CN117338303A - Temperature-control viscosity multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring - Google Patents
Temperature-control viscosity multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring Download PDFInfo
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- CN117338303A CN117338303A CN202311644831.8A CN202311644831A CN117338303A CN 117338303 A CN117338303 A CN 117338303A CN 202311644831 A CN202311644831 A CN 202311644831A CN 117338303 A CN117338303 A CN 117338303A
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Abstract
The invention provides a temperature-control adhesive multi-channel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring, which comprises a flexible basal layer, a flexible packaging layer, a temperature-control adhesive hydrogel interface layer and a stretchable conducting layer integrating an internal circuit and an electrode, wherein the flexible basal layer and the flexible packaging layer are jointly constructed to form a flexible frame main body, the stretchable conducting layer is arranged in the flexible frame main body, the temperature-control adhesive hydrogel interface layer is arranged on the flexible packaging layer and is used for adhering to intracranial brain tissues, and the temperature-control adhesive hydrogel interface layer is formed by ultraviolet-initiated polymerization of temperature-control adhesive hydrogel porous microspheres, ammonium sulfonate zwitterionic monomers, amide monomers, acrylate hydrophobic monomers, an initiator and a cross-linking agent. The temperature-control adhesive multichannel hydrogel electrode has excellent flexibility and conductivity, can realize seamless attachment and benign stripping with craniocerebral tissues through temperature control, and avoids craniocerebral tissue damage.
Description
Technical Field
The invention relates to the technical field of biomedical devices, in particular to a temperature-control viscosity multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring.
Background
Craniotomy is one of the most important procedures in the neurosurgery field for the treatment of various diseases and injuries related to intracranial structures. The operation is to make bone flap on skull to expose brain tissue and provide direct visual field and operation space for the treatment of pathological changes, tumor excision, vascular repair, cerebral trauma repair, etc. In craniotomy research, surgical planning and navigation techniques become important research directions. These techniques utilize advanced imaging and computer-aided systems to provide detailed brain structure images and real-time navigation guidance to a physician to help determine surgical approaches, locate lesions, avoid important functional areas, etc. In addition, there have been studies on new instruments and techniques for specific diseases and surgical procedures, such as minimally invasive surgical techniques, laser surgery, nerve monitoring, and electroencephalogram monitoring. These techniques have been developed to improve the accuracy, safety and rehabilitation of patients. Although craniotomy has achieved significant success in treating intracranial diseases, there are still some potential risks and complications such as infection, hemorrhage, cerebral edema, nerve function damage, and the like. Accordingly, researchers have been working to develop new preventive and therapeutic strategies including anti-infective measures, bleeding control techniques, the use of neuroprotective agents, etc., to reduce the incidence of surgical complications and improve patient progression.
In craniotomy, intracranial electroencephalogram monitoring can provide detailed information about brain functions and electrophysiological states, and becomes one of the most key information indexes for feeding back intracranial health states of patients. By monitoring the brain electrical activity, a doctor can understand the neural activity pattern, brain electrical rhythm, brain electrical abnormality, etc. of the patient. Such information is critical to locating important functional areas, judging brain functional status, and assessing surgical risk. For example, in brain tumor resection surgery, by monitoring brain electrical activity, a physician can determine functional areas around a tumor and avoid damage to those areas, thereby maximizing the protection of the patient's neurological function. In addition, intracranial electroencephalogram monitoring can help doctors to timely detect and treat complications in operation, such as cerebral ischemia, epileptic seizure and the like, and take corresponding measures to intervene and treat. For example, when an abnormal pattern of brain electrical activity is detected, the physician may immediately adjust the surgical strategy, reduce damage to brain tissue, and take medication to control seizures. The intracranial electroencephalogram monitoring can also provide real-time feedback information to help doctors evaluate the effect and curative effect of the operation. By monitoring the change of the brain electrical activity, a doctor can judge the influence of the operation wound on the brain function and adjust the operation strategy in time to achieve the optimal treatment effect. The real-time monitoring and feedback mechanism can help doctors to make decisions in the operation process, and the accuracy and safety of the operation are ensured.
Traditional intracranial electroencephalogram monitoring performs acquisition and recording of electroencephalogram signals by implanting electrodes into the cranium of a patient. This monitoring approach provides accurate brain electrical activity information to some extent, but also has some drawbacks and limitations. Intracranial electroencephalogram monitoring by implanted electrodes is an invasive procedure with certain risks including infection, hemorrhage, brain tissue damage, and the like. In addition, patients need to undergo long-term hospitalization observation and monitoring after implantation of the electrodes, increasing the burden and medical costs of the patients. Intracranial electroencephalogram monitoring by implanted electrodes can only provide limited monitoring range and spatial resolution. Due to the limitations of the number and location of implanted electrodes, conventional monitoring methods can only monitor a limited brain area, while the location of the implanted electrodes cannot be moved at will. The implanted electrodes often need to be connected to an external data collection module and the analysis process is cumbersome. At the same time, the number of implanted electrodes is small, the acquired data is limited, and complex signal processing and analysis are needed to extract useful information. Moreover, the traditional implanted electrode is often rigid, high in modulus and poor in stretchability, and cannot be attached to a brain tissue interface in a conformal manner, so that the quality of acquired brain electrical signals is greatly affected. Stimulation of the implanted electrodes may cause an inflammatory response in brain tissue. In addition, due to the fixed position of the electrode, the movement and deformation of brain tissues cannot be followed, so that the accuracy of a monitoring result is limited, and the rigid brain electrode is easy to cause brain tissue damage in the process of putting in and taking out. Therefore, there is an urgent need to develop an epidermal electrode having superior adhesion, flexibility, and conformability to intracranial brain tissue, while preventing brain tissue damage during the exfoliation process.
