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CN-115399777-B - Flexible double-sided nerve probe and preparation method thereof

CN115399777BCN 115399777 BCN115399777 BCN 115399777BCN-115399777-B

Abstract

The invention provides a flexible double-sided nerve probe and a preparation method thereof, wherein the probe comprises a first insulating layer, a conducting wire layer and a second insulating layer which are sequentially arranged from bottom to top, the first insulating layer and the second insulating layer are flexible polymer insulating layers, a bottom electrode point communicated with the conducting wire layer is arranged on the first insulating layer, a top electrode point communicated with the conducting wire layer is arranged on the second insulating layer, the top electrode point and the bottom electrode point are both formed by nuclear magnetic compatible materials, and omnibearing electroencephalogram acquisition and directional electric stimulation are realized through the bottom electrode point and the top electrode point. The probe provided by the invention has the electrode point structure with double-sided arrangement, can meet the requirements of omnibearing electroencephalogram acquisition, has higher electrode point density, and can perform directional electric stimulation, so that the accuracy of neural activity intervention can be improved.

Inventors

  • LIU JINGQUAN
  • CAO JIAWEI
  • WANG LONGCHUN
  • GUO ZHEJUN

Assignees

  • 上海交通大学
  • 上海交通大学

Dates

Publication Date
20260421
Application Date
20220902
Priority Date
20220902

Claims (9)

  1. 1. The flexible double-sided nerve probe is characterized by comprising a first insulating layer, a wire layer and a second insulating layer which are sequentially arranged from bottom to top; The first insulating layer and the second insulating layer are flexible polymer insulating layers, a bottom electrode point communicated with the conducting wire layer is arranged on the first insulating layer, a top electrode point communicated with the conducting wire layer is arranged on the second insulating layer, the top electrode point and the bottom electrode point are both formed by adopting nuclear magnetic compatible materials, and omnibearing electroencephalogram acquisition and directional electric stimulation are realized through the bottom electrode point and the top electrode point; The tail end of the probe is provided with a tail end connector, the tail end connector is used for being electrically connected with an external circuit, the conducting wire layer is used for conducting nerve signals from the top electrode point and the bottom electrode point to the tail end connector, and the bottom electrode point and the top electrode point are both carbon electrode points; The bottom electrode point and the top electrode point are formed through laser direct writing, and the diameters of the top electrode point and the bottom electrode point are 10-200 microns.
  2. 2. The flexible two-sided nerve probe of claim 1, wherein the geometry of the top electrode points and the bottom electrode points is any one or a combination of any of a circle, rectangle, and triangle.
  3. 3. The flexible two-sided nerve probe of claim 1, wherein the top electrode points and the bottom electrode points each comprise a collection point and a stimulation point, and the collection points and the stimulation points are arranged in a manner that is set according to brain region distribution.
  4. 4. The flexible double-sided nerve probe according to claim 1, wherein the material of the flexible polymer insulating layer is any one of non-photosensitive polyimide, photosensitive polyimide and parylene, and the thickness of the probe is 1-50 micrometers.
  5. 5. The flexible two-sided nerve probe of claim 1, wherein the wire layer comprises a conductive layer and an adhesive layer for adhering the conductive layer to the first insulating layer, the conductive layer is located above the adhesive layer, the adhesive layer has a thickness of 10-100 nanometers, and the conductive layer has a thickness of 200-500 nanometers.
  6. 6. The flexible two-sided nerve probe of claim 1, wherein the implantation end of the probe is provided with a steel needle auxiliary implantation hole for the penetration of a steel needle to facilitate implantation of the probe to a desired location.
  7. 7. A method of preparing the flexible two-sided nerve probe of any one of claims 1-6, comprising: Providing a substrate, and depositing a layer of metal on the substrate to form a sacrificial layer; Spin-coating and patterning the sacrificial layer to obtain a first insulating layer, and forming a bottom electrode point at each electrode point of the first insulating layer by adopting a micromachining process; Sequentially depositing an adhesion layer and a conductive layer on the first insulating layer, spin-coating positive photoresist as a mask, and performing pre-baking, exposure, development and post-baking, and etching by adopting an ion beam or wet method to obtain a wire layer; Spin-coating and patterning a second insulating layer on the patterned wire layer, and forming a top electrode point at each electrode point of the second insulating layer by adopting a micromachining process; and corroding or dissolving the sacrificial layer to finish the release of the electrode, thereby obtaining the flexible double-sided nerve probe.
  8. 8. The method of claim 7, wherein the providing a substrate and depositing a metal layer on the substrate forms a sacrificial layer, wherein the sacrificial layer is made of aluminum metal, and the thickness of the sacrificial layer is greater than 200nm.
  9. 9. A method of preparing the flexible two-sided nerve probe of any one of claims 1-6, comprising: providing a substrate; forming a first insulating layer on the substrate; forming a bottom electrode point at the electrode point of the first insulating layer by using a micromachining process; sequentially depositing an adhesive layer and a conductive layer on the first insulating layer, throwing positive photoresist on the conductive layer, developing after exposure, and post-baking, and then forming a wire layer by wet etching; forming a second insulating layer on the wire layer; forming a top electrode point at the electrode point of the second insulating layer by using a micromachining process; Throwing positive photoresist on the second insulating layer, developing and baking after photoetching to form grooves around electrode points of the top layer and the whole outline of the electrode, and etching out the tail end connecting port which is not covered by the positive photoresist and the whole outline of the electrode; finally, the formed electrode is torn off from the substrate, and the flexible double-sided nerve probe is obtained.

