A bioelectronic interface based on acoustic field and preparation method thereof

Abstract

The present invention discloses a method for preparing a bioelectronic interface based on an acoustic field, comprising the following steps: (1) preparing a pre-curing solution of a conductive hydrogel bioelectronic interface, comprising a scaffold material and a conductive filler material, the two materials being mixed and having a neutral pH; (2) forming the conductive hydrogel bioelectronic interface, wherein the pre-curing solution prepared in step (1) is photocured and cross-linked into a hydrogel patch; (3) preparing an anchoring agent solution, wherein the anchoring agent solution is acidic; (4) applying an appropriate amount of the prepared anchoring agent solution to the surface of biological tissue, subjecting the anchoring agent solution to ultrasonic cavitation for a certain period of time, and then immediately covering the ultrasonically treated biological tissue region containing the anchoring agent solution with the hydrogel patch, thereby forming a bioelectronic interface based on an acoustic field. The bioelectronic interface prepared by the present invention has strong adhesion performance, controllable adhesion time and space, reversible adhesion, and appropriate water absorption and swelling characteristics.

Description

Technical Field

[0001] The present invention relates to the technical field of new biointerface materials, and in particular to a bioelectronic interface based on an acoustic field and a preparation method thereof. Background Art

[0002] The integration of humans and machines is becoming increasingly widespread in the biomedical field, and bioelectronic interfaces provide an effective means for human-machine interaction. Conductive hydrogels, by introducing conductive materials to enhance the mechanical and electrical properties of hydrogels, have been demonstrated to be promising interfacial bridging materials between biological tissues and machines. Therefore, bioelectronic interfaces based on conductive hydrogels are expected to become the most ideal human-machine interface, promoting the long-term, reliable, and efficient interaction between complex and powerful machines and humans into an everyday reality. For example, they are popular in areas such as drug delivery, tissue and organ repair, sensors and actuators (physiological signal recording, electrical stimulation), and soft material wearable devices.

[0003] Because conductive bioelectronic interfaces are often used in liquid and dynamic environments, their application presents challenges. For example, it is difficult to maintain seamless interface fusion in wet and dynamic environments. This hinders the formation of stable and tight mechanical and electronic coupling at the tissue-electronic interface, reducing the fidelity of electrical signal transmission.

[0004] In order to achieve strong adhesion at the conductive bioelectronic interface, many technical solutions have been proposed: chemical bonding (covalent bonding, ionic bonding, free radical polymerization, metal coordination bonding); interparticle interactions (hydrogen bonding, van der Waals forces, electrostatic interactions, cation-π interactions, π-π, hydrophobic interactions, host-guest interactions); molecular topology and physical entanglement; mechanical effects of micro-nanostructures (physical suction, interfacial fluid mechanics, mechanical interlocking). However, in practical applications, the following problems still arise: (1) The interface bridging material is easily corroded by water molecules and prone to adhesion failure. The main material of the bioelectronic interface has moderate water absorption and swelling properties in liquid environments such as blood, tissue fluid, and drugs, which is also not available in many existing technologies; (2) The disadvantage of the interface adhesion method based on physical effects is that the adhesion between the interfaces is weak and it is difficult to maintain conformity under dynamic conditions; (3) The disadvantage of the chemical bonding method is that the adhesion lacks controllability. When applied (such as the installation and removal of wearable devices or wound management patches), not only the adhesion strength needs to be controllable in time and space, but also the debonding performance needs to be controlled.

[0005] Therefore, there is an urgent need to provide a new type of acoustic field-based bioelectronic interface and its preparation method to solve the above problems. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a bioelectronic interface based on an acoustic field and a preparation method thereof, which has the advantages of strong adhesion performance, controllable adhesion time and space, reversible adhesion, and appropriate water absorption and swelling properties.

