CN115486848A - Multi-electrode contact micro carbon-based biological nerve regulation probe and preparation method thereof - Google Patents

Abstract

The invention provides a multi-electrode contact micro carbon-based biological nerve regulation probe and a preparation method thereof, belonging to the technical field of probes and comprising the following steps: the carbon-based conductive film layer is arranged in the area of the surface of the probe body except the head of the electrode, a plurality of electrode stimulating contacts and corresponding electrode leads are formed after laser etching and are distributed at intervals along the circumferential direction of the probe body respectively, each electrode lead extends to the tail of the probe body from the corresponding electrode stimulating contact respectively, and each electrode lead is connected to external equipment from a lead welding point through an electrode external lead respectively; and the insulating layer is arranged in the middle area of the probe body, covers the surfaces of the electrode leads and fills gaps among the electrode leads. The probe of the invention has more flexible texture and less damage to brain tissues; the carbon-based conductive film is used as an electrode stimulation contact and a lead in the brain, so that induction current is not easy to generate, brain tissue is prevented from being damaged, and a detection and stimulation device is prevented; realize the multi-electrode stimulating contact on the single micro-probe.

Description

Multi-electrode contact micro carbon-based biological nerve regulation probe and preparation method thereof

Technical Field

The invention relates to the technical field of probes, in particular to a multi-electrode contact micro carbon-based biological nerve regulation and control probe and a preparation method thereof.

Background

Cortical electroencephalography (ECoG) arrays and Deep Brain Stimulation (DBS) are commonly used as invasive Brain tissue stimulation and information acquisition technologies, and are currently applied to Brain Computer Interface (BCI) treatment and research in medical treatment.

The DBS electrode is mainly made of hard metal, such as platinum-titanium alloy, platinum-iridium alloy, stainless steel, tungsten wire, and the like. The ECoG electrodes are mainly Utah Electrode (UEA) and Michigan Electrode. Compared with DBS electrodes, the DBS electrodes form an electrode array, and can stimulate and record activity information of single neurons at high spatial and temporal resolution; each electrode column is provided with a plurality of electrode contacts, the integration level of the electrode contacts is higher, neuron activities at different depths can be detected and stimulated, ECoG electrodes such as other electrodes and Michigan arrays and DBS electrodes are fine semiconductor material hard electrodes which are brittle and easy to break, and scar tissues (scartissue) can be generated after the rigid metal electrodes are implanted because biological brain tissues are soft; meanwhile, in the multi-modal stimulation and detection information extraction process of nuclear magnetic resonance and the like, under the action of metal, a large undetected 'shadow' exists near the metal probe, so that local information cannot be extracted and detected, and the electrode stimulation and information extraction effects are reduced; and the metal electrode is easy to generate magnetic induction current, thereby damaging brain tissues and testing instruments.

Disclosure of Invention

In order to solve the technical problems, the invention provides a multi-electrode contact micro carbon-based biological nerve regulation and control probe and a preparation method thereof.

The technical problem solved by the invention can be realized by adopting the following technical scheme:

a biological neuromodulation probe for a multi-electrode contact, comprising:

the probe comprises a probe body, wherein an electrode head is formed at the head of the probe body;

the carbon-based conductive film layer is arranged on the surface of the probe body except the head of the electrode, and is subjected to laser etching to form a plurality of electrode stimulation contacts and corresponding electrode leads, the electrode stimulation contacts and the electrode leads are distributed at intervals along the circumferential direction of the probe body respectively, each electrode lead extends to the tail of the probe body from the corresponding electrode stimulation contact, a lead welding point is arranged on each electrode lead, and the lead welding points are connected to external equipment through an electrode external lead;

and the insulating layer is arranged in the middle area of the probe body, covers the surfaces of the electrode leads and fills gaps among the electrode leads.

Preferably, the probe body comprises an inner core and an outer core, and the outer core is coated on the outer surface of the inner core.

Preferably, the probe body is made of a non-metal material, and the non-metal material is any one of quartz glass fiber or optical fiber.

Preferably, the probe body has a diameter of 50 to 300 micrometers.

Preferably, the insulating layer is made of a high polymer material, and the high polymer material at least includes any one of polyimide or paraxylene polymer.

Preferably, the thickness of the insulating layer is 510 to 30 micrometers.

Preferably, the electrode head is any one of arrow-shaped, hemispherical, or pseudo-tadpole-shaped.

Preferably, the lateral distance between two adjacent electrode leads is in the range of 5 micrometers to 15 micrometers.

Preferably, the electrode stimulation contacts are of the same area.

The invention also provides a preparation method of the biological nerve regulation probe with the multi-electrode contact, which is used for preparing the biological nerve regulation probe with the multi-electrode contact and comprises the following steps:

step S1, carrying out plasma cleaning on a probe body;

s2, forming a carbon-based conductive thin film layer on the surface of the probe body;

step S3, carrying out laser etching on the carbon-based conductive film layer to form a plurality of electrode stimulation contacts and corresponding electrode leads, wherein the electrode stimulation contacts and the electrode leads are positioned on the surface of the probe body except the head of the electrode and are distributed at intervals along the circumferential direction of the probe body, each electrode lead extends to the tail of the probe body from the corresponding electrode stimulation contact, a lead welding point is arranged on each electrode lead, and the lead welding points are connected to an external device through an electrode external lead;

s4, forming a high polymer material layer on the surface as an insulating layer, and etching the insulating layer to expose a window of a region corresponding to the electrode stimulation contact and a window corresponding to the electrode lead at the tail of the probe body;

and S5, heating the electrode head to form the electrode head in a preset shape.