Disclosure of Invention
Aiming at the characteristics of large interface curvature, low modulus and easy damage of the brain tissue during operation, the invention provides the temperature-control viscosity multichannel hydrogel electrode for monitoring the brain tissue during operation and the preparation method thereof.
The technical scheme for solving the technical problems is as follows:
in a first aspect, the invention provides a temperature-control adhesive multi-channel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring, which comprises a flexible basal layer, a flexible packaging layer, a temperature-control adhesive hydrogel interface layer and a stretchable conducting layer integrated with an internal circuit and an electrode, wherein the flexible basal layer and the flexible packaging layer are jointly constructed to form a flexible frame main body, the stretchable conducting layer is arranged in the flexible frame main body, the electrode extends out of the flexible main body frame through a window on the flexible packaging layer (2), and the temperature-control adhesive hydrogel interface layer is arranged on the flexible packaging layer and covers the electrode and is used for adhering with intracranial brain tissues; the components of the temperature-control adhesive hydrogel interface layer comprise temperature-control adhesive hydrogel porous microspheres, ammonium sulfonate zwitterionic monomers, amide monomers, acrylate hydrophobic monomers, an initiator and a cross-linking agent, and the components are polymerized by ultraviolet initiation to form the temperature-control adhesive hydrogel interface layer; the viscosity of the temperature-control viscous hydrogel interface layer changes at different temperatures, and seamless integration and benign stripping of the temperature-control viscous hydrogel interface layer and craniocerebral tissues can be realized through temperature control.
The principle of the invention is as follows: when the temperature of the temperature-control adhesive hydrogel interface layer is reduced, N-isopropyl acrylamide molecular chains wound in the temperature-control adhesive hydrogel porous microspheres are in a hydrophilic state, the temperature-control adhesive hydrogel porous microspheres absorb water rapidly, and ammonium sulfonate zwitterionic molecular chains, olefinic acid ester hydrophobic chains and catechol groups in the temperature-control adhesive hydrogel porous microspheres respectively establish electrostatic bonds, hydrophobic interactions, schiff bases, michael addition reactions and hydrogen bonds with the surface of the cranium, so that the temperature-control adhesive hydrogel interface layer and the cranium tissue can be bonded in a seamless integrated manner; after electroencephalogram collection in operation is completed, the temperature is raised, the temperature-control viscous hydrogel interface layer is heated, N-isopropyl acrylamide molecular chains wound in the temperature-control viscous hydrogel porous microspheres are subjected to phase change and are in a hydrophobic state, the temperature-control viscous hydrogel porous microspheres are rapidly dehydrated to generate an interface hydration layer, electrostatic bonds, hydrophobic interactions, schiff bases, michael addition reactions and hydrogen bonds between the temperature-control viscous hydrogel interface layer and the surface of cranium are damaged, viscosity is reduced, and benign stripping of the temperature-control viscous multichannel hydrogel electrode is realized.
The beneficial effects of the invention are as follows:
the temperature-control adhesive multi-channel hydrogel electrode can realize rapid water absorption and dehydration through temperature regulation and control of the hydrophilic/hydrophobic state of the hydrogel porous microspheres so as to realize dynamic recombination of interfacial chemical adhesion and physical adhesion, further realize rapid regulation and control of the adhesion, further ensure seamless integration with craniocerebral tissues when acquiring brain electrical signals, improve the signal fidelity, reduce the adhesion when heating up and reducing the adhesion when the brain electrical signals are acquired, realize benign stripping and avoid brain tissue damage;
according to the temperature-control adhesive hydrogel interface layer provided by the invention, through modification of the zwitterionic group, the ester group hydrophobic group and the catechol group, electrostatic bonds, hydrophobic interactions, schiff base, michael addition reactions and hydrogen bonds are respectively established with the surface of the cranium, so that the viscosity of the multichannel hydrogel electrode is remarkably improved;
the temperature-control adhesive hydrogel interface layer provided by the invention has excellent biocompatibility, and can realize long-time brain electrical monitoring without causing brain tissue inflammatory reaction.
According to the scheme, the temperature-control viscous hydrogel porous microsphere is formed by coating a conductive polymer coating outside a hydrogel base sphere and grafting a grafting chain containing catechol groups, wherein the hydrogel base sphere is a poly-N-isopropyl acrylamide/carboxyl microsphere.
According to the scheme, the stretchable conductive layer integrated with the inner circuit and the electrodes comprises a plurality of electrodes, the inner circuit is branched, and the plurality of electrodes are arranged at the branch ends of the inner circuit; the temperature-control viscous hydrogel interface layer comprises a plurality of temperature-control viscous hydrogel sheets which are respectively in one-to-one correspondence with the electrodes, and the temperature-control viscous hydrogel sheets are respectively covered on the corresponding electrodes.
The invention improves the resolution ratio of brain electrical signal detection by integrating the multichannel electrode array, has excellent flexibility and stretchability, can realize environment-friendly attachment with the surface of intracranial brain tissue, and improves the anti-motion artifact capability of the temperature control adhesive multichannel hydrogel electrode.
According to the scheme, the materials of the flexible substrate layer and the flexible packaging layer are Polydimethylsiloxane (PDMS).