[0007] To solve the above technical problems, the present invention adopts a technical solution: providing a method for preparing a bioelectronic interface based on an acoustic field, comprising the following steps:

[0008] (1) Preparing a conductive hydrogel bioelectronic interface pre-curing solution: the pre-curing solution includes a scaffold material and a conductive filling material, wherein the scaffold material is a mixture of acrylamide AM and polyethylene glycol diacrylate PEGDA, and the two materials have a neutral pH;

[0009] (2) Conductive hydrogel bioelectronic interface formation: photocuring and cross-linking the pre-cured solution prepared in step (1) into a hydrogel patch;

[0010] (3) preparing an anchoring agent solution: the anchoring agent solution is acidic;

[0011] (4) Applying an appropriate amount of the prepared anchoring solution to the surface of the biological tissue, applying ultrasound to the anchoring solution for ultrasonic cavitation for a certain period of time, and then immediately covering the ultrasonically treated biological tissue area containing the anchoring solution with the hydrogel patch prepared in step (2), thereby forming a bioelectronic interface based on the acoustic field.

[0012] In a preferred embodiment of the present invention, the pre-curing solution further includes a photoinitiator, a light-blocking agent, and a dispersant.

[0013] Furthermore, the specific steps of preparing the conductive hydrogel bioelectronic interface pre-curing solution in step (1) include:

[0014] Dissolve acrylamide AM, polyethylene glycol diacrylate PEGDA, photoinitiator, light blocker, conductive material solution, and dispersant in deionized water, stir the mixture until a clear solution is obtained, and then use an ultrasonic cleaner to shake for five minutes;

[0015] Among them, the mass concentration of acrylamide is 12wt.% to 35wt.%; the mass concentration of polyethylene glycol diacrylate is 0.02wt.% to 0.002wt.%; the mass concentration of photoinitiator is 0.02wt.% to 0.08wt.%; the mass concentration of light-blocking agent is 0.002wt.% to 0.008wt.%; the mass concentration of conductive material solution with a specification of 10mg / ml is 0.002wt.% to 0.02wt.%; and the mass concentration of dispersant is 0.1wt.% to 2wt.%.

[0016] Furthermore, the photoinitiator is one or more of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, phenyl bis (2,4,6-trimethylbenzoyl) phosphine oxide, and Irgacure series photoinitiators.

[0017] Furthermore, the conductive filling material is one or more of carbon nanotubes, MXene, graphene, conductive polymers, and conductive metal particles.

[0018] In a preferred embodiment of the present invention, the anchoring agent solution further comprises one of a gelatin solution, a chitosan nanocrystal solution, and an aldehyde-functionalized cellulose nanocrystal solution.

[0019] In a preferred embodiment of the present invention, the specific steps of preparing the anchoring agent solution in step (3) include:

[0020] The anchoring agent powder is dissolved in a 1% Hac solution to prepare a 2% anchoring agent solution, and the solution is stirred with a glass rod until it is clear, and then ultrasonically shaken in an ultrasonic cleaning machine for five minutes.

[0021] In a preferred embodiment of the present invention, in step (4), the time and space of adhesion and the strength of adhesion are controlled by changing the parameters of applying ultrasonic waves.

[0022] Furthermore, the parameters include the distance between the ultrasonic probe and the tissue surface, the energy of the ultrasonic wave, the duration of applying the ultrasonic wave, and the location of selecting the ultrasonic wave and the anchor solution.

[0023] In order to solve the above technical problems, another technical solution adopted by the present invention is: to provide a bioelectronic interface prepared by the method for preparing a bioelectronic interface based on an acoustic field as described in any of the above items.

[0024] The beneficial effects of the present invention are as follows: the present invention provides a wet environment-usable bioelectronic interface with spatiotemporally controllable and reversible adhesion based on acoustic field viscosity enhancement, which has the following advantages:

[0025] (1) Adhesion enhancement. Enhances interfacial adhesion without the need for any chemical bond formation. Under the action of the acoustic field, a cavitation effect is formed with the surface of the biological tissue, pushing the anchor molecules deeper into the tissue and enhancing the adhesion between the interfaces.

[0026] (2) Wet adhesion is controllable and reversible in time and space. By changing the parameters of the ultrasonic wave application, the time and space of adhesion and the strength of adhesion can be controlled. Specifically, the distance between the ultrasonic probe and the tissue surface and the energy of the sound wave can control the degree of adhesion enhancement (adhesion force) and the spatial depth of adhesion. By choosing when to apply ultrasound and the location of the ultrasound wave and the anchor solution, the adhesion time and the two-dimensional space of adhesion enhancement can be controlled.

