CN113729717A - Preparation method and structure of flexible electrode probe - Google Patents
Preparation method and structure of flexible electrode probe Download PDFInfo
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- CN113729717A CN113729717A CN202110911011.5A CN202110911011A CN113729717A CN 113729717 A CN113729717 A CN 113729717A CN 202110911011 A CN202110911011 A CN 202110911011A CN 113729717 A CN113729717 A CN 113729717A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/25—Bioelectric electrodes therefor
- A61B5/262—Needle electrodes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/25—Bioelectric electrodes therefor
- A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
- A61B5/294—Bioelectric electrodes therefor specially adapted for particular uses for nerve conduction study [NCS]
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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
Abstract
The preparation method comprises the steps of preparing a mold, wherein the mold comprises a groove matched with the structure of an electrode probe to be processed, placing a region to be implanted of the electrode probe to be processed in the groove, injecting a target solution into the groove to enable the region to be implanted to be completely immersed in the target solution, and then curing the region to be implanted to form a target coating on the region to be implanted to obtain the flexible electrode probe; the thickness of the target coating is larger than or equal to a preset thickness threshold value, and the sectional area of the flexible electrode probe is smaller than a preset sectional area. Based on the embodiment of the application, the target coating on the flexible electrode probe can improve the strength of the flexible electrode probe, an additional guiding device is not needed to be used during implantation, and the sectional area of the flexible electrode probe coated with the target coating is smaller, so that when the flexible electrode probe is used, a large area of skull does not need to be removed.
Description
Technical Field
The invention belongs to the field of flexible electrode probe preparation, and particularly relates to a preparation method and a structure of a flexible electrode probe.
Background
Implantable nerve probes are the most widely used tool for recording single-cell, sub-millisecond resolution neural activity, and existing implantable nerve probes include hard silicon-based probes and flexible electrode probes. Fig. 1a, 1b and 1c are schematic diagrams illustrating the effect of a conventional implanted hard silicon-based probe, which will cause rejection reaction after implantation, resulting in necrosis of peripheral nerves, chronic inflammation and inactivation of neuronal cells in the implanted region, and thus degradation of signals received by the implantable neural probe over time. Fig. 2a, 2b and 2c are schematic diagrams illustrating the effect of a conventional implanted flexible electrode probe, and it can be seen that the implanted flexible electrode has a small young's modulus, and the neuron generation status after implantation is good, and the rejection response is little.
However, since the young's modulus of the flexible electrode probe is smaller than that of brain tissue, it cannot be directly implanted into the brain. Fig. 3 is a schematic structural view of a conventional needle-shaped guide device for guiding the implantation of a flexible electrode probe, which is attached to the needle-shaped guide device to assist the implantation of the flexible electrode probe into the brain tissue, and is withdrawn after the flexible electrode probe is implanted into the brain tissue. This procedure inevitably adds complexity to the implantation and requires a high level of operator skill. Although a special surgical robot is used to help implant the flexible electrode probe, fig. 4 is a schematic structural diagram of a surgical robot, which increases the equipment investment cost and the surgical cost. Also, when the needle-like introducer is withdrawn, secondary damage may be caused to the brain tissue and the flexible electrode probe may be deviated from the intended implantation site. In addition, in the existing process of implanting the flexible electrode probe, fig. 5 is a schematic wound diagram of a research object when the existing flexible electrode probe is implanted, in order to ensure an operation space, a skull with a considerable area of the research object needs to be removed to fully expose brain tissues, so that the operation wound area is increased, and the postoperative recovery period from the implantation of the flexible electrode probe to the acquisition of electroencephalogram signals is further prolonged.
Disclosure of Invention
In order to solve the problems that the strength of a flexible electrode probe in the prior art is insufficient, a needle-shaped lead-in device needs to be attached to implant into a brain, and a large-area skull needs to be removed when the flexible electrode probe is used, the embodiment of the application provides a preparation method and a structure of the flexible electrode probe, which can improve the strength of the flexible electrode probe, and can ensure that the sectional area of the flexible electrode probe coated with a target coating is smaller without using an additional lead-in device when being implanted, so that the large-area skull does not need to be removed when the flexible electrode probe is used.
