WO2019015520A1 - Surface modification method for flexible stretchable line, and use thereof - Google Patents

Abstract

The present invention provides a surface modification method for a flexible stretchable line, and use thereof. Said method can significantly improve the cytocompatibility and histocompatibility of a conductive line and the line stability of the conductive line directly contacting the cell/tissue, and the conductivity performance can still be well maintained after a long-time cell co-culture or implantation in vivo; the Faraday cage effect caused by a surface oxide layer is overcome, and the formed electrode can generate a stable electric field, improving the functionality of the conductive line; said method has simple steps and is easy to operate, can perform surface treatment without a special instrument, and is used for large-scale preparation of a functional flexible line; a flexible stretchable line subjected to direct surface modification or multiple surface modifications can be widely used in conductive lines which are in direct contact or indirect contact with cells or tissues, and can be used in the fields of tissue engineering, biosensing, photoelectric materials, etc. Said method can quickly realize large-scale industrial preparation, and can be used in the fields of wearable electronic devices, implanted medical instruments, etc.

Description

Surface modification method of flexible stretchable line and its application Technical field

The invention belongs to the field of electronic circuits, and in particular relates to a surface modification method of a flexible stretchable line and an application thereof.

Background technique

With the development of biotechnology, wearable devices and implantable flexible electronic devices have been greatly developed, but the wearable or implantable devices that are actually used in the human body have been greatly limited by technology. The reason is that existing flexible circuits, especially those that are in direct contact with cells or tissues, do not provide sufficient biological (cell/tissue) compatibility, which causes them to fail due to local environmental deterioration after implantation in the body. Effect or performance damage to the original function.

We have proposed a method and application for the preparation of a flexible stretchable electrical circuit and circuit. The method is essentially a simple and convenient and versatile liquid metal patterning technique that allows liquid metal patterning to be achieved simply and quickly on a wide variety of substrates. The preparation method is simple and rapid, and the amount of liquid metal is small, no additional external force is required, the pattern does not generate cracks, the line width is controllable, and the resolution is high, and is suitable for mass production. The circuit prepared according to this method has excellent flexibility and stretchability, and is suitable for circuits of various line widths (line widths up to 1 micron). And indium gallium, two kinds of liquid metal element compounds, are various high-performance semiconductor materials which are commonly used in themselves, so the preparation method can be extended to the preparation of various semiconductors.

Summary of the invention

Accordingly, it is an object of the present invention to overcome the deficiencies of the prior art and to provide a method of surface modification of a flexible stretchable line and its use.

Before describing the present invention, the terms used herein are defined as follows:

The term "PDMS" means: polydimethylsiloxane. The "PDMS" solution described herein includes a prepolymer and a curing agent in a ratio of 5:1 to 50:1.

The term "Smooth-on series of materials" refers to a series of commercially available materials such as silicone, rubber, resin and polyurethane developed and sold by the US company Smooth-on. Such as Smooth-on Ecoflex series, Smooth-on Dragon Skin series, etc.

The term "Smooth-on Ecoflex Series" refers to a range of silicone rubbers developed and sold by the US company Smooth-on, including Ecoflex 0010, Ecoflex 0020, Ecoflex 0030, Ecoflex 0050, and the like. It is super soft, strong and elastic after curing, and does not shrink.

The term “Smooth-on Dragon Skin Series” refers to a series of silicone rubber developed and sold by American smooth-on company, including Dragon Skin 10, Dragon Skin 20, Dragon Skin 30, and Dragon Skin FX. It is soft after curing and has high stretchability and recovery.

The term "PET" means: polyethylene terephthalate.

The term "polymer" means a molecule having a relative molecular mass of more than 10,000.

The term "elastomer" means a soft material that has both flexibility and tensile properties, such as PDMS, Smooth-on series materials, and the like.

The term "original patterned layer" refers to a layer that is patterned on a substrate material using liquid metal particles.

The term "Fibronectin" means: fibronectin;

The term "Collagen I/III" means: collagen I/III;

The term "Laminin" means: laminin;

The term "Gelatin" means: gelatin;

The term "PLGA" means: a polylactic acid-glycolic acid copolymer;

The term "PCL" means: polycaprolactone;

The term "PLCL" means: polylactic acid-polycaprolactone;

The term "PEIE" means: ethoxylated polyethyleneimine.