According to the scheme, in the components of the temperature-control adhesive hydrogel interface layer, the ammonium sulfonate zwitterionic monomer is one or more of methacryloyl ethyl Sulfobetaine (SBMA) or 3-dimethyl (methacryloyloxy ethyl) propanesulfonate (DMPS), the amide monomer is one or more of acrylamide, N-dimethylacrylamide monomer and derivatives thereof, the acrylate hydrophobic monomer is one or more of 2-phenoxyethyl acrylate, benzyl acrylate, 2- (2-phenoxyethoxy) ethyl acrylate, 2 (phenylsulfonyl) ethyl acrylate and 2-methoxyethyl acrylate, the crosslinking agent is one or more of N, N' -methylenebisacrylamide, poly (ethylene glycol) acrylate, and the initiator is one or more of alpha-ketoglutaric acid, irgacure2959, irgacure1173, ammonium Persulfate (APS) and potassium persulfate (KPS).
According to the scheme, in the temperature-control adhesive hydrogel interface layer, the mass fractions of the temperature-control adhesive hydrogel porous microspheres, the ammonium sulfonate zwitterionic monomer, the amide monomer, the acrylate hydrophobic monomer, the initiator and the cross-linking agent are respectively 10 wt-30 wt%, 10 wt-15 wt%, 15 wt-25-wt%, 5 wt-10 wt%, 0.01 wt-0.05 wt%, 0.02 wt-0.1 wt%, and the balance of water.
According to the scheme, the poly N-isopropyl acrylamide/carboxyl microsphere is obtained by inverse emulsion polymerization of N-isopropyl acrylamide monomer and carboxyl macromolecular chain, and the conductive macromolecular coating is any one or more of PEDOT PSS, polypyrrole, polyaniline and derivatives thereof.
According to the scheme, the N-isopropyl acrylamide monomer is one or more of N-isopropyl acrylamide monomer and derivatives thereof, and the carboxyl macromolecular chain is one or more of polyaspartic acid, polylysine, alginic acid, transparent methacrylic acid and derivatives thereof; the grafting chain containing catechol group is any one or more of dopamine and its derivatives.
According to the scheme, the mass fractions of the N-isopropyl acrylamide monomer, the carboxyl macromolecular chain, the conductive macromolecular coating and the grafting chain containing catechol groups in the temperature-control viscous hydrogel porous microsphere are respectively 15 wt-20 wt%, 2.5 wt-5 wt%, 10 wt-15 wt% and 5 wt-10 wt%.
According to the scheme, the preparation method of the temperature-control viscous hydrogel porous microsphere comprises the following steps:
s1, dissolving 10-30 mmol of N-isopropyl acrylamide monomer and 2-5 mmol of carboxyl macromolecular chain in a mixed solution of deionized water and cyclohexane, magnetically stirring until the solution is uniformly mixed, and then degassing for 0.5-1h, wherein the volume ratio of the deionized water to the cyclohexane in the mixed solution is 1: 1-8.
S2, sequentially adding APS with mass fractions of 0.02-0.04 and wt% and TEMED accelerator with mass fractions of 0.001-0.005 and wt% into the solution, magnetically stirring, fully polymerizing to obtain the poly N-isopropyl acrylamide/carboxyl microsphere, and centrifugally washing for later use.
S3, adding the poly N-isopropyl acrylamide/carboxyl microsphere into a solution containing 50-100ml of conductive molecular monomers, magnetically stirring uniformly, sequentially adding APS with mass fractions of 0.02-0.04 wt% and TEMED accelerator with mass fractions of 0.001-0.005 wt% into the solution, magnetically stirring fully, polymerizing to obtain the conductive polymer coating modified poly N-isopropyl acrylamide/carboxyl microsphere, and centrifugally washing for later use, wherein the mass fraction of the conductive molecular monomers is 5-10 wt%.
S4, dissolving the conductive polymer coating modified poly N-isopropyl acrylamide/carboxyl microsphere in deionized water, adding 5-15 mmol of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and 5-15 mmol of N-hydroxy thiosuccinimide, magnetically stirring, mixing and degassing.
S5, slowly dissolving 5-15 mmol of catechol group-containing monomer into the solution, sealing and fully stirring for 12 hours, dialyzing and freeze-drying to obtain the catechol group grafted chain modified temperature-controlled viscous hydrogel porous microsphere.
According to the scheme, the conductive molecular monomer is one or more of EDOT, PSS, pyrrole and aniline.
In a second aspect, the invention provides a method for preparing the temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring, which comprises the following steps:
s1, spin-coating polydimethylsiloxane prepolymer liquid on glass, fully reducing to be diffused, and curing in an oven to complete preparation of a flexible substrate layer;
s2, peeling the flexible substrate layer from the glass, attaching a PVC mask layer, obtaining a multi-channel electrode array pattern through laser engraving, adopting a screen printing process to realize patterning preparation of the stretchable conducting layer on the flexible substrate layer, and sputtering gold to obtain an electrode after the flexible substrate layer is placed in an oven to be cured;
s3, stripping the PVC mask from the flexible substrate layer, and bonding the flexible packaging layer after grafting hydroxyl on the flexible substrate layer through oxygen plasma treatment;
s4, dropwise adding a benzophenone solution into the flexible device, injecting a temperature-control viscous hydrogel premix, removing a die after ultraviolet curing for one hour to obtain a temperature-control viscous multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring, wherein the temperature-control viscous hydrogel premix is prepared by dissolving temperature-control viscous hydrogel porous microspheres, an amide monomer ammonium sulfonate zwitterionic monomer, an amide monomer, an acrylate hydrophobic monomer, an initiator and a crosslinking agent in water, and stirring and dissolving.
The preparation method has simple process and high preparation efficiency.
