step S5 includes:
and etching the fibroin functional layer, the polymer packaging layer and the polymer substrate layer on the sacrificial layer to prepare the grid structure.
Preferably, the step S6 includes:
s61: carrying out second photoetching patterning on the aluminum mask layer;
s62: etching the fibroin functional layer and the polymer packaging layer on the electrode material layer to prepare an electrode site for recording cortex electroencephalogram signals and a connection site for transmitting the recorded cortex electroencephalogram signals to electroencephalogram signal acquisition equipment.
Preferably, the step S7 includes:
s71: carrying out third photoetching patterning on the aluminum mask layer;
s72: and etching the fibroin functional layer on the polymer packaging layer according to a pre-designed shape and position, and immersing the etched structure into a solvent containing a drug to be loaded to prepare the fibroin drug release carrier.
Preferably, the step S8 includes:
and releasing the sacrificial layer on the structure obtained in the step S7 to prepare the bidirectional cortical brain electrode with the function of collecting cortical brain signals and the function of medicine stimulation.
The invention also provides a bidirectional cortical brain electrode prepared by one of the above bidirectional cortical brain electrode preparation methods.
Compared with the prior art, the invention has the following beneficial effects:
1. the method adopts the photoetching process taking aluminum as a hard mask and the MEMS process to prepare the bidirectional cortical brain electrode with the function of collecting cortical brain signals and the function of medicine stimulation in a fusion manner, the two processes have good compatibility and micron-sized processing precision, and the position overlapping of a fibroin medicine release carrier and an electrode site is avoided, so that the medicine stimulation effect cannot interfere the collection of high-quality cortical brain signals;
2. the shape and the position of the fibroin drug release carrier can be designed in advance according to actual use requirements, and the loading of drugs on different positions of the fibroin drug release carrier can be realized, so that the study on the space-time distribution characteristic of the drugs acting on a cerebral cortex connecting network is facilitated, and the in-situ evaluation on the disease intervention and treatment effect of the drugs is facilitated;
3. the invention can simultaneously evaluate the influence of drug molecules on the nerve discharge activity of multiple brain areas in situ, and can timely and controllably perform drug intervention treatment on related brain diseases such as epilepsy while dynamically acquiring cortical electroencephalogram signals.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
Fig. 1 is a schematic flow chart of a method for preparing a bidirectional cortical electroencephalogram according to an embodiment of the present invention, in which: 1-a substrate, 2-a sacrificial layer, 3-a polymer substrate layer, 4-an electrode material layer, 5-a polymer packaging layer, 6-a fibroin functional layer, 7-an aluminum mask layer, 8-a grid structure, 9-an electrode site and 10-a connecting site;
FIG. 2 is a schematic diagram of cortical electroencephalogram power spectral density curves for rest, epilepsy, and phenobarbital release states, according to an embodiment of the present invention;
fig. 3 is a schematic diagram of voltage signals of channels of cortical electroencephalograms of an epileptic rat before and after drug release according to an embodiment of the present invention;
FIG. 4 is a cortical electroencephalogram of rest, epilepsy, and phenobarbital treatment states provided by an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to the accompanying drawings in conjunction with the following detailed description. It should be understood that the description is intended to be exemplary only, and is not intended to limit the scope of the present invention.
Example one
The embodiment provides a method for preparing a bidirectional cortical electroencephalogram, which comprises the following steps as shown in fig. 1:
s1: a polymeric substrate layer is prepared.
In this step, the specific process of preparing the polymer substrate layer comprises:
s11: a substrate 1 is provided, and a sacrificial layer 2 is grown on the substrate 1.
In this step, a silicon wafer is selected as a substrate 1, and a cleaning solution (e.g., concentrated H) is first used2SO4) Cleaning the silicon wafer, and growing SiO on the surface of the substrate 1 by adopting PECVD2As the sacrificial layer 2. Of course, other suitable materials may be selected for the substrate 1 and the sacrificial layer 2, and are not limited herein.
As an example, the thickness of the sacrificial layer 2 is 1-3 μm. In the present embodiment, the thickness of the sacrificial layer 2 is 2 μm. In other embodiments, the thickness of the sacrificial layer 2 may also be 1 μm, 1.5 μm, 2.5 μm, 3 μm, etc.