To achieve the above object, a first aspect of the present invention provides a method of preparing a flexible stretchable conductive circuit, the method comprising the steps of:

1) using liquid metal mixed with a volatile liquid solvent to prepare liquid metal particles having a core-shell structure;

2) using the liquid metal particles prepared in the above step 1), drawing a pattern on the selected original pattern layer material, leaving a pattern of liquid metal particles after the liquid in the liquid metal particles is completely volatilized;

3) casting a polymer solution on the pattern obtained in the above step 2) to form a peeling layer;

4) After the elastic prepolymer is solidified or after the polymer solvent is volatilized, the polymer film is carefully peeled off from the substrate to obtain the flexible stretchable conductive line.

A preparation method according to the first aspect of the invention, wherein:

The liquid metal in the step 1) is selected from one or more of the following: gallium, mercury, gallium indium alloy, gallium indium tin alloy and antimony tin lead indium alloy, the volatile liquid solvent is selected from the group consisting of: liquid at room temperature Alcohol, ketone or ether;

The method of drawing in step 2) is selected from one or more of the following: hand-drawn, missing letter plate, screen printing, inkjet printing, and microfluidic channel filling;

The polymer solution in the step 3) is selected from the group consisting of PDMS, modified PDMS, Smooth-on series materials, PLGA, PCL, PLCL and other degradable polymer solutions. Preferably, the ratio of the PDMS prepolymer to the curing agent can be 5:1 to 30:1, preferably 5:1 to 25:1, more preferably 10:1 to 20:1, most preferably 10:1; the modified PDMS components include a prepolymer, a curing agent , PEIE (ethoxylated polyethyleneimine), the ratio is 100:20:1 to 600:20:1, preferably 200:20:1 to 600:20:1, more preferably 200:20:1 400:20:1, most preferably 200:20:1, the proportion of Smooth–on AB components is 1:1 to 4:1, preferably 1:1 to 3:1, more preferably 1:1 to 2: 1, most preferably 1:1.

According to the preparation method of the first aspect of the invention, the method further comprises:

5) performing direct surface modification or multiple surface modification on the flexible stretchable conductive circuit obtained in the step 4), wherein the direct surface modification is directly performing surface bioactive substance modification, and the multiple surface modification is chemical modification first. Surface bioactive substance modification; and/or

6), using a polymer elastomer surface package.

Preferably, the surface bioactive substance modification comprises: using a microfluidic technology, designing a microfluidic chip suitable for the shape of the line for different circuit patterns, adding extracellular matrix proteins, cells/bioactive substances or organisms to the chip. Active topical modification of the active drug; and/or

The chemical modification comprises: reacting the inorganic salt with the liquid metal and the surface oxide layer, and depositing the formed nanoparticles on the surface of the line to form a surface metal layer with a controllable thickness of several nanometers to several micrometers.

More preferably, the extracellular matrix protein is selected from one or more of the group consisting of fibronectin, collagen I/III, laminin and gelatin;

The cell/biologically active substance is selected from one or more of the following: DNA, RNA, and protein;

The bioactive drug is selected from one or more of the group consisting of rapamycin, everolimus, and paclitaxel; and/or

The inorganic salt is selected from one or more of the group consisting of HAuCl ₄ , AgNO ₃ , CuCl ₂ , HCl, Na ₂ CO ₃ and NaHCO ₃ .

Still preferably, the polymeric elastomer is selected from one or more of the following: PET, polydimethylsiloxane, and Smooth-on series materials, preferably, the Smooth-on series material is selected from the group consisting of Smooth-on Ecoflex series and Smooth-on Dragon Skin collection.

A second aspect of the invention provides a flexible stretchable electrically conductive circuit produced by the method of the first aspect.

A third aspect of the invention provides an implantable medical device comprising the stretchable conductive circuit of the second aspect.

A fourth aspect of the invention provides an electrostimulation chip/electrode or electrotransfection chip/electrode, the chip/electrode of the stretchable conductive line of the second aspect.

A fifth aspect of the present invention provides a wearable electronic device, the wearable electronic device comprising:

a stretchable conductive circuit according to the second aspect of the invention; or

A chip/electrode according to the fourth aspect of the invention.