[0027] (3) Possessing appropriate water swelling properties. The material system of the bioelectronic interface contains hydrophilic functional groups hydroxyl and amino groups, and has a large porous structure, so it can provide appropriate swelling, which helps to quickly absorb blood, tissue exudates, and sweat. At the same time, it will not cause excessive swelling and volume expansion, which will cause mechanical stimulation to tissues and wounds.

[0028] Therefore, the novel bioelectronic interface described in the present invention has significant advantages, including strong adhesion performance, controllable adhesion time and space, reversible adhesion, and appropriate water absorption and swelling properties, and can be used in fields such as temperature or human motion monitoring. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 1 is a schematic diagram of the three-dimensional structure of a preferred embodiment of the bioelectronic interface prepared in Example 1 of the present invention;

[0030] Figure 2 is a performance schematic diagram of the bioelectronic interface;

[0031] Figure 3 This is a schematic diagram comparing the shear strength of the interface patch with and without ultrasonic action;

[0032] Figure 4 It is a schematic diagram of the relationship between the acoustic field action parameters and the adhesion strength of the interface patch;

[0033] Figure 5 is a schematic diagram of the swelling and absorption rate and volume expansion rate of the bioelectronic interface when immersed in phosphate buffered saline (PBS) and deionized water;

[0034] Figure 6 is a schematic diagram of physiological signals generated by real-time monitoring of finger and wrist area activities when the bioelectronic interface is applied to the finger and wrist;

[0035] Figure 7 Schematic diagram comparing the conductivity of different examples of the bioelectronic interface. DETAILED DESCRIPTION

[0036] The preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more precise definition of the protection scope of the present invention.

[0037] The embodiments of the present invention include:

[0038] Example 1:

[0039] A method for preparing a bioelectronic interface based on an acoustic field comprises the following steps:

[0040] (1) Preparing a conductive hydrogel bioelectronic interface pre-curing solution: The pre-curing solution includes a scaffold material and a conductive filler material. The scaffold material is acrylamide AM and polyethylene glycol diacrylate PEGDA. The conductive filler material is one or more of carbon nanotubes, MXene, graphene, conductive polymers, and conductive metal particles to ensure that the interface patch has good electrical properties. In this embodiment, the conductive filler material is MXene. The two materials are mixed and have a neutral pH of pH = 7. The specific steps include:

[0041] 3.5 g acrylamide (AM), 1 mg polyethylene glycol diacrylate (PEGDA), 5 mg phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (photoinitiator), 0.5 mg light blocker (UVAM-001) and 1 mg MXene (Ti3C2) solution (10 mg / ml) were added, and 0.1 g SDS (Sodium dodecyl sulfate) was dissolved in 10 ml of deionized water. The mixture was stirred until a clear solution was obtained, and then shaken in an ultrasonic cleaner for five minutes.

[0042] (2) Conductive hydrogel bioelectronic interface formation: photocuring and cross-linking the pre-cured solution prepared in step (1) into a hydrogel patch;

[0043] Select a suitable mold, apply a layer of anti-stick coating on the surface of the mold, and match the mold size with the required patch size (15mm wide × 40mm long). Pour the prepared pre-curing solution into the mold. The thickness of the pre-curing solution in the mold is about 2mm. Gently vibrate or use gas jet to remove bubbles in the pre-curing solution. Place the filled mold under ultraviolet light, start the ultraviolet light source, and set the exposure time to 20 minutes. During the exposure process under ultraviolet light, the pre-curing solution gradually solidifies into a patch shape. When the interface patch is completely cured, turn off the ultraviolet light source and remove the mold. Carefully remove the patch from the mold to avoid damaging the patch surface. This hydrogel is recorded as PAMS.