S12: and forming a polymer substrate layer 3 on the surface of the sacrificial layer 2.
In this step, polyimide is spin-coated and cured on the surface of the sacrificial layer 2 as the polymer substrate layer 3. Of course, other suitable materials may be selected for the polymer base layer 3, and are not limited herein.
As an example, the thickness of the polymeric substrate layer 3 is 1-3 μm. In the present example, the thickness of the polymeric substrate layer 3 is 2 μm. In other embodiments, the thickness of the polymer base layer 3 may also be 1 μm, 1.5 μm, 2.5 μm, 3 μm, etc.
S2: and preparing a polymer encapsulation layer.
In this step, the specific process of preparing the polymer encapsulation layer includes:
s21: and growing an electrode material layer 4 on the surface of the polymer substrate layer 3.
In the step, the surface of the polymer substrate layer 3 is firstly patterned with the LC100A photoresist through an ultraviolet lithography process, then a layer of chromium/gold alloy is prepared through an electron beam evaporation deposition process, and is patterned through a stripping process to obtain the electrode material layer 4. Of course, the photoresist used in the ultraviolet lithography process may also be other suitable photoresists, and the electrode material layer 4 may also be selected from other suitable materials, which is not limited herein.
As an example, the photoresist has a thickness of 1-3 μm. In this embodiment, the photoresist has a thickness of 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, and the like.
As an example, the thickness of the chromium/gold alloy layer is 1nm/100nm to 2nm/200 nm. In this example, the thickness of the chromium/gold alloy layer was 1.5nm/150 nm. In other embodiments, the thickness of the chromium/gold alloy layer may also be 1nm/100nm, 1.25nm/125nm, 1.75nm/175nm, 2nm/200nm, and the like.
S22: and forming a polymer packaging layer 5 on the surface of the electrode material layer 4.
In this step, polyimide is spin-coated and cured on the surface of the electrode material layer 4 to serve as a polymer encapsulation layer 5. Of course, other suitable materials may be selected for the polymer encapsulation layer 5, and are not limited herein.
As an example, the thickness of the polymer encapsulation layer 5 is 1-3 μm. In the present embodiment, the thickness of the polymer encapsulation layer 5 is 2 μm. In other embodiments, the thickness of the polymer encapsulation layer 5 may also be 1 μm, 1.5 μm, 2.5 μm, 3 μm, and the like.
S3: and preparing the fibroin functional layer 6.
In the step, 6-7 wt% of fibroin aqueous solution is spin-coated on the polymer packaging layer 5, standing overnight for drying, and then treating with 70% (v/v) methanol for 2min to finally obtain the fibroin functional layer 6 with the thickness of 1-2 μm. The fibroin functional layer 6 can be used as a mask and a drug release carrier.
In this example, the aqueous fibroin solution used was an aqueous solution containing 7 wt% fibroin. In other embodiments, the aqueous fibroin solution can also be an aqueous solution containing 6 wt%, 6.25 wt%, 6.5 wt%, 6.75 wt% fibroin.
In the step, the preparation process of the fibroin aqueous solution is as follows: placing silkworm cocoon in 0.02M Na2CO3Boiling in water solution for 30min, washing with distilled water for 3 times (30 min each time) to remove Na2CO3And sericin. After the degummed cocoons were dried in air for 12h, they were dissolved in 9.3M LiBr solution and dissolved at 60 ℃ for 4 h. Dialyzed in distilled water using Slide-A-Lyzer dialysis cassette for 2 d. Subsequently, the mixture was centrifuged at 18000rpm for 20min 2 times. The final concentration of the aqueous fibroin solution was determined to be about 6-7 wt% by measuring the volume and final dry weight of the solution.
S4: an aluminum mask layer 7 is prepared.
In the step, a layer of aluminum is sputtered and deposited on the surface of the fibroin functional layer 6, and the aluminum mask layer 7 is prepared by performing first photoetching patterning through an ultraviolet photoetching process and an aluminum corrosion process.