A sixth aspect of the invention provides an electrical stimulation treatment method, the method comprising:

An electrostimulation chip/electrode according to the fourth aspect of the invention; and/or

A stretchable conductive circuit as in the second aspect of the invention.

A seventh aspect of the invention provides a gene transfection method, the method comprising:

An electrostimulation chip/electrode according to the fourth aspect of the invention; and/or

A stretchable conductive circuit as in the second aspect of the invention.

An eighth aspect of the invention provides a protein transfection method, the method comprising:

An electrostimulation chip/electrode according to the fourth aspect of the invention; and/or

A stretchable conductive circuit as in the second aspect of the invention.

A ninth aspect of the invention provides the use of a flexible stretchable electrically conductive circuit made in accordance with the method of the first aspect of the invention in the manufacture of a device or device medical device for use in surgery and/or electrical stimulation therapy.

A tenth aspect of the invention provides a method of preparing a semiconductor material, the method comprising the steps of:

1) mixing ultrasonic waves to prepare liquid particles having a core-shell structure;

2) using the liquid particles prepared in the above step 1), drawing a pattern on the selected original pattern layer material, leaving a pattern composed of liquid particles after the liquid is completely volatilized;

3) casting a polymer solution on the pattern obtained in the above step 2) to form a peeling layer;

4) After the elastic prepolymer is solidified or the polymer solvent is volatilized, the polymer film is carefully peeled off from the substrate to obtain.

The specific technical solutions of the present invention will be further described as follows in conjunction with the concept of the present invention:

SUMMARY OF THE INVENTION It is an object of the present invention to improve flexible conductive traces by performing various surface modifications on the surface of the circuit and expanding related biological applications. The surface chemical technology and microfluidic technology are mainly used to surface modify the flexible circuit based on liquid metal and polymer to improve its functionality and improve its biocompatibility. On this basis, expand the relevant biological applications.

1, flexible stretchable line preparation

Use liquid metal (mainly: gallium, mercury, gallium indium alloy, gallium indium tin alloy, antimony tin, lead indium alloy and other low melting point metals) and volatile liquids (mainly refers to low boiling solvents such as liquid alcohol at room temperature) A substance, a ketone substance or an ether substance, etc., is mixed with ultrasonic waves to prepare a liquid metal particle having a core-shell structure. Using the liquid metal particles prepared above, the upper pattern is drawn on the original pattern layer material selected by hand drawing, missing letter board, screen printing, ink jet printing, and micro flow channel filling. After all the liquids in the liquid metal particles are volatilized, a pattern composed of liquid metal particles is left, and a polymer solution such as PDMS, Smooth-on series materials or the like is cast on the pattern to form a peeling layer. The liquid polymer can partially penetrate into the gaps of the stacked liquid metal particles to form a porous structure. The thickness of the release layer is determined by the speed and time of the silicone rubber. After the elastic prepolymer is solidified or the polymer solvent is volatilized, the polymer film is carefully peeled off from the substrate, and the peeling step enables the liquid metal to be crosslinked to impart excellent conductivity to the pattern. The amount of liquid metal contained in the pattern formed on the original pattern layer and the peeling layer is also different depending on the affinity (adhesion) force of the original pattern layer and the peeling layer. For example, with this method, different types of lines having the shape and thickness as shown in FIG. 1 can be prepared on a large scale.

2, direct surface modification and application

Direct surface modification refers to the use of microfluidic technology to design a microfluidic chip suitable for the shape of the line for different line patterns (Fig. 2), and to add extracellular matrix proteins to the chip (eg Fibronectin, Collagen I/III, Laminin). , Gelatin, etc., cells/bioactive substances (such as DNA, RNA, protein, etc.), or bioactive drugs (such as rapamycin, everolimus, paclitaxel, etc.) and other substances for local surface modification to enhance their biology Compatibility (Figure 3), line stability, improved degradability, etc.

As a stretchable conductive line for implants: Directly surface modified lines can be used for electrical conduction, directly for use or by polymer elastomer surface encapsulation (PET, different ratios of polydimethylsiloxane [PDMS] ] and Smooth-on series materials [such as Smooth-on Ecoflex series, Smooth-on Dragon Skin series] are used for implant lines (Figure 4).