[0044] (3) Preparing an anchoring agent solution: The anchoring agent solution has a long molecular chain and is viscous. It can be a chitosan solution, a gelatin solution, a chitosan nanocrystal solution, or an aldehyde-functionalized cellulose nanocrystal solution. In this embodiment, chitosan is used as the anchoring agent. The anchoring agent solution needs to be acidic, with a pH of 5. The specific steps include:

[0045] A 2% chitosan solution was prepared by dissolving chitosan powder in a 1% HAc solution, stirring with a glass rod until clear, and then ultrasonically oscillating in an ultrasonic cleaner for five minutes. Chitosan acts as a suture between the hydrogel and the biological tissue, stitching the two existing networks together at the molecular scale.

[0046] (4) Apply an appropriate amount of the prepared anchoring agent solution to the surface of the biological tissue, and then use an ultrasonic transducer (20kHz) to apply ultrasound to the anchoring agent solution. Under the action of ultrasonic cavitation, the chitosan anchoring agent molecules are pushed deep into the tissue. Then, the hydrogel patch prepared in step (2) is immediately covered with the biological tissue area containing the anchoring agent solution that has been ultrasonically treated. This will trigger the gelation of the anchoring agent on the adhesion interface, that is, form a bioelectronic interface based on the acoustic field, such as Figure 1 shown.

[0047] Specific experimental plan: Fresh pig skin was used to simulate the surface of human tissue and organs, stored in a refrigerator at -20°C, and thawed at 5°C. To form enhanced bioadhesion, the anchoring agent solution was first applied to the tissue surface, and then the ultrasonic transducer was immersed in the chitosan solution for a certain period of time, usually for 1 minute, with an intensity of 120W cm -2 For in vivo tissue, ultrasound was applied intermittently, periodically turning it on for 4 seconds and then off for 4 seconds. Immediately after ultrasound exposure, the hydrogel interface was placed on top of the anchoring agent and ultrasound area, forming an acoustic field-based bioelectronic interface.

[0048] See Figure 2 The performance of the bioelectronic interface prepared by the preparation method described in Example 1 of the present invention was demonstrated by the following tests:

[0049] (1) Characterization of adhesion energy (characterization of interfacial adhesion)

[0050] The 180° lap shear test was performed using an Instron machine, using a force of 4 N to preload the joint to a size of 15 × 2.5 × 40 mm. 3 The measurements were performed on the hydrogel-tissue composites for more than 1 hour after the formation of the hydrogel-tissue composites. For the peel test, the hydrogel-tissue composites (15×2.5×40 mm) adhered with anchoring liquid were used. 3), a rigid polyethylene terephthalate (PET) film was attached to the outer surface of the specimen using Krazy glue to prevent axial deformation during the test. The free end of the tissue was fixed with a mechanical clamp, while the hydrogel interface patch was clamped and connected to the test element of the machine. Instron applied unidirectional tension while recording force and displacement, and the loading rate was kept constant at 0.5mm / s. Adhesion energy was calculated as the ratio of force to contact area of ​​the conjugate. Compared with the hydrogel-tissue conjugate prepared without ultrasonic treatment as the control group, the bioelectronic interface described in this patent has stronger adhesion. As Figure 3 As shown in the figure, the shear strength of the interface patch treated with ultrasound is much higher than that of the interface patch without ultrasound treatment.

[0051] (2) Adhesion reversibility (method for achieving reversible adhesion)

[0052] Because adhesion relies on the acid-base properties of the chitosan solution, the de-adhesion of the interface patch can be controlled using a phosphate buffer solution (alkaline). The specific method is as follows: the biological tissue-hydrogel composite is immersed in an alkaline phosphate buffer solution. As the pH increases, the interactions between the chitosan and the biological tissue-hydrogel interface are destroyed, such as hydrogen bonds, thereby achieving reversible control of adhesion.

[0053] (3) Adhesion spatiotemporal controllability

[0054] The adhesion between the bioelectronic interface and the tissue interface is controllable in time and space. Figure 4 As shown, Figure 4 (a) shows the relationship between ultrasound power of different powers and adhesion strength; as the ultrasound power applied to the anchor solution increases, the shear strength gradually increases. Figure 4 (b) shows the relationship between the spatial position of the ultrasound probe and the adhesion strength; as the distance between the ultrasound probe and the skin increases in the anchoring solution, the shear strength gradually decreases. Figure 4 (c) shows the relationship between ultrasound application time and adhesion strength. As the duration of ultrasound application in the anchoring solution increases, the shear strength gradually increases, with the rate of increase showing a slowing trend. The figure demonstrates that adhesion strength is correlated with ultrasound power, ultrasound spatial location, and ultrasound application time. To control the time and space of adhesion, simply adjust the ultrasound intensity, location, and duration.