Description

Flexible double-sided nerve probe and preparation method thereof Technical Field The invention relates to the technical field of brain-computer interface nerve microelectrodes, in particular to a flexible double-sided nerve probe and a preparation method thereof. Background The implanted brain-computer interface is an important tool for brain science and brain-like research, can be directly contacted with neurons, can acquire and transmit richer information with brain neurons, and has important significance for brain science research, brain disease diagnosis and treatment and brain-computer interaction research. The implantable brain-computer interface can accurately interact with the brain using electricity and diagnose diseases by monitoring the electrical activity of the brain, bringing a very optimistic prospect. In addition, brain-computer interface technology can also restore vision and hearing, generate synthetic speech, and help treat obsessive-compulsive disorder, addiction, parkinsonism and other diseases. The interface characteristic of the implant and the neuron is the key of brain-computer interaction, and the essence of the electroencephalogram signal acquisition and the neuron electrical stimulation is the charge transmission and regulation between the electrode and the neuron. The flexible implanted brain-computer interface has unique advantages in the aspect of low damage, but the traditional flexible electrode array has insufficient acquisition channels, the acquisition neuron number can not meet the requirements of neuroscience research and nerve encoding and decoding, the implanted electrode is usually a single-sided electrode, the omnibearing acquisition of brain-computer signals is not facilitated, and the implanted electrode material can generate artifacts, heat and certain displacement in fMRI. The design that the arrangement density of the electrode points changes along with the brain region realizes that the arrangement of the electrode points in different brain regions and different cortex depth space densities and the directionality of stimulation are adjustable, and the omnibearing stimulation function of the electrode points is improved. For prior art searches, it was found by the florfenhough biomedical engineering institute Thomas Stieglitz et al, sensors and Actuators A:physical,2001,90 (3): 203-211, that write articles "Flexible biomedical microdevices with double-sided electrode arrangements for neural applications", proposed a flexible double sided electrode using aluminum hard mask patterning, prepared by multi-step spin coating, deposition and etching processes, which required multi-step exposure in patterning the various layers of material, complicated the preparation process, and simultaneously, after the electrode front side patterning was completed, the flexible substrate was separated from the rigid substrate and flipped over for attachment, which is detrimental to large area batch preparation, and the process required extreme care, as the thin film had to be very smoothly placed on the wafer to ensure proper, uniform and repeatable etching. It is difficult to accurately position the film on the wafer during the process and place it without trapping any bubbles or bending the film, which makes the manufacturing process time consuming and prone to large yield losses. The Switzerland Songxi institute of federal regulations S.Metz et al in Biosens.bioelectron.19,1309-1318 (2004) write articles "Flexible polyimide probes with microelectrodes and embedded microfluidic channels for simultaneous drug delivery and multi-channel monitoring of bioelectric activity", proposed a double sided polyimide structure fabricated using lamination techniques, also incorporating microfluidic channels. The process is relatively simple because only one metallization step is required to make contacts on both sides. However, this technique cannot be used to create a structure with two electrode points at the same location on both sides. In addition, the electrode points on the top surface of the prepared probe are concave, and the electrode points on the bottom surface are not concave, so that the two surfaces of the probe have different current density distribution, and the acquisition and stimulation effects of nerve signals are affected. In summary, forming electrode points on both sides of the nerve probe can improve the density of nerve signal acquisition, realize the omnidirectional nerve signal acquisition and stimulation, and further meet the requirements of multiple brain areas and high density in rodent research. Therefore, there is a need to develop a flexible probe electrode with a double-sided electrode structure and good processing characteristics for application to biological tissues. Disclosure of Invention Aiming at the defects in the prior art, the invention aims to provide a flexible double-sided nerve probe and a preparation method thereof. According to one aspect of the