In this embodiment, the photoresist used in the uv lithography process is LC 100A. In other embodiments, the photoresist used in the uv lithography process may also be other suitable photoresists, which are not limited herein.
As an example, the photoresist has a thickness of 1-3 μm. In this embodiment, the photoresist has a thickness of 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, and the like.
In this example, the aluminum etching process employed 1.3 wt% NH at a 6:1 volume ratio4F solution and 1.6 wt% HF solution. In other embodiments, the aluminum etching process may also use other suitable acidic etching solutions, which are not limited herein.
As an example, the thickness of the aluminum mask layer 7 is 200-400 nm. In this embodiment, the thickness of the aluminum mask layer 7 is 300 nm. In other embodiments, the thickness of the aluminum mask layer 7 may also be 200nm, 250nm, 350nm, 400nm, and the like.
S5: a lattice structure 8 is prepared.
In the step, the fibroin functional layer 6, the polymer packaging layer 5 and the polymer substrate layer 3 are etched on the sacrificial layer 2 through a microwave plasma process to prepare a grid structure 8.
S6: electrode sites 9 and attachment sites 10 were prepared.
In this step, the specific process of preparing the electrode site 9 and the connection site 10 includes:
s61: and carrying out second photoetching patterning on the aluminum mask layer 7.
In this step, a second photolithography patterning is performed on the aluminum mask layer 7 by an ultraviolet photolithography process and an aluminum etching process.
In this embodiment, the photoresist used in the uv lithography process is LC 100A. In other embodiments, the photoresist used in the uv lithography process may also be other suitable photoresists, which are not limited herein.
As an example, the photoresist has a thickness of 1-3 μm. In this embodiment, the photoresist has a thickness of 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, and the like.
In this example, the aluminum etching process employed 1.3 wt% NH at a 6:1 volume ratio4F solution and 1.6 wt% HF solution. In other embodiments, the aluminum etching process may also use other suitable acidic etching solutions, which are not limited herein.
S62: etching the fibroin functional layer 6 and the polymer packaging layer 5 on the electrode material layer 4 to prepare an electrode site 9 for recording cortex electroencephalogram signals and a connection site 10 for transmitting the recorded cortex electroencephalogram signals to electroencephalogram signal acquisition equipment.
In the step, the fibroin functional layer 6 and the polymer packaging layer 5 are etched on the electrode material layer 4 through a microwave plasma process, and an electrode site 9 and a connection site 10 exposed in the air are prepared. The electrode sites 9 are directly contacted with cerebral cortical cells to record the generated cortical electroencephalo signals. The connection site 10 is electrically connected with the flexible printed circuit through the anisotropic conductive adhesive under the conditions that the temperature is 160-.
S7: preparing the fibroin drug release carrier.
In the step, the specific process for preparing the fibroin drug release carrier comprises the following steps:
s71: and carrying out third photoetching patterning on the aluminum mask layer 7.
In this step, a third photolithography patterning is performed on the aluminum mask layer 7 by an ultraviolet photolithography process and an aluminum etching process.
In this embodiment, the photoresist used in the uv lithography process is LC 100A. In other embodiments, the photoresist used in the uv lithography process may also be other suitable photoresists, which are not limited herein.
As an example, the photoresist has a thickness of 1-3 μm. In this embodiment, the photoresist has a thickness of 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, and the like.
In this example, the aluminum etching process employed 1.3 wt% NH at a 6:1 volume ratio4F solution and 1.6 wt% HF solution. In other embodiments, the aluminum etching process may also use other suitable acidic etching solutions, which are not limited herein.
S72: and etching the fibroin functional layer 6 on the polymer packaging layer 5 according to a pre-designed shape and position, and immersing the etched structure into a solvent containing a drug to be loaded to prepare the fibroin drug release carrier.
In the step, the fibroin functional layer 6 is etched on the polymer packaging layer 5 through an oxygen plasma process according to a pre-designed shape and position, and the residual aluminum mask layer 7 is etched by using an aluminum corrosive liquid. And immersing the etched structure into a solvent containing the drug to be loaded to prepare the fibroin drug release carrier.