[0055] (4) Hydrogel swelling experiment

[0056] The water absorption and swelling behavior of the hydrogel interface patch were investigated. The hydrogel interface patch was cut into rectangular blocks and their initial mass was measured using an electronic balance. The hydrogel samples were immersed in deionized water and phosphate buffer solution for 24 hours, respectively. The swollen hydrogels were removed at predetermined intervals (15 minutes, 12 hours, 20 hours, and 24 hours). The surface water of the hydrogel samples was removed using absorbent paper, and their weight was measured.

[0057] Where W S is the mass of the hydrogel after swelling, and W0 is the initial weight of the hydrogel sample.

[0058] Represented by, where l0 is the initial length of the hydrogel, w0 is the initial width of the hydrogel, Δl is the length change after the hydrogel swells, and Δw is the width change after the hydrogel swells.

[0059] The bioelectronic interface has appropriate water absorption and swelling behavior. After being soaked in phosphate buffer and deionized water, the mass of the hydrogel bioelectronic interface patch increased by about 50% after rapid water absorption for 15 minutes, and then swelled very quickly over the next 12 hours, and then the swelling and absorption rate gradually slowed down until it leveled off. Figure 5 (d) This is also reflected in the volume expansion, with a lateral expansion ratio of about 1.5, as shown in Figure 5 (f) The hydrogel's swelling ratio consistently reached between 2.5 and 3.5 after 24 hours, attributed to the abundant pores within the hydrogel interface patch and the abundant hydrophilic groups on the MXene surface. Appropriate swelling facilitates rapid absorption of blood and tissue exudates while minimizing excessive swelling and volume expansion, which could mechanically irritate tissues and wounds. This property provides a foundation for the interface patch's application in wound repair.

[0060] (5) Human motion sensing applications

[0061] Sensing tests of the sample hydrogels were conducted using a ChenHua CHI 660E electrochemical workstation, which was fixed to the human body surface, with electrodes connected to the workstation via wires. IT curves and impedance-time curves were obtained for the corresponding movements of the measured area at a voltage of 1V, with each movement repeated at least five times. The hydrogels prepared in this study can also be converted into electrodes for monitoring physiological electrical signals such as respiration and electrocardiogram.

[0062] Taking the bioelectronic interface as an example, which is used to monitor physiological signals generated by finger and wrist area activities in real time, the interface patch can experience strain as the interface deforms, causing corresponding resistance changes. The bioelectronic interface is connected to the finger joint to monitor bending movements at three angles: 30°, 60°, and 90°. Figure 6(i) As shown. This bioelectronic interface can accurately monitor the amplitude of finger movement, and the resistance will also change accordingly as the finger amplitude changes. In addition, similarly, this bioelectronic interface can be applied to the wrist, such as Figure 6 (j) shows the real-time monitoring of the physiological signals generated by the movement of the part. This also confirms that the bioelectronic interface can still be used for continuous, stable and accurate movement monitoring.

[0063] Example 2:

[0064] A method for preparing a bioelectronic interface based on an acoustic field comprises the following steps:

[0065] (1) Preparation of conductive hydrogel bioelectronic interface pre-curing solution:

[0066] 1.65 g acrylamide (AM), 0.27 mg polyethylene glycol diacrylate (PEGDA), 2.8 mg phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (photoinitiator), 0.28 mg light blocker (UVAM-001) and 1 mg MXene (Ti3C2) solution (10 mg / ml) were added, and 13.6 mg SDS (Sodium dodecyl sulfate) was dissolved in 10 ml of deionized water. The mixture was stirred until a clear solution was obtained, and then shaken in an ultrasonic cleaner for five minutes.

