Reversible adhesive flexible electrode material based on zinc ion activation and preparation method and application thereof

Abstract

The invention relates to a reversible adhesive flexible electrode material based on zinc ion activation, which is characterized in that polydimethylsiloxane is used as a main chain, and functionalization capable of responding to metal ions is realized through sulfydryl-alkene click reaction and subsequent imidazolation modification. The invention also provides a preparation method and application of the electrode material. The elastomer material disclosed by the invention has remarkably enhanced adhesive force, and can be stably attached to the surfaces of soft tissues such as cerebral cortex and spinal cord; under the action of Zn or after a competitive ligand is introduced, the adhesive force is reduced, and mild stripping is realized. The material is simple in preparation process and excellent in biocompatibility, can be used for constructing a large-area flexible electrode, is suitable for acute and chronic nerve electrophysiological signal acquisition, and is particularly suitable for epilepsy lesion positioning and brain function research.

Description

Technical Field

[0001] This invention relates to the field of flexible electronic materials technology, and more specifically, to reversible adhesive flexible electrode materials based on zinc ion activation, their preparation methods, and applications. Background Technology

[0002] Electroencephalography (EEG) and spinal cord electrophysiological signal acquisition have important applications in areas such as epileptic focus localization, neural circuit research, and brain-machine interface (BMI). Traditional flexible electrodes typically rely on van der Waals forces or physical adhesion to tissue surfaces, resulting in limited adhesion, unstable contact, and a tendency for signal loss. Furthermore, some existing materials that enhance adhesion rely on ultraviolet light, heating, or chemical cross-linking triggers, but these methods are not suitable for the in vivo microenvironment and pose potential biosafety risks. Metal ions (such as Zn²⁺) are naturally present in vivo and exhibit good biocompatibility. Controllable and reversible adhesion behavior can be achieved using metal-ligand complexation, but there are currently no flexible electrode material systems built based on this mechanism.

[0003] Chinese patent document CN120754436A discloses a multi-level self-anchored flexible deep brain stimulation electrode and its preparation method, belonging to the field of medical device technology. It employs a biomimetic root-octopus tentacle composite structure of "main electrode base - secondary fractal arm - tertiary self-anchoring end," integrating intelligent materials such as carbon nanotube / PDMS composite fiber, thermosensitive PNIPAMAm hydrogel, and biodegradable PLGA-gelatin composite material to construct a dual anchoring mechanism of mechanical locking and bio-fusion. The distributed electrode array includes platinum-iridium alloy, graphene / PDMS, and titanium nitride nanoelectrodes, achieving cross-scale stimulation from the nucleus level to the single-cell level. The intelligent control system addresses brain tissue displacement and chronic inflammation issues through pressure feedback degradation and flexible interconnection technology. This electrode has a 5-8 times larger contact area than traditional products, achieving stimulation precision at the single-cell level, and is suitable for long-term deep brain stimulation treatment of neurological diseases such as Parkinson's disease and epilepsy, demonstrating significant clinical application value.

[0004] Currently, there are no reports on reversible adhesive flexible electrode materials based on zinc ion activation. Summary of the Invention

[0005] The purpose of this invention is to provide a reversibly adhesive flexible spinal cord electrical stimulation electrode with biocompatibility, reversible adhesion, and large-area coverage, activated by zinc ions, and its preparation method, so as to realize multi-channel, large-area, and reversible cortical or spinal cord electrical signal acquisition in vivo.

[0006] This invention proposes a reversible adhesive flexible PDMS electrode material triggered by Zn²⁺. Through simple molecular structure design and metal-ligand interaction, the electrode achieves reversible adhesion, which can quickly and stably adhere to the cerebral cortex or spinal cord surface, realize high-quality local field potential (LFP) signal acquisition, and can be gently peeled off through complexation reaction when needed.