3, multiple surface modification

Compared to direct surface modification, multiple surface modification overcomes the "Faraday cage" effect caused by poor conductivity of the surface of the core-shell structure of the above-mentioned lines. First, HAuCl ₄ , AgNO ₃ , CuCl ₂ , HCl, Na ₂ CO ₃ , NaHCO ₃ and other substances are reacted with the liquid metal and the surface oxide layer, and the substituted Au, Ag, Cu and other nanoparticles are deposited on the surface of the line to form a number. A surface metal layer with a controllable thickness from nanometers to several micrometers (Fig. 5), which greatly enhances the surface conductivity. After the above chemical modification, the surface bioactive substance is modified.

As a functional line for implants: lines with multiple surface modifications, due to overcoming the "Faraday cage" effect, can apply an electric field for electrostimulation of chips/electrodes or electrotransfer chips/electrodes, successfully implemented for Tissue electrical stimulation (Figure 7) or electrotransfection (gene transfection / protein transfection) (Figure 8), stable and reliable performance.

The surface modification method of the flexible stretchable line of the present invention may have, but is not limited to, the following beneficial effects:

1. Significantly improve the cell compatibility and histocompatibility of the conductive line;

2. The line stability of the direct contact between the conductive line and the cell/tissue is obviously improved, and the electrical conductivity is still well maintained after long-time cell co-culture or in vivo implantation;

3. Overcoming the Faraday cage effect caused by the surface oxide layer, as the electrode can generate a stable electric field and improve the functionality of the conductive line;

4. The method has the advantages of simple steps, easy operation, surface treatment without special instruments, and large-scale preparation of functional flexible circuits;

5. Flexible stretchable lines with direct surface modification or multiple surface modification can be widely used in conductive lines in direct contact or indirect contact with cells or tissues for tissue engineering, biosensing, optoelectronic materials, etc.;

6, can quickly achieve industrial-scale large-scale preparation, for wearable electronic devices, implantable medical devices and other fields.

BRIEF DESCRIPTION OF THE DRAWINGS

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, in which:

Figure 1 shows a liquid metal ink used in the method of the present invention and a prepared flexible conductive circuit;

Figure 2 shows a mold design, a physical map and a microfluidic chip used in the method of the present invention;

Figure 3 shows a microfluidic chip after partial surface modification using the method of the present invention. Specifically, a is a checkerboard pattern in which liquid metal and PDMS alternate; b is a partial enlarged view of a; c is an endothelial cell The state of adhesion on the liquid metal; df is a fluorescent confocal pattern obtained by using the cell death staining kit after one week of culture, and the cell activity is very good; gh is a three-dimensional reconstructed fluorescent confocal pattern corresponding to df;

Figure 4 shows the circuit before and after surface encapsulation using the method of the present invention;

Figure 5 is a circuit diagram showing before and after partial surface chemical modification using the method of the present invention;

Figure 6 shows a flexible conductive circuit prepared in Embodiment 2 of the present invention;

Figure 7 shows electrical stimulation of rat lymph nodes by an electro-stimulation chip/electrode prepared by the method of the present invention;

Figure 8 shows the delivery and expression of green fluorescent protein particle DNA by an electrotransfection chip/electrode prepared by the method of the present invention.

The best way to implement the invention

The invention is further illustrated by the following examples, which are intended to be in no way intended to

This section provides a general description of the materials used in the tests of the present invention and the test methods. While many of the materials and methods of operation used to accomplish the objectives of the present invention are well known in the art, the present invention is still described in detail herein. It will be apparent to those skilled in the art that, in the context, the materials and methods of operation of the present invention are well known in the art unless otherwise specified.

