Flexible wireless biological interface based on hydrogel and liquid metal and preparation method thereof

Abstract

The invention relates to a flexible wireless biological interface based on hydrogel and liquid metal and a preparation method, and belongs to the field of bioelectronics. The flexible wireless biological interface comprises a hydrogel substrate, a middle circuit layer and a hydrogel packaging layer, is of a sandwich structure and is applied to a cardiac pacemaker, and the manufacturing process comprises the steps that a hydrogel precursor solution is poured into a template to manufacture the hydrogel substrate and the packaging layer; preparing printing conductive ink; printing a liquid metal circuit pattern on the hydrogel substrate by using a template printing method; placing the components at the corresponding circuit positions, and dropwise adding liquid metal at the pin positions of the components; a nickel layer is pasted at the tail end of the circuit to serve as a stimulation output interface; and packaging a circuit by using the hydrogel packaging layer to prepare the flexible wireless cardiac pacemaker based on the hydrogel and the liquid metal. According to the invention, a liquid metal circuit is printed at one time by using a template printing technology, and a bioelectronic device can be manufactured on a hydrogel substrate.

Description

Technical Field

[0001] The present invention relates to the technical field of bioelectronics, and in particular to a flexible wireless bio-interface based on hydrogel and liquid metal and a preparation method thereof. Background Art

[0002] With the prevalence of heart disease, pacemakers are gaining attention for treating arrhythmias. Traditional pacemakers, due to their rigid electrodes and external power supply, increase the risk of infection. Mechanical mismatches can damage tissue and lead to functional failure. Long-term use also poses risks such as infection and battery depletion, causing discomfort and risks for patients. Therefore, the development of flexible, wireless, and biocompatible pacemakers has become a research hotspot.

[0003] Hydrogels, composed of a network of cross-linked polymer chains, exhibit excellent biocompatibility and flexibility, holding great promise in the biomedical field. They are stable in biological environments, maintain close contact with tissues, and minimize implant trauma and immune responses. Their mechanical properties can be tailored to suit different tissues and organs, but their low electrical conductivity limits their application in biosensors.

[0004] Liquid metal is liquid at room temperature, soft and self-healing. Its self-healing property makes soft electronic devices resistant to damage and is widely used in the field of soft electronics. Liquid metal also has high biocompatibility and is safe and reliable for use in medical electronics and biomedical equipment.

[0005] Therefore, the application of hydrogels and liquid metals brings new possibilities for improving pacemaker technology. Combining the characteristics of the two can develop safer, more reliable, and more comfortable pacemakers, providing effective treatment for heart patients and reducing the complications and discomfort of traditional models. Summary of the Invention

[0006] The purpose of the present invention is to provide a flexible wireless cardiac pacemaker based on hydrogel and liquid metal and a preparation method thereof, using a simple template printing technology to obtain a stretchable circuit pattern on the soft hydrogel to solve the current problems of insufficient mechanical matching between implantable bioelectronic devices and biological tissues, insufficient circuit stretchability and insufficient device biocompatibility.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: a flexible wireless biointerface based on hydrogel and liquid metal, applied to a pacemaker, comprising a hydrogel encapsulation layer and an intermediate circuit layer;

[0008] The hydrogel encapsulation layer comprises a hydrogel base and a hydrogel encapsulation layer; an intermediate circuit layer is provided on the hydrogel base, and the intermediate circuit layer is encapsulated by the hydrogel encapsulation layer, so that the intermediate circuit layer is encapsulated between the hydrogel base and the hydrogel encapsulation layer;

[0009] The intermediate circuit layer includes a circuit pattern printed with conductive ink and a pacemaker circuit arranged on the circuit pattern; the conductive ink is nickel-doped eutectic gallium-indium alloy.