[0007] The flexible spinal cord electrical stimulation electrode material provided by this invention is based on a PDMS backbone. The PDMS segments are functionalized via a thiol-olefin click reaction, introducing imidazole groups that can complex with Zn²⁺. Simultaneously, the crosslinking density is controlled by adjusting the molecular weight of the PDMS. This electrical stimulation electrode material exhibits rapidly enhanced adhesion in the presence of Zn²⁺, while the adhesion weakens upon removal of Zn²⁺ or the introduction of a complexing competitor, achieving reversible regulation.

[0008] In a first aspect, the present invention provides a reversible adhesive flexible electrode material based on zinc ion activation, wherein the reversible adhesive flexible electrode material is prepared by the following method:

[0009] Step 1: Dithiothreitol (DTT), dimethyl benzoate, and vinyl-terminated polydimethylsiloxane were prepolymerized and dispersed under a nitrogen atmosphere to obtain a silica gel mixture; after ultraviolet irradiation, a high-viscosity polyborosilane was obtained, denoted as PDMS-OH.

[0010] Step 2: Add PDMS-OH, vinylimidazole, and dimethyl benzoate, and prepolymerize and disperse under a nitrogen atmosphere to obtain a silica gel mixture, which is then irradiated with ultraviolet light to obtain PDMS-IM;

[0011] Step 3: Sputter the conductive circuit onto the PDMS-IM flexible substrate and encapsulate it with PDMS-IM to expose only the electrode sites, thus obtaining a reversible adhesive flexible electrode material.

[0012] As a preferred example, in the silica gel mixture described in step 1, the amount of dithiothreitol is 50-300 mg, the amount of benzoin dimethyl ether is 5-100 mg, the amount of vinyl-terminated polydimethylsiloxane is 1-10 g, and the ultraviolet irradiation time is 15-60 min.

[0013] As a preferred example, the vinyl-terminated polydimethylsiloxane described in step 1 has a molecular weight of 4 kg / mol to 50 kg / mol.

[0014] As a preferred example, in step 2, the PDMS-OH is 1-10g, the dimethyl benzoate is 5-100mg, and the vinylimidazole is 50-300mg; the ultraviolet irradiation time is 5-15min.

[0015] As a preferred example, the step 3 of sputtering the conductive circuit onto PDMS-IM involves first uniformly sputtering gold onto PDMS-IM, and then, as needed, coating other conductive materials or their dispersions to obtain a conductive composite electrode with a conductive network on its surface.

[0016] As a preferred example, the other conductive material mentioned in step 3 is any one of metal particles, metal wires, metal sheets, carbon nanomaterials, conductive polymers, or ceramic materials; the dispersion is any one of deionized water, ethanol, or tetrahydrofuran.

[0017] Secondly, this invention provides a method for preparing a reversible adhesive flexible electrode material based on zinc ion activation, the specific steps of which are as follows:

[0018] Step 1: Dithiothreitol (DTT), dimethyl benzoate, and vinyl-terminated polydimethylsiloxane were prepolymerized and dispersed under a nitrogen atmosphere to obtain a silica gel mixture; after ultraviolet irradiation, a high-viscosity polyborosilane was obtained, denoted as PDMS-OH.

[0019] Step 2: Add PDMS-OH, vinylimidazole, and dimethyl benzoate, and prepolymerize and disperse under a nitrogen atmosphere to obtain a silica gel mixture, which is then irradiated with ultraviolet light to obtain PDMS-IM;

[0020] Step 3: Sputter conductive circuits onto a PDMS-IM flexible substrate and encapsulate them with PDMS-IM to expose only the electrode sites, thus obtaining a reversible adhesive flexible electrode material.

