WO2025111963A1 - Minimally invasive implant fiber electrode of sheath-core structure and method for preparing same - Google Patents

Abstract

The present disclosure relates to the field of electrophysiological detection and monitoring technology, and in particular, to a minimally invasive implant fiber electrode of a sheath-core structure and a method for preparing same. The method comprises: 1, preparation of printing pastes: separately preparing a conductive paste and an encapsulation paste; 2, loading of pastes: loading the prepared conductive paste into an inner channel, and loading the encapsulation paste into an outer channel; 3, determination of printing track and implant printing: determining a track of printing with the assistance of a magnetic resonance image, drilling using a surgical instrument or directly inserting a coaxial injection needle at a target position, and printing the electrode; and 4, interface design: inserting, after the printing is finished, a lead wire into an end of the uncured coaxial fiber electrode, and allowing the conductive paste and the encapsulation paste to cure in a natural state. The present disclosure significantly reduces the manufacture complexity and cost, greatly reduces surgical traumas, and improves the biocompatibility and long-term stability of the electrode.

Description

A minimally invasive implantable skin-core fiber electrode and a preparation method thereof Technical Field

The invention belongs to the technical field of electrophysiological detection and monitoring, and in particular relates to a skin-core structure fiber electrode for minimally invasive implantation and a preparation method thereof.

Background Art

With the development of science and technology, the monitoring of neuroelectrophysiological signals has become an important means of diagnosing various neurological diseases and one of the key ways to reveal the pathogenesis of diseases. It is widely used in epilepsy monitoring, neural repair and other fields. Although surface electrodes have the advantage of being non-invasive, implantable electrodes can obtain bioelectric signals with higher accuracy, which is crucial for a deep understanding of physiological mechanisms and disease changes. In addition, implantable electrodes can achieve long-term detection, which is of great significance for long-term tracking of diseases and evaluation of treatment effects. Therefore, implantable electrodes show irreplaceable advantages in the field of neuroelectrophysiological signal detection and have broad application prospects.

However, the shape and size of traditional hard or two-dimensional thin-film implant electrodes are difficult to adapt to individual differences and special circumstances of the implant site; traditional electrode implantation requires highly invasive surgery, which causes great pain to patients and may cause tissue damage and infection during the implantation process; the production process of traditional hard implant electrodes is complicated and lengthy, and cannot adapt to the differences between individuals and sites. It is difficult to customize them, and the production cost is high. It is impossible to customize them quickly and use them immediately; some existing electrodes use conductive fillers such as metal particles, which have potential toxicity problems. At the same time, the electrodes lack a packaging layer, which poses a safety hazard and affects the functional stability and long-term reliability of the electrodes. Existing minimally invasive implant electrode technologies, such as those that rely on catheter-assisted implantation, have the risk of positioning deviation, and the method of using degradable materials to temporarily improve mechanical properties has a long degradation time, poor tissue adaptability and comfort, and is prone to acute damage during the implantation process.

An injectable electrode reported in the prior art literature (Advanced healthcare materials, 2019, 8(23): 1900892). The electrode is made of prepolymer and silver microparticle materials. After being injected into the target position by syringe, the material solidifies to form an electrode. This method can reduce surgical trauma and infection risks, but this solution cannot form a fibrous structure, and it is difficult to effectively encapsulate and protect the conductor in one step, and it is difficult to truly achieve on-demand preparation and stable use in specific parts. In addition, the silver filler used in this paper is potentially toxic and easily oxidized, which will affect the functional stability, safety and long-term reliability of the electrode. Therefore, the development of new implantable electrodes using safe materials and less trauma is the current technical demand and development direction.

After continuous exploration and optimization, the applicant successfully adopted a minimally invasive implantation method to achieve efficient and accurate in-situ curing electrode preparation. In terms of material selection, the solution uses carbon fiber as the skeleton material, and selects conductive polymers with good biocompatibility as the active layer, and silicone that is non-toxic to organisms as the coating substrate to ensure that the electrode has good biological stability.

Before the injection, the components are fully mixed to obtain a flowable prepolymer suitable for injection. The prepolymers are then placed in different syringe needles, and the different components are kept separate through coaxial flexible connection pipes, and are formed and cured in situ at the ends to form a skin-core structure. The front needle of the injection printing device directly penetrates into a specific tissue site, and then continuously prints fiber electrodes at the target monitoring position, and the skin-core structure electrode is obtained after the polymer is naturally cured.