[0010] The pacemaker circuit includes a wireless energy transmission module, a pulse modulation circuit and a stimulation output interface connected in series;

[0011] The wireless energy transmission module uses a wireless charging receiving chip; the input end of the wireless charging receiving chip is connected to one end of the wireless coil through a first diode, and the other end of the wireless coil is grounded; a capacitor C1 is connected between the two ends of the wireless coil, and a capacitor C2 is connected between the input end of the wireless charging receiving chip and the ground; the output end of the wireless charging receiving chip is connected to the pulse modulation circuit;

[0012] The pulse modulation circuit uses a timer; the power input terminal of the timer is connected to the output terminal of the wireless charging receiving chip, and a capacitor C3 is connected between the low trigger terminal of the timer and the ground terminal; the output terminal of the timer serves as the output terminal of the circuit; the reset terminal of the timer is connected to the high trigger terminal of the timer through resistors R1 and R2 in sequence; the node between the resistors R1 and R2 is connected to the discharge terminal of the timer, and a series branch of a second diode and a third diode is further connected in parallel across the two ends of the resistor R2; the node between the second diode and the third diode is connected to the low trigger terminal of the timer; and the control voltage terminal of the timer is grounded through capacitor C4;

[0013] Stimulation output interface, connect the output end of the circuit to nickel tape to form a stimulation output interface.

[0014] The preparation method of a flexible wireless bio-interface based on hydrogel and liquid metal comprises the following steps:

[0015] (1) pouring a hydrogel polymer solution into a template and then UV curing the solution to obtain a hydrogel substrate;

[0016] (2) mixing and stirring the eutectic gallium-indium alloy and nickel powder to obtain a conductive ink;

[0017] (3) printing a liquid metal circuit pattern on a hydrogel substrate using a template printing method;

[0018] (4) After removing the template, the electronic components in the pacemaker circuit are placed on the corresponding circuit positions, and liquid metal is dripped at the pin positions of each component to ensure the formation between the component and the circuit;

[0019] (5) Paste a nickel layer on the output end of the circuit as a stimulation output interface;

[0020] (6) pouring the hydrogel polymer solution into the template and UV curing it to obtain a hydrogel encapsulation layer;

[0021] (7) The pacemaker circuit is encapsulated using a hydrogel encapsulation layer to prepare a flexible wireless cardiac pacemaker based on hydrogel and liquid metal.

[0022] The hydrogel substrate and the encapsulation layer are respectively formed by an in-situ free radical crosslinking copolymerization reaction of a reaction system consisting of acrylamide, alginate, N,N'-methylenebisacrylamide, ammonium persulfate, N,N,N'N'-tetramethylethylenediamine and water.

[0023] The reaction system of the hydrogel substrate and the encapsulation layer is obtained by the following steps:

[0024] At room temperature, acrylamide and alginate are dissolved in water and mixed to obtain a mixed solution, a crosslinking agent N,N'-methylenebisacrylamide and an initiator ammonium persulfate are added, and a catalyst N,N,N'N'-tetramethylethylenediamine is added, and the mixture is uniformly mixed to obtain a polymer solution; specifically,

[0025] Dissolve acrylamide in deionized water, place it on a blender, and stir it continuously at a temperature of 20-30°C and a rotation speed of 300-800 rpm for 5-60 minutes to obtain a 16-20 wt% acrylamide solution; dissolve alginate in deionized water, place it on a blender, and stir it continuously at a temperature of 20-30°C and a rotation speed of 500-1500 rpm for 6-12 hours to obtain a 3-5 wt% alginate solution; mix 4-6 mL of acrylamide solution and 3-5 mL of alginate solution, place it on a blender, and stir it at a temperature of 20-30°C and a rotation speed of 400-1000 rpm for 5-40 minutes to obtain a uniform composite solution; add 350-400 μL of N,N'-methylenebisacrylamide aqueous solution (0.1-0.3 g / 100 mL) and 95-110 μL of ammonium persulfate aqueous solution (0.1-0.3 mol / L) are stirred continuously at a temperature of 20-30°C and a rotation speed of 400-1000 rpm for 5-30 minutes; 3-8 μL of N,N,N'N'-tetramethylethylenediamine is added and stirred continuously at a temperature of 20-30°C and a rotation speed of 400-1000 rpm for 2-10 minutes to obtain a uniform polymer solution.

[0026] The hydrogel encapsulation layer is cured by ultraviolet polymerization, that is, irradiated under an ultraviolet lamp with a power of 120-500W and a wavelength of 312-365nm for 20-60 minutes.

[0027] The conductive ink is prepared by mixing a eutectic gallium-indium alloy consisting of 70-80 wt% gallium and 20-30 wt% indium and 30-80 nm nickel particles in a mass ratio of 95-98:5-2.

[0028] The conductive ink is obtained by sealing and stirring for 18-48 hours in an environment with a temperature of 20-30°C.