[0021] As a preferred example, in the silica gel mixture described in step 1, the amount of dithiothreitol is 50-300 mg, the amount of benzoin dimethyl ether is 5-100 mg, and the amount of vinyl-terminated polydimethylsiloxane is 1-10 g; The ultraviolet irradiation time is 15-60 min. In step 1, the molecular weight of the vinyl-terminated polydimethylsiloxane is 4 kg / mol-50 kg / mol. In step 2, the amount of PDMS-OH is 1-10 g, the amount of benzoin dimethyl ether is 5-100 mg, and the amount of vinylimidazole is 50-300 mg. The ultraviolet irradiation time is 5-15 min. In step 3, the conductive circuit is sputtered onto PDMS-IM. First, gold is uniformly sputtered onto PDMS-IM, and then other conductive materials or their dispersions are coated as needed to obtain a conductive composite electrode with a conductive network on the surface. The other conductive materials in step 3 are any one of metal particles, metal wires, metal sheets, carbon nanomaterials, conductive polymers, or ceramic materials. The dispersion is any one of deionized water, ethanol, or tetrahydrofuran.

[0022] Thirdly, this invention provides the application of zinc ion-activated reversible adhesive flexible electrode material in electrode fabrication.

[0023] As a preferred example, the electrode is a flexible spinal cord electrical stimulation electrode used for acquiring neurophysiological signals.

[0024] The advantages of this invention are:

[0025] (1) Bio-friendly triggering method: Zn²⁺ is a naturally occurring ion in the body, avoiding additional light sources or heating steps.

[0026] (2) Simple molecular design: PDMS chain segment functionalization is achieved through two-step reaction without the need for complex synthesis.

[0027] (3) Strong reversible adhesion: Metal ion complexation provides adjustable adhesion force, which is suitable for in vivo reversible electrode applications.

[0028] (4) Large area coverage capability: Flexible materials can conformally contact the brain sulci and gyri, improving the stability of signal acquisition.

[0029] (5) Suitable for acute and chronic experiments: The material is soft and biocompatible, and can be used to fabricate electrodes of different sizes.

[0030] The zinc ion-activated flexible electrode material provided by this invention can be used for rapid and stable adhesion to the cerebral cortex or spinal cord surface, achieving high-quality local field potential (LFP) signal acquisition, and can be gently peeled off through a complexation reaction when needed. The material of this invention is based on a PDMS backbone, and the PDMS segments are functionalized through a thiol-olefin click reaction to introduce imidazole groups that can complex with Zn²⁺. Simultaneously, the crosslinking density and mechanical strength are controlled by the molecular weight of PDMS. The material exhibits rapidly enhanced adhesion in the presence of Zn²⁺, while the adhesion weakens upon removal of Zn²⁺ or the introduction of a complexation competitor, achieving reversible regulation. Attached Figure Description

[0031] Figure 1 These are schematic diagrams of the reaction for preparing PDMS-IM in Examples 1-8 and diagrams of the mechanism of reversible adhesion.

[0032] Figure 2 The images show the infrared spectra of the final product PDMS-IM from Examples 1-8. The spectra show that dithiothreitol, boric acid, and vinyl PDMS reacted successfully, generating a cross-linked structure using double bonds. Simultaneously, dithiothreitol and boric acid introduced a large number of hydroxyl groups.

[0033] Figure 3 This refers to the tensile strength of the flexible materials prepared in Examples 1-8. It can be seen that the hardness of the material can be adjusted by regulating the imidazole grafting degree and the molecular weight of the precursor.

[0034] Figure 4The adhesion strength between the flexible material prepared in Example 1 and the glass slide is significantly different from that of the glass slide with zinc ions. The adhesion strength between the sample with the same ratio and the glass slide with zinc ions decreases rapidly.

[0035] Figure 5 The electrode is made of the flexible material prepared in Example 1. After being implanted in mice, the impedance is more stable and the impedance decreases over time.

