CN109663208B

CN109663208B - Flexible nerve electrode based on multilayer stacked structure substrate and manufacturing method

Info

Publication number: CN109663208B
Application number: CN201910115917.9A
Authority: CN
Inventors: 张文光; 谢颉; 周旭晖; 李伟
Original assignee: Shanghai Jiaotong University
Current assignee: Shanghai Jiaotong University
Priority date: 2019-02-15
Filing date: 2019-02-15
Publication date: 2022-04-26
Anticipated expiration: 2039-02-15
Also published as: CN109663208A

Abstract

The invention discloses a flexible nerve electrode based on a multilayer stacked structure substrate, which comprises a conductive part and a substrate connected with the conductive part, and is characterized in that the substrate is formed by stacking at least two layers of polymers with different Young modulus according to a sandwich-like structure. The invention also discloses a manufacturing method of the flexible nerve electrode, and each layer of polymer of the substrate is processed by the MEMS process, so that the volume and the manufacturing difficulty of the substrate are reduced. The invention has small volume, can be conveniently implanted into brain tissue, can be well adapted to nerve tissue after being implanted into the brain tissue, can effectively relieve the contradiction between the difficulty of electrode implantation and the nerve injury degree caused by the electrode, and has simpler processing technology.

Description

Flexible nerve electrode based on multilayer stacked structure substrate and manufacturing method

Technical Field

The invention relates to the field of flexible nerve electrodes, in particular to a flexible nerve electrode based on a multilayer stacked structure substrate and a manufacturing method thereof.

Background

Neuroscience and neuro-engineering require research into the electrical activity of brain neurons to understand the mechanisms by which the brain generates, transmits, and processes information. The implanted nerve electrode is used as a sensing device and can record the electrical activity of the nervous system. The nerve electrode can also apply electrical stimulation to specific areas of the brain or peripheral nerves to inhibit abnormal nerve signals, is used for treating diseases such as Parkinson's disease or other chronic pains and can also restore the movement of paralyzed limbs through functional electrical stimulation. Since the neural electrode is implanted in a living body, its size, structure, biocompatibility and biostability must be considered.

Despite the more widespread clinical use of implantable neural electrodes in recent years, long-term stimulation to record neuronal neural activity remains a significant challenge, among othersMismatches between the electrode and the neural tissue can cause tissue adverse reactions that affect the electrode life and the quality of the recorded neural electrical signals. Most of the developed nerve electrodes at present adopt silicon as a substrate material, and the silicon has good biocompatibility and has the advantage of being compatible with a microelectronic processing process of a CMOS (complementary metal oxide semiconductor). However, the Young's modulus of silicon can reach about several hundred GPa, and the hardness of brain tissue is about 10^-6Gpa, mechanical mismatch caused by the difference in hardness between brain tissue and silicon substrate nerve electrodes, aggravates chronic inflammation caused by fretting damage, which is one of the causes of tissue damage and influences the long-term stability of the electrodes. In this regard, more and more researchers are considering young's modulus as an optimal design factor for neural electrodes. The Young modulus reflects the flexibility degree of the electrode, the flexible electrode can be well matched with the nervous tissue after being implanted into the brain tissue, damage to the nervous tissue is reduced, the service life of the electrode is prolonged, and the working stability of the electrode is improved.

The existing flexible electrode is mainly realized by a flexible substrate material, and materials such as polyimide, parylene and SU-8 have high mechanical matching with brain tissue due to small Young modulus, so that the flexible electrode is widely applied to the manufacture of the flexible electrode. However, the flexible electrode has great difficulty in the process of implanting into brain tissue, is very easy to warp, and is difficult to reach a target position or cannot be implanted. Therefore, the implantation of the flexible electrode usually needs to be assisted by an auxiliary tool or the implantation rigidity is increased by the degradable coating, and the implantation process is complicated.

Therefore, those skilled in the art have devoted themselves to develop a flexible neural electrode based on a substrate with a multi-layer stacked structure and a manufacturing method thereof, which can be conveniently implanted into brain tissue, can be well adapted to neural tissue after being implanted into brain tissue, and has a simple and easy-to-implement manufacturing process.