Drawings
FIG. 1 is a three-dimensional schematic diagram of a temperature-controlled adhesive multichannel hydrogel electrode for intracranial electroencephalogram monitoring in example 1 of the present invention;
FIG. 2 is a schematic diagram of a manufacturing process of a temperature-controlled adhesive multichannel hydrogel electrode for intracranial electroencephalogram monitoring in embodiment 2 of the invention;
FIG. 3 is a flow chart of the preparation of temperature-controlled adhesive multichannel hydrogel microspheres for intracranial electroencephalogram monitoring in example 1 of the present invention;
FIG. 4 is a schematic diagram of an interfacial layer of a temperature-controlled adhesive hydrogel of the temperature-controlled adhesive multichannel hydrogel electrode for intracranial electroencephalogram monitoring in example 1 of the present invention;
FIG. 5 is a schematic diagram of the viscosity control of a temperature-controlled viscosity multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to the invention;
FIG. 6 is a schematic illustration of a temperature controlled adhesive multichannel hydrogel electrode monitoring for intra-operative intracranial electroencephalogram monitoring according to the present invention;
fig. 7 is a graph of temperature-controlled viscosity multichannel hydrogel electrode brain electrical monitoring signals for intra-operative intracranial brain electrical monitoring in example 2 of the present invention.
In the figure, 1 is a temperature-control adhesive hydrogel interface layer, 1-1 is poly N-isopropyl acrylamide-polyaspartic acid-PEDOT/PSS-dopamine (PPD) hydrogel microsphere, 1-2 is a poly 3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (PDMPS) molecular chain, 1-3 is a poly N, N-dimethyl acrylamide (PDMAA) molecular chain, and 1-4 is poly methoxyethyl acrylate(PMEA) molecular chain, 1-5 is H 2 O,2 is a flexible packaging layer, 3 is a stretchable conducting layer, 3-1 is an ECC conducting composite material, 3-2 is an Au coating, 4 is a flexible substrate layer, 5 is glass, 6 is a PVC mask layer, and 7 is a benzophenone solution; 8 is a polymethyl methacrylate (PMMA) mold, 9 is a glass stirring rod, 10 is a beaker, 11 is an N-isopropyl acrylamide-polyaspartic acid prepolymer solution, 12 is a three-necked flask, 13 is a magnetic stirrer, 14 is a magneton, 15 is a centrifuge tube, 16 is a poly-N-isopropyl acrylamide-polyaspartic acid (PNIPAM-PASP) microsphere, 17 is an oscillator, 18 is a 3, 4-ethylenedioxythiophene/polystyrene sulfonate (EDOT/PSS) prepolymer solution, 19 is a poly-N-isopropyl acrylamide-polyaspartic acid-PEDOT/PSS (PP) hydrogel microsphere, 20 is a centrifuge, 21 is a separating funnel, 22 is a dopamine hydrochloride (DA) -1-ethyl- (3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) solution, 23 is a freeze dryer, 24 is a temperature-controlled viscous porous hydrogel microsphere, 25 is a hydrogen bond, 26 is an electrostatic coupling, 27 is a physical cross-linking, 29 is a covalent cross-linking, 30 is a hydrophobic interaction, 30 is a hydration layer, 31 is a brain electrical signal layer, 32 is a brain electrical signal, and 34 is a skin-controlled-size electrode, and a commercial skin tissue is a multichannel collecting electrode is 35.
Detailed Description
The principles and features of the present invention are described below with reference to the drawings and specific embodiments, the examples being provided for illustration only and not for the purpose of limiting the invention.
Example 1
As shown in fig. 1 and 4, the embodiment provides a temperature-controlled adhesive multi-channel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring, which comprises a flexible basal layer 4, a flexible packaging layer 2, a temperature-controlled adhesive hydrogel interface layer 1 and a stretchable conducting layer 3 integrated with an internal circuit and an electrode, wherein the flexible basal layer 4 and the flexible packaging layer 2 are jointly constructed to form a flexible frame main body, the stretchable conducting layer 3 is arranged in the flexible frame main body, the electrode extends out of the flexible main body frame through a window on the flexible packaging layer 2, and the temperature-controlled adhesive hydrogel interface layer 1 is arranged on the flexible packaging layer 2 and covers the electrode for adhering with intracranial brain tissues; the components of the temperature-control adhesive hydrogel interface layer 1 comprise temperature-control adhesive hydrogel porous microspheres, ammonium sulfonate zwitterionic monomers, amide monomers, acrylate hydrophobic monomers, an initiator and a cross-linking agent, and the components are polymerized by ultraviolet initiation to form the temperature-control adhesive hydrogel interface layer; the viscosity of the temperature-control viscous hydrogel interface layer changes at different temperatures, and seamless integration and benign stripping of the temperature-control viscous hydrogel interface layer and craniocerebral tissues can be realized through temperature control.
The method of using the multichannel hydrogel electrode of this embodiment is shown in fig. 5: in the intracranial electroencephalogram monitoring process, the temperature-control adhesive multichannel hydrogel electrode 32 is attached to the surface of the intracranial brain tissue 33, and after the temperature-control adhesive microsphere 1-1 in the temperature-control adhesive hydrogel interface layer absorbs interface tissue fluid, chemical adhesion and physical adhesion are established with the brain tissue, so that seamless integration is realized. After the electroencephalogram signals are collected, the temperature is raised, the viscous hydrogel interface layer 1 is controlled by temperature, a hydration layer 30 is generated, the chemical adhesion and physical adhesion of the interface are reduced, and finally benign stripping is realized.
