CN101884530A - Flexible Probe Electrode and Its Implantation Tool for Recording Electrical Signals of Neural Activity - Google Patents

Abstract

The invention discloses a flexible probe electrode for recording nerve activity electrical signals, which comprises: a flexible substrate, electrode sites, metal wiring, lead welding points and a flexible insulating layer, wherein the electrode sites and the metal wiring are both It is arranged on a flexible substrate, and each electrode site is connected to the corresponding lead soldering point by a metal connection wire drawn out. There is a flexible insulating layer on the surface of the metal connecting wire, and there is no flexible insulating layer at the electrode site and the metal soldering point. The invention also discloses an implant tool for piercing the flexible probe electrode into tissue. Utilizing the present invention, the electrode has good flexibility and biocompatibility, reduces tissue damage, thus ensures the long-term stability of the electrode work, solves the problem that the hardness of the flexible electrode itself cannot meet the hardness of implantation, and improves the existing The probe-type electrode is easy to cause tissue damage and the long-term recording of the electrode is unstable.

Description

Flexible Probe Electrode and Its Implantation Tool for Recording Electrical Signals of Neural Activity

technical field

The invention relates to the technical fields of neurobiology, material science and microelectronics, in particular to a flexible probe electrode for recording nerve activity electrical signals and an implant tool for piercing the flexible probe electrode into tissue.

Background technique

Electrodes, as a key device for extracting electrophysiological activity signals, are used to perform functional electrical stimulation on biological tissues or record biological activity electrical signals. In many cases, electrodes need to be inserted into biological tissues to achieve the purpose of recording. The electrodes currently used to record electrical signals of nerve activity are based on materials with certain strength such as silicon, metal or glass. The electrodes of these materials can be easily penetrated into biological tissues due to their good strength and hardness and ensure Accuracy of penetration position. However, electrodes with high hardness between soft tissues have extremely poor biocompatibility, which may cause implantation failure or probe electrode failure after a period of time. This is due to the high hardness of the pierced electrodes, long-term placement in the living body will damage the surrounding nerve cells, causing them to degenerate or even die, causing the probe electrodes to lose their recording objects, resulting in implantation failure. Even if the probe electrode is pierced for a long period of time, the nerve cells are not damaged at all, but because the body's rejection reaction will be triggered after the probe electrode is implanted for a long time, a layer of sheath-like fibrous layer tissue will be formed around it. , affect the recording effect of the electrode, and cause the long-term stability of the electrode to be affected. Moreover, the movement of the organism will also cause a slight change in the recording position of the electrode, and the high hardness of the electrode cannot deform it to adapt to this change, which will also lead to long-term instability of the recorded electrical signal.

In order to maintain the long-term stability of the recorded electrical signal without damaging nerve tissue and cells, the present invention proposes a flexible probe electrode based on a polymer substrate. Because this kind of electrode uses a biocompatible polymer material as a flexible substrate, it can be bent and deformed to adapt to the change of the recording position, so it is not easy to cause nerve cell damage, but because of its low hardness, it is not easy or even impossible to be stabbed. Into the soft biological tissue, it is impossible to guarantee the accuracy of the puncture position. Therefore, on the basis of the flexible probe electrode, the present invention proposes an implant tool to help it penetrate into the tissue. The combination of the two can not only maintain the advantages of the existing probe-type electrodes but also make up for their shortcomings.

Contents of the invention

(1) Technical problems to be solved

In view of this, the main purpose of the present invention is to provide a flexible probe electrode and its implantation tool for recording nerve activity electrical signals, so as to ensure the long-term stability of the electrode work and solve the problem that the hardness of the flexible electrode itself cannot meet the implantation hardness. The problem.

(2) Technical solution

In order to achieve the above object, the present invention provides a flexible probe electrode for recording nerve activity electrical signals, including: a flexible substrate, electrode sites, metal wiring, lead solder joints and flexible insulating layers, wherein the electrode sites and the metal wires are set on the flexible substrate, and each electrode site is connected to the corresponding lead soldering point by the metal wire drawn out, the surface of the metal wire has a flexible insulating layer, and there is no flexibility at the electrode site and the metal soldering point Insulation.

In the above solution, the metal wires are biocompatible gold, platinum, titanium nitride or iridium oxide.

In the above solution, both the flexible substrate and the flexible insulating layer are made of biocompatible polyimide or parylene.

In order to achieve the above object, the present invention also provides an implant tool, including a carrier and a surface modification of the carrier. The carrier is made of a material that is biocompatible and has a certain hardness. The surface modification of the carrier is made of polyethylene made from diol.

In the above solution, the biocompatible material with a certain hardness for making the carrier is silicon or glass.

In the above scheme, the surface modification of the carrier is achieved by coating the carrier with hot-melt polyethylene glycol at high temperature.