Disclosure of Invention

In view of the above defects in the prior art, the technical problem to be solved by the present invention is how to solve the problems of great difficulty, complicated implantation process and complicated substrate manufacturing in the process of implanting the traditional flexible electrode into the brain tissue through a reasonable design.

In order to achieve the purpose, the invention provides a flexible nerve electrode based on a substrate with a multilayer stacked structure, which comprises a conductive part and a substrate connected with the conductive part, and is characterized in that the substrate is formed by stacking at least two layers of polymers with different Young moduli according to a sandwich-like structure.

Further, the number of the polymer layers is three, and the Young modulus of the outermost layer polymer and the Young modulus of the innermost layer polymer are both larger than that of the middle layer polymer, or the Young modulus of the middle layer polymer is larger than that of the outermost layer polymer and that of the innermost layer polymer.

Furthermore, the Young's modulus of the polymers in each layer is 5.5Gpa for the polymer in the middle layer, and 8.5Gpa for the polymers in the other two layers.

Furthermore, the polymer of each layer has the same shape and size, and is of a handle-shaped structure with a wedge-shaped angle at one end.

Further, the corner tip of the wedge-shaped angle is a round angle.

Further, the polymer of each layer has the same density and poisson's ratio.

Further, the thickness of each layer of the polymer is 0 to 10 μm.

Further, the polymer material is polyimide, parylene or SU-8.

The invention also discloses a manufacturing method of the flexible nerve electrode based on the substrate with the multilayer stacked structure, which realizes that each polymeric layer has different Young modulus by selecting materials with different Young modulus or adjusting parameters of the same polymer material in the curing process.

Further, the flexible neural electrode is manufactured based on a MEMS process.

Compared with the prior art, the flexible neural electrode based on the multilayer stacked structure substrate and the manufacturing method thereof provided by the invention have the following beneficial effects:

1) the substrate is stacked by adopting polymers with different Young moduli according to a sandwich-like structure to form a handle-shaped shape with one end being a wedge-shaped fillet, so that compared with a common flexible electrode, the flexible electrode is not easy to warp and is convenient to implant;

2) the polymer material is made of polyimide and other materials with smaller Young modulus, and is well adapted to the nervous tissue after being implanted into the brain tissue, so that damage to the nervous tissue is reduced; and the polymers are connected through functional groups, so that the long and stable working life is ensured

3) The method is simple and easy to control by selecting materials with different Young modulus or controlling related parameters in the curing process to change the Young modulus of the polymer of the adjacent layer;

4) the substrate polymer is manufactured through a processing process based on an MEMS (micro-electromechanical systems) process, and compared with a processing process of a polymer-silicon combined nerve electrode, the processing process is simpler.

The conception, the specific structure and the technical effects of the present invention will be further described with reference to the accompanying drawings to fully understand the objects, the features and the effects of the present invention.

Drawings

FIG. 1 is a schematic view of a substrate with a multi-layer stack structure of a flexible neural electrode according to a preferred embodiment of the present invention;

FIG. 2 is a schematic substrate view of a three-layer polymer layer stack according to another preferred embodiment of the present invention;

FIG. 3 is a front view of an embodiment of a substrate of the three-layer stack shown in FIG. 2;

FIG. 4 is a side view of an embodiment of a substrate of the three-layer stack structure shown in FIG. 2; .

Detailed Description

The technical contents of the preferred embodiments of the present invention will be more clearly and easily understood by referring to the drawings attached to the specification. The present invention may be embodied in many different forms of embodiments and the scope of the invention is not limited to the embodiments set forth herein.

In the drawings, structurally identical elements are represented by like reference numerals, and structurally or functionally similar elements are represented by like reference numerals throughout the several views. The size and thickness of each component shown in the drawings are arbitrarily illustrated, and the present invention is not limited to the size and thickness of each component. The thickness of the components may be exaggerated where appropriate in the figures to improve clarity.

Example one

FIG. 1 is a schematic view of a substrate of a multi-layered stack structure of a flexible neural electrode according to a preferred embodiment of the present invention.

In this embodiment, the flexible neural electrode is composed of a conductive portion and a substrate 1 connected to the conductive portion.

