CN111956220B - Preparation method of bidirectional cortical brain electrode and bidirectional cortical brain electrode prepared by same - Google Patents
Preparation method of bidirectional cortical brain electrode and bidirectional cortical brain electrode prepared by same Download PDFInfo
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- G—PHYSICS
- G03—PHOTOGRAPHY; CINEMATOGRAPHY; ANALOGOUS TECHNIQUES USING WAVES OTHER THAN OPTICAL WAVES; ELECTROGRAPHY; HOLOGRAPHY
- G03F—PHOTOMECHANICAL PRODUCTION OF TEXTURED OR PATTERNED SURFACES, e.g. FOR PRINTING, FOR PROCESSING OF SEMICONDUCTOR DEVICES; MATERIALS THEREFOR; ORIGINALS THEREFOR; APPARATUS SPECIALLY ADAPTED THEREFOR
- G03F7/00—Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printing surfaces; Materials therefor, e.g. comprising photoresists; Apparatus specially adapted therefor
- G03F7/20—Exposure; Apparatus therefor
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
- A61B2562/12—Manufacturing methods specially adapted for producing sensors for in-vivo measurements
- A61B2562/125—Manufacturing methods specially adapted for producing sensors for in-vivo measurements characterised by the manufacture of electrodes
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- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Abstract
The invention discloses a preparation method of a bidirectional cortical brain electrode and the bidirectional cortical brain electrode prepared by the preparation method. The preparation method of the bidirectional cortical brain electrode comprises the following steps: s1: preparing a polymeric substrate layer; s2: preparing a polymer encapsulation 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 the bidirectional cortical brain electrode. The invention can avoid overlapping of the positions of the fibroin drug release carrier and the electrode sites, so that the drug stimulation effect can not interfere with the acquisition of the cortex brain electrical signals; the invention is beneficial to researching the space-time distribution characteristics of the drug acting on the cerebral cortex connecting network and is also beneficial to in-situ evaluation of the disease intervention treatment effect of the drug; the invention can dynamically collect the cortex brain electrical signals and simultaneously perform the drug intervention treatment of the related brain diseases in time and controllably.
Description
Technical Field
The invention relates to the technical field of neuroscience, in particular to a preparation method of a bidirectional cortical brain electrode and the bidirectional cortical brain electrode prepared by the same.
Background
In recent years, with the promotion of worldwide brain planning, electroencephalogram signal acquisition is becoming more important. At present, by virtue of development of flexible electronics and development of related advanced biological materials, the electroencephalogram signal acquisition and monitoring taking a flexible neural electrode as a main tool is an important and basic research platform for researching a cerebral cortex nerve connection channel and advanced cognitive functions, and is also a powerful tool for diagnosing, monitoring, early warning, regulating and treating various nerve diseases (such as epilepsy, alzheimer disease, parkinsonism, depression and the like).
Nerve electrodes can be classified into noninvasive, minimally invasive and invasive types according to the degree of trauma to the subject when in use. The signal-to-noise ratio of the noninvasive nerve electrode electroencephalogram signal is poor due to the attenuation of the skull obstruction, and the noninvasive nerve electrode electroencephalogram signal is more suitable for the development and the application of noninvasive brain-computer interfaces and the early warning and monitoring of brain-related diseases. Minimally invasive nerve electrodes are implanted by surgical or surgical robots into deep nuclei within the brain and are difficult to use to explore the conductive pathways of neuronal discharges in different brain regions due to their spatial distribution limitations. Although the cortical brain electrode needs to be subjected to the craniotomy, the surgical risk is reduced to the greatest extent through the ultrathin flexible electrode substrate and the mechanical biocompatible material.