[0029] The pacemaker circuit has the following working process:

[0030] When the wireless coil generates an induced current, the induced current is rectified by capacitor C1, capacitor C2, the first switching diode and the wireless charging receiving chip, and the AC current is converted into a DC current to power the pulse modulation circuit;

[0031] The pulse modulation circuit switches the output high and low levels through the charge and discharge cycle of capacitor C3, and realizes self-oscillation by comparing with the internal threshold of the timer, thereby outputting periodic rectangular pulses.

[0032] The pacemaker circuit adjusts the pulse output frequency by adjusting the resistance in the pulse modulation circuit:

[0033]

[0034] T H =0.693×R1×C

[0035] T L =0.693×R2×C

[0036]

[0037] Where f represents the pulse frequency, T H Indicates the positive pulse width, T L represents the negative pulse width, R1 and R2 represent the resistance values ​​of resistor R1 and resistor R2 respectively, C represents the capacitance value of capacitor C3, and q represents the duty cycle.

[0038] The present invention has the following beneficial effects and advantages:

[0039] 1. The wireless bio-interface of the present invention adopts biocompatible hydrogel and flowable liquid metal, which can meet the biocompatibility, mechanical matching and circuit stretchability and bending with biological tissues, while realizing wireless energy transmission and reducing implant trauma.

[0040] 2. The wireless bio-interface and preparation method thereof of the present invention realize the preparation of high-precision wires through a template printing method, without relying on sophisticated instruments for complex processing.

[0041] 3. The solution of the present invention can solve the interfacial bonding problem between liquid metal and polyacrylamide-based hydrogel, and realize circuit design and component integration on polyacrylamide-based hydrogel.

[0042] 4. The present invention can realize device function integration, breaking through the limitation that similar devices in the prior art are mostly single-function strain stress sensors. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 Schematic diagram of the structure of a flexible wireless pacemaker based on hydrogel and liquid metal;

[0044] Figure 2 Schematic diagram of the present application integrating electronic components on a conductive circuit;

[0045] Figure 3 Schematic diagram of the hydrogel network segment structure of the present application;

[0046] Figure 4 Figure 3 Schematic diagram of the chemical structure of medium chain 101;

[0047] Figure 5 Figure 3 Schematic diagram of the chemical structure of medium chain 102;

[0048] Figure 6 Schematic diagram of the chemical structure between the hydrogel and the conductive ink in this application;

[0049] Figure 7 Photos of stretching and recovery after printing liquid metal on hydrogel;

[0050] Figure 8 Schematic diagram of the shape of the hydrogel substrate used in this application;

[0051] Figure 9 Schematic diagram of the present application after printing conductors with liquid metal;

[0052] Figure 10 A circuit diagram of the device of the present application;

[0053] Figure 11 Device electrical stimulation signal performance test diagram of this application.

[0054] In the figure: 1-Alginate-doped polyacrylamide (SA-doped PAAm) hydrogel; 101-Acrylamide (PAAm) polymer chain; 102-Polyacrylamide / sodium alginate polymer chain (PAAm / SA) polymer chain; 2-Wireless charging module; 3-Pulse modulation circuit; 4-Stimulation output interface; 401 nickel layer; 5-Alginate-doped polyacrylamide (SA-doped PAAm) hydrogel encapsulation layer; 6-Conductive ink; 7-Wireless receiving coil; 8-Chip capacitor; 9-Switching diode; 10-Wireless charging receiving chip; 11-Chip resistor; 12-Timer. DETAILED DESCRIPTION

[0055] In order to further illustrate the technical means and effects taken by the present invention to achieve the predetermined invention object, the present invention is described in detail below with reference to the examples. It should be understood that the following examples are only used to illustrate the present invention, not to limit the present invention.

[0056] A flexible wireless biointerface (pacemaker) based on hydrogel and liquid metal, comprising a sandwich structure comprising a hydrogel substrate, an intermediate circuit layer, and a hydrogel encapsulation layer. The circuit layer comprises a circuit pattern and electronic components printed with conductive ink; the conductive ink is nickel particle-doped eutectic gallium-indium alloy (EGaIn).

[0057] The hydrogel substrate and the encapsulation layer are formed by in-situ free radical cross-linking copolymerization of acrylamide solution, alginate solution, N,N'-methylenebisacrylamide, ammonium persulfate, N,N,N'N'-tetramethylethylenediamine and deionized water.