The reagents and instruments used in the following examples are as follows:

Reagents:

PET was purchased from Sigma Aldrich Company of the United States, PDMS and cell culture dishes were purchased from Dow-corning Company, rapamycin, everolimus and paclitaxel were purchased from Shanghai Maclean Biochemical Technology Co., Ltd.;

HAuCl ₄ , AgNO ₃ , CuCl ₂ , HCl, Na ₂ CO ₃ , NaHCO ₃ , purchased from Sigma Aldrich, USA;

Fibronectin, Collagen I/III, Laminin, Gelatin, purchased from Sigma Aldrich, USA;

DMEM, Opti-DMEM cell culture fluid, purchased from Life technologies, USA;

Fibroblasts were purchased from ScienCell, USA.

instrument:

Vacuum oven, purchased from Shanghai Qixin Scientific Instrument Co., Ltd., model DZF-6020; oven, purchased from Shanghai Pudong Rongfeng Scientific Instrument Co., Ltd., model DHG-9030A; ultrasonic cell crusher, purchased from Bianxin Ultrasonic Company, model S-450D; scanning electron microscope, purchased from Hitachi, model S4800; manual screen printing station, purchased from Guangzhou Junyu screen printing equipment, model 23*30cm; precision universal meter purchased from Fluke electronic instrumentation company, model 8846A; dynamic machinery Analyzer, model DMA Q800. Piezoelectric nozzle, purchased from Konica Corporation of Japan, model KM512NX 35PL. HD video microscope optilia, purchased from the Swedish optilia company, model M30X-E320. Electroporation instrument, model BTX ECM830, was purchased from BTX Corporation of the United States. The cell incubator, model, was purchased from Thermo 371 and was purchased from Thermo Scientific, USA.

Example 1

This example is intended to illustrate a flexible stretchable conductive circuit prepared using the method of the present invention.

1 g of liquid indium gallium eutectic alloy (EGaIn Ga 75.5% wt In 24.5% wt) was placed in 1 ml of a mixed solution of n-octanol and glycerol (volume octanol: glycerol = 80:20), used Ultrasonic cell disruption was sonicated for 60 s at 30% amplitude to obtain a suspension of gray liquid metal. The metal was dispersed into small particles of innumerable micro-nano size, and the average particle size of the small particles was 1500 nm. The core of the small particles is a liquid metal, and the outside is surrounded by a thin oxide film. In order to achieve complete transfer, the PET film was selected as the original pattern layer, and the PDMS solution was configured in a ratio of PDMS prepolymer: curing agent mass ratio of 10:1. An electrode pattern of 500 micrometers line width (Fig. 5) was prepared on a PET film using screen printing techniques and its width was measured with a high definition video microscope. The pattern was placed in an oven at 80 degrees Celsius for 30 minutes. The PDMS solution was cast over the pattern on the PET film, degassed in a vacuum oven for 10 min, placed in a silicone machine at a speed of 500 rpm for 60 s to obtain a thickness of 220 micron PDMS. It was then cured in an oven at 80 degrees Celsius for 30 minutes. After the PDMS was cured, the PDMS was carefully peeled off from the original pattern layer (PET film). Thus, the pattern of liquid metal is transferred to the PDMS and has good electrical conductivity to obtain a flexible stretchable conductive line.

Example 2

This example is intended to illustrate a flexible stretchable conductive circuit prepared using the method of the present invention.

1 g of liquid indium gallium eutectic alloy (EGaIn Ga 75.5% wt In 24.5% wt) was placed in 1 ml of a mixed solution of n-octanol and glycerol (volume octanol: glycerol = 80:20), used Ultrasonic cell disruption was sonicated for 20 min at 30% amplitude to obtain a suspension of gray liquid metal. The metal was dispersed into small particles of innumerable micro-nano size, and the average particle size of the small particles was 800 nm. The core of the small particles is a liquid metal, and the outside is surrounded by a thin oxide film. In order to achieve complete transfer, the PET film was selected as the original pattern layer, and the PDMS solution was disposed in a ratio of PDMS prepolymer: curing agent mass ratio of 10:1. An electrode pattern of 200 micrometers line width (Fig. 6) was fabricated on a PET film using screen printing techniques and its width was measured with a high definition video microscope. The pattern was placed in an oven at 80 degrees Celsius for 30 minutes. The PDMS solution was cast over the pattern on the PET film, degassed in a vacuum oven for 10 min, and placed in a silicone machine at a speed of 2000 rpm for 120 s to obtain a thickness of 50 micron PDMS. It was then cured in an oven at 80 degrees Celsius for 30 minutes. After the PDMS was cured, the PDMS was carefully peeled off from the original pattern layer (PET film). Thus, the pattern of liquid metal is transferred to the PDMS and has good electrical conductivity to obtain a flexible stretchable conductive line.