In living animal model experiments requiring craniotomy surgery, the bidirectional cortical brain electrode combined with drug stimulation can effectively evaluate the effect of cell type specific in vitro culture biomolecules and drugs on brain tissues. By virtue of the cortical brain electrical data with rich time domain, frequency domain and spatial distribution, the brain electrical propagation effect and the structural connection of the cortical brain network under normal conditions and drug intervention can be researched. In the neurosurgical clinical field, cortical electroencephalogram monitoring is a key technique to preoperatively locate epileptic lesions in epileptic patients and to determine surgical treatment regimens. The long-time high-frequency nerve discharge in the epileptic seizure process often causes damage to the brain, compared with the traditional intravenous injection and blood circulation administration methods, the drug (such as phenobarbital, lamotrigine, adenosine and the like) is released in the brain more quickly, the effect is better, the treatment of the epileptic is very beneficial, and the bidirectional cortical brain electrode combined with the drug stimulation is beneficial to realizing the diagnosis and treatment of the epileptic and dynamically monitoring the treatment process.
However, there are still many disadvantages of the existing bi-directional cortical brain electrodes combined with drug stimulation, including overlapping positions of the drug release layer and the electrode site may occur, resulting in interference of the drug stimulation effect with collection of cortical brain electrical signals; the shape and the position of the drug release layer cannot be designed according to the actual use requirement; when the medicine is used, the medicine is usually administered firstly, and then the cortex brain electrical signal is collected, and as the medicine release speed is high, the cortex brain electrode cannot collect the cortex brain electrical signal at the first time of medicine release, and the medicine intervention treatment of the related brain diseases can not be timely and controllably carried out while the dynamic collection of the cortex brain electrical signal is not realized.
Disclosure of Invention
The invention aims to provide a preparation method of a bidirectional cortical brain electrode and the bidirectional cortical brain electrode prepared by the preparation method, so as to overcome the defects in the prior art.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
in one aspect, the invention provides a method for preparing a bidirectional cortical brain electrode, which comprises the following steps:
s1: preparing a polymeric substrate layer;
s2: preparing a polymer encapsulation 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 the bidirectional cortical brain electrode.
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 basal layer;
s22: and forming a polymer packaging layer on the surface of the electrode material layer.
Preferably, the step S3 includes:
and spin-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 through first photoetching and patterning.
Preferably, the step S5 includes:
and etching the fibroin functional layer, the polymer packaging layer and the polymer basal layer on the sacrificial layer to prepare a grid structure.
Preferably, the step S6 includes:
s61: performing a second photoetching patterning on the aluminum mask layer;
s62: and etching the fibroin functional layer and the polymer packaging layer on the electrode material layer to prepare an electrode site for recording the cortex electroencephalogram signals and a connecting site for transmitting the recorded cortex electroencephalogram signals to electroencephalogram signal acquisition equipment.
Preferably, the step S7 includes:
s71: performing 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:
releasing the sacrificial layer on the structure obtained in the step S7 to prepare the bidirectional cortical brain electrode with the function of collecting the cortical brain signals and the function of drug stimulation.
The invention also provides a bidirectional cortical brain electrode prepared by one of the preparation methods of the bidirectional cortical brain electrode.
Compared with the prior art, the invention has the following beneficial effects:
1. the invention adopts the photoetching technology taking aluminum as a hard mask plate and the MEMS technology to prepare the bidirectional cortical brain electrode with the function of collecting the cortical brain electrical signals and the function of stimulating the drugs, the two technologies have better compatibility and micron-sized processing precision, and the position overlapping of a fibroin drug release carrier and electrode sites is avoided, so that the drug stimulation effect does not interfere with the collection of the high-quality cortical brain electrical signals;
2. the shape and the position of the fibroin drug release carrier can be designed in advance according to actual use requirements, so that drugs can be loaded on different positions of the fibroin drug release carrier, the spatial-temporal distribution characteristics of the drugs acting on a cerebral cortex connection network can be studied, and the disease intervention treatment effect of the drugs can be evaluated in situ;
3. the invention can evaluate the influence of drug molecules on the nerve discharge activity of the multiple brain regions simultaneously in situ, and can perform the drug intervention treatment of related brain diseases such as epilepsy in time and controllably while dynamically collecting the cortex brain signals.