[0058] The hydrogel encapsulation layer comprises the following steps: dissolving acrylamide in deionized water, placing the mixture on a stirrer, stirring continuously at a temperature of 25° C. and a rotation speed of 500 rpm for 20 minutes to obtain an 18.7 wt% acrylamide solution; dissolving alginate in deionized water, placing the mixture on a stirrer, stirring continuously at a temperature of 25° C. and a rotation speed of 1000 rpm for 8 hours to obtain a 4 wt% alginate solution; mixing 5.5 mL of acrylamide solution and 4 mL of alginate solution, placing the mixture on a stirrer, stirring at a temperature of 25° C. and a rotation speed of 800 rpm for 15 minutes to obtain a uniform composite solution; adding 375 μL of N,N'-methylenebisacrylamide (0.2 g / 100 mL) and 102 μL of ammonium persulfate (0.2 mol / L) to the composite solution, stirring continuously at a temperature of 25° C. and a rotation speed of 800 rpm for 10 minutes; adding 5 μL of N,N,N'N'-tetramethylethylenediamine was stirred at 800 rpm for 5 minutes at a temperature of 25°C to obtain a uniform polymer solution.

[0059] The hydrogel encapsulation layer is cured by ultraviolet polymerization, that is, irradiated under an ultraviolet lamp with a power of 180W and a wavelength of 365nm for 40 minutes.

[0060] The circuit layer conductive ink is prepared by mixing a eutectic gallium-indium alloy (melting point is 15° C.) consisting of 75.5 wt % gallium and 24.5 wt % indium and 50 nm nickel particles.

[0061] The conductive ink in the circuit layer is obtained by sealing and stirring at a temperature of 25° C. for 24 hours.

[0062] The conductive layer includes three modules: wireless energy transmission module, pulse circuit and stimulation output interface, among which the electronic components include wireless coil, switching diode, chip capacitor, chip resistor, wireless charging receiving chip and timer.

[0063] A method for preparing a flexible wireless cardiac pacemaker based on hydrogel and liquid metal comprises the following steps:

[0064] (1) pouring a hydrogel polymer solution into a template and subjecting it to UV curing to obtain a hydrogel substrate 1 and an encapsulation layer 5;

[0065] (2) mixing and stirring the eutectic gallium-indium alloy and nickel powder to obtain a conductive ink;

[0066] (3) printing a liquid metal circuit pattern on the hydrogel substrate 1 using a template printing method, wherein a scraper is used for large-area filling and a brush is used for fine filling;

[0067] (4) After carefully removing the template, place the microcontroller unit, resistors, capacitors and other electronic components in the corresponding circuit positions, and drip liquid metal at the pin positions of each component to ensure stable formation between the components and the circuit;

[0068] (5) Paste a nickel layer at the end of the circuit as a stimulation output interface;

[0069] (6) The circuit is encapsulated using the hydrogel encapsulation layer 5 to prepare a flexible wireless cardiac pacemaker based on hydrogel and liquid metal.

[0070] like Figure 1 Figure 2 shows a schematic diagram of the structure of a flexible wireless cardiac pacemaker based on hydrogel and liquid metal according to the present invention, which includes a hydrogel substrate 1, a wireless charging module 2, a pulse modulation circuit 3, a stimulation output interface 4, and a hydrogel encapsulation layer 5. The wireless charging module 2, pulse modulation circuit 3, and stimulation output interface 4 are embedded in the hydrogel substrate 1 and the hydrogel encapsulation layer 5.

[0071] like Figure 2 As shown, the wireless charging module 2 is composed of a wire 6, a wireless coil 7, a switching diode 9, a chip capacitor 8 and a wireless charging receiving chip 10; the pulse modulation circuit 3 is composed of a wire 6, a switching diode 9, a chip resistor 11, a timer 12 and a chip capacitor 8; the stimulation output interface 4 is composed of two squares composed of a nickel layer 401.

[0072] like Figure 3 Schematic diagram of the chemical structure of the hydrogel substrate 1 and the encapsulation layer 5 of the present invention is shown. The hydrogel substrate 1 and the encapsulation layer 5 are both formed by the entanglement of a first layer of rigid hydrogel network 101 and a second layer of flexible hydrogel network 102.

[0073] like Figure 4 As shown, the first layer of rigid hydrogel network 101 is composed of polyacrylamide polymer chains. In polyacrylamide gels, the polymers are covalently cross-linked via N,N'-methylenebisacrylamide. k and l represent the degree of polymerization (i.e., the number of repeating units) and can range from 50,000 to 200,000.