[0036] Figure 6 The flexible electrode obtained in Example 1 was applied to the epidural space of a mouse to record field potentials. This allowed for the recording of changes in field potential intensity and frequency during seizures in a mouse epilepsy model, which is of great significance for the study of the mechanism. Detailed Implementation

[0037] The present invention will be further described below with reference to the accompanying drawings and embodiments. It should be understood that these embodiments are illustrative and not intended to limit the scope of the invention. The implementation conditions used in the embodiments may be further adjusted depending on available resources. Implementation conditions not specified are typically standard experimental conditions.

[0038] Example 1

[0039] (1) Weigh 12 mg of dithiothreitol, 32 mg of benzoin dimethyl ether, and 5 g of vinyl-terminated polydimethylsiloxane and add them to the reaction flask. Purge with nitrogen and stir thoroughly to disperse the prepolymer completely, and obtain a silica gel mixture. The molecular weight of polydimethylsiloxane is 8 kg / mol.

[0040] (2) While stirring, the silica gel mixture obtained in step (1) was irradiated with ultraviolet light for 15 min to obtain PDMS-OH;

[0041] (3) Add 1-10 g of PDMS-OH, 5-100 mg of benzoin dimethyl ether and 50-300 mg of vinyl imidazole to a reaction flask, purge with nitrogen, stir thoroughly to disperse the prepolymer, and irradiate with ultraviolet light for 15-60 min to obtain imidazole-terminated long-chain silane, denoted as PDMS-IM.

[0042] (4) First, uniformly coat / sputter gold onto the PDMS-IM obtained in step (3), and then continue to coat other conductive materials or their dispersions as needed to obtain a conductive composite material electrode with a conductive network on the surface.

[0043] Example 2: Same as Example 1, but the molecular weight of the polydimethylsiloxane in step (1) is 4 kg / mol.

[0044] Example 3: Same as Example 1, but the mass of dithiothreitol and vinyl-terminated polydimethylsiloxane in step (1) is 24 mg and 5 g, respectively.

[0045] Example 4: Same as Example 1, but the ultraviolet irradiation time in step (2) is 35 min.

[0046] Example 5: Same as Example 1, but in step (3), the mass of boric acid and vinyl-terminated polydimethylsiloxane is 60 mg and 5 g, respectively.

[0047] Example 6: Same as Example 1, but in step (3), the weights of boric acid and vinyl-terminated polydimethylsiloxane are 240 mg and 5 g, respectively.

[0048] Example 7: Same as Example 1, but the conductive network solution in step (3) is a one-dimensional conductive material such as carbon nanotubes.

[0049] Example 8: Same as Example 1, but in step (3), the conductive material is replaced with two-dimensional conductive fillers such as graphene.

[0050] Figure 1 These are schematic diagrams of the reaction for preparing PDMS-IM in Examples 1-8 and diagrams of the mechanism of reversible adhesion.

[0051] Figure 2 The images show the infrared spectra of the final product PDMS-IM from Examples 1-8. The spectra show that dithiothreitol, boric acid, and vinyl PDMS reacted successfully, generating a cross-linked structure using double bonds. Simultaneously, dithiothreitol and boric acid introduced a large number of hydroxyl groups.

[0052] Figure 3 The tensile strength test results of the flexible materials prepared in Examples 1–8 are shown. The tensile strength tests were performed using an electronic universal testing machine. The samples were prepared as strips, subjected to uniaxial tension until fracture, and the stress-strain curves were recorded and the tensile strength calculated. Figure 3 As can be seen, by adjusting the grafting degree of the imidazole group and the molecular weight of the precursor, the tensile strength of the flexible material can be controlled within a certain range, thereby achieving adjustable soft and hard properties of the material.

[0053] Figure 4The adhesion strength test results between the flexible material prepared in Example 1 and different glass slides are shown. Specifically, the flexible material prepared in Example 1 was attached to ordinary glass slides and glass slides with zinc ions introduced on their surface, respectively. After standing for 10 minutes under the same contact area and contact pressure conditions, a peel test was performed using a tensile testing device. The maximum peel force generated during the peeling process was recorded and converted into the adhesion strength. The test results show that the adhesion strength between the flexible material and the glass slide with zinc ions is significantly reduced compared with that of ordinary glass slides, indicating that the introduction of zinc ions can effectively weaken the adhesion between the flexible material and the substrate.

