CN108903916B - Implantation needle and implantation method of flexible implantation type biosensor and photoelectric device - Google Patents

Abstract

The invention discloses an implant needle of a flexible implantable biosensor and an optoelectronic device and an implantation method thereof. The design of the implant needle is based on the variable cross-sectional size and the top opening design of the flexible implantable biosensor and the optoelectronic device. , the front end of the implant needle adopts a variable cross-section with a sudden or gradual cross-section, and a matching hole is opened at the top of the flexible implantable biosensor and optoelectronic device. Only the front end of the implant needle can pass through the hole, and the variable cross-section is used to limit the position of the sensor. and the device are sent to a designated location inside the biological tissue. After the implanted needle is pulled out, the sensor and device with leads remain in the biological tissue to complete the next detection and treatment function. The invention has simple structure, convenient preparation, low cost, little damage to biological tissues, and the implantation position is precise and controllable. In addition, the method of the present invention only needs to change the size of the implant needle, and can be used for the implantation of flexible implantable biosensors and optoelectronic devices in various biological tissues, and has a wide range of uses.

Description

Implantation needle and implantation method of flexible implantable biosensor and optoelectronic device

Technical Field

The invention relates to an implantable needle for flexible implantable biosensors and optoelectronic devices and an implantation method thereof, which can be used for the implantation of flexible implantable biosensors and optoelectronic devices in biological tissues. The implantable needle has a simple structure and is easy to prepare. Convenient and low-cost; the implantation process is simple and causes little damage.

Background technique

The ever-accelerating pace of modern life puts people's bodies and minds often under high pressure, and neurological diseases such as depression and epilepsy have increased significantly. At the same time, the global population is gradually transitioning to an aging population, and neurodegenerative diseases, muscle atrophy and other diseases have gradually increased and become A big burden on society. Traditional treatments for diseases such as the nervous system and muscle tissue often use a combination of drugs and surgery. However, long-term use of drugs is prone to major side effects, and due to the limitations of people's current understanding of the brain and nerves, the risks of surgery are also high. larger. In order to solve these problems, new technologies such as implantable biosensors, optogenetic devices, and nerve/muscle electrodes have been developed, bringing hope to the majority of patients. With the continuous innovation and development of new technologies, implantable biological/optical/electrical devices are gradually being applied, and are being used for the rehabilitation of patients with Parkinson's disease, epilepsy, motor neuron disorders, stroke, depression, muscle atrophy and other diseases. Play an active therapeutic role.

Traditional implantable biosensors and optoelectronic devices have many advantages such as excellent performance and high reliability. However, their substrates are hard and brittle, making it difficult to withstand large deformations. They are also mismatched with the low modulus of biological tissues, which can easily cause large biological trauma and induce strong inflammatory responses. Immune protein encapsulation of the device makes the device ineffective, shortening the service life of the implantable device. To this end, flexible implantable biosensors and optoelectronic devices based on ultra-thin polymers have been prepared. These flexible devices can withstand bending, fit well with biological tissues, and effectively reduce inflammatory responses, greatly improving the service life of the device and reducing the damage of implanted devices to biological tissues.

The thickness of flexible implantable biosensors and optoelectronic devices is usually only a dozen microns. Due to the instability of the pressure rod, such ultra-thin devices are difficult to be directly implanted into biological tissues, which brings great obstacles to their application and promotion. Therefore, many commercial flexible implantable biosensors and optoelectronic devices still use hard substrates such as silicon and metal as supports to be implanted into biological tissues.

In order to solve the problem of implanting flexible implantable biosensors and optoelectronic devices into biological tissues, several methods have been developed, mainly divided into three types: increasing device thickness, degradable biological coatings, and hard carrier transportation.

The way to increase the thickness of the device is to increase the thickness of the insulating polymer wrapping layer during device preparation or to add a metal layer in the middle of the device. In this way, the bending stiffness of the entire device is improved, and to a certain extent it can be implanted in softer biological tissues such as the brain.

The method of degradable bio-coating is to infiltrate a layer of biodegradable materials such as silk protein, polyethylene glycol, maltose, polyglycolic acid, polylactic acid-polyglycolic acid copolymer (PLGA), etc. on the surface of flexible biological/optical/electrical devices, which increases the size of the entire device and its bending stiffness so that it can be implanted in biological tissues.

The hard carrier transportation method generally uses materials with a large elastic modulus such as epoxy resin and stainless steel as carriers, and uses biodegradable coatings such as silk protein and polyethylene glycol as adhesives. Flexible biological/optical/electrical devices are bonded to the carrier and implanted into biological tissues together. After the liquid inside the biological tissue dissolves the adhesive, the carrier is pulled out.

Typically, existing methods of implanting flexible implantable biosensors and optoelectronic devices each have their own limitations.

First, the disadvantage of the implantation method based on increasing the thickness of the device is that it increases the size of the device, causes greater trauma to biological tissues, and is not suitable for some biological tissues with higher modulus, such as muscles. At the same time, the mismatch between the modulus of the hard carrier and the biological tissue will cause severe mechanical damage and inflammatory reactions.