The embodiment of the application provides a preparation method of a flexible electrode probe, which comprises the following steps:
preparing a mould; the mould comprises a groove matched with the structure of the electrode probe to be processed;
placing a region to be implanted of the electrode probe to be processed in the groove;
injecting a target solution into the groove to enable the area to be implanted to be completely immersed in the target solution;
curing the area to be implanted to form a target coating on the area to be implanted to obtain a flexible electrode probe; the thickness of the target coating is larger than or equal to a preset thickness threshold value, and the sectional area of the flexible electrode probe is smaller than a preset sectional area.
Further, the preset thickness threshold is 10 μm.
Further, the predetermined sectional area is 2000 μm 2.
Further, preparing the mold includes:
preparing a mold by using a two-photon printing technology and flexible polydimethylsiloxane; the mould comprises a groove matched with the structure of the electrode probe to be processed;
and treating the inner wall of the groove by using isopropanol so that the inner wall of the groove has hydrophilicity.
Further, before the region to be implanted of the electrode probe to be processed is placed in the groove, the method further comprises the following steps:
and (5) dripping deionized water into the groove.
Further, the depth of the groove is 20 μm or more.
Further, the target solution includes a protein solution, a polylactic acid-glycolic acid copolymer solution, or a chitosan solution.
Further, the method further comprises a step of preparing a target solution comprising:
obtaining a biomass material, a first solution and a second solution;
placing the biomass material in a first solution for heating treatment to obtain a sample;
placing the sample in a second solution for dissolving treatment to obtain a first mixed system;
carrying out distillation dialysis and centrifugal treatment on the first mixed system to obtain a second mixed system;
filtering and concentrating the second mixed system to obtain a target solution; the mass fraction of the sample in the target solution is greater than or equal to a preset mass fraction threshold value.
Further, the biomass material comprises silkworm cocoon, the first solution comprises a sodium carbonate solution, and the second solution comprises a lithium bromide solution.
Further, the biomass material is placed in a first solution for heat treatment to obtain a sample, comprising:
placing the silkworm cocoon in a sodium carbonate solution, and heating for 60min to obtain a heated silkworm cocoon;
placing the heated silkworm cocoons in distilled water for rinsing treatment, and removing sodium carbonate and sericin to obtain degummed silkworm cocoons;
and (4) drying and placing the degummed silkworm cocoons for more than 12 hours to obtain a sample.
Further, placing the sample in a second solution for dissolution treatment to obtain a first mixed system, comprising:
and (3) placing the sample in a lithium bromide solution at 60 ℃ for dissolving for 4h to obtain a first mixed system.
Further, the first mixed system is subjected to distillation dialysis and centrifugation treatment to obtain a second mixed system, which comprises:
putting the first mixed system into distilled water for dialysis for 48 hours to obtain a dialyzed first mixed system;
carrying out multiple centrifugal treatments on the dialyzed first mixed system to obtain a second mixed system; the rotating speed of the centrifugal treatment is 1800r/min, and the time of each centrifugal treatment is 20 min; the second mixing system is silk protein solution.
Further, the concentration of the second mixed system was 7%.
Further, the second mixed system is filtered and concentrated to obtain a protein solution, which comprises:
putting 50ml of silk protein solution into a bag filter, and putting the bag filter in an environment at 4 ℃ for concentration treatment to obtain a target solution; the mass fraction of the fibroin in the target solution is 28%.
Further, the method further comprises a step of preparing an electrode probe to be processed, comprising:
preparing a substrate; the substrate comprises a base and a sacrificial layer arranged on the base;
patterning the sacrificial layer to form a first electrode layer on the sacrificial layer;
preparing a metal wiring layer on the first electrode layer;
preparing a second electrode layer on the metal wiring layer, and carrying out graphical processing on the second electrode layer to form a connecting part, a lead structure and a contact end part of the exposed electrode;
repeating the steps: preparing a metal wiring layer on the second electrode layer, preparing a third electrode layer on the metal wiring layer, and carrying out graphical processing on the third electrode layer to form a connecting part, a lead structure and a contact end part of the exposed electrode;
and releasing the sacrificial layer to obtain the electrode probe to be processed.
Further, the patterning process is performed on the sacrificial layer, so that after the first electrode layer is formed on the sacrificial layer, the method further includes:
an insulating layer is prepared on the first electrode support layer.