[0054] Figure 5 The impedance changes of the flexible material prepared in Example 1 after it was fabricated into an electrode and implanted into mice are illustrated. Specifically, the flexible material was fabricated into an electrode structure and implanted into the dura mater of mice. Periodic impedance tests were performed on the implanted electrode using an LCR impedance meter, and the changes in electrode impedance over time were recorded. The test results show that the flexible electrode has relatively stable impedance characteristics in the in vivo environment, and the impedance decreases over time.

[0055] Figure 6 The results of field potential recording using the flexible electrode prepared in Example 1 in a mouse epilepsy model are shown. In the specific implementation, experimental mice C57 (8w) were fixed to a stereotaxic apparatus under anesthesia. First, a cannula was implanted at coordinates x = +2.3 mm, y = -2.8 mm, z = -1.0 mm relative to the anterior fontanelle (Bregma) for subsequent injection of epilepsy-inducing drugs. Subsequently, a craniotomy was performed in the mouse's somatosensory cortex region to create a cranial window approximately 4.6 mm × 4.6 mm in size.

[0056] The flexible electrode array prepared in Example 1 was attached to the exposed dura mater surface, ensuring full contact between the functional areas of the electrodes and the brain tissue. A glass slide was then placed over the electrodes, and the electrodes, slide, connector, and guide sleeve were fixed to the skull surface using dental resin to ensure the stability of the implanted structure. The epilepsy model was established by injecting an epilepsy-inducing drug into the guide sleeve, specifically injecting a 500 nL solution of 4-aminopyridine (4-AP) into the target brain region. After injection, electrophysiological signals were collected from the mice while they were in a free-moving state. The electrophysiological signals were recorded in real time using a data acquisition system connected to the flexible electrodes. During the epileptic seizure, typical time segments of the epileptic discharge phase were extracted from the complete recorded signals for analysis, and the amplitude changes and frequency characteristics of the field potential signals were processed and compared. Experimental results show that the flexible electrodes can stably record significant changes in the intensity and frequency of field potential signals during epileptic seizures in vivo, indicating that the flexible electrodes are suitable for in vivo neural signal monitoring and have important application value for research on epilepsy-related mechanisms.

[0057] In the above embodiments 2-8, the changes in material parameters illustrate that different parameter conditions can change the relative softness and hardness of the material, but will not change the material's essential properties. That is, no matter how the proportion changes (within a given range), the material can form bonds with the structure and also interact with the conductive gold particles on the surface. In this way, the adhesion is very tight and the surface circuit will not fall off, thus achieving the purpose of long-term stability.

[0058] The above embodiments are only for illustrating the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the content of the present invention and implement it accordingly. They should not be construed as limiting the scope of protection of the present invention. All equivalent transformations or modifications made in accordance with the spirit and essence of the present invention should be covered within the scope of protection of the present invention.

Claims

1. A reversible adhesive flexible electrode material based on zinc ion activation, characterized in that, The reversible adhesive flexible electrode material is prepared by the following method: Step 1: Dithiothreitol, benzoin dimethyl ether, and vinyl-terminated polydimethylsiloxane were prepolymerized and dispersed under a nitrogen atmosphere to obtain a silica gel mixture; after ultraviolet irradiation, a high-viscosity polyborosilane was obtained, denoted as PDMS-OH. Step 2: Add PDMS-OH, vinylimidazole, and dimethyl benzoate, and prepolymerize and disperse under a nitrogen atmosphere to obtain a silica gel mixture, which is then irradiated with ultraviolet light to obtain PDMS-IM; Step 3: Sputter the conductive circuit onto the PDMS-IM flexible substrate and encapsulate it with PDMS-IM to expose only the electrode sites, thus obtaining a reversible adhesive flexible electrode material.