Summary of the invention

In view of the defects existing in the above-mentioned prior art, in order to solve the problems of poor conformability, difficulty in electrode customization, complex implantation process, large implantation trauma and high risk of infection in traditional implanted electrodes, the present invention provides a new method for manufacturing coaxial fiber electrodes that are minimally invasively implanted and in situ formed. The present invention uses materials with good biocompatibility to make printing slurry and adopts a minimally invasive implantation preparation method, which significantly reduces the manufacturing complexity and cost, greatly reduces surgical trauma, and improves the biocompatibility and long-term stability of the electrode.

The present invention adopts materials with good biocompatibility to prepare slurry with rheological properties suitable for printing, and uses a syringe to minimally invasively implant the slurry into the biological tissue of the target part through a coaxial channel and quickly solidify it, and prints the coaxial electrode in situ. Thanks to the characteristics of rapid in situ solidification, the electrode can be closely combined with the biological tissue, and can be quickly prepared at a fixed point in the body. At the same time, there is no need for large-area incision and exposure, and it has the advantages of small incisions for minimally invasive implantation, and realizes the in situ printing and minimally invasive implantation of fiber electrodes. In situ solidification can accurately position the electrode at a specific monitoring point according to the anatomical structure and needs of the organism. This precise positioning helps to obtain more accurate and individualized monitoring results. The fiber electrode skin-core structure has the characteristics of self-encapsulation, which can effectively protect the electrode material from the influence of the external environment, help to extend the service life of the electrode, and avoid the instability of the electrode performance during use. The present invention provides a new strategy for minimally invasive implantation and in situ preparation of electrophysiological monitoring electrodes.

In order to achieve the above object, the present invention adopts the following technical solutions:

In one aspect, the present invention provides a method for preparing a skin-core structure fiber electrode for minimally invasive implantation, comprising the following steps:

(1) Making printing paste: preparing conductive paste and encapsulation paste respectively;

Wherein, the conductive paste comprises the following components in percentage by mass: 0-85% conductive filler, 15-90% polymer matrix material, and 0-10% additive;

The encapsulation slurry comprises a polymer capable of rapid prototyping and nano silicon dioxide with a mass concentration of 0-20%;

Among them, adding PEG to the conductive paste helps to improve its dispersibility, allowing CNF to be evenly dispersed in the conductive polymer, thereby improving the rheological properties of the paste. As the main component, silica gel can be combined with CNF, conductive polymer and PEG to give the conductive paste semi-cured properties and formability. At the same time, the encapsulation paste is usually composed of non-toxic materials such as silica gel to protect the electrode and provide biocompatibility. The main function of the encapsulation paste is to cover the conductive paste to form a protective film for the electrode. Protective layer, thereby improving the stability and biocompatibility of the electrode.

The electrode slurry adopts an injectable rheological precursor, which remains in a plastic flow state when injected into the body. It can autonomously conform to the surface morphology of the target tissue and "lock" the optimal highly fitting interface after subsequent in situ curing, thereby ensuring the accurate conformity of the electrode to the biological tissue and improving the stability after implantation.

(2) Loading slurry: The conductive slurry and encapsulation slurry prepared in step (1) are loaded into two syringes respectively and connected to the inner tube and outer tube of the coaxial needle respectively; in this way, the different components can be kept separated so as to be combined at the end to form a coaxial fiber, forming a skin-core structure.

(3) Determine the printing trajectory and implant the print: Use magnetic resonance imaging (MRI) to assist in determining the printing trajectory, use surgical instruments to drill holes at the target location, or directly insert a coaxial needle to start printing the electrode;

During the printing process, the conductive layer slurry of the inner channel is first printed with a length of 0.01-20 mm to form an exposure monitoring point, and then the inner layer and the outer layer are printed synchronously to form a coaxial fiber electrode;

Minimally invasive implantation using a medical syringe can directly inject and solidify the electrode conductive slurry into the target biological body to construct an implantable electrode, avoiding the traditional hard electrode implantation method that requires large-area open surgical exposure and can significantly reduce surgical trauma.

One-step forming of skin-core structure implantable electrode: Using coaxial needle, the one-piece forming of skin-core structure implantable electrode is realized. In this process, the encapsulation layer slurry is injected into the outer channel, and the conductive layer slurry is injected into the inner channel. After the conductive layer slurry is extruded for a section as a signal detection point, the encapsulation layer slurry and the conductive layer slurry are extruded synchronously, so that the encapsulation layer and the conductive layer are formed in one piece at the same time, simplifying the preparation process of the electrode.

(4) Interface design: After the printing in the above step (3) is completed, take the wire and insert it into the end of the coaxial fiber electrode that has not yet solidified, so that the conductive paste and the encapsulation paste are solidified and formed in a natural state.