Second, the disadvantages of implantation methods based on degradable biological coatings are that the coating process is complex, the coating thickness cannot be accurately controlled, and it is not suitable for some biological tissues with high modulus such as muscles.

Third, the disadvantages of the implantation method based on hard carriers are that the carrier processing is complex, the bonding process is difficult, and the cost is high. In addition, the decomposition of the adhesive takes a long time. During this time, the hard carrier remains in the tissue, which will cause a certain degree of inflammatory reaction.

Summary of the invention

In order to solve the above problems, the purpose of the present invention is to propose a method for implanting a flexible implantable biosensor and an optoelectronic device, using an implant needle of variable cross-sectional size combined with a flexible implantable biosensor or optoelectronic device with a front hole. Realize; the cross-sectional area of the front end part of the implant needle shrinks, and forms a boss with a sudden change in area or a frustum with a gradual change in area with the back end part; the front end opening of the flexible implantable biosensor or optoelectronic device, Only the front part of the implant needle can pass through the hole; when implanting biological tissue, pass the front end of the implant needle through the front opening of the flexible implantable biosensor or optoelectronic device, and rely on the implant needle to push the device into the biological tissue. After the device is delivered to the designated location, the implant needle is pulled out, and the flexible implantable biosensor or optoelectronic device remains inside the biological tissue.

In the above technical solution, the implant needle with a variable cross-section design can be a boss with a sudden change in cross-sectional size or a gradual frustum, and can be prepared by but not limited to integrated processing, outer coating, outer hollow tube and the like.

The main body of the implant needle can be made of metal, optical fiber, epoxy resin or carbon fiber.

The coating mentioned in the above-mentioned outer coating method can be fibroin, polyethylene glycol, maltose, polyglycolic acid, polylactic acid polyglycolic acid copolymer (PLGA), etc.

The front opening of the flexible implantable biosensor and optoelectronic device can only allow the front end of the implantation needle to pass through, and the opening forms include but are not limited to any shapes that meet the use conditions, such as circle, square, diamond, polygon, etc.

The implant needle of the present invention adopts a cross-section design with a sudden or gradual change in cross section. The flexible implantable biosensor and the optoelectronic device have a matching hole on the top, and only the front end of the implant needle can pass through the hole. The mating hole passes through the front end of the implant needle, and the flexible implantable biosensor and optoelectronic device are sent into the designated position inside the biological tissue through the boss or cone-shaped limiter. After the implant needle is pulled out, the lead is implanted The biosensor and photoelectric device remain in the biological tissue to complete the next detection and treatment function. The invention is suitable for the precise positioning and implantation of flexible implantable biosensors and optoelectronic devices in the living body, such as flexible brain LEDs in optogenetics, flexible deep brain electrodes, implantable flexible muscle electrodes, and neural repair/ Flexible implantable microstructures for control/electrical stimulation, etc. The implant needle can be removed immediately after the device is implanted, which can effectively reduce mechanical damage and inflammatory reactions caused by the hard carrier.

The invention has simple structure, convenient preparation, low cost, little damage to biological tissues, and the implantation position is precise and controllable. In addition, the method of the present invention only needs to change the size of the implant needle, and can be used for the implantation of flexible implantable biosensors and optoelectronic devices in various biological tissues, and has a wide range of uses.

Description of drawings

Figure 1 is an assembly diagram of the flexible implantable biosensor, optoelectronic device and implant needle proposed in the present invention during implantation.

Figure 2 is a schematic diagram of the flexible implantable biosensor and optoelectronic device implantation method proposed in the present invention.

FIG. 3 is a schematic diagram of the implant needle design and processing scheme proposed in the present invention.

Figure 4 is a design diagram of the top opening of the flexible implantable biosensor and optoelectronic device proposed in the present invention.

Figure 5 is a schematic diagram of a variable cross-section implant needle;

Figure 6 is a schematic diagram of the process of implanting a flexible device into a simulated brain with an implant needle.

In the picture: 1-flexible backing 2-biosensor and optoelectronic device leads and functional parts 3-top opening of backing 4-rear part of implant needle 5-front part of implant needle 6-biological tissue 7-integrated processing Molded boss implant needle 8 - Integrated processing and forming of spade-shaped implant needle 9 - Integrated processing and molding of frustum implant needle 10 - Coating 11 - Implantation needle body 12 - Hollow sleeve 13 - Implantation needle body.

Detailed ways

The content of the present invention will be further described below in conjunction with the accompanying drawings and examples.

Figure 1 is an assembly diagram of the flexible implantable biosensor, optoelectronic device and implant needle before implantation.

The cross-sectional area of the front part 5 of the implant needle shrinks, and forms a boss with a sudden change in area or a frustum with a gradual change in area together with the large cross-sectional area part 4 of the rear end; the front-end opening 3 of the flexible implantable biosensor or optoelectronic device, implant Only the front part 5 of the insertion needle can pass through this hole (Fig. 1a). Before implanting into the biological soft tissue, the small cross-sectional area 5 of the front end of the implant needle is passed through the front end opening 3 (Fig. 1b) of the flexible implantable biosensor and the optoelectronic device to form a fit.