[0067] (2) Conductive hydrogel bioelectronic interface formation: photocuring and cross-linking the pre-cured solution prepared in step (1) into a hydrogel patch;

[0068] (3) Preparation of anchoring agent solution: In this embodiment, chitosan is used as the anchoring agent, and the anchoring agent solution needs to be acidic, with a pH of 4.5. The specific steps include:

[0069] A 2% chitosan solution was prepared by dissolving chitosan powder in a 1% Hac solution, stirring the solution with a glass rod until it was clear, and then ultrasonically vibrating the solution in an ultrasonic cleaning machine for five minutes.

[0070] (4) Apply an appropriate amount of the prepared anchoring solution to the surface of the biological tissue. Then, ultrasonic waves are applied to the anchoring solution using an ultrasonic transducer (20 kHz). Under the action of ultrasonic cavitation, the chitosan anchoring molecules are pushed deep into the tissue. The hydrogel patch prepared in step (2) is then immediately applied to the ultrasonically treated biological tissue area containing the anchoring solution. This triggers the gelation of the anchoring agent at the adhesion interface, thus forming an acoustic field-based bioelectronic interface.

[0071] Specific experimental plan: Fresh pig skin was used to simulate the surface of human tissue and organs, stored in a refrigerator at -20°C, and thawed at 5°C. To form enhanced bioadhesion, the anchoring agent solution was first applied to the tissue surface, and then the ultrasonic transducer was immersed in the chitosan solution for a certain period of time, usually for 1 minute, with an intensity of 120W cm -2 For in vivo tissue, ultrasound was applied intermittently, periodically turning it on for 4 seconds and then off for 4 seconds. Immediately after ultrasound exposure, the hydrogel interface was placed on top of the anchoring agent and ultrasound area, forming an acoustic field-based bioelectronic interface.

[0072] Example 3:

[0073] A method for preparing a bioelectronic interface based on an acoustic field comprises the following steps:

[0074] (1) Preparation of conductive hydrogel bioelectronic interface pre-curing solution:

[0075] 4.77 g acrylamide (AM), 2.7 mg polyethylene glycol diacrylate (PEGDA), 10.9 mg phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (photoinitiator), 1.1 mg light blocker (UVAM-001) and 1 mg MXene (Ti3C2) solution (10 mg / ml) were added, and 0.27 g SDS (Sodium dodecyl sulfate) was dissolved in 10 ml of deionized water. The mixture was stirred until a clear solution was obtained, and then shaken in an ultrasonic cleaner for five minutes.

[0076] (2) Conductive hydrogel bioelectronic interface formation: photocuring and cross-linking the pre-cured solution prepared in step (1) into a hydrogel patch;

[0077] (3) Preparation of anchoring agent solution: In this embodiment, chitosan is used as the anchoring agent, and the anchoring agent solution needs to be acidic, with a pH of 5.5. The specific steps include:

[0078] A 2% chitosan solution was prepared by dissolving chitosan powder in a 1% Hac solution, stirring the solution with a glass rod until it was clear, and then ultrasonically vibrating the solution in an ultrasonic cleaning machine for five minutes.

[0079] (4) Apply an appropriate amount of the prepared anchoring solution to the surface of the biological tissue. Then, ultrasonic waves are applied to the anchoring solution using an ultrasonic transducer (20 kHz). Under the action of ultrasonic cavitation, the chitosan anchoring molecules are pushed deep into the tissue. The hydrogel patch prepared in step (2) is then immediately applied to the ultrasonically treated biological tissue area containing the anchoring solution. This triggers the gelation of the anchoring agent at the adhesion interface, thus forming an acoustic field-based bioelectronic interface.

[0080] Specific experimental plan: Fresh pig skin was used to simulate the surface of human tissue and organs, stored in a refrigerator at -20°C, and thawed at 5°C. To form enhanced bioadhesion, the anchoring agent solution was first applied to the tissue surface, and then the ultrasonic transducer was immersed in the chitosan solution for a certain period of time, usually for 1 minute, with an intensity of 120W cm -2 For in vivo tissue, ultrasound was applied intermittently, periodically turning it on for 4 seconds and then off for 4 seconds. Immediately after ultrasound exposure, the hydrogel interface was placed on top of the anchoring agent and ultrasound area, forming an acoustic field-based bioelectronic interface.