Drawings
In order to more clearly illustrate the embodiments of the invention or the technical solutions in the prior art, the drawings that are required in the embodiments or the description of the prior art will be briefly described, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic flow chart of a method for preparing a bidirectional cortical brain electrode according to an embodiment of the invention, wherein: the electrode comprises a 1-substrate, a 2-sacrificial layer, a 3-polymer basal layer, a 4-electrode material layer, a 5-polymer packaging layer, a 6-fibroin functional layer, a 7-aluminum mask layer, an 8-grid structure, 9-electrode sites and 10-connection sites;
FIG. 2 is a graph showing the electrical power spectral density of cortical brain in resting, epileptic and phenobarbital released states according to one embodiment of the present invention;
fig. 3 is a schematic diagram of voltage signals of each channel of cortex brain electricity of an epileptic rat before and after drug release according to an embodiment of the present invention;
fig. 4 is a graph of cortical electroencephalogram for rest, epilepsy, and phenobarbital therapy states provided in accordance with an embodiment of the present invention.
Detailed Description
The objects, technical solutions and advantages of the present invention will become more apparent by the following detailed description of the present invention with reference to the accompanying drawings. It should be understood that the description is only illustrative and is not intended to limit the scope of the invention.
Example 1
The embodiment provides a preparation method of a bidirectional cortical brain electrode, as shown in fig. 1, comprising the following steps:
s1: a polymeric substrate layer is prepared.
In this step, the specific process for preparing the polymeric substrate layer comprises:
s11: a substrate 1 is provided and a sacrificial layer 2 is grown on said substrate 1.
In this step, a silicon wafer is selected as the substrate 1, and a cleaning solution (e.g., concentrated H 2 SO 4 ) Cleaning the silicon wafer, and growing SiO on the surface of the substrate 1 by PECVD 2 As the sacrificial layer 2. Of course, other suitable materials may be selected for the substrate 1 and the sacrificial layer 2, which is not limited herein.
As an example, the thickness of the sacrificial layer 2 is 1-3 μm. In this 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: a polymer base layer 3 is formed 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 base layer 3. Of course, other suitable materials for the polymeric substrate layer 3 may be selected, without limitation.
As an example, the polymeric substrate layer 3 has a thickness of 1-3 μm. In this embodiment, the thickness of the polymeric substrate layer 3 is 2 μm. In other embodiments, the polymeric substrate layer 3 may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, etc.
S2: and preparing a polymer packaging layer.
In this step, the specific process for preparing the polymer encapsulation layer includes:
s21: and growing an electrode material layer 4 on the surface of the polymer substrate layer 3.
In this step, the LC100A photoresist is patterned on the surface of the polymer substrate layer 3 by an ultraviolet lithography process, and then a chromium/gold alloy layer is prepared by an electron beam evaporation deposition process, and the electrode material layer 4 is patterned by a stripping process. Of course, the photoresist used in the ultraviolet lithography process may be other suitable photoresist, and the electrode material layer 4 may be made of other suitable materials, which is not limited herein.
The photoresist has a thickness of 1-3 μm, as an example. In this embodiment, the thickness of the photoresist is 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, etc.
As an example, the thickness of the chromium/gold alloy layer is 1nm/100nm-2nm/200nm. In this example, the chromium/gold alloy layer has a thickness of 1.5nm/150nm. In other embodiments, the chromium/gold alloy layer may also have a thickness of 1nm/100nm, 1.25nm/125nm, 1.75nm/175nm, 2nm/200nm, etc.
S22: a polymer encapsulation layer 5 is formed 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 as the polymer encapsulation layer 5. Of course, other suitable materials for the polymer encapsulation layer 5 may be selected, which is not limited herein.
The thickness of the polymer encapsulation layer 5 is, as an example, 1-3 μm. In this 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, etc.
S3: the fibroin functional layer 6 was prepared.