In this embodiment, the drug to be loaded may be selected according to actual needs, and the solvent is a deionized water solution, so that the drug to be loaded is more easily dispersed and dissolved. In other embodiments, the solvent may also be other suitable solutions, and is not limited herein.
In this step, the shape and the position of the fibroin drug release carrier can be designed in advance according to actual use requirements, and the loading of drugs on different positions of the fibroin drug release carrier can be realized, so that the study on the space-time distribution characteristics of the drugs acting on the cerebral cortex connecting network is facilitated, and the in-situ evaluation on the disease intervention treatment effect of the drugs is facilitated.
S8: preparing bidirectional cortical brain electrodes.
In this step, the sacrificial layer 2 on the structure obtained in the step S7 is released, and the bidirectional cortical brain electrode having the function of collecting cortical brain signals and the function of drug stimulation is prepared.
In the embodiment, the design of the grid structure can enable the prepared bidirectional cortical brain electrode to be spontaneously and conformally attached to the surface of the cerebral cortex, and the grid structure has good process compatibility with the preparation of a single-layer flexible electrode, so that the stable and high-signal-quality cortical brain electrode monitoring can be well compatible with the operation of living brain tissues.
The two-way cortex brain electrode that the preparation has collection cortex electroencephalogram signal function and medicine stimulus function is fused to the photoetching technology and the MEMS technology that this embodiment adopted to use aluminium to be the hard mask version, and two kinds of process compatibility are better, and all have the machining precision of micron order, have avoided fibroin medicine release carrier with the position of electrode site overlaps to make the medicine stimulus effect can not disturb the collection of high quality cortex electroencephalogram signal.
The bidirectional functions of acquiring electroencephalogram signals and stimulating medicines of the bidirectional cortical brain electrode prepared in the first embodiment are verified by adopting a penicillin-induced epileptic rat model.
In this embodiment, the cortical brain electrode after releasing the sacrificial layer is immersed in a phenobarbital solution with a certain concentration to realize drug loading of the fibroin functional layer, so as to obtain a bidirectional cortical brain electrode with a cortical brain signal collecting function and a drug stimulation function. Monofocal epilepsy in rats was induced by subcutaneous injection of penicillin (2.5. mu.L of 800U/. mu.L of aqueous penicillin sodium solution). The bidirectional cortical electroencephalogram electrode is conformally pasted on the surface of the intracranial cortex of a rat, and the electroencephalogram signals and abnormal paroxysmal discharge signals of all brain areas of the rat are dynamically monitored in real time. The bidirectional cortical electroencephalograph detects rapid electroencephalogram signal release accompanied by epileptic seizure, and in a cortical electroencephalogram Power Spectrum Density (PSD) curve shown in FIG. 2, the 0-40Hz electroencephalogram energy distribution is obviously higher than that in a resting state (especially higher frequency of about 5-40 Hz) under penicillin-induced epilepsy. After the bidirectional cortical electroencephalogram electrode is conformally adhered to the surface of the intracranial cortex of a rat and electroencephalogram signals are normally collected, the fibroin drug release carrier starts to stimulate phenobarbital to the brain of the epileptic seizure in situ. The cortical electroencephalogram voltage signals monitored in situ at the same time in fig. 3 show that after phenobarbital is released, the previous epileptic discharge signals are obviously weakened, and the bidirectional cortical electroencephalogram electrodes can timely and controllably perform drug intervention treatment on epilepsy while dynamically acquiring cortical electroencephalogram signals. About 10 mg of phenobarbital loaded in the silk matrix was released and diffused directly in the cerebrospinal fluid into the brain tissue of the seizure rats, which significantly stabilized the cortical electroencephalogram (ECoG) spectrum and effectively suppressed the seizure symptoms, as shown in fig. 4.
Example two
This example provides a bi-directional cortical brain electrode prepared using the preparation method of example one.