2. The reversible adhesive flexible electrode material according to claim 1, characterized in that, In the silica gel mixture described in step 1, the amount of dithiothreitol is 50-300 mg, the amount of benzoin dimethyl ether is 5-100 mg, the amount of vinyl-terminated polydimethylsiloxane is 1-10 g, and the ultraviolet irradiation time is 15-60 min.

3. The reversible adhesive flexible electrode material according to claim 1, characterized in that, The vinyl-terminated polydimethylsiloxane described in step 1 has a molecular weight of 4 kg / mol to 50 kg / mol.

4. The reversible adhesive flexible electrode material according to claim 1, characterized in that, In step 2, the PDMS-OH is 1-10g, the dimethyl benzoate is 5-100mg, and the vinylimidazole is 50-300mg; the ultraviolet irradiation time is 5-15min.

5. The reversible adhesive flexible electrode material according to claim 1, characterized in that, Step 3, which involves sputtering the conductive circuit onto PDMS-IM, first uniformly sputters gold onto PDMS-IM, and then, as needed, continues to coat it with other conductive materials or their dispersions, thus obtaining a conductive composite electrode with a conductive network on its surface.

6. The reversible adhesive flexible electrode material according to claim 5, characterized in that, The other conductive materials mentioned in step 3 are any one of metal particles, metal wires, metal sheets, carbon nanomaterials, conductive polymers, or ceramic materials; the dispersion is any one of deionized water, ethanol, or tetrahydrofuran.

7. A method for preparing a reversible adhesive flexible electrode material based on zinc ion activation, characterized in that, The specific steps are as follows: Step 1: Dithiothreitol, benzoin dimethyl ether, and vinyl-terminated polydimethylsiloxane were prepolymerized and dispersed under a nitrogen atmosphere to obtain a silica gel mixture; after ultraviolet irradiation, a high-viscosity polyborosilane was obtained, denoted as PDMS-OH. Step 2: Add PDMS-OH, vinylimidazole, and dimethyl benzoate, and prepolymerize and disperse under a nitrogen atmosphere to obtain a silica gel mixture, which is then irradiated with ultraviolet light to obtain PDMS-IM; Step 3: Sputter conductive circuits onto a PDMS-IM flexible substrate and encapsulate them with PDMS-IM to expose only the electrode sites, thus obtaining a reversible adhesive flexible electrode material.

8. The preparation method according to claim 7, characterized in that, In the silica gel mixture described in step 1, the amount of dithiothreitol is 50-300 mg, the amount of benzoin dimethyl ether is 5-100 mg, and the amount of vinyl-terminated polydimethylsiloxane is 1-10 g. The ultraviolet irradiation time is 15-60 min. In step 1, the molecular weight of the vinyl-terminated polydimethylsiloxane is 4 kg / mol-50 kg / mol. In step 2, the amount of PDMS-OH is 1-10 g, the amount of benzoin dimethyl ether is 5-100 mg, and the amount of vinylimidazole is 50-300 mg. The ultraviolet irradiation time is 5-15 min. In step 3, the conductive circuit is sputtered onto PDMS-IM. First, gold is uniformly sputtered onto PDMS-IM, and then other conductive materials or their dispersions are coated as needed to obtain a conductive composite electrode with a conductive network on the surface. The other conductive materials in step 3 are any one of metal particles, metal wires, metal sheets, carbon nanomaterials, conductive polymers, or ceramic materials. The dispersion is any one of deionized water, ethanol, or tetrahydrofuran.

9. The application of the zinc ion-activated reversible adhesive flexible electrode material according to any one of claims 1-6 in the preparation of electrodes.

10. The application according to claim 9, characterized in that, The electrode is a flexible spinal cord electrical stimulation electrode used for acquiring neurophysiological signals.

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