[0074] like Figure 5 As shown, the second layer of flexible hydrogel network 102 is composed of alginate-polyacrylamide polymer chains. In the alginate-polyacrylamide hybrid gel, the two polymer networks are interwoven, covalently crosslinked between the amine groups on the polyacrylamide and the carboxyl groups on the alginate. m and n represent the degree of polymerization (i.e., the number of repeating units), and the value of n is not fixed, ranging from 80,000 to 300,000.

[0075] like Figure 6 As shown, the conductive ink 6 is composed of eutectic gallium-indium alloy and nickel powder. The doping of nickel powder promotes the oxidation of the surface of the eutectic gallium-indium alloy, forming a thin Ga2O3 layer. When the conductive ink 6 is printed on the hydrogel substrate 1, the -OH bonds in Ga2O3 and the hydrogel substrate 1 attract each other to form a dense interface.

[0076] like Figure 7 As shown in the figure, when the hydrogel and conductive ink are subjected to stress and tensile deformation, gallium atoms are continuously added to the interface and bonded with -OH groups; after the stress disappears, the conductive ink and hydrogel shrink simultaneously and return to their original state.

[0077] Example 1:

[0078] First, acrylamide was dissolved in deionized water, placed on a stirrer and stirred continuously at a temperature of 25°C and a speed of 500 rpm for 20 minutes to obtain an 18.7 wt% acrylamide solution; alginate was dissolved in deionized water, placed on a stirrer and stirred continuously at a temperature of 25°C and a speed of 1000 rpm for 8 hours to obtain a 4 wt% alginate solution; the two solutions were mixed and placed on a stirrer, stirred at a temperature of 25°C and a speed of 800 rpm for 15 minutes to obtain a uniform composite solution; 375 μL N,N'-methylenebisacrylamide (0.2 g / 100 mL) and 102 μL ammonium persulfate (0.2 mol / L) were added to the composite solution, and stirred continuously at a temperature of 25°C and a speed of 800 rpm for 10 minutes; 5 μL N,N,N'N'-tetramethylethylenediamine was added, and stirred continuously at a temperature of 25°C and a speed of 800 rpm for 5 minutes to obtain a uniform polymer solution.

[0079] The polymer solution was poured into the substrate template and cured by ultraviolet polymerization, i.e., irradiated under an ultraviolet lamp with a power of 180 W and a wavelength of 365 nm for 40 min to obtain a hydrogel substrate 1 with a thickness of 0.5 cm. The specific dimensions are as follows: Figure 8 shown.

[0080] The preparation steps of conductive ink 6 include: mixing a eutectic gallium-indium alloy (melting point 15°C) composed of 75.5wt% gallium and 24.5wt% indium with nickel particles with a particle size of 45-55nm (average 50nm) in a weight ratio of 97:3, and sealing and stirring for 24 hours at a temperature of 25°C.

[0081] The obtained hydrogel substrate 1 is spread flat on a PET film, a pattern template is placed on the surface of the hydrogel substrate 1, a conductive ink 6 is applied with a scraper, and a small pattern is filled with a brush. After the filling is completed, the pattern template is slowly peeled off to obtain a conductor. The pattern template is a metal template, a PET template or a PI template, such as Figure 9 As shown. Among them, the wire width is 500μm and the thickness is the thickness of the template used. Afterwards, the microcontroller unit, resistors, capacitors and other electronic components 7-12 are placed on the corresponding circuit positions, gently pressed, and eutectic gallium-indium alloy is dripped at the pin position of each component to ensure stable formation between the components and the circuit. Nickel tape 401 is pasted at the end of the circuit as a stimulation output interface 4 to form a circuit. Finally, the polymer solution is poured on top of the circuit, and after ultraviolet irradiation (under ultraviolet light with a power of 180W and a wavelength of 365nm for 40 minutes), a hydrogel encapsulation layer 5 with a thickness of 0.3cm is formed to encapsulate the circuit, and a flexible wireless pacemaker based on hydrogel and liquid metal is obtained.