As shown in fig. 1, the substrate 1 is formed by stacking at least two layers of polymers with different young's moduli according to a sandwich-like structure, and the number of layers and young's moduli of the polymers may be determined according to the bending degree of the brain tissue space and the implantation path to be actually implanted. Preferably, the smaller the brain tissue space to be implanted, the more tortuous or fragile the implantation path, the fewer layers of polymer should be chosen to reduce the volume of the substrate 1; the young's modulus of the polymer should be smaller to facilitate less traumatic passage through the implant path.

Based on the substrate 1 with the multilayer stacked structure, the polymer layer with the larger Young modulus can support and fix the shape of the whole flexible nerve electrode in the implantation process, and the polymer layer with the smaller Young modulus optimizes the softness of the whole flexible nerve electrode, so that the risk of damaging brain tissue in the implantation process and after implantation can be reduced. The substrate 1 has the advantages that the Young modulus of the inner layer polymer is larger, the Young modulus of the outer layer polymer is smaller, the flexible nerve electrode is better matched with the nerve tissue after being implanted into the brain tissue, the mechanical matching performance is better, the damage to the nerve tissue is reduced, and the flexible nerve electrode is suitable for scenes with wider implantation paths and low requirements on the rigidity of the nerve electrode; the Young modulus of the outer polymer is high, the flexible nerve electrode can be maintained not to be warped easily in the implantation process, and the flexible nerve electrode is suitable for occasions with narrow and complex implantation path space and high requirements on the rigidity of the nerve electrode. Preferably, the young's modulus of the polymer layer may exhibit a gradient decreasing from outside to inside, a gradient increasing from outside to inside, or a staggered arrangement.

In this example, as shown in fig. 1, three layers of polymers are stacked in a sandwich-like structure, and the young's modulus of the middle layer of polymer is 5.5Gpa, and the young's modulus of the outermost and innermost layers of polymer is 8.5 Gpa. Compared with the Young modulus of the three-layer polymer which is gradually increased or gradually decreased, the Young modulus 'big-small-big' mode of the embodiment is adopted for stacking, so that certain rigidity is not easy to warp in the implantation process of the nerve electrode, certain buffering deformation is realized, and the relatively stable working environment of the conductive part can be ensured, so that signal acquisition or electric output interference is smaller, the monitoring or treatment effect of the nerve electrode is improved, and the service life of the nerve electrode is prolonged.

The polymer materials of each layer of the substrate 1 should be selected from materials with good biocompatibility, the silicon substrate is mature at present, and considering that the Young modulus of the silicon material can reach about hundreds of Gpa, while the small Young modulus of the polyimide, the parylene, the SU-8 and the like which are commonly used for the flexible nerve electrode based on the single-layer substrate is larger in adjacent polymerization difficulty with the silicon material, preferably, the polymers of each layer are all made of materials with small Young modulus and good biocompatibility, such as the polyimide, the parylene, the SU-8 and the like. Due to the characteristics of the polymers, the stacking of the polymers of each layer is realized by connecting a large number of functional groups on the surfaces of the polymers, so that the polymers of each layer are not easy to fall off, and the long and stable service life is ensured.

Example two

Fig. 2 is a schematic view illustrating a substrate based on a multi-layered stack structure according to another preferred embodiment of the present invention, and fig. 3 and 4 are a front view and a side view, respectively, illustrating the substrate of fig. 2.

For the convenience of implantation, each layer of the polymer is preferably uniform in shape and size and is a handle-like structure with a wedge-shaped angle at one end. In order to avoid the injury of the brain tissue or the nerve tissue of the wedge angle during the implantation process or after the implantation, the angle tip of the wedge angle is preferably a round angle.

To keep the deformation properties of the polymers of the layers the same and to prevent too large a difference in young's modulus for relative movement between the polymers of the layers along the abutting surfaces under an external force, it is preferred that the poisson's ratios of the polymers of the layers are the same.

In order to prevent the flexible nerve electrode from moving relative to the implantation position or from overturning due to non-corresponding gravity center and torque, the density of each layer of polymer is preferably the same and is greater than the cerebrospinal fluid density in consideration of the brain tissue environment where the flexible nerve electrode substrate 1 is located.