In the preparation method, the conductive filler in step (1) is selected from a mixture of one or more of carbon materials, conductive polymers, and metal conductive materials;

The polymer matrix material is platinum two-component silica gel;

The additive is selected from a mixture of one or more of polyethylene glycol (PEG) and glycerol.

In the preparation method, the carbon material is selected from a mixture of one or more of carbon nanofibers (CNF), carbon nanotubes, graphene, and carbon black.

In the preparation method, the conductive polymer is selected from a mixture of one or more of poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) (PEDOT:PSS), polypyrrole, and polyaniline.

The preparation method, the metal conductive material is selected from gold nanowires/sheets/particles, silver nanowires/sheets/particles, copper nanowires/sheets/particles, A mixture of one or more of threads/sheets/particles.

In the preparation method, the encapsulation slurry in step (1) is silica gel.

In the preparation method, the particle size of the nano silicon dioxide in step (1) is 1-100 nm.

In the preparation method, the conductive paste and the encapsulation paste are both injectable rheological bodies.

In the preparation method, the curing time in step (4) is 5-30 minutes.

In a second aspect, the present invention provides a skin-core structure fiber electrode for minimally invasive implantation, which is prepared by any of the preparation methods described above.

Compared with the prior art, the present invention has the following beneficial effects:

1. Minimally invasive implantation technology: Compared with traditional hard implant electrodes that require highly invasive open surgery, the present invention adopts a minimally invasive injection implantation method, which can significantly reduce the surgical wound surface, reduce the risk of trauma caused by anesthesia and incision, and make the electrode implantation process safer and more reliable.

2. Flexible preparation: The present invention adopts an injectable flowable polymer, which avoids the tedious steps of designing electrodes according to application requirements before surgery. Different amounts of electrode slurry can be prepared according to specific application requirements, and the length of the fiber electrode can be adjusted, thereby realizing flexible and convenient electrode preparation without complicated prefabricated mold design.

3. Selection of biocompatible materials: The present invention uses carbon fiber as the skeleton material, conductive polymers with good biocompatibility as the active layer, and non-toxic silica gel as the coating substrate. These materials have good biostability and compatibility, making the electrode more stable and reliable in the body.

4. Realize self-packaging of electrodes: The present invention adopts coaxial needle high-precision printing technology. The inner core is a conductive functional layer and the outer shell is a packaging layer. This enables the electrode to have long-term and stable self-packaging performance after implantation. Direct contact between the functional layer and the tissue and effective isolation from the outside can be achieved without additional operation.

5. Good conformability: When printing and injecting into the target site, the slurry of the present invention is still in a plastic flow state, and can conform to the tissue surface morphology autonomously, and lock the best highly fitting interface in the subsequent in-situ curing process, thereby ensuring the accurate conformal coordination between the electrode and the biological tissue and improving the implantation stability.

6. Simple process and low production cost: The present invention adopts safe materials and injection in-situ curing preparation method, which makes the electrode preparation process simpler and faster, reduces the production complexity and cost, and provides a better solution for the preparation of implantable neuroelectrophysiological signal monitoring electrodes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a schematic diagram of minimally invasive implantation of a coaxial fiber electrode according to the present invention, wherein: ① encapsulation layer slurry; ② conductive layer slurry; ③ coaxial structure; ④ exposure monitoring point: conductive layer;

FIG2 is a top view of a coaxial fiber electrode;

FIG3 is a cross-sectional view of a coaxial fiber electrode.

DETAILED DESCRIPTION

The present invention will be further described below with reference to the accompanying drawings and embodiments.

Embodiment 1:

First, carbon nanofibers, PEDOT:PSS, PEG and silica gel were weighed in a mass ratio of 10%, 25%, 5% and 60% respectively, and placed in a deaerator for stirring for 2 minutes to ensure that the conductive layer slurry is fully uniform. Then, the encapsulation layer slurry was prepared by mixing the platinum and two-component silica gel in proportion, and then adding 5% nano-silica and placing in a deaerator for stirring for 2 minutes to eliminate bubbles and ensure uniform mixing.

Set the machine running program and the appropriate air pressure (2.5kg/cm ³ for the conductive layer and 3.5kg/cm ³ for the encapsulation layer), inject the prepared conductive layer slurry and encapsulation layer slurry into two syringes respectively, and place the pistons into the syringes respectively. The two syringes are connected to the two ends of the coaxial needle respectively, where the conductive layer slurry is connected to the inner channel and the encapsulation layer slurry is connected to the outer channel (as shown in Figure 1), and then connect the syringe-air pump connector and start printing to prepare the electrode. During the printing process, the conductive layer slurry of the inner channel is first printed with a length of 2mm to form an exposure monitoring point, and then the inner and outer layers are printed synchronously to form a coaxial fiber electrode.