Further, the method further comprises:
placing a region to be implanted of an electrode probe to be processed in a target solution, and carrying out curing treatment on the electrode probe to be processed, so that a target coating is formed on the region to be implanted, thereby obtaining the flexible electrode probe, which comprises the following steps:
sterilizing and cleaning the to-be-implanted area of the to-be-treated electrode probe to obtain a sterilized and cleaned to-be-treated electrode probe;
at room temperature, immersing the to-be-implanted area of the electrode probe to be treated after the disinfection and cleaning treatment into a target solution;
and taking the electrode probe to be processed out of the target solution, and placing the electrode probe in the air for 10min to solidify the target solution on the area to be implanted to form a target coating, thereby obtaining the flexible electrode probe.
Correspondingly, the embodiment of the application also provides a flexible electrode probe, which comprises a region to be implanted and a flexible buffer strip;
the area to be implanted is connected with the flexible buffer belt;
the area to be implanted is coated with a target coating, the thickness of the target coating is greater than or equal to 10 μm, and the cross-sectional area of the flexible electrode probe is less than 2000 μm 2.
Further, the length of the region to be implanted is 5.05 mm.
Further, the flexible electrode probe further comprises a plurality of recording channels;
the distance between every two recording channels is 0.15 mm.
The embodiment of the application has the following beneficial effects:
the preparation method comprises the steps of preparing a mold, wherein the mold comprises a groove matched with the structure of an electrode probe to be processed, placing a region to be implanted of the electrode probe to be processed in the groove, injecting a target solution into the groove to enable the region to be implanted to be completely immersed in the target solution, and then curing the region to be implanted to form a target coating on the region to be implanted to obtain the flexible electrode probe; the thickness of the target coating is larger than or equal to a preset thickness threshold value, and the sectional area of the flexible electrode probe is smaller than a preset sectional area. Based on this application embodiment, the intensity of flexible electrode probe can be improved to the target coating on the flexible electrode probe, need not to use extra gatherer when implanting, can reduce the requirement to operating personnel, need not to retrieve gatherer, can reduce the deviation of the implantation of flexible electrode probe. In addition, the sectional area of the flexible electrode probe coated with the target coating is smaller, so that when the flexible electrode probe is used, a large area of skull does not need to be removed, the wound of a research object can be reduced, the postoperative recovery period is shortened, and electroencephalogram signals are recorded as soon as possible.
Drawings
In order to more clearly illustrate the technical solutions and advantages of the embodiments of the present application or 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 application, and other drawings can be obtained by those skilled in the art without creative efforts.
FIGS. 1a, 1b and 1c are schematic diagrams illustrating the effect of a conventional implanted hard silicon-based probe;
FIGS. 2a, 2b and 2c are schematic views illustrating the effect of a conventional implanted flexible electrode probe;
FIG. 3 is a schematic structural diagram of a prior art needle-like guide device for guiding the implantation of a flexible electrode probe;
FIG. 4 is a schematic view of a surgical robot;
FIG. 5 is a schematic illustration of a wound of a subject with an existing flexible electrode probe implanted;
FIG. 6 is a schematic flow chart of a method for manufacturing a flexible electrode probe according to an embodiment of the present disclosure;
FIG. 7 is a schematic view of a process for preparing an electrode probe to be processed according to an embodiment of the present disclosure;
FIG. 8 is a schematic diagram of a method for preparing an electrode probe to be processed according to an embodiment of the present disclosure;
FIG. 9 is a schematic flow chart of a process for preparing a target solution provided in an embodiment of the present application;
FIG. 10 is a schematic diagram of a standard surgical robot according to an embodiment of the present application;
FIG. 11 is a schematic diagram of a flexible electrode probe and an implanted flexible electrode probe according to an embodiment of the present disclosure;
fig. 12 is a schematic structural diagram of a flexible electrode probe according to an embodiment of the present application.
Detailed Description
To make the objects, technical solutions and advantages of the present application more clear, embodiments of the present application will be described in further detail below with reference to the accompanying drawings. It should be apparent that the described embodiment is only one embodiment of the present application and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
An "embodiment" as referred to herein relates to a particular feature, structure, or characteristic that may be included in at least one implementation of the present application. In the description of the embodiments of the present application, it should be understood that the terms "upper", "lower", and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience in describing the present application and simplifying the description, but do not indicate or imply that the structures referred to must have a specific orientation, be constructed in a specific orientation, and be operated, and thus should not be construed as limiting the present application. The terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Moreover, the terms "first," "second," and the like are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the application described herein are capable of operation in other sequences than described or illustrated herein. Furthermore, the terms "comprising," "having," and "being," as well as any variations thereof, are intended to cover non-exclusive inclusions.