Example 3

This example is intended to illustrate the direct surface modification of flexible stretchable conductive traces using the method of the present invention.

Using microfluidic technology, design a microfluidic chip suitable for the shape of the line for different line patterns (Fig. 2), add 1ml of Fibronectin solution with a concentration of 1mg/ml to the chip, cover the surface of the stretched line, and at 37 °C After incubating for 4 hours in the incubator, it was taken out and gently washed once with PBS solution of pH 7.4, and used directly for planting cells. The surface-modified tensile conductive line exhibited good biocompatibility, the cells adhered well to the surface, and remained well active after 7 days of culture (Fig. 3).

Example 4

This example is intended to illustrate the direct surface modification of flexible stretchable conductive traces using the method of the present invention.

Using microfluidic technology, design a microfluidic chip suitable for the shape of the line for different line patterns. Add 2ml of Fibronectin solution with a concentration of 1mg/ml to the chip, cover the surface of the stretched line, and incubate in a 37°C incubator. After 6 hours, it was taken out and gently washed once with a PBS solution of pH 7.4, and it was directly used for planting cells. The surface-modified tensile conductive line exhibits good biocompatibility, the cells adhere well to the surface, and maintain good activity after 7 days of culture.

Example 5

This example is intended to illustrate the multiple surface modification of flexible stretchable conductive traces using the method of the present invention.

The tensile conductive line prepared in Example 1 was placed in a 50 ml solution of 0.01 mol/L of HAuCl ₄ and taken out after soaking for 3 minutes; in the process, HAuCl _{4 was} reacted with the liquid metal and the surface oxide layer to be replaced. The formed Au nanoparticles are deposited on the surface of the wiring to form a surface metal layer of a controllable thickness of several nanometers to several micrometers (Fig. 5), thereby greatly enhancing the surface conductivity. Next, the above treated sample was taken out in 50 ml of a 0.1 mol/L NaHCO ₃ solution, and further taken out for 3 minutes; in the process, NaHCO ₃ reacted with the remaining HAuCl ₄ in the sample to remove it. . Next, the treated sample was placed in a beaker containing 2 L of high-purity water, stirred at a low speed for 4 hours or more, and water was changed every hour; in the process, the inorganic salts remaining in the sample were mostly removed. After the above chemical modification, the surface bioactive substance was modified, and the modification method was the same as in Example 2.

Example 6

This embodiment is for explaining the surface sealing method of the polymer elastomer provided by the present invention.

The liquid metal of the flexible conductive line obtained in Example 1 was faced upward, the PDMS solution was disposed in a ratio of a PDMS prepolymer: curing agent mass ratio of 10:1, and the flexible circuit was poured with a pre-configured PDMS solution, and The air bubbles were degassed in a vacuum oven for 10 min, and placed in a silicone machine at a speed of 500 rpm for 60 s to obtain a package having a total thickness of 450 μm. Then, it is cured in an oven at 80 degrees Celsius for 30 minutes. After curing, the packaged conductive lines are cut according to the needs of the line, that is, the surface of the polymer elastomer is encapsulated (Fig. 4).

Example 7

This embodiment is for explaining the preparation method of the electro-stimulation chip/electrode provided by the present invention.

A certain chip/electrode pattern was designed in advance by CAD software, and the corresponding screen printing template was processed, and the electrode pattern shown in FIG. 7 was obtained on the PET film by screen printing technology. The pattern was placed in an oven at 80 degrees Celsius for 30 minutes. The PDMS solution was cast over the pattern on the PET film, degassed in a vacuum oven for 10 min, placed in a silicone machine at a speed of 1000 rpm for 60 s to obtain a thickness of 80 micron PDMS. It was then cured in an oven at 80 degrees Celsius for 30 minutes. After the PDMS was cured, the PDMS was carefully peeled off from the original pattern layer (PET film). Thus, the pattern of liquid metal is transferred to the PDMS and has good electrical conductivity. The above sample was cut and subjected to direct surface modification using the method described in Example 2 to obtain a flexible stretchable chip/electrode as shown in Fig. 7 for lymph node electrical stimulation.