After printing, take the wire and insert it into the end of the uncured coaxial fiber electrode, so that the conductive paste and the encapsulation paste are cured and formed in a natural state for 10 minutes.

Through microscopic observation (as shown in Figures 2 and 3), it can be clearly seen that the encapsulation layer completely wraps the conductive layer, and a fiber electrode with a skin-core structure is successfully prepared, proving that the invention can achieve the desired goal.

Embodiment 2:

First, carbon nanofibers, PEDOT:PSS, PEG and silica gel were weighed in a mass ratio of 10%, 25%, 7.5% and 57.5%, respectively, and placed in a deaerator for stirring for 2 minutes to ensure that the conductive layer slurry is fully uniform. Then, the encapsulation layer slurry was prepared by mixing the platinum and two-component silica gel in proportion, and then adding 10% of nano-silica and placing in a deaerator for stirring for 2 minutes to eliminate bubbles and ensure uniform mixing.

Set the machine running program and the appropriate air pressure (2kg/cm ³ for the conductive layer and 3kg/cm ³ for the encapsulation layer), inject the prepared conductive layer slurry and encapsulation layer slurry into two syringes respectively, and put the pistons into the syringes respectively. The two syringes are connected to the two ends of the coaxial needle respectively, where the conductive layer slurry is connected to the inner channel, and the encapsulation layer slurry is connected to the outer channel. Then, after connecting the syringe-air pump connector, printing starts for electrode preparation, and a fiber electrode with a skin-core structure is successfully prepared. During the printing process, the conductive layer slurry of the inner channel is first printed with a length of 5mm to form an exposure monitoring point, and then the inner and outer layers are printed synchronously to form a coaxial fiber electrode.

After printing, take the wire and insert it into the end of the uncured coaxial fiber electrode, so that the conductive paste and the encapsulation paste are cured and formed in a natural state for 13 minutes.

Claims (10)

A method for preparing a skin-core structure fiber electrode for minimally invasive implantation, characterized in that it comprises the following steps: (1) Making printing paste: preparing conductive paste and encapsulation paste respectively; Wherein, the conductive paste comprises the following components in percentage by mass: 0-85% conductive filler, 15-90% polymer matrix material, and 0-10% additive; The encapsulation slurry comprises a polymer capable of rapid prototyping and nano silicon dioxide with a mass concentration of 0-20%; (2) Loading slurry: Load the conductive slurry and encapsulation slurry prepared in step (1) into two syringes respectively, and connect them to the inner pipe and outer pipe of the coaxial needle respectively; (3) Determine the printing trajectory and implant the print: Use magnetic resonance imaging to assist in determining the printing trajectory, use surgical instruments to drill holes at the target location, or directly insert a coaxial needle to start printing the electrode; During the printing process, the conductive layer slurry of the inner channel is first printed with a length of 0.01-20 mm to form an exposure monitoring point, and then the inner layer and the outer layer are printed synchronously to form a coaxial fiber electrode; (4) Interface design: After the printing in the above step (3) is completed, take the wire and insert it into the end of the coaxial fiber electrode that has not yet solidified, so that the conductive paste and the encapsulation paste are solidified and formed in a natural state. The preparation method according to claim 1, characterized in that the conductive filler in step (1) is selected from a mixture of one or more of carbon materials, conductive polymers, and metal conductive materials; The polymer matrix material is platinum two-component silica gel; The additive is selected from a mixture of one or more of polyethylene glycol and glycerol. The preparation method according to claim 2, characterized in that the carbon material is selected from a mixture of one or more of carbon nanofibers, carbon nanotubes, graphene, and carbon black. The preparation method according to claim 2, characterized in that the conductive polymer is selected from a mixture of one or more of poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid), polypyrrole, and polyaniline. The preparation method according to claim 2, characterized in that the metal conductive material is selected from a mixture of one or more of gold nanowires/sheets/particles, silver nanowires/sheets/particles, and copper nanowires/sheets/particles. The preparation method according to claim 1, characterized in that the encapsulation slurry in step (1) is silica gel. The preparation method according to claim 1, characterized in that the particle size of the nano-silicon dioxide in step (1) is 1-100 nm. The preparation method according to claim 1 is characterized in that the conductive paste and the encapsulation paste are both injectable rheological bodies. The preparation method according to claim 1, characterized in that the curing time in step (4) is 5-30 minutes. A skin-core structure fiber electrode for minimally invasive implantation, characterized in that it is prepared by the preparation method according to any one of claims 1-9.