In the following, a specific embodiment of a method for manufacturing a flexible electrode probe according to the present application is described, and fig. 6 is a schematic flow chart of a method for manufacturing a flexible electrode probe according to the embodiment of the present application, and the present specification provides the method operation steps as shown in the embodiment or the flow chart, but more or less operation steps can be included based on conventional or non-inventive labor. The sequence of steps recited in the embodiments is only one of many execution sequences, and does not represent the only execution sequence, and in the actual execution, the steps can be executed in the sequence of the method shown in the embodiment or the drawings or executed in parallel. As shown in fig. 6:
s601: preparing a mould; the mold includes a recess that matches the structure of the electrode probe to be processed.
In the embodiment of the application, a mold can be prepared by using a two-photon printing technology and flexible Polydimethylsiloxane (pdms), the mold is provided with a groove matched with the structure of the electrode probe to be processed, and then the inner wall of the groove is processed by using isopropanol, so that the inner wall of the groove has hydrophilicity, and further, when the target solution is subsequently dripped into the groove, the target solution cannot overflow from the groove.
In an alternative embodiment, the mold may include a recess and a fixing end portion that match the structure of the electrode probe to be processed. The fixing end portion may be disposed in the groove, the fixing end portion may also be disposed at an end portion of the groove, and a top of the fixing end portion and an inner top of the groove may have a plane difference.
In the embodiment of the present application, the depth of the groove may be 20 μm or more. The depth of the groove can be other fixed values, the application is not limited in particular, and the thickness of the subsequent target coating can be controlled by changing the depth of the groove.
S603: and placing the to-be-implanted region of the to-be-processed electrode probe in the groove.
In the embodiment of the application, the electrode probe to be processed can comprise a region to be implanted and a flexible buffer strip, and the region to be implanted is connected with the flexible buffer strip.
In the embodiment of the application, before the area to be implanted of the electrode probe to be processed is arranged in the groove, deionized water can be dripped into the groove, so that when the area to be implanted of the electrode probe to be processed is arranged in the groove, each probe of the electrode probe to be processed can be attached in the corresponding groove by utilizing the tension of the electrode probe to be processed, and the electrode probe to be processed and the groove are conveniently matched and aligned correspondingly. And then, waiting for 30min to evaporate the deionized water completely, and then performing subsequent operation.
In the embodiment of the application, 70% alcohol can be used for sterilizing the to-be-implanted area of the to-be-treated electrode probe, the sterilized to-be-treated electrode probe is transferred into deionized water, then, the flexible buffer belt of the to-be-treated electrode probe, namely, the substrate is fixed at the fixed end part of the mold, and the to-be-implanted area of the to-be-treated electrode probe is placed in the groove by using the forceps under a body type microscope.
In the embodiment of the application, the region to be implanted of the electrode probe to be processed can be placed in the groove, and the region to be implanted of the electrode probe to be processed and a part of the flexible buffer strip connected with the region to be implanted can also be placed in the groove. Alternatively, the area to be implanted and one third of the area of the flexible buffer strip connected to the area to be implanted can be placed in the recess.
In the implementation of the present application, before the region to be implanted of the electrode probe to be processed is placed in the groove, the electrode probe to be processed may be prepared, fig. 7 is a schematic flow chart of preparing the electrode probe to be processed according to an embodiment of the present application, and fig. 8 is a schematic diagram of preparing the electrode probe to be processed according to an embodiment of the present application. In an alternative embodiment, the electrode probe to be treated may be prepared using the method steps shown in FIG. 7:
s701: preparing a substrate; the substrate includes a base and a sacrificial layer disposed on the base.
In the embodiment of the application, a substrate can be obtained, and then a sacrificial layer is generated on the upper surface of the substrate.
In an alternative embodiment, the material of the substrate may be silicon dioxide, SiO2. The material of the sacrificial layer may be nickel Ni. A in fig. 8 illustrates a schematic structural diagram of the substrate.