Example 8

This embodiment is for explaining the preparation method of the electrotransfection chip/electrode provided by the present invention.

A certain chip/electrode pattern was designed in advance by CAD software, and the corresponding screen printing template was processed, and the electrode pattern shown in FIG. 5 was obtained on the PET film by screen printing technology. The pattern was placed in an oven at 80 degrees Celsius for 30 minutes. The PDMS solution was cast over the pattern on the PET film, degassed in a vacuum oven for 10 min, placed in a silicone machine at a speed of 1000 rpm for 60 s to obtain a thickness of 80 micron PDMS. It was then cured in an oven at 80 degrees Celsius for 30 minutes. After the PDMS was cured, the PDMS was carefully peeled off from the original pattern layer (PET film). Thus, the pattern of liquid metal is transferred to the PDMS and has good electrical conductivity. The above sample was cut and subjected to multiple surface modification by the method described in Example 5 to obtain a flexible stretchable chip/electrode as shown in FIG. 5, which greatly enhanced surface conductivity and was used for cell green fluorescent protein particles. DNA electroporation experiments and successful delivery of green fluorescent protein DNA DNA and expression (Figure 8).

Test example 1

This test example is used to illustrate that the electro-stimulation chip/electrode prepared by the present invention is used for electrically stimulating rat lymph nodes.

First, a rat weighing 300 g was pre-injected with 2 ml of a pentobarbital solution having a mass ratio of 0.5%. After about 15 minutes, the rats were fully anesthetized. Next, the subcutaneous layer of the rat was opened using a pre-sterilized scalpel to find the lymph node. Then, the two semi-circular electrodes of the flexible electro-stimulation chip prepared in Example 6 are closely attached to the lymph nodes, and the other end of the chip is respectively connected to the positive and negative electrodes of the electroporation device, and electrical stimulation is performed, and the voltage is 100 V, and the voltage pulse pulse is applied. The width is 100ms and the pulse interval is 1s for 6 times. After the operation, disinfection and suture were performed, and normal feeding was performed. After 1 week, changes in physiological indexes related to lymph nodes were detected.

Test example 2

This test example is intended to illustrate that the electrostimulation chip/electrode prepared by the present invention is used to effect gene transfection.

First, the electrotransfection chip prepared in Example 8 was placed in a cell culture dish, and a pre-prepared DMEM cell culture medium containing fibroblasts was added and cultured in a 37 ° C cell incubator for 3 days until the cell fusion degree After reaching 80-90% or more, it was subjected to electrotransfection experiments. First, the above-mentioned chip covered with fibroblasts was washed three times with a PBS solution having a pH of 7.4, and the PBS solution was discarded. Then, 2 ml of a pre-configured green fluorescent protein DNA solution was added over the electrode at a concentration of 40 ug/ml and incubated for 5 minutes at room temperature. Next, the chip was connected to the positive and negative electrodes of the electroporation device (Fig. 8), and electrical stimulation was performed. The voltage was 80 V, the voltage pulse width was 100 μs, and the pulse interval was 1 s, which lasted 5 times. After performing electrical stimulation, place the above electrode in a new cell culture dish, add 15 ml of Opti-DMEM solution specially used for electroporation cell culture, and place it in a 37 °C cell incubator for 24 hours. The observation of green fluorescent protein expression by focusing microscope showed that green fluorescent protein was successfully transfected and expressed, and the transfection efficiency was above 95% (Fig. 8).

While the invention has been described in detail, it is obvious that various changes in the various conditions can be made without departing from the spirit and scope of the invention. It is to be understood that the invention is not limited to the embodiments, but is intended to be included within the scope of the appended claims.