In the step, 6-7wt% of fibroin aqueous solution is spin-coated on the polymer encapsulation layer 5, and the polymer encapsulation layer is left to stand overnight for drying, and then treated with 70% (v/v) methanol for 2min, so that the fibroin functional layer 6 with the thickness of 1-2 mu m is finally obtained. The fibroin functional layer 6 can serve as a mask and a drug release carrier.
In this example, the aqueous fibroin solution was an aqueous solution containing 7wt% fibroin. In other embodiments, the aqueous fibroin solution can also be an aqueous solution containing 6wt%, 6.25wt%, 6.5wt%, 6.75wt% fibroin.
In this step, the preparation process of the silk fibroin aqueous solution is as follows: silkworm cocoons are treated with 0.02M Na 2 CO 3 Boiling in water for 30min, washing with distilled water for 3 times (30 min each time) to remove Na 2 CO 3 And sericin. After the degummed cocoons were dried in air for 12h, they were dissolved in 9.3M LiBr solution and at 60 ℃ for 4h. The Slide-A-Lyzer dialysis cassette was used to dialyze against distilled water for 2d. Subsequently, the mixture was centrifuged at 18000rpm for 20 minutes 2 times. The concentration of the final silk protein aqueous solution was determined to be about 6-7wt% by measuring the volume and final dry weight of the solution.
S4: an aluminum mask layer 7 was prepared.
In this 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 and patterning through an ultraviolet photoetching process and an aluminum corrosion process.
In this embodiment, the photoresist used in the ultraviolet lithography process is LC100A. In other embodiments, the photoresist used in the ultraviolet lithography process may be other suitable photoresist, which is not limited herein.
The photoresist has a thickness of 1-3 μm, as an example. In this embodiment, the thickness of the photoresist is 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, etc.
In this example, the aluminum etch process employed a volume ratio of 6:1 of 1.3wt% NH 4 The F solution and 1.6wt% HF solution were mixed to prepare a buffered hydrofluoric acid solution. In other embodiments, the aluminum etching process may also employ other suitable acidic etching solutions, without limitation.
The thickness of the aluminum mask layer 7 is 200-400nm as an example. In this embodiment, the thickness of the aluminum mask layer 7 is 300nm. In other embodiments, the thickness of the aluminum mask layer 7 may be 200nm, 250nm, 350nm, 400nm, etc.
S5: the lattice structure 8 is prepared.
In this step, the mesh structure 8 is prepared by etching the fibroin functional layer 6, the polymer encapsulation layer 5 and the polymer base layer 3 on the sacrificial layer 2 by a microwave plasma process.
S6: electrode sites 9 and ligation sites 10 were prepared.
In this step, the specific process for preparing the electrode sites 9 and the connection sites 10 includes:
s61: a second photolithographic patterning is performed on the aluminum mask layer 7.
In this step, the 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 ultraviolet lithography process is LC100A. In other embodiments, the photoresist used in the ultraviolet lithography process may be other suitable photoresist, which is not limited herein.
The photoresist has a thickness of 1-3 μm, as an example. In this embodiment, the thickness of the photoresist is 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, etc.
In this example, the aluminum etch process employed a volume ratio of 6:1 of 1.3wt% NH 4 F solution and 1.6wtThe% HF solution was mixed to prepare a buffered hydrofluoric acid solution. In other embodiments, the aluminum etching process may also employ other suitable acidic etching solutions, without limitation.
S62: and 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 the cortex electroencephalogram signals and a connecting site 10 for transmitting the recorded cortex electroencephalogram signals to an electroencephalogram signal acquisition device.
In this step, the fibroin functional layer 6 and the polymer encapsulation layer 5 are etched on the electrode material layer 4 by a microwave plasma process, so as to prepare electrode sites 9 and connection sites 10 exposed in the air. The electrode sites 9 are directly contacted with cerebral cortex cells to record the generated cortex brain electrical signals. The connection site 10 is electrically connected with a flexible printed circuit through an anisotropic conductive adhesive under the conditions of 160-180 ℃ (e.g. 170 ℃) and 0.5-0.7MPa (e.g. 0.6 MPa) of pressure, and recorded cortex electroencephalogram signals are transmitted to an electroencephalogram signal acquisition device so as to realize real-time monitoring of cortex electroencephalogram signals.