[0081] The shear strength of Examples 1 to 3 was experimentally tested, and the shear strength of the interface patch obtained in Example 1 was measured to be 9.2 kPa under ultrasound; the shear strength of the interface patch obtained in Example 2 was measured to be 6.6 kPa under ultrasound; and the shear strength of the interface patch obtained in Example 3 was measured to be 5.2 kPa under ultrasound.

[0082] Example 4:

[0083] This example differs from Example 1 in that the anchoring agent solution is prepared differently: chitosan powder is dissolved in PBS to prepare a 2% chitosan solution, which is then stirred with a glass rod until clear and then subjected to ultrasonic vibration in an ultrasonic cleaner for five minutes. The remaining steps are identical to those in Example 1 and are not further described here.

[0084] Adhesion tests comparing the anchoring solutions provided in this example with those in Example 1 yielded the following data: The neutral chitosan solution, used as the anchoring solution, achieved a shear strength of 3 kPa between the bioelectronic interface and the biological tissue; the acidic chitosan solution, used as the anchoring solution, achieved a shear strength of 9.2 kPa. This indicates that the pH difference between the anchoring solution and the bioelectronic interface patch is crucial for strong adhesion.

[0085] Example 5: This example differs from Example 1 in that the anchoring agent solution prepared is different:

[0086] Gelatin powder was dissolved in 1% Hac solution to prepare 2% gelatin solution, and stirred with a glass rod until clear, and ultrasonically vibrated in an ultrasonic cleaning machine for 5 minutes. The remaining steps were the same as those in Example 1 and are not described here.

[0087] Example 6:

[0088] Chitosan nanocrystal powder was dissolved in 1% HaC solution to prepare 2% chitosan nanocrystal solution, stirred with a glass rod until clear, and ultrasonically vibrated in an ultrasonic cleaning machine for five minutes. The remaining steps were the same as in Example 1 and are not described here.

[0089] The shear strength of Examples 5 and 6 was experimentally tested, and it was found that when the anchoring agent solution was a gelatin solution, the shear strength of the bioelectronic interface patch measured under ultrasound was 5.5 kPa; when the anchoring agent solution was a chitosan nanocrystal solution, the shear strength of the bioelectronic interface patch measured under ultrasound was 6.2 kPa.

[0090] To facilitate the comparison of the adhesion of the bioelectronic interface patches prepared in the above examples, the shear strength data comparison table is as follows:

[0091] Example 1 2 3 4 5 6 Shear strength (kPa) 9.2 6.6 5.2 3 5.5 6.2

[0092] Example 7:

[0093] This embodiment differs from embodiment 1 in that a different conductive hydrogel bioelectronic interface pre-curing solution is prepared: 3.5 g acrylamide (AM), 1 mg polyethylene glycol diacrylate (PEGDA), 5 mg phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (photoinitiator), 0.5 mg light blocker (UVAM-001), and 1 mg MXene (Ti3C2) solution (10 mg / ml) are dissolved in 10 ml of deionized water. The mixture is stirred until a clear solution is obtained, and then shaken in an ultrasonic cleaner for five minutes. This is recorded as PAM1. The remaining steps are the same as those in embodiment 1 and are not repeated here.

[0094] Example 8:

[0095] This embodiment differs from Example 1 in that a different conductive hydrogel bioelectronic interface pre-curing solution is prepared: 3.5 g acrylamide (AM), 1 mg polyethylene glycol diacrylate (PEGDA), 5 mg phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (photoinitiator), 0.5 mg light blocker (UVAM-001), and 3 mg MXene (Ti3C2) solution (10 mg / ml) are dissolved in 10 ml of deionized water. The mixture is stirred until a clear solution is obtained, and then shaken in an ultrasonic cleaner for five minutes. This is recorded as PAM3. The remaining steps are the same as in Example 1 and are not repeated here.

[0096] The conductive hydrogel bioelectronic interface pre-curing solution prepared without adding conductive material and dispersant was used as the control group (PA). The performance of the bioelectronic interface conductivity of Examples 1, 7, and 8 was verified with the control group. Figure 7As shown, the preferred formula PAMS (ie, Example 1): adding 1 mg MXene and 0.1 g SDS to 1 mg PEGDA and 3.5 g AM can achieve the maximum conductivity, which is about 4E-4.