S703: and patterning the sacrificial layer to form a first electrode layer on the sacrificial layer.
In the embodiment of the application, the sacrificial layer can be subjected to patterning treatment, and then a plurality of bottom electrode layers can be prepared on the sacrificial layer. A schematic structural diagram of a plurality of bottom electrodes fabricated on the sacrificial layer is illustrated in b of fig. 8.
S705: and preparing a metal wiring layer on the first electrode layer.
In this embodiment of the application, after obtaining a plurality of bottom electrode layers, a photoresist may be coated on the bottom electrode layers, for example, a photoresist with a model number of SU8-2000.5 may be coated to form bottom photolithography layers, c in fig. 8 illustrates a structural schematic diagram of coating the photoresist on the bottom electrode layers, and then an insulating layer may be prepared on the bottom photolithography layer corresponding to any first electrode layer, d in fig. 8 illustrates a structural schematic diagram of preparing the insulating layer on the bottom photolithography layer, and then a metal wiring layer may be prepared on the first electrode layer, and the metal wiring layer may be formed by stacking 10nm of Cr and 100nm of Au. And e in fig. 8 illustrates a structural schematic diagram of preparing a metal wiring layer on the electrode layer.
S707: and preparing a second electrode layer on the metal wiring layer, and carrying out patterning treatment on the second electrode layer to form a connecting part of the exposed electrode, a lead structure and a contact end part.
In the embodiment of the application, an electrode isolation layer can be coated on the surface of the metal wiring layer in a spinning mode, and the electrode isolation layer is subjected to patterning processing to expose the connecting part, the lead structure and the contact end part of the exposed electrode, wherein the insulation layer is a channel for connecting the separated metal wiring layer and the exposed electrode. Fig. 8 f is a schematic structural view illustrating the preparation of the second electrode layer on the metal wiring layer.
In this embodiment of the application, after the second electrode layer is prepared, a photoresist may be coated on the first electrode layer, the second electrode layer, and the insulating layer, fig. 8 g illustrates a schematic structural diagram of coating a photoresist on the first electrode layer, the second electrode layer, and the insulating layer, for example, a photoresist of SU8-2000.5 may be coated to form a middle layer photoresist layer, and then an insulating layer may be prepared on a middle layer photoresist layer corresponding to any first electrode layer of the first electrode layer, and fig. 8h illustrates a schematic structural diagram of preparing an insulating layer on the middle layer photoresist layer. Further steps may be repeated: and preparing a metal wiring layer on the second electrode layer, preparing a fourth electrode layer on the prepared metal wiring layer, and carrying out patterning treatment on the fourth electrode layer to form a connecting part, a lead structure and a contact end part of the exposed electrode, namely forming a multilayer lead structure and an electrode layer. By the multi-layer wiring and increasing the number of electrode layers, the number and density of channels of the flexible electrode probe can be increased. Then, the connection portion of each exposed electrode may be connected and patterned to form the exposed electrode.
S709: and releasing the sacrificial layer to obtain the electrode probe to be processed.
In the embodiment of the application, the sacrificial layer can be released along the connecting surface of the substrate and the sacrificial layer, and the electrode probe to be processed is obtained. I in FIG. 8 illustrates a schematic structural diagram of the electrode probe to be processed.
S605: injecting the target solution into the groove so that the region to be implanted is completely immersed in the target solution.
In the embodiment of the application, a micro printing nozzle can be adopted to drip the target solution into the groove, so that the area to be implanted is completely immersed into the target solution.
In the embodiment of the present application, before injecting the target solution into the groove, the target solution may be prepared, wherein the target solution may be, but not limited to, a protein solution, a poly (lactic-co-glycolic acid) solution, or a chitosan solution.
Fig. 9 is a schematic flow chart of preparing a target solution according to an embodiment of the present application. In an alternative embodiment, the steps of the method shown in fig. 9 may be used to prepare a target solution, which may be a protein solution, and the specific steps are as follows:
s901: a biomass material, a first solution, and a second solution are obtained.
In an embodiment of the present application, the biomass material may include silkworm cocoons, the first solution may include a sodium carbonate solution, and the second solution may include a lithium bromide solution.
S903: and placing the biomass material in the first solution for heating treatment to obtain a sample.