The temperature-control adhesive hydrogel interface layer 1 is heated to 38-42 ℃ to realize benign stripping of the cranium brain tissue. The temperature-rising phase change of the temperature-control viscous hydrogel interface layer is realized by the existing heating mode of an external heating source, for example, a copper foil heat-conducting layer is adopted for heating, after the electroencephalogram signals are collected, the copper foil heat-conducting layer is attached above the flexible basal layer of the multichannel hydrogel electrode to heat the whole multichannel hydrogel electrode, so that the temperature-control viscous hydrogel interface layer is heated and peeled off from cranium brain tissues; the adhesive hydrogel interface layer may also be warmed by other means of radiant heating.
When the temperature of the temperature-control adhesive hydrogel interface layer is reduced, N-isopropyl acrylamide molecular chains wound in the temperature-control adhesive hydrogel porous microspheres are in a hydrophilic state, the temperature-control adhesive hydrogel porous microspheres absorb water rapidly, and ammonium sulfonate zwitterionic molecular chains, olefinic acid ester hydrophobic chains and catechol groups in the temperature-control adhesive hydrogel porous microspheres respectively establish electrostatic bonds, hydrophobic interactions, schiff bases, michael addition reactions and hydrogen bonds with the surface of the cranium, so that the temperature-control adhesive hydrogel interface layer and the cranium tissue can be bonded in a seamless integrated manner; after electroencephalogram collection in operation is completed, the temperature is raised, the temperature-control viscous hydrogel interface layer is heated, N-isopropyl acrylamide molecular chains wound in the temperature-control viscous hydrogel porous microspheres are subjected to phase change and are in a hydrophobic state, the temperature-control viscous hydrogel porous microspheres are rapidly dehydrated to generate an interface hydration layer, electrostatic bonds, hydrophobic interactions, schiff bases, michael addition reactions and hydrogen bonds between the temperature-control viscous hydrogel interface layer and the surface of cranium are damaged, viscosity is reduced, and benign stripping of the temperature-control viscous multichannel hydrogel electrode is realized.
Preferably, the temperature-control viscous hydrogel porous microsphere 1-1 is formed by coating a conductive polymer coating outside a hydrogel base sphere and grafting a grafting chain containing catechol groups, wherein the hydrogel base sphere is a poly-N-isopropyl acrylamide/carboxyl microsphere;
in some preferred embodiments, the stretchable conductive layer integrated with the internal circuit and the electrodes includes a plurality of electrodes, the internal circuit being branched, the plurality of electrodes being disposed at branched ends of the internal circuit; the temperature-control viscous hydrogel interface layer comprises a plurality of temperature-control viscous hydrogel sheets which are respectively in one-to-one correspondence with the electrodes, and the temperature-control viscous hydrogel sheets are respectively covered on the corresponding electrodes. The stretchable conducting layer integrates a multi-channel electrode array, can improve the resolution of brain electrical signal detection, has excellent flexibility and stretchability, can realize conformal attachment with the surface of intracranial brain tissue, and improves the motion artifact resistance of the electrode.
Preferably, the stretchable conductive layer is obtained by sputtering gold on the EEC conductive composite.
The EEC conductive composite material is formed by cured conductive silver paste, wherein the conductive silver paste is formed by mixing micron-sized silver flakes and Polydimethylsiloxane (PDMS) in a ratio of 2:1.
Preferably, the material of the flexible substrate layer and the flexible encapsulation layer is Polydimethylsiloxane (PDMS).
According to the scheme, in the components of the temperature-control adhesive hydrogel interface layer, the ammonium sulfonate zwitterionic monomer is methacryloyl ethyl Sulfobetaine (SBMA) or 3-dimethyl (methacryloyloxy ethyl) ammonium propane sulfonate (DMPS), the amide monomer is any one or more of acrylamide, N-dimethylacrylamide monomer and derivatives thereof, the acrylate hydrophobic monomer is one or more of 2-phenoxyethyl acrylate (PEA), benzyl acrylate (BZA), 2- (2-phenoxyethoxy) ethyl acrylate (PDEA), 2 (phenylsulfonyl) ethyl acrylate (PSEA) and 2-methoxyethyl acrylate (MEA), the cross-linking agent is one or more of N, N' -methylenebisacrylamide, poly (ethylene glycol) acrylate (PEGDA), and the initiator is one or more of alpha-ketoglutaric acid, irgacure2959, irgacure1173, ammonium Persulfate (APS) and potassium persulfate (KPS).
According to the scheme, in the temperature-control adhesive hydrogel interface layer, the mass fractions of the temperature-control adhesive hydrogel porous microspheres, the ammonium sulfonate zwitterionic monomer, the amide monomer, the acrylate hydrophobic monomer, the initiator and the cross-linking agent are respectively 10 wt-30 wt%, 10 wt-15 wt%, 15 wt-25-wt%, 5 wt-10 wt%, 0.01 wt-0.05 wt%, 0.02 wt-0.1 wt%, and the balance of water.
According to the scheme, the poly N-isopropyl acrylamide/carboxyl microsphere is obtained by inverse emulsion polymerization of N-isopropyl acrylamide monomer and carboxyl macromolecular chain, and the conductive macromolecular coating is any one or more of PEDOT PSS, polypyrrole, polyaniline and derivatives thereof. The conductive polymer coating is polymerized by conductive molecular monomers, wherein the conductive molecular monomers are one or more of EDOT: PSS, pyrrole and aniline.
According to the scheme, the N-isopropyl acrylamide monomer is one or more of N-isopropyl acrylamide monomer and derivatives thereof, and the carboxyl macromolecular chain is one or more of polyaspartic acid, polylysine, alginic acid, transparent methacrylic acid and derivatives thereof; the grafting chain containing catechol group is any one or more of dopamine and its derivatives.