S7: preparing fibroin drug release carrier.
In the step, the specific process for preparing the fibroin drug release carrier comprises the following steps:
s71: a third photolithographic patterning is performed on the aluminum mask layer 7.
In this step, the 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 ultraviolet lithography process is LC100A. In other embodiments, the photoresist used in the ultraviolet lithography process may be other suitable photoresist, which is not limited herein.
The photoresist has a thickness of 1-3 μm, as an example. In this embodiment, the thickness of the photoresist is 2 μm. In other embodiments, the photoresist may also have a thickness of 1 μm, 1.5 μm, 2.5 μm, 3 μm, etc.
In the present embodiment, the aluminum corrosionThe etching process adopts 1.3wt% NH with the volume ratio of 6:1 4 The F solution and 1.6wt% HF solution were mixed to prepare a buffered hydrofluoric acid solution. In other embodiments, the aluminum etching process may also employ other suitable acidic etching solutions, without limitation.
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 this step, the fibroin functional layer 6 is etched on the polymer encapsulation layer 5 by an oxygen plasma process according to a pre-designed shape and position, and the residual aluminum mask layer 7 is etched away with an aluminum etching solution. Immersing the etched structure into a solvent containing a 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 deionized water solution, so that the drug to be loaded is easier to be dispersed and dissolved. In other embodiments, the solvent may also be other suitable solutions, without limitation.
In the step, the shape and the position of the fibroin drug release carrier can be designed in advance according to actual use requirements, so that drugs can be loaded on different positions of the fibroin drug release carrier, the spatial and temporal distribution characteristics of the drugs acting on a cerebral cortex connection network can be studied, and the disease intervention treatment effect of the drugs can be evaluated in situ.
S8: preparing the bidirectional cortical brain electrode.
In the step, the sacrificial layer 2 on the structure obtained in the step S7 is released, and the bidirectional cortical brain electrode with the function of collecting the cortical brain signals and the function of medicine 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 has good process compatibility with the preparation of the single-layer flexible electrode, so that the stable and high-signal-quality cortical brain electrical monitoring can be well compatible with living brain tissue operation.
In the embodiment, the two-way cortical brain electrode with the function of collecting the cortical brain signals and the function of stimulating the drugs is prepared by adopting the fusion of the photoetching process and the MEMS process which take aluminum as a hard mask, the two processes are good in compatibility and have micron-sized processing precision, and the position overlapping of the fibroin drug release carrier and the electrode site is avoided, so that the drug stimulation effect cannot interfere with the collection of the high-quality cortical brain signals.
The two-way function of the two-way cortical brain electrode prepared in the first embodiment for acquiring brain electrical signals and drug stimulation is verified by adopting a penicillin-induced epileptic rat model.
In the embodiment, the cortical brain electrode after releasing the sacrificial layer is immersed in a phenobarbital solution with a certain concentration, so that the medicine loading of the fibroin functional layer is realized, and the bidirectional cortical brain electrode with the functions of collecting the cortical brain signal and stimulating the medicine is obtained. Monofocal seizures in rats were induced by subcutaneous injection of penicillin (2.5 μl800U/μl penicillin sodium aqueous solution). The bidirectional cortical brain electrode is conformally coated on the surface of rat intracranial material, and brain electrical signals and abnormal sudden discharge signals of each brain region are dynamically monitored in real time. The bidirectional cortical brain electrode detects rapid electroencephalogram signal emission accompanied by epileptic seizure, and in the cortical brain Power Spectral Density (PSD) curve shown in figure 2, the brain electric energy distribution of 0-40Hz under the condition of penicillin-induced epileptic seizure is obviously higher than that of a resting state (particularly, higher frequency of about 5-40 Hz). After the bidirectional cortical brain electrode is conformally coated on the surface of rat intracranial material and the brain electrical signals are normally collected, the fibroin drug release carrier starts to stimulate the phenobarbital in situ on the brain of the epileptic seizure. The cortical brain voltage signals monitored in situ in fig. 3 show that after the phenobarbital is released, the prior epileptiform discharge signals are obviously weakened, which indicates that the bidirectional cortical brain electrode can perform the drug intervention treatment of the epilepsy in time and controllably while the cortical brain signals are dynamically acquired. About 10 mg of phenobarbital loaded in the silk matrix is released and directly diffused in the cerebrospinal fluid into brain tissue of epileptic seizure rats, the phenobarbital significantly stabilizes the cortical brain electrical (ECoG) spectrum and the epileptic symptoms are effectively inhibited, as shown in fig. 4.