Compared with the prior art, the invention has the following advantages:
1. the method adopts the photoetching process taking aluminum as a hard mask and the MEMS process to prepare the bidirectional cortical brain electrode with the function of collecting cortical brain signals and the function of medicine stimulation in a fusion manner, the two processes have good compatibility and micron-sized processing precision, and the position overlapping of a fibroin medicine release carrier and an electrode site is avoided, so that the medicine stimulation effect cannot interfere the collection of high-quality cortical brain signals;
2. the shape and the position of the fibroin drug release carrier can be designed in advance according to actual use requirements, and the loading of drugs on different positions of the fibroin drug release carrier can be realized, so that the study on the space-time distribution characteristic of the drugs acting on a cerebral cortex connecting network is facilitated, and the in-situ evaluation on the disease intervention and treatment effect of the drugs is facilitated;
3. the invention can simultaneously evaluate the influence of drug molecules on the nerve discharge activity of multiple brain areas in situ, and can timely and controllably perform drug intervention treatment on related brain diseases such as epilepsy while dynamically acquiring cortical electroencephalogram signals.
It should be noted that the above examples are only for illustrative purposes and should not be construed as limiting the scope of the present invention. While the invention has been described with reference to a preferred embodiment, those skilled in the art will appreciate that various changes can be made in the invention without departing from the spirit and scope of the invention, and all such changes are intended to be within the scope of the invention as defined and equivalents thereof.

Claims (10)

1. A preparation method of a bidirectional cortical brain electrode is characterized by comprising the following steps:
s1: preparing a polymeric substrate layer (3);
s2: preparing a polymer encapsulation layer (5);
s3: preparing a fibroin functional layer (6);
s4: preparing an aluminum mask layer (7);
s5: preparing a grid structure (8);
s6: preparing electrode sites (9) and connection sites (10);
s7: preparing a fibroin drug release carrier;
s8: preparing bidirectional cortical brain electrodes.
2. The bi-directional cortical brain electrode preparing method of claim 1, wherein said step S1 includes:
s11: providing a substrate (1), and growing a sacrificial layer (2) on the substrate (1);
s12: and forming a polymer substrate layer (3) on the surface of the sacrificial layer (2).
3. The bi-directional cortical brain electrode preparing method of claim 2, wherein said step S2 includes:
s21: growing an electrode material layer (4) on the surface of the polymer substrate layer (3);
s22: and forming a polymer packaging layer (5) on the surface of the electrode material layer (4).
4. The bi-directional cortical brain electrode preparing method of claim 3, wherein said step S3 includes:
and spinning and coating a fibroin solution on the polymer packaging layer (5) to prepare a fibroin functional layer (6).
5. The bi-directional cortical brain electrode preparing method of claim 4, wherein said step S4 includes:
and sputtering and depositing a layer of aluminum on the surface of the fibroin functional layer (6), and preparing an aluminum mask layer (7) by first photoetching and patterning.
6. The bi-directional cortical brain electrode preparing method of claim 5, wherein said step S5 includes:
and etching the fibroin functional layer (6), the polymer packaging layer (5) and the polymer substrate layer (3) on the sacrificial layer (2) to prepare a grid structure (8).
7. The bi-directional cortical brain electrode preparing method of claim 6, wherein said step S6 includes:
s61: carrying out second photoetching patterning on the aluminum mask layer (7);
s62: etching on the electrode material layer (4) fibroin functional layer (6) with polymer encapsulation layer (5), preparing and obtaining electrode site (9) that are used for recording cortex electroencephalogram signal and be used for transmitting the cortex electroencephalogram signal of record to connection site (10) of electroencephalogram signal collection equipment.
8. The bi-directional cortical brain electrode preparing method of claim 7, wherein said step S7 includes:
s71: carrying out third photoetching patterning on the aluminum mask layer (7);
s72: and etching the fibroin functional layer (6) on the polymer packaging layer (5) according to a pre-designed shape and position, and immersing the etched structure into a solvent containing a drug to be loaded to prepare the fibroin drug release carrier.
9. The bi-directional cortical brain electrode preparing method of claim 8, wherein said step S8 includes:
and (4) releasing the sacrificial layer (2) on the structure obtained in the step (S7) to prepare the bidirectional cortical brain electrode with the function of collecting cortical brain signals and the function of medicine stimulation.
10. A bi-directional cortical brain electrode prepared by one of the methods of preparing a bi-directional cortical brain electrode claimed in claims 1-9.
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