According to the scheme, the mass fractions of the N-isopropyl acrylamide monomer, the carboxyl macromolecular chain, the conductive macromolecular coating and the grafting chain containing catechol groups in the temperature-control viscous hydrogel porous microsphere are respectively 15 wt-20 wt%, 2.5 wt-5 wt%, 10 wt-15 wt% and 5 wt-10 wt%.
As shown in fig. 3, the embodiment also provides a preparation method of the temperature-controlled viscous hydrogel porous microsphere, which specifically comprises the following steps:
s1, dissolving 10-30 mmol of N-isopropyl acrylamide and 2-5 mmol of polyaspartic acid in a beaker 10 filled with 50-100ml of a mixed solution of deionized water and cyclohexane (the mass ratio of water to cyclohexane is 1:3), fully stirring for 10 min by using a glass stirring rod 9 until the solution is uniformly mixed, and degassing for 0.5-1h to obtain N-isopropyl acrylamide-polyaspartic acid prepolymer 11.
S2, adding the prepolymer 11 into a three-neck flask 12 for emulsion polymerization, fully stirring by a magnetic stirrer 13, wherein the rotating speed of a magnet 14 is 300-1000 r/min, sequentially adding APS (APS) with the mass fraction of 0.02-0.04 wt% and TEMED (terminal equipment) accelerator with the mass fraction of 0.001-0.005 wt%, fully magnetically stirring, and then polymerizing to obtain poly-N-isopropyl acrylamide/polyaspartic acid microspheres 16, loading the poly-N-isopropyl acrylamide/polyaspartic acid microspheres 16 into a 50 ml centrifuge tube, and fully oscillating and washing for 10 min by an oscillator 17 for later use.
S3, adding the poly N-isopropyl acrylamide/polyaspartic acid microsphere 16 into 50-100ml of solution 18 containing conductive molecular monomer EDOT: PSS, wherein the mass fraction of the conductive molecular monomer is 5-10 wt%, magnetically stirring uniformly, sequentially adding APS with the mass fraction of 0.02-0.04-wt% and TEMED accelerator with the mass fraction of 0.001-0.005 wt% into the solution, magnetically stirring fully, polymerizing to obtain the poly N-isopropyl acrylamide/carboxyl microsphere 19 modified by PEDOT: PSS coating, and centrifugally washing in a centrifuge 20 (rotating speed 10000, time 10-30 min) for later use.
S4, dissolving PEDOT (polyether-urethane-acrylate) PSS coating modified poly-N-isopropyl acrylamide/polyaspartic acid microsphere 19 in deionized water, preparing 5-15 mmol of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, 5-15 mmol of N-hydroxysulfosuccinimide and 5-15 mmol of Dopamine (DA) hydrochloride anchoring solution 22, magnetically stirring, mixing and degassing.
S5, slowly dripping the anchoring liquid 22 into the solution through a separating funnel 21, sealing and fully stirring for 12 hours, dialyzing to obtain 48-h fully swelling temperature-controlled viscous hydrogel porous microspheres, and further adding the fully swelling temperature-controlled viscous hydrogel porous microspheres into a freeze dryer 23 for fully freeze drying to obtain the temperature-controlled viscous hydrogel porous microspheres 24.
Example 2
As shown in fig. 2, the embodiment provides a method for preparing the temperature-controlled viscosity multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring, which comprises the following steps:
s1, sufficiently cleaning a glass 5 substrate by adopting a 100W ultrasonic cleaner for 20min, drying by nitrogen for 5min, spin-coating Polydimethylsiloxane (PDMS) prepolymer solution (the mass ratio of the prepolymer to the curing agent is 10:1), sufficiently standing and diffusing for 5min, and placing in an oven for curing at 90 degrees for 2h to finish the preparation of the flexible substrate layer 4.
S2, peeling the flexible substrate layer 4 from the glass 5 substrate, attaching a PVC mask layer 6 with the thickness of 0.2mm, and obtaining the multi-channel electrode array pattern by laser engraving (the power is 60W, and the speed is 40 mm/S). And patterning and preparing an ECC conductive composite material layer 3-1 on the PDMS substrate layer by adopting a screen printing process, placing the ECC conductive composite material layer in a 160-DEG oven for curing for 2 hours, and sputtering a gold coating 3-2 on the ECC conductive composite material layer by adopting a gold target magnetron sputtering method for 15 minutes to obtain the stretchable conductive layer 3.
S3, stripping the PVC mask layer 6 from the flexible substrate layer 4, grafting hydroxyl groups on the flexible substrate layer 4 through oxygen plasma treatment (125W, 2 min), and bonding the flexible packaging layer (PDMS packaging layer) 2 and carrying out 10N load lamination for 5min to realize seamless integration of the two layers.
S4, dropwise adding a 95% benzophenone solution 7 (the mass ratio of ethanol to benzophenone is 95:5) into the flexible device for 5min, injecting a temperature-control adhesive hydrogel prepolymerization solution, and removing the PMMA die 8 after 365nm ultraviolet curing for one hour to form a temperature-control adhesive hydrogel interface layer, thereby obtaining the temperature-control adhesive multichannel hydrogel electrode 32.
The temperature-control viscous hydrogel prepolymer is prepared by dissolving temperature-control viscous hydrogel porous microspheres, ammonium sulfonate zwitterionic monomers, amide monomers, olefinic acid ester hydrophobic monomers, an initiator and a crosslinking agent in water, and magnetically stirring until the components are completely dissolved.