Example two
This example provides a bi-directional cortical brain electrode prepared using the method of example one.
Compared with the prior art, the invention has the following advantages:
1. the invention adopts the photoetching technology taking aluminum as a hard mask plate and the MEMS technology to prepare the bidirectional cortical brain electrode with the function of collecting the cortical brain electrical signals and the function of stimulating the drugs, the two technologies have better compatibility and micron-sized processing precision, and the position overlapping of a fibroin drug release carrier and electrode sites is avoided, so that the drug stimulation effect does not interfere with the collection of the high-quality cortical brain electrical signals;
2. the shape and the position of the fibroin drug release carrier can be designed in advance according to actual use requirements, so that drugs can be loaded on different positions of the fibroin drug release carrier, the spatial-temporal distribution characteristics of the drugs acting on a cerebral cortex connection network can be studied, and the disease intervention treatment effect of the drugs can be evaluated in situ;
3. the invention can evaluate the influence of drug molecules on the nerve discharge activity of the multiple brain regions simultaneously in situ, and can perform the drug intervention treatment of related brain diseases such as epilepsy in time and controllably while dynamically collecting the cortex brain signals.
It should be noted that the above embodiments are for illustrative purposes only and should not be taken as limiting the scope of the invention. While the invention has been described with particularity and detail in connection with what is presently deemed to be the most practical and preferred embodiment, it will be apparent to those of ordinary skill in the art that various modifications may be made without departing from the spirit and scope of the invention, and it is intended to cover all such modifications as fall within the true spirit and scope of the invention.
Claims (7)
1. The preparation method of the bidirectional cortical brain electrode is characterized by comprising the following steps of:
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); the step S4 includes: sputtering and depositing a layer of aluminum on the surface of the fibroin functional layer (6), and preparing an aluminum mask layer (7) through first photoetching and patterning;
s5: preparing a lattice structure (8);
s6: preparing an electrode site (9) and a connecting site (10); the step S6 includes:
s61: performing a second photolithographic patterning on the aluminium mask layer (7);
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 brain electrical signals and a connecting site (10) for transmitting the recorded cortex brain electrical signals to brain electrical signal acquisition equipment;
s7: preparing a fibroin drug release carrier; the step S7 includes:
s71: performing a third photolithographic patterning on the aluminum mask layer (7);
s72: 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 in a solvent containing a drug to be loaded to prepare a fibroin drug release carrier;
s8: preparing the bidirectional cortical brain electrode.
2. The method for preparing a bi-directional cortical brain electrode according to claim 1, wherein the step S1 comprises:
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 method for preparing a bi-directional cortical brain electrode according to claim 2, wherein the step S2 comprises:
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 method for preparing a bi-directional cortical brain electrode according to claim 3, wherein the step S3 comprises:
and spin-coating a fibroin solution on the polymer packaging layer (5) to prepare a fibroin functional layer (6).
5. The method for preparing a bi-directional cortical brain electrode according to claim 2, wherein the step S5 comprises:
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).
6. The method for preparing a bi-directional cortical brain electrode according to claim 1, wherein the step S8 comprises:
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 the cortical brain signals and the function of drug stimulation.
7. A bi-directional cortical brain electrode prepared by one of the bi-directional cortical brain electrode preparation methods of claims 1-6.
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