Furthermore, considering that the present embodiment can be applied to various tissues of different individuals, preferably, the length a, the width b, the angle α of the wedge angle and the fillet radius R of the handle-like structure, and the thickness h of each layer of polymer can be adjusted according to actual conditions.

In this example, the Poisson's ratio of each layer of polymer was 0.33, and the density of each layer of polymer was 1470kg/m³。

To ensure optimum implantation, it is preferred that the total length a of each layer of polymer is set to 2.5-5mm, the width b is set to 100-200 μm, the wedge angle α is set to 30-50 °, and the radius R of the wedge angle is set to 5-15 μm. Due to spatial limitations of the brain tissue, the monolayer polymer thickness h is preferably 0-10 μm.

In this example, the total length a of each layer of polymer was set to 3mm, the width b to 120 μm, the wedge angle α to 45 °, the radius R of the wedge angle to 10 μm, and the thickness h of each layer to 5 μm.

Considering direct contact with nerve tissue, it is preferable that the young modulus of the polymer in direct contact therewith is not more than 20Gpa, preventing damage to local tissue, and the problem that the nerve electrode having a higher young modulus is easily slipped under an external force.

EXAMPLE III

In the process of manufacturing the flexible neural electrode based on the substrate with the multi-layer stacked structure, the polymers of each layer can be selected from materials with different Young's moduli, or can be selected from the same material and controlled in the curing process so as to form the polymers with different Young's moduli of each layer.

In addition, since the volume of the nerve electrode is mainly determined by the substrate 1, it is important to reduce the size of the substrate 1 and obtain a smaller nerve electrode by selecting an appropriate processing method. Considering that the substrate 1 of the present embodiment is stacked by a sandwich-like structure, the present embodiment manufactures the polymers with different young's moduli based on the Micro-Electro-Mechanical Systems (abbreviated as MEMS) process, the process flow is simpler than the process flow of the polymer-silicon combined neural electrode, and the MEMS process can complete the connection of the polymers of the layers of the substrate 1 and the connection of the substrate 1 and the conductive portion in a smaller space range.

It should be noted that the substrate 1 based on the multi-layer stacked structure according to the present invention may be connected to the conductive part in a structure similar to a pencil stick and a pencil lead, and the conductive part is wrapped around the circumference of the substrate of the multi-layer stacked structure, or the conductive part may be sandwiched in a sandwich structure of handle-like adjacent polymer layers, similar to the embodiment.

The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.

Claims

1. The flexible nerve electrode based on the multilayer stacked structure substrate comprises a conductive part and the substrate connected with the conductive part, and is characterized in that the substrate is formed by stacking three layers of polymers with different Young moduli according to a sandwich-like structure, the Young modulus of the middle layer of polymer is 5.5Gpa, the Young moduli of the outermost layer of polymer and the innermost layer of polymer are 8.5Gpa, and the substrate is configured to wrap or sandwich the conductive part.

2. The flexible neural electrode based on a substrate with a multi-layered stacked structure of claim 1, wherein each layer of said polymer has a uniform shape and size and is a handle-like structure with a wedge-shaped angle at one end.

3. The flexible neural electrode based on a multi-layered stacked structural substrate of claim 2, wherein a corner tip of the wedge angle is a rounded corner.

4. The flexible neural electrode based on a substrate with a multi-layered stacked structure of claim 2, wherein the density and poisson's ratio of each layer of said polymer are the same.

5. The flexible neural electrode based on a substrate with a multi-layered stacked structure according to claim 2, wherein each layer of the polymer has a thickness of 0-10 μm.

6. The flexible neural electrode based on a multilayer stacked structure substrate of claim 1, wherein the polymer material is polyimide, parylene, or SU-8.

7. A method for manufacturing a flexible neural electrode based on a substrate with a multi-layered stacked structure according to any one of claims 1-6, wherein the different Young's moduli of the polymers in each layer are achieved by selecting materials with different Young's moduli, or adjusting parameters of the same polymer material during curing.

8. The method of claim 7, wherein the flexible neural electrode is fabricated based on a MEMS process.