The amide molecular chain is mainly poly N, N-dimethylacrylamide monomer (PDMAA) 1-3, the ammonium sulfonate zwitterionic molecular chain is mainly PDMPS1-2, the acrylate hydrophobic molecular chain is mainly poly 2-methoxy ethyl acrylate (PMEA) 1-4, the cross-linking agent is mainly PEGDA, and the initiator is alpha-ketoglutaric acid.
The structure of the formed temperature-control adhesive hydrogel interface layer is shown in figure 4, and is poly (N-isopropyl acrylamide) -dopamine-3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate-methoxyethyl acrylate (PDDM) hydrogel interface layer, wherein 1-1 is poly N-isopropyl acrylamide-polyaspartic acid-PEDOT/PSS-dopamine (PPD) hydrogel microsphere, 1-2 is poly 3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (PDMPS) molecular chain, 1-3 is poly N, N-dimethyl acrylamide (PDMAA) molecular chain, 1-4 is poly methoxyethyl acrylate (PMEA) molecular chain, and 1-5 is H 2 O。
As shown in fig. 5, the viscosity control mechanism of the temperature-controlled viscous hydrogel interface layer 1 is as follows: when the temperature of the temperature-control adhesive hydrogel interface layer 1 is reduced, the N-isopropyl acrylamide polymer chain 22 entangled in the temperature-control adhesive hydrogel porous microspheres 24 is in a hydrophilic state, the temperature-control adhesive hydrogel porous microspheres 24 absorb water rapidly, and the ammonium sulfonate zwitterionic polymer chain 1-2, the acrylic acid ester hydrophobic chain 1-4 and the catechol group 1-1 in the temperature-control adhesive hydrogel porous microspheres in the temperature-control adhesive hydrogel interface layer respectively establish an electrostatic bond 26, a hydrophobic interaction 29, schiff base, michael addition reaction and hydrogen bonds 25 with craniocerebral tissues to realize seamless integration with the craniocerebral tissues; after the electroencephalogram collection in the operation is completed, the temperature is raised, the temperature-control viscous hydrogel interface layer is heated, the phase change of the N-isopropyl acrylamide molecular chain 22 wound in the temperature-control viscous hydrogel porous microsphere is performed, the phase change is in a hydrophobic state, the temperature-control viscous hydrogel porous microsphere 24 is rapidly dehydrated to generate an interface hydration layer 30, the electrostatic bond 26, the hydrophobic interaction 29, the Schiff base and the Michael addition reaction between the temperature-control viscous hydrogel interface layer 1 and the cranium surface and the hydrogen bond 25 are damaged, the viscosity is reduced, and the benign stripping of the hydrogel electrode 32 is realized.
As shown in fig. 7, the temperature-controlled adhesive multi-channel hydrogel electrode 32 collects the electroencephalogram signal 35 with a larger amplitude and a higher signal-to-noise ratio, while the commercial electrode collects the electroencephalogram signal 34 with lower fidelity, so that the temperature-controlled adhesive multi-channel hydrogel electrode 32 exhibits significant advantages in intra-operative intracranial electroencephalogram monitoring.
The foregoing is only illustrative of the present invention and is not to be construed as limiting thereof, but rather as various modifications, equivalent arrangements, improvements, etc., within the spirit and principles of the present invention.
Claims (10)
1. The temperature-control adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring is characterized by comprising a flexible basal layer (4), a flexible packaging layer (2), a temperature-control adhesive hydrogel interface layer (1) and a stretchable conducting layer (3) integrated with an internal circuit and an electrode, wherein the flexible basal layer (4) and the flexible packaging layer (2) are jointly constructed to form a flexible frame main body, the stretchable conducting layer (3) is arranged in the flexible frame main body, the electrode extends out of the flexible main body frame through a window on the flexible packaging layer (2), and the temperature-control adhesive hydrogel interface layer (1) is arranged on the flexible packaging layer (2) and covers the electrode for adhering with intracranial brain tissues; wherein,
the components of the temperature-control adhesive hydrogel interface layer (1) comprise temperature-control adhesive hydrogel porous microspheres (1-1), ammonium sulfonate zwitterionic monomers, amide monomers, acrylate hydrophobic monomers, an initiator and a cross-linking agent, and the components are polymerized by ultraviolet initiation to form the temperature-control adhesive hydrogel interface layer (1);
the viscosity of the temperature-control viscous hydrogel interface layer (1) is changed at different temperatures, and seamless integration and benign stripping of the temperature-control viscous hydrogel interface layer and cranium tissues can be realized through temperature control.
2. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to claim 1, wherein the temperature-controlled adhesive hydrogel porous microsphere (1-1) is formed by coating a conductive polymer coating outside a hydrogel base sphere and grafting a grafting chain containing catechol groups, and the hydrogel base sphere is a poly-N-isopropyl acrylamide/carboxyl microsphere.
3. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to claim 1, wherein the stretchable conductive layer (3) integrating the inner circuit and the electrode comprises a plurality of electrodes, the inner circuit is branched, and a plurality of the electrodes are arranged at branched ends of the inner circuit; the temperature-control viscous hydrogel interface layer (1) comprises a plurality of temperature-control viscous hydrogel sheets which are respectively in one-to-one correspondence with the electrodes, and the temperature-control viscous hydrogel sheets are respectively covered on the corresponding electrodes.
4. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to claim 1, wherein the materials of the flexible substrate layer (4) and the flexible encapsulation layer (2) are polydimethylsiloxane.
5. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to claim 4, wherein the weight percentages of the temperature-controlled adhesive hydrogel porous microspheres, ammonium sulfonate zwitterionic monomers, amide monomers, acrylate hydrophobic monomers, initiators and cross-linking agents in the temperature-controlled adhesive hydrogel interface layer (1) are respectively 10 wt% -30 wt%, 10 wt% -15 wt%, 15 wt% -25 wt%, 5 wt% -10 wt%, 0.01 wt% -0.05 wt%, 0.02 wt% -0.1 wt%, and the balance of water, the ammonium sulfonate zwitterionic monomers are any one or more of methacrylamidestaine or 3-dimethyl (methacryloxyethyl) propanesulfonate, the amide monomers are any one or more of acrylamide, N-dimethylacrylamide monomers and derivatives thereof, the acrylate hydrophobic monomers are 2-phenoxyethyl acrylate, benzyl acrylate, 2- (2-phenoxyethoxy) acrylic acid, 2- (2-methoxy) ethyl acrylate and one or more of the cross-linking agents are any one or more of N, N-bis (methyl) acrylic acid and one or more of the acrylic acid, and the cross-linking agents are irgar-29-methyl (or more of the acrylic acid and the one or more of the acrylic acid and the p-methyl (29) and p-methyl) acrylic acid are irgar and the one or more of the acrylic acid and the p-methyl (p) and p-methyl) are used.
6. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to any one of claims 2 to 5, wherein the poly-N-isopropylacrylamide/carboxyl microsphere is obtained by inverse emulsion polymerization of N-isopropylacrylamide monomer and carboxyl macromolecular chain, and the conductive macromolecular coating is any one or more of PEDOT PSS, polypyrrole, polyaniline and derivatives thereof.
7. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to claim 6, wherein the N-isopropyl acrylamide monomer is one or more of an N-isopropyl acrylamide monomer and a derivative thereof, and the carboxyl macromolecular chain is any one or more of polyaspartic acid, polylysine, alginic acid, hyaluronic acid and a derivative thereof; the grafting chain containing catechol group is any one or more of dopamine and derivatives thereof.
8. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring according to claim 7, wherein the mass fractions of the N-isopropyl acrylamide monomer, the carboxyl macromolecular chain, the conductive macromolecular coating and the catechol group-containing graft chain in the temperature-controlled adhesive hydrogel porous microsphere are respectively 15 wt% -20 wt%, 2.5 wt% -5 wt%, 10 wt% -15 wt% and 5 wt% -10 wt%.
9. The temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring of claim 6, wherein the preparation method of the temperature-controlled adhesive hydrogel porous microsphere is as follows:
s1, dissolving 10-30 mmol of N-isopropyl acrylamide monomer and 2-5 mmol of carboxyl macromolecular chain in 50-100ml of mixed solution of deionized water and cyclohexane, magnetically stirring until the solution is uniformly mixed, and then degassing for 0.5-1h, wherein the volume ratio of the deionized water to the cyclohexane in the mixed solution is 1: 1-8;
s2, sequentially adding APS with mass fractions of 0.02-0.04 and wt% and TEMED accelerator with mass fractions of 0.001-0.005 and wt% into the solution, magnetically stirring, fully polymerizing to obtain poly-N-isopropyl acrylamide/carboxyl microsphere, and centrifugally washing for later use;
s3, adding the poly N-isopropyl acrylamide/carboxyl microsphere into 50-100ml of solution containing conductive molecular monomers, magnetically stirring uniformly, sequentially adding APS with mass fractions of 0.02-0.04 wt% and TEMED accelerator with mass fractions of 0.001-0.005 wt% into the solution, magnetically stirring fully, polymerizing to obtain the poly N-isopropyl acrylamide/carboxyl microsphere modified by a conductive polymer coating, and centrifugally washing for later use, wherein the mass fraction of the conductive molecular monomers is 5-10 wt%;
s4, dissolving the conductive polymer coating modified poly N-isopropyl acrylamide/carboxyl microsphere in deionized water, adding 5-15 mmol of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride and 5-15 mmol of N-hydroxy thiosuccinimide activated carboxyl, magnetically stirring, mixing and degassing;
s5, slowly dissolving 5-15 mmol of catechol group-containing monomer into the solution, sealing and fully stirring for 12 hours, dialyzing and freeze-drying to obtain the catechol group grafted chain modified temperature-controlled viscous hydrogel porous microsphere, centrifuging and washing, and then adding into a freeze dryer for fully freeze-drying.
10. The method for preparing the temperature-controlled adhesive multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring as recited in any one of claims 1 to 9, comprising the following steps:
s1, spin-coating a polydimethylsiloxane prepolymer solution on glass (5), fully stirring and diffusing, and placing the mixture in an oven for curing to finish the preparation of a flexible substrate layer (4);
s2, stripping the flexible substrate layer (4) from the glass (5), attaching a PVC mask layer, obtaining a multi-channel electrode array pattern through laser engraving, adopting a screen printing process to realize patterning preparation of the stretchable conductive layer on the flexible substrate layer, and sputtering gold to obtain the stretchable conductive layer after the flexible substrate layer is placed in an oven to be cured;
s3, stripping the PVC mask from the flexible substrate layer, and bonding the flexible packaging layer (2) after grafting hydroxyl on the flexible substrate layer through oxygen plasma treatment;
s4, dropwise adding a benzophenone solution into the flexible device, injecting a temperature-control viscous hydrogel premix, removing a die after ultraviolet curing for one hour to obtain the temperature-control viscous multichannel hydrogel electrode for intra-operative intracranial electroencephalogram monitoring, wherein the temperature-control viscous hydrogel premix is prepared by dissolving temperature-control viscous hydrogel porous microspheres, an amide monomer ammonium sulfonate zwitterionic monomer, an amide monomer, an acrylate hydrophobic monomer, an initiator and a crosslinking agent in water, and stirring and dissolving.
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