Claims (15)

1. A method for preparing a flexible stretchable conductive line, characterized in that the method comprises the steps of:

   1) using liquid metal mixed with a volatile liquid solvent to prepare liquid metal particles having a core-shell structure;

   2) using the liquid metal particles prepared in the above step 1), drawing a pattern on the selected original pattern layer material, leaving a pattern of liquid metal particles after the liquid in the liquid metal particles is completely volatilized;

   3) casting a polymer solution on the pattern obtained in the above step 2) to form a peeling layer;

   4) After the elastic prepolymer is solidified or after the polymer solvent is volatilized, the polymer film is carefully peeled off from the substrate to obtain the flexible stretchable conductive line.
2. The method of claim 1 wherein:

   The liquid metal in the step 1) is selected from one or more of the following: gallium, mercury, gallium indium alloy, gallium indium tin alloy and antimony tin lead indium alloy, the volatile liquid solvent is selected from the group consisting of: liquid at room temperature Alcohol, ketone or ether;

   The method of drawing in step 2) is selected from one or more of the following: hand-drawn, missing letter plate, screen printing, inkjet printing, and microfluidic channel filling;

   The polymer solution in the step 3) is selected from one or more of the following degradable polymer solutions: PDMS, PDMS doped with PEIE, Smooth-on series materials, PLGA, PCL and PLCL.
3. The method according to claim 1 or 2, wherein the method further comprises:

   5) performing direct surface modification or multiple surface modification on the flexible stretchable conductive circuit obtained in the step 4), wherein the direct surface modification is directly performing surface bioactive substance modification, and the multiple surface modification is chemical modification first. Surface bioactive substance modification; and/or

   6), using a polymer elastomer surface package.
4. The method of claim 3 wherein:

   The surface bioactive substance modification comprises: using a microfluidic technology to design a microfluidic chip suitable for the shape of the line for different line patterns, adding extracellular matrix proteins, cells/bioactive substances or bioactive drugs to the chip. Partial surface modification; and/or

   The chemical modification comprises: reacting the inorganic salt with the liquid metal and the surface oxide layer, and depositing the formed nanoparticles on the surface of the line to form a surface metal layer with a controllable thickness of several nanometers to several micrometers.
5. The method of claim 4 wherein:

   The extracellular matrix protein is selected from one or more of the group consisting of fibronectin, collagen I/III, laminin and gelatin;

   The cell/biologically active substance is selected from one or more of the following: DNA, RNA, and protein;

   The bioactive drug is selected from one or more of the group consisting of rapamycin, everolimus, and paclitaxel; and/or

   The inorganic salt is selected from one or more of the group consisting of HAuCl ₄ , AgNO ₃ , CuCl ₂ , HCl, Na ₂ CO ₃ and NaHCO ₃ .
6. The method according to any one of claims 3-5, wherein the polymeric elastomer is selected from one or more of the following: PET, polydimethylsiloxane, and Smooth-on series materials, preferably The Smooth-on series of materials are selected from the Smooth-on Ecoflex series and the Smooth-on Dragon Skin series.
7. A flexible stretchable conductive circuit made by the method of any of claims 1-6.
8. An implantable medical device, comprising the stretchable conductive circuit of claim 7.
9. An electrostimulation chip/electrode or electrotransfection chip/electrode, characterized in that the chip/electrode comprises the stretchable electrically conductive line of claim 7.
10. A wearable electronic device, comprising:

    The stretchable conductive circuit of claim 7; or

    The chip/electrode of claim 9.
11. An electrical stimulation treatment method, characterized in that the method adopts:

    The electro-stimulation chip/electrode of claim 9; and/or

    The stretchable conductive circuit of claim 7.
12. A gene transfection method, characterized in that the method adopts:

    The electro-stimulation chip/electrode of claim 9; and/or

    The stretchable conductive circuit of claim 7.
13. A protein transfection method, characterized in that the method employs:

    The electro-stimulation chip/electrode of claim 9; and/or

    The stretchable conductive circuit of claim 7.
14. Use of a flexible stretchable electrically conductive circuit made according to the method of any of claims 1-6 for the preparation of a device or device for surgical and/or electrical stimulation therapy.
15. A method of preparing a semiconductor material, characterized in that the method comprises the steps of:

    1) mixing ultrasonic waves to prepare liquid particles having a core-shell structure;

    2) using the liquid particles prepared in the above step 1), drawing a pattern on the selected original pattern layer material, leaving a pattern composed of liquid particles after the liquid is completely volatilized;

    3) casting a polymer solution on the pattern obtained in the above step 2) to form a peeling layer;

    4) After the elastic prepolymer is solidified or the polymer solvent is volatilized, the polymer film is carefully peeled off from the substrate to obtain.

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