In the embodiment of the application, the biomass material can be placed in the first solution for heating treatment to obtain the biomass material after heating treatment, and then the biomass material after heating treatment is rinsed to obtain the biomass material after degumming, and then the biomass material after degumming is dried to obtain the sample.
In an alternative embodiment, the silkworm cocoon may be placed in a sodium carbonate solution to be heated for 60min to obtain a heated silkworm cocoon, the heated silkworm cocoon is further placed in distilled water to be rinsed to remove sodium carbonate and sericin to obtain a degummed silkworm cocoon, and the degummed silkworm cocoon is dried and placed for more than 12h to obtain a sample. Specifically, after placing the silkworm cocoon in 0.02mol/L sodium carbonate aqueous solution to boil for 60min, rinsing the silkworm cocoon in distilled water for 3 times, wherein the rinsing time is 30min each time, removing sodium carbonate and sericin to obtain the degummed silkworm cocoon, and drying the degummed silkworm cocoon for more than 12h to obtain a sample, namely the dried degummed silkworm cocoon.
S905: and placing the sample in a second solution for dissolving treatment to obtain a first mixed system.
In the embodiment of the application, a sample can be placed in a 9.3mol/L lithium bromide solution at 60 ℃ for dissolving for 4 hours to obtain a first mixed system. Namely, the dried degummed silkworm cocoon is dissolved in a lithium bromide solution to obtain a dissolved first mixed system.
S907: and carrying out distillation dialysis and centrifugal treatment on the first mixed system to obtain a second mixed system.
In this application embodiment, dialysis treatment may be performed on the first mixed system to obtain a first mixed system after dialysis treatment, and then, centrifugation treatment may be performed on the first mixed system after dialysis treatment for a plurality of times to obtain a second mixed system.
In an alternative embodiment, the first mixed system after dialysis treatment may be centrifuged 2 times, the rotation speed of the centrifugation may be 1800r/min, and the time of each centrifugation may be 20 min.
In an alternative embodiment, the first mixed system may be dialyzed in distilled water for 48h to obtain a dialyzed first mixed system, and then centrifuged twice at 1800r/min for 20min to obtain a second mixed system, i.e. a silk protein solution.
In the present example, the concentration of the solution can be determined by measuring the volume of the solution and the final dry weight of the solute after the second mixed system is obtained. In an alternative embodiment, the concentration of the second mixed system may be 7%, i.e. the concentration of the silk protein solution may be 7%.
S909: filtering and concentrating the second mixed system to obtain a protein solution; the mass fraction of the sample in the protein solution is greater than or equal to a preset mass fraction threshold value.
In the embodiment of the application, a certain volume of the second mixed system can be taken for filtration and concentration treatment to obtain the target solution.
In an alternative embodiment, 50ml of silk protein solution with a concentration of 7% can be placed in a bag filter and placed in an environment at 4 ℃ for concentration treatment until the mass fraction of the silk protein in the target solution reaches 28%, and the target solution for coating the flexible electrode probe can be obtained.
S607: curing the area to be implanted to form a target coating on the area to be implanted to obtain a flexible electrode probe; the thickness of the target coating is larger than or equal to a preset thickness threshold value, and the sectional area of the flexible electrode probe is smaller than a preset sectional area.
In the embodiment of the present application, the predetermined thickness threshold may be 10 μm. That is, the thickness of the target coating layer on the surface of the flexible electrode probe is more than 10 μm after curing, so that the strength of the flexible electrode probe can be improved, the flexible electrode probe can be implanted into the brain without attaching a needle-shaped introduction device, and even if the flexible electrode probe is temporarily hardened, the flexible electrode probe can be implanted without using an additional introduction device. The preset thickness threshold may also be other values, and the application is not particularly limited.
In the embodiment of the present application, the predetermined cross-sectional area may be 2000 μm2. Due to the electrode probe to be processedWith a very small cross-section, the cross-sectional area of the flexible electrode probe may be less than 2000 μm2 when the target coating on the surface of the flexible electrode probe is cured, so that when using the flexible electrode probe, no large area of the skull bone needs to be removed. The predetermined cross-sectional area may be other values, and the present application is not limited specifically.
In the embodiment of the present application, after the target coating is formed on the region to be implanted, the mold may be slightly bent, so that the electrode probe to be processed and the target coating on the surface thereof are separated from the mold, resulting in a flexible electrode probe.