[0097] Throughout this specification, references to terms such as "one embodiment," "example," or "specific example" indicate that the specific features, structures, materials, or characteristics described in connection with that embodiment or example are included in at least one embodiment or example of the present invention. In this specification, schematic representations of these terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0098] The preferred embodiments of the present invention disclosed above are intended only to help illustrate the present invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the present invention to the specific embodiments described. Obviously, many modifications and variations are possible based on the content of this specification. These embodiments are selected and described in detail in this specification to better explain the principles and practical applications of the present invention, thereby enabling those skilled in the art to better understand and utilize the present invention. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing a bioelectronic interface based on an acoustic field, characterized in that: The following steps are involved: (1) Preparing a conductive hydrogel bioelectronic interface pre-curing solution: the pre-curing solution includes a scaffold material, a conductive filling material, a photoinitiator, a light-blocking agent, and a dispersant. The scaffold material is a mixture of acrylamide AM and polyethylene glycol diacrylate PEGDA, and the two materials have a neutral pH. The mass concentration of acrylamide is 12 wt.% to 35 wt.%; the mass concentration of polyethylene glycol diacrylate is 0.02 wt.% to 0.002 wt.%; the mass concentration of the photoinitiator is 0.02 wt.% to 0.08 wt.%; the mass concentration of the light-blocking agent is 0.002 wt.% to 0.008 wt.%; the mass concentration of the conductive filler is 0.002 wt.% to 0.02 wt.%, and the conductive filler is added in a 10 mg / ml solution; the mass concentration of the dispersant is 0.1 wt.% to 2 wt.%; The photoinitiator is one or more of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate, phenyl bis (2,4,6-trimethylbenzoyl) phosphine oxide, and Irgacure series photoinitiators; The conductive filling material is one or more of carbon nanotubes, MXene, graphene, conductive polymers, and conductive metal particles; The dispersant is sodium dodecyl sulfate SDS; (2) Conductive hydrogel bioelectronic interface formation: photocuring and cross-linking the pre-cured solution prepared in step (1) into a hydrogel patch; (3) preparing an anchoring agent solution: the anchoring agent solution is acidic and includes a chitosan solution; (4) Apply an appropriate amount of the prepared anchoring solution to the surface of the biological tissue, apply ultrasound to the anchoring solution for ultrasonic cavitation for a certain period of time, and then immediately cover the ultrasonically treated biological tissue area containing the anchoring solution with the hydrogel patch prepared in step (2), thereby forming a bioelectronic interface based on the acoustic field.

2. The method for preparing a bioelectronic interface based on an acoustic field according to claim 1, characterized in that: The specific steps of step (1) preparing the conductive hydrogel bioelectronic interface pre-curing solution include: Dissolve acrylamide AM, polyethylene glycol diacrylate PEGDA, photoinitiator, light-blocking agent, conductive filler material solution, and dispersant in deionized water, stir the mixture until a clear solution is obtained, and then vibrate it in an ultrasonic cleaner for five minutes.

3. The method for preparing a bioelectronic interface based on an acoustic field according to claim 1, wherein: The specific steps of preparing the anchoring agent solution in step (3) include: The anchoring agent powder is dissolved in a 1% HaC solution to prepare a 2% anchoring agent solution, and the solution is stirred with a glass rod until it becomes clear, and then ultrasonically shaken in an ultrasonic cleaning machine for five minutes.

4. The method for preparing a bioelectronic interface based on an acoustic field according to claim 1, wherein: In step (4), the time and space of adhesion and the strength of adhesion are controlled by changing the parameters of the applied ultrasonic action.

5. The method for preparing a bioelectronic interface based on an acoustic field according to claim 4, characterized in that: The parameters include the distance between the ultrasound probe and the tissue surface, the energy of the ultrasound, the duration of application of the ultrasound, and the location of the ultrasound and anchor solution.

6. A bioelectronic interface prepared by the method for preparing a bioelectronic interface based on an acoustic field according to any one of claims 1 to 5.

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