(3) Beneficial effects

As can be seen from the foregoing technical solutions, the present invention has the following beneficial effects:

1. The flexible probe electrode and its implantation tool for recording nerve activity electrical signals provided by the present invention can make the electrode have Very good flexibility and biocompatibility, reducing tissue damage, thus ensuring the long-term stability of the electrode work; using materials with high hardness and good biocompatibility to make implant tools, and using materials with good biocompatibility Polyethylene glycol (PEG) combines the two, making it easy for the flexible probe electrode to be accurately inserted into the recording position, which solves the problem that the hardness of the flexible electrode itself cannot meet the hardness of the implant.

2. Compared with the currently used probe-type electrodes based on silicon, metal wire or glass with higher hardness, the present invention not only retains the advantages of being able to easily and accurately penetrate into the position to be recorded, but also improves the existing probe Type electrodes are easy to cause tissue damage and the electrode is not stable enough for long-term recording of electrical signals.

Description of drawings

Fig. 1 is the process flow chart of flexible probe electrode manufacturing method among the present invention;

Fig. 2 is the schematic structural view that flexible probe electrode is not covered upper layer insulating layer among the present invention;

Fig. 3 is a structural schematic diagram of the overall appearance of the flexible probe electrode in the present invention;

Fig. 4 is the process flow chart of carrier production method in the present invention;

Fig. 5 is a structural schematic diagram of the overall appearance of the carrier in the present invention;

Fig. 6 is a schematic structural view of the overall structure after the electrode in Fig. 2 is bonded to the carrier in Fig. 4 according to the embodiment of the present invention;

Fig. 7 is a schematic diagram of the embodiment of the present invention in which the overall structure of Fig. 5 penetrates into a living body;

Fig. 8 is a schematic diagram of the structure of the embodiment of the present invention when the carrier in Fig. 4 is pulled out from the living body.

Detailed ways

In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be described in further detail below in conjunction with specific embodiments and with reference to the accompanying drawings.

The flexible probe electrode for recording neural activity electrical signals provided by the present invention includes a flexible substrate, electrode sites, metal wiring, lead welding points and a flexible insulating layer, wherein the electrode sites and metal wiring are all set On the flexible substrate, each electrode site is connected to the corresponding lead soldering point by a metal connection wire drawn out. There is a flexible insulating layer on the surface of the metal connecting wire, and there is no flexible insulating layer at the electrode site and the metal soldering point. The metal connection is made of biocompatible materials such as gold, platinum, titanium nitride or iridium oxide. Both the flexible base and the flexible insulating layer are made of biocompatible materials such as polyimide or parylene.

The flexible probe electrode for recording nerve activity electrical signals provided by the present invention can also be divided into three areas, namely a functional area, a wiring area and a pad area. The functional area includes electrode sites that can record nerve activity electrical signals or perform stimulation, the wiring area includes a wiring structure that enables the functional area and the pad area to form a one-to-one electrical connection, and the pad area includes a probe that can realize Needle electrode and metal pad structure for electrical connection with external equipment and instruments. The electrode sites in the functional area and the metal pad structure in the pad area are formed by depositing a metal film on a flexible polymer substrate with good biocompatibility, and the connection area between the two is a two-way structure. A sandwich structure in which a metal film is sandwiched between layers of polymer material.

The implant tool provided by the present invention includes a carrier and a surface modification of the carrier. The carrier is made of a biocompatible material with a certain hardness, and is used for carrying flexible probe electrodes. The surface modification of the carrier is made of polyethylene glycol, which is used to bond the flexible probe electrode and the carrier together. The biocompatible and rigid material used to make the carrier is silicon or glass. The surface modification of the carrier is achieved by coating the carrier with hot-melt polyethylene glycol at high temperature.

The PEG described in the present invention is liquid at a temperature higher than 50°C, but condenses into a solid at room temperature, and the PEG condensed into a solid can be dissolved by biological fluids. Therefore, the hot-melt PEG is coated on the carrier area, so that the flexible probe electrode is adsorbed by the hot-melt PEG and the carrier, and they are placed at room temperature, and the PEG condenses into a solid, so that the flexible probe electrode and the carrier are bonded together Forming a whole with high hardness, this whole is easy to be accurately inserted into the position to be recorded in the nerve tissue. When the whole body is pierced into the biological tissue, the solid PEG used to bond the flexible probe electrode and the carrier is dissolved when it encounters the biological fluid, and the flexible probe electrode is separated from the carrier. At this time, the carrier can be pulled out of the biological tissue. Only the flexible probe electrodes are left in the biological tissue to record the electrical signals of neural activity. When the carrier is pulled out of the biological tissue, it will not deviate from the insertion position with the flexible probe electrode. This is because, taking the polyimide substrate and silicon as examples, the polyimide substrate and silicon are both hydrophobic. The PEG solution dissolved in the body is hydrophilic. Due to the effect of surface energy, the interface of the two hydrophobic materials has strong adhesion in the aqueous solution, while the interface of the hydrophobic material and the interface of the hydrophilic material has no adhesion in the aqueous solution. It is easy to be separated.