In an alternative embodiment, a hole with a diameter of 0.5mm-0.7mm can be drilled in the skull of the subject, and then the flexible electrode probe can be manually implanted into the region to be implanted of the subject by means of a common 3D positioning instrument, and fig. 10 is a schematic structural diagram of a standard surgical robot provided in the application example, and the flexible electrode probe can be implanted into the region to be implanted of the subject by means of the standard surgical robot. After the flexible electrode probe is implanted, the hole may be sealed with flexible bio-gel and the skull surface may be covered with dental cement.
In an optional embodiment, after the target solution and the electrode probe to be processed are prepared, a sterilization and cleaning process may be further performed on the region to be implanted of the electrode probe to be processed to obtain the electrode probe to be processed after the sterilization and cleaning process, then, at room temperature, the region to be implanted of the electrode probe to be processed after the sterilization and cleaning process is immersed in the target solution, and then, the electrode probe to be processed is taken out of the target solution and placed in the air for 10min, so that the target solution is cured on the region to be implanted to form a target coating, thereby obtaining the flexible electrode probe. Fig. 11 is a schematic diagram of a flexible electrode probe and an implanted flexible electrode probe according to an embodiment of the present disclosure.
By adopting the preparation method of the flexible electrode probe provided by the embodiment of the application, the target coating on the obtained flexible electrode probe can improve the strength of the flexible electrode probe, an additional lead-in device is not needed to be used during implantation, the requirement on operators can be reduced, the lead-in device is not needed to be recycled, and the implantation deviation of the flexible electrode probe can be reduced. In addition, the sectional area of the flexible electrode probe coated with the target coating is smaller, so that when the flexible electrode probe is used, a large area of skull does not need to be removed, the wound of a research object can be reduced, the postoperative recovery period is shortened, and electroencephalogram signals are recorded as soon as possible.
Fig. 12 is a schematic structural diagram of a flexible electrode probe according to an embodiment of the present application, and as shown in fig. 12, the flexible electrode probe may include an area to be implanted and a flexible buffer zone, where the area to be implanted is connected to the flexible buffer zone; the region to be implanted may be coated with a target coating, the target coating may have a thickness of 10 μm or more, and the cross-sectional area of the flexible electrode probe may be less than 2000 μm 2.
In the embodiment of the present application, the region to be implanted may include a region to be implanted, and the length of the region to be implanted may be 5.05 mm.
In this embodiment, the flexible electrode probe further includes a plurality of recording channels, and a distance between every two recording channels may be 0.15 mm.
In an alternative embodiment, the flexible electrode probe may include 128 recording channels, and the distance between no two recording channels may be 0.15 mm.
In the embodiment of the present application, the length of the flexible buffer strip may be 8.82 mm. The distance between every two of the flexible electrode probes may be 0.25 nm.
The structure and the preparation method in the embodiment of the application are based on the same application concept.
By adopting the flexible electrode probe provided by the embodiment of the application, the target coating on the flexible electrode probe can improve the strength of the flexible electrode probe, an additional lead-in device is not needed to be used when the flexible electrode probe is implanted, the requirement on an operator can be reduced, the lead-in device is not needed to be recycled, and the implanted deviation of the flexible electrode probe can be reduced. In addition, the sectional area of the flexible electrode probe coated with the target coating is smaller, so that when the flexible electrode probe is used, a large area of skull does not need to be removed, the wound of a research object can be reduced, the postoperative recovery period is shortened, and electroencephalogram signals are recorded as soon as possible.
According to the preparation method of the flexible electrode probe or the specific embodiment of the flexible electrode probe provided by the application, the preparation method can comprise the steps of preparing a mold, wherein the mold comprises a groove matched with the structure of the electrode probe to be processed, then placing a region to be implanted of the electrode probe to be processed in the groove, injecting a target solution into the groove, completely immersing the region to be implanted in the target solution, and then carrying out curing treatment on the region to be implanted, so that a target coating is formed on the region to be implanted, and the flexible electrode probe is obtained; the thickness of the target coating is larger than or equal to a preset thickness threshold value, and the sectional area of the flexible electrode probe is smaller than a preset sectional area. Based on this application embodiment, the intensity of flexible electrode probe can be improved to the target coating on the flexible electrode probe, need not to use extra gatherer when implanting, can reduce the requirement to operating personnel, need not to retrieve gatherer, can reduce the deviation of the implantation of flexible electrode probe. In addition, the sectional area of the flexible electrode probe coated with the target coating is smaller, so that when the flexible electrode probe is used, a large area of skull does not need to be removed, the wound of a research object can be reduced, the postoperative recovery period is shortened, and electroencephalogram signals are recorded as soon as possible.