[0082] The circuit diagram of the flexible wireless cardiac pacemaker prepared in this embodiment is shown in FIG. Figure 10 As shown in Figure 2, the output curve of the electrical stimulation signal is as follows: Figure 11 As shown, the output voltage signal is measured by an oscilloscope. As shown in the figure, the frequency is 16Hz, the pulse voltage is 4.5-4.6V, and the pulse width is 5.47ms. By adjusting the size of the resistor in the pulse modulation circuit, the pulse output frequency can be adjusted. The oscillation period of the multivibrator composed of the timer is proportional to the value of the external timing component, which is convenient for adjusting the pulse frequency. R1 and R2 control the duty cycle q. The calculation method is, where f represents the pulse frequency, T H Indicates the positive pulse width, T L Indicates negative pulse width:

[0083]

[0084] T H =0.693×R1×C

[0085] TL =0.693×R2×C

[0086]

[0087] After the external transmitting coil is connected to the power supply and placed on the coil 7, the coil 7 generates an induced current. The induced current is rectified by the chip capacitor 8, the switching diode 9 and the wireless charging receiving chip 10, and the AC current is converted into DC current, which powers the pulse modulation circuit 3. The pulse modulation circuit 3 is essentially a multivibrator. It switches the output high and low levels through the charge and discharge cycle of the capacitor, and achieves self-oscillation by comparing with the internal threshold of the timer 12, thereby outputting periodic rectangular pulses.

[0088] The pacemaker described in this application can be attached to the surface of biological tissue, powered by an external transmitting coil to achieve internal electrical stimulation, while also exhibiting good biocompatibility. The hydrogel- and liquid metal-based flexible wireless pacemaker described in this application is suitable for use in wearable or implantable medical devices and can be effectively used for cardiac electrical stimulation therapy.

Claims

1. Flexible wireless bio-interface based on hydrogel and liquid metal, characterized by: including a hydrogel encapsulation layer and an intermediate circuit layer; The hydrogel encapsulation layer comprises a hydrogel base and a hydrogel encapsulation layer; an intermediate circuit layer is provided on the hydrogel base, and the intermediate circuit layer is encapsulated by the hydrogel encapsulation layer, so that the intermediate circuit layer is encapsulated between the hydrogel base and the hydrogel encapsulation layer; The intermediate circuit layer includes a circuit pattern printed with conductive ink and a pacemaker circuit arranged on the circuit pattern; the conductive ink is nickel-doped eutectic gallium-indium alloy.

2. The flexible wireless biointerface based on hydrogel and liquid metal according to claim 1, characterized in that: The pacemaker circuit includes a wireless energy transmission module, a pulse modulation circuit and a stimulation output interface connected in series; The wireless energy transmission module uses a wireless charging receiving chip; the input end of the wireless charging receiving chip is connected to one end of the wireless coil through a first diode, and the other end of the wireless coil is grounded; a capacitor C1 is connected between the two ends of the wireless coil, and a capacitor C2 is connected between the input end of the wireless charging receiving chip and the ground; the output end of the wireless charging receiving chip is connected to the pulse modulation circuit; The pulse modulation circuit uses a timer; the power input terminal of the timer is connected to the output terminal of the wireless charging receiving chip, and a capacitor C3 is connected between the low trigger terminal of the timer and the ground terminal; the output terminal of the timer serves as the output terminal of the circuit; the reset terminal of the timer is connected to the high trigger terminal of the timer through resistors R1 and R2 in sequence; the node between the resistors R1 and R2 is connected to the discharge terminal of the timer, and a series branch of a second diode and a third diode is further connected in parallel across the two ends of the resistor R2; the node between the second diode and the third diode is connected to the low trigger terminal of the timer; and the control voltage terminal of the timer is grounded through capacitor C4; Stimulation output interface, connect the output end of the circuit to nickel tape to form a stimulation output interface.

3. The method for preparing a flexible wireless bio-interface based on hydrogel and liquid metal according to any one of claims 1 to 2, characterized in that: The steps include: (1) pouring a hydrogel polymer solution into a template and then UV curing the solution to obtain a hydrogel substrate; (2) mixing and stirring the eutectic gallium-indium alloy and nickel powder to obtain a conductive ink; (3) printing a liquid metal circuit pattern on a hydrogel substrate using a template printing method; (4) After removing the template, the electronic components in the pacemaker circuit are placed on the corresponding circuit positions, and liquid metal is dripped at the pin positions of each component to ensure the formation between the component and the circuit; (5) Paste a nickel layer on the output end of the circuit as a stimulation output interface; (6) pouring the hydrogel polymer solution into the template and UV curing it to obtain a hydrogel encapsulation layer; (7) The pacemaker circuit is encapsulated using a hydrogel encapsulation layer to prepare a flexible wireless cardiac pacemaker based on hydrogel and liquid metal.