Figure 2 is a schematic diagram of the flexible implantable biosensor and optoelectronic device implantation method proposed by the present invention. The front end portion 5 of the implant needle has passed through the front end opening 3 of the flexible implantable biosensor and the optoelectronic device to form a fit (Fig. 2a). During implantation, as the implant needle penetrates into the biological tissue, the flexible implantable biosensor and optoelectronic device are also brought into the biological tissue (Figure 2b).

After being implanted in the designated location, the implant needle can be pulled out immediately, and the flexible implantable biosensor and optoelectronic device remain in the biological tissue (Figure 2c).

Figure 3 is a schematic diagram of the design and processing scheme of the implant needle proposed in the present invention. The implant needle can be prepared by, but is not limited to, integrated processing and molding (a boss with a sudden change in cross-sectional size or a gradually changing frustum), an outer coating, a hollow outer tube, etc.

In the integrated processing and molding method, the cross-section of the front end of the implanted needle is reduced through mechanical processing or chemical etching on the pre-prepared fine needle head.

The method of reducing the cross-sectional area may be, but is not limited to, boss variable cross-sectional processing (FIG. 3a), shovel-shaped variable cross-sectional processing (FIG. 3b), smooth transition variable cross-sectional processing (FIG. 3c), etc.

In the thin needle coating method, a layer of coating 10 is wrapped on the outside of the thin implant needle 11, but the needle tip is not coated with the coating (Fig. 3d), thereby expanding the cross-sectional area of the rear end of the implant needle.

As an example, but not limiting the content of the present invention, the method of removing the coating on the tip of the fine implant needle 11 may be to first immerse the fine implant needle in the silk protein solution, lift it up and solidify, and then immerse the needle tip part in the artificial cerebrospinal fluid. , remove the coating on the needle tip.

In the method of using a thin implant needle with a hollow sleeve, a hollow sleeve is placed outside the thin implant needle 13 to expand the cross-sectional area of the rear end of the implant needle (Fig. 3e).

As an example, a laser cutting machine is used to cut polyimide tape instead of a flexible brain electrode (Figure 4a). The implanted part of this electrode has a width of 450um and a length of about 7mm. There is a round hole with a diameter of about 200um at the front end of the electrode. The overall thickness is 53um (Figure 4b).

The implanted needle uses the thinnest acupuncture needle on the market, with a diameter of 160um. In order to increase the cross-sectional area of the rear end of the implanted needle, this experiment uses biocompatible water-soluble PEG-2000. Its appearance is a white solid with a melting point of approximately 51±2°C. Weigh 5g of PEG-2000 into a beaker. Place it in an oven at 80°C until it is completely dissolved (Figure 5a). Soak the acupuncture needle in the solution, lift it out and solidify at room temperature. The PEG-2000 infiltrated on the surface of the acupuncture needle solidifies, and the needle tip is scraped off mechanically. PEG-2000 was used to obtain an implant needle with variable cross-section (Figure 5b). From the light microscope image, it can be seen that after the back end of the implant needle is wrapped with a coating, its diameter becomes 250um, forming an implant needle with variable cross-section.

During implantation, the implant needle is passed through the front opening of the flexible brain electrode, and agarose is used as a substitute to simulate the brain. The implant needle and the flexible brain electrode are implanted into it. After implanting into the designated position, pull it out. The needle is implanted and the flexible brain electrode remains in the agarose (Figure 6).

Claims (2)

1. The implantation needle of a kind of flexible implantation type biological sensor and photoelectric device, characterized by that, implantation needle and flexible implantation type biological sensor or photoelectric device of front end trompil of the variable cross-section size cooperate to realize the implantation of the flexible implantation type biological sensor or photoelectric device;

the cross section area of the front end part of the implantation needle is contracted, and a boss with abrupt change of area or a frustum with gradual change of area is formed with the rear end part of the implantation needle; the front end opening of the flexible implantable biological sensor or the photoelectric device can only enable the front end part of the implantation needle to pass through, and the shape of the opening is round or any polygon meeting the requirement of use;

the implantation needle with the variable cross-section size is formed by wrapping a coating, the coating is wrapped on the implantation needle main body to integrally form a variable cross section, specifically, a layer of coating is wrapped outside the implantation needle, and the tip part is not wrapped with the coating, so that the cross section area of the rear end of the implantation needle is enlarged; the coating is fibroin, polyethylene glycol, maltose, polyglycolic acid or polylactic acid-polyglycolic acid copolymer (PLGA);

when the biological tissue is implanted, the front end of the implantation needle penetrates through the front end opening of the flexible implantation type biological sensor or the photoelectric device, the implantation needle is used for pushing the device into the biological tissue, the implantation needle is pulled out after the device is sent to a designated position, and the flexible implantation type biological sensor or the photoelectric device is reserved in the biological tissue.

2. The flexible implantable biosensor and the implant needle of the photoelectric device according to claim 1, wherein the main body of the implant needle is made of metal, optical fiber or carbon fiber material.