It should be noted that: the foregoing sequence of the embodiments of the present application is for description only and does not represent the superiority and inferiority of the embodiments, and the specific embodiments are described in the specification, and other embodiments are also within the scope of the appended claims. In some cases, the actions or steps recited in the claims can be performed in the order of execution in different embodiments and achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown or connected to enable the desired results to be achieved, and in some embodiments, multitasking and parallel processing may also be possible or may be advantageous.
All the embodiments in the present specification are described in a progressive manner, and the same and similar parts among the embodiments may be referred to each other, and each embodiment is described with emphasis on differences from other embodiments. In particular, for the structural embodiment, since it is based on the method embodiment, the description is simple, and the relevant points can be referred to the partial description of the method embodiment.
The foregoing is a preferred embodiment of the present invention, and it should be noted that it would be apparent to those skilled in the art that various modifications and enhancements can be made without departing from the principles of the invention, and such modifications and enhancements are also considered to be within the scope of the invention.
Claims (10)
1. A preparation method of a flexible electrode probe is characterized by comprising the following steps:
preparing a mould; the mould comprises a groove matched with the structure of the electrode probe to be processed;
placing the to-be-implanted region of the to-be-processed electrode probe in the groove;
injecting a target solution into the groove to enable the area to be implanted to be completely immersed in the target solution;
curing the to-be-implanted region to form a target coating on the to-be-implanted region to obtain a flexible electrode probe; the thickness of the target coating is larger than or equal to a preset thickness threshold value, and the sectional area of the flexible electrode probe is smaller than a preset sectional area.
2. The method according to claim 1, wherein the preset thickness threshold is 10 μ ι η.
3. The method of claim 1, wherein the predetermined cross-sectional area is 2000 μm2。
4. The method of claim 1, wherein the depth of the groove is 20 μm or greater.
5. The method of claim 1, further comprising the step of preparing a target solution comprising:
obtaining a biomass material, a first solution and a second solution;
placing the biomass material in the first solution for heating treatment to obtain a sample;
placing the sample in the second solution for dissolving treatment to obtain a first mixed system;
carrying out distillation dialysis and centrifugal treatment on the first mixed system to obtain a second mixed system;
filtering and concentrating the second mixed system to obtain a target solution; the mass fraction of the sample in the target solution is greater than or equal to a preset mass fraction threshold value.
6. The method according to claim 1, further comprising a step of preparing the electrode probe to be processed, comprising:
preparing a substrate; the substrate comprises a base and a sacrificial layer arranged on the base;
patterning the sacrificial layer to form a first electrode layer on the sacrificial layer;
preparing a metal wiring layer on the first electrode layer;
preparing a second electrode layer on the metal wiring layer, and carrying out patterning treatment on the second electrode layer to form a connecting part, a lead structure and a contact end part of an exposed electrode;
repeating the steps: preparing a metal wiring layer on the second electrode layer, preparing a third electrode layer on the metal wiring layer, and carrying out patterning treatment on the third electrode layer to form a connecting part, a lead structure and a contact end part of an exposed electrode until a multilayer lead structure and an electrode layer are formed;
and releasing the sacrificial layer to obtain the electrode probe to be processed.
7. The method of claim 1, wherein patterning the sacrificial layer such that after forming the first electrode layer on the sacrificial layer, further comprises:
and preparing an insulating layer on the first electrode layer.
8. A flexible electrode probe is characterized by comprising a region to be implanted and a flexible buffer strip;
the region to be implanted is connected with the flexible buffer zone;
the area to be implanted is coated with a target coating, the thickness of the target coating is more than or equal to 10 mu m, and the sectional area of the flexible electrode probe is less than 2000 mu m2。
9. The flexible electrode probe of claim 8, wherein the length of the region to be implanted is 5.05 mm.
10. The flexible electrode probe of claim 8, further comprising a plurality of recording channels;
the distance between every two recording channels is 0.15 mm.
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