Example 1

The preparation method of the flexible probe-type electrode based on the polymer substrate of the present invention is further described below in conjunction with the accompanying drawings by taking polyimide polymer as an example

1. Soak the silicon wafer 1 in a mixture of concentrated sulfuric acid and hydrogen peroxide (5:1), boil it, rinse it with a large amount of deionized water, blow dry, and dry it in a 250° oven to remove the surface moisture of the silicon wafer. Evaporate 300nm thick metal aluminum 2 as a sacrificial layer, (as shown in Figure 1(a)).

2. Spin-coat polyimide photoresist 3, pre-baked to form the underlying polyimide film, photoetch the electrode morphology, and finally cure with a stepwise heating method to obtain a polyimide film with a thickness of about 5 microns. The amine film was used as the bottom insulating material of the microelectrode, (as shown in Fig. 1(b)).

3. A patterned titanium-gold metal film 4 is formed by metal sputtering and lift-off with adhesive. The Ti/Au metal layer 4 is used to form the electrode point of the electrode, the soldering point of the connection wire and the external lead wire, (as shown in FIG. 1( c )).

4. On the metal layer 4, the upper polyimide film 3 is formed by the method of throwing glue and pre-baking again, and the electrode morphology, electrode positions and solder joints are photoetched, and finally cured to obtain a polyimide film with a thickness of about 5 microns. The imide film was used as the upper insulating material of the microelectrode (as shown in Fig. 1(d)).

5. The Al sacrificial layer 2 is etched away by acid etching or electrochemical etching, so that the electrode 10 is released from the silicon substrate 1 (as shown in FIG. 1( e )).

Example 2

The method of making the carrier will be further described by taking silicon material as an example in conjunction with the accompanying drawings.

1. Prepare and clean the SOI substrate 7 (as shown in FIG. 4( a )).

2. The photoresist is spin-coated, and the shape of the carrier 11 is photo-etched after pre-baking (as shown in FIG. 4( b )).

3. Etching away the SiO ₂ layer 6 in the SOI substrate 7 with HF to release the carrier 11 (as shown in FIG. 4(c)).

Example 3

The method of penetrating the flexible probe electrode into the biological tissue with the help of the implant tool will be further described below in conjunction with the accompanying drawings.

1. Coat the hot-melt PEG on the carrier 11, clamp the flexible probe electrode 10 with tweezers 9, put it on the carrier 11, then cool, and the PEG is solidified. At this time, the carrier 11, the electrode 10 and the solid PEG 8 Form a hard whole, (as shown in Figure 6).

2. Use tweezers 9 to pierce the probe electrode 10 into the position to be recorded in the biological tissue 12, and the solid PEG 8 will dissolve in body fluid, (as shown in Figure 7).

3. Use tweezers 9 to pull out the carrier 11 from the body, leaving only the flexible probe electrode 10 in the body 12 (as shown in FIG. 8 ).

Using this method has the advantages of easy and precise penetration into the recording position, no tissue damage, and good reliability of long-term recorded electrical signals.

The specific embodiments described above have further described the purpose, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above descriptions are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims (6)

1. A flexible probe electrode for recording nerve activity electrical signals, comprising: flexible substrate, electrode sites, metal wiring, lead solder joints and flexible insulating layer, wherein the electrode sites and metal wiring are all arranged on On the flexible substrate, each electrode site is connected to the corresponding lead soldering point by an outgoing metal connection. There is a flexible insulating layer on the surface of the metal connecting wire, and there is no flexible insulating layer at the electrode site and the metal soldering point. 2 . The flexible probe electrode for recording nerve activity electrical signals according to claim 1 , wherein the metal wiring is made of biocompatible gold, platinum, titanium nitride or iridium oxide. 3. The flexible probe electrode for recording nerve activity electrical signals according to claim 1, characterized in that, the flexible substrate and the flexible insulating layer are all made of biocompatible polyimide or polyimide toluene. 4. An implant tool, comprising a carrier and a surface modification of the carrier. The carrier is made of a biocompatible material with a certain hardness, and the surface modification of the carrier is made of polyethylene glycol. 5 . The implant tool according to claim 4 , wherein the biocompatible material with a certain hardness for making the carrier is silicon or glass. 6 . 6. The implant tool according to claim 4, characterized in that, the surface modification of the carrier is achieved by coating the carrier with polyethylene glycol that is melted at a high temperature.

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