4. The method for preparing a flexible wireless bio-interface based on hydrogel and liquid metal according to claim 3, characterized in that: The hydrogel substrate and the encapsulation layer are respectively formed by an in-situ free radical crosslinking copolymerization reaction of a reaction system consisting of acrylamide, alginate, N,N'-methylenebisacrylamide, ammonium persulfate, N,N,N'N'-tetramethylethylenediamine and water.

5. The method for preparing a flexible wireless device based on hydrogel and liquid metal according to claim 3, characterized in that: The reaction system of the hydrogel substrate and the encapsulation layer is obtained by the following steps: At room temperature, acrylamide and alginate are dissolved in water and mixed to obtain a mixed solution, a crosslinking agent N,N'-methylenebisacrylamide and an initiator ammonium persulfate are added, and a catalyst N,N,N'N'-tetramethylethylenediamine is added, and the mixture is uniformly mixed to obtain a polymer solution; specifically, Dissolve acrylamide in deionized water, place it on a blender and stir it continuously at a temperature of 20-30°C and a rotation speed of 300-800 rpm for 5-60 minutes to obtain a 16-20 wt% acrylamide solution; dissolve alginate in deionized water, place it on a blender and stir it continuously at a temperature of 20-30°C and a rotation speed of 500-1500 rpm for 6-12 hours to obtain a 3-5 wt% alginate solution; mix 4-6 mL of acrylamide solution and 3-5 mL of alginate solution and place it on a blender. The mixture was stirred on a stirrer at a temperature of 20-30° C. and a speed of 400-1000 rpm for 5-40 minutes to obtain a uniform composite solution; 350-400 μL of an aqueous solution of N,N'-methylenebisacrylamide (0.1-0.3 g / 100 mL) and 95-110 μL of an aqueous solution of ammonium persulfate (0.1-0.3 mol / L) were added to the composite solution, and the mixture was stirred continuously at a temperature of 20-30° C. and a speed of 400-1000 rpm for 5-30 minutes; 3-8 μL of N,N,N'N'-tetramethylethylenediamine was added, and the mixture was stirred continuously at a temperature of 20-30° C. and a speed of 400-1000 rpm for 2-10 minutes to obtain a uniform polymer solution.

6. The method for preparing a flexible wireless bio-interface based on hydrogel and liquid metal according to claim 3, characterized in that: The hydrogel encapsulation layer is cured by ultraviolet polymerization, that is, irradiated under an ultraviolet lamp with a power of 120-500W and a wavelength of 312-365nm for 20-60 minutes.

7. The method for preparing a flexible wireless bio-interface based on hydrogel and liquid metal according to claim 3, characterized in that: The conductive ink is prepared by mixing a eutectic gallium-indium alloy consisting of 70-80 wt% gallium and 20-30 wt% indium and 30-80 nm nickel particles in a mass ratio of 95-98:5-2.

8. The method for preparing a flexible wireless bio-interface based on hydrogel and liquid metal according to claim 3, characterized in that: The conductive ink is obtained by sealing and stirring for 18-48 hours in an environment with a temperature of 20-30°C.

9. The method for preparing a flexible wireless bio-interface based on hydrogel and liquid metal according to claim 3, characterized in that: The pacemaker circuit has the following working process: When the wireless coil generates an induced current, the induced current is rectified by capacitor C1, capacitor C2, the first switching diode and the wireless charging receiving chip, and the AC current is converted into a DC current to power the pulse modulation circuit; The pulse modulation circuit switches the output high and low levels through the charge and discharge cycle of capacitor C3, and realizes self-oscillation by comparing with the internal threshold of the timer, thereby outputting periodic rectangular pulses.

10. The method for preparing a flexible wireless bio-interface based on hydrogel and liquid metal according to claim 3, characterized in that: The pacemaker circuit adjusts the pulse output frequency by adjusting the resistance in the pulse modulation circuit: T H =0.693×R1×C T L =0.693×R2×C Where f represents the pulse frequency, T H Indicates the positive pulse width, T L Represents the negative pulse width, R1 and R2 represent the resistance values ​​of resistor R1 and resistor R2 respectively, C represents the capacitance value of capacitor C3, and q represents the duty cycle.

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