The technical scheme of the invention has the advantages or beneficial effects that:

the invention adopts the relatively fine flexible glass fiber or optical fiber body, the texture of which is relatively flexible, and can reduce the local scar of the nerve tissue, the carbon-based conductive film is used as the electrode stimulating contact and the electrode lead in the brain, and the like, in the multi-mode stimulating and detecting information extraction process of nuclear magnetic resonance and the like, induction current is not easy to generate, brain tissue damage and a detecting and stimulating device are avoided, noise can be reduced, the signal-to-noise ratio is improved, and the problem that the shadow of the electrode shielding part of a brain picture is large is also reduced, and the problem that a single electrode of a single graphene material only can form the single electrode stimulating contact is solved, particularly the nuclear magnetic resonance and the like are allowed to work simultaneously, the magnetic interference shielding range of the probe is small, the multi-electrode stimulating contact on the single fine probe is realized, the preparation process is simple, the control is easy to realize, and the probe is suitable for the processing and the batch production of fine electrodes.

Drawings

FIG. 1 is a schematic diagram of a biological neuromodulation probe with multiple electrode contacts according to a preferred embodiment of the present invention;

FIG. 2 isbase:Sub>A cross-sectional view taken along line A-A ofbase:Sub>A biological neuromodulation probe forbase:Sub>A multiple-electrode contact, in accordance withbase:Sub>A preferred embodiment of the present invention;

FIG. 3 is a B-B cross-sectional view of a biological neuromodulation probe for a multiple-electrode contact, in accordance with a preferred embodiment of the present invention;

FIG. 4 is a schematic diagram of the connection of the electrode leads at the tail of the probe to an external device according to the preferred embodiment of the invention;

FIG. 5 is a schematic diagram of the connection of the flattened structure of the probe tail electrode lead to an external device by Wire Bond in accordance with the preferred embodiment of the present invention;

FIG. 6 is a schematic diagram of the connection of the flat-structured tail electrode leads of the probe with the ACF and FPC to external devices according to the preferred embodiment of the present invention;

FIG. 7 is a schematic flow chart of a method for preparing a biological neuromodulation probe with multiple electrode contacts according to a preferred embodiment of the invention;

FIGS. 8 a-8 b are schematic views of a probe having an arrowhead-shaped or hemispherical-shaped electrode head formed in a method of manufacturing a probe according to a preferred embodiment of the invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.

The invention is further described with reference to the following drawings and specific examples, which are not intended to be limiting.

In accordance with the above-mentioned problems in the prior art, there is provided in a preferred embodiment of the present invention, a biological neuromodulation probe with multiple electrode contacts, which belongs to the technical field of probes, as shown in fig. 1 to 3, and comprises:

the probe comprises a probe body 1, wherein an electrode head part 13 is formed at the head part of the probe body 1;

specifically, the probe body 1 is made of a non-metallic material, and the non-metallic material may be at least one of quartz glass fiber or optical fiber. The quartz glass fiber or the optical fiber is specifically composed of an inner core 11 and an outer core 12, the outer core 12 is wrapped on the outer surface of the inner core 11, the front end of the quartz glass fiber or the optical fiber is an electrode head 13, and the electrode head 13 can be arrowhead-shaped or hemispherical, also can be pseudo-tadpole-shaped, or can be arranged in other shapes according to actual needs.

Further, when the depth is shallow, the probe can be implanted independently; rigid cannula fixation may also be used to assist in probe implantation when implanted deeper. The electrode head 13 is arrowhead-shaped or hemispherical through a heating process, so that the rigid sleeve can be conveniently fixed and deeply implanted, and the electrode head can be anchored at a specified position of a biological tissue to locally stabilize the electrode.

In the present embodiment, the diameter of the probe body 1 is 50 to 300 micrometers.

Specifically, in this embodiment, the probe body 1 uses an optical fiber as a base material, and can realize photoelectric stimulation and signal acquisition.

The carbon-based conductive film layer is arranged in a region of the surface of the probe body 1 except the electrode head 13, a plurality of electrode stimulation contacts 21 and corresponding electrode leads 22 are formed after laser etching, the plurality of electrode stimulation contacts 21 and the electrode leads 22 are distributed at intervals along the circumferential direction of the probe body 1 respectively, each electrode lead 22 extends from the corresponding electrode stimulation contact 21 to the tail of the probe body 1, a lead welding point 221 is arranged on each electrode lead 22, and the lead welding point 221 is connected to external equipment through an electrode external lead, as shown in fig. 4;

specifically, the carbon-based conductive thin film layer may be made of a carbon-based conductive material, and the carbon-based conductive material may be Graphene (RGO).

Further, the carbon-based conductive film can be a single layer or a plurality of layers; for example, when carbon-based conductive thin films are prepared by using carbon nanotubes, a single wall or a double wall can be selected according to the requirement of electrical conductivity, so that the thickness requirement of the electrical conductivity can be met.

In a preferred embodiment, the lateral distance between two adjacent electrode leads 22 is in a range from 5 micrometers to 15 micrometers.

In a preferred embodiment, the electrode stimulation contacts 21 have the same area.

Specifically, in this embodiment, the number of the electrode stimulation contacts 21 may include a plurality of, for example, 4, 6, or 8, or a larger number according to actual needs, the plurality of electrode stimulation contacts 21 are arranged at intervals, and the areas of the plurality of electrode stimulation contacts 21 are the same.

Further, it is also possible to design the electrode stimulation contacts 21 with different areas, and the areas of the plurality of electrode stimulation contacts 21 are sequentially increased (or decreased) or sequentially increased (or decreased) along the directions of the two sides.

And the insulating layer 3 is arranged in the middle area of the probe body, and the insulating layer 3 covers the surface of the electrode leads 22 and fills gaps among the electrode leads 22. In a preferred embodiment, the insulating layer 3 is made of a polymer material, the polymer material at least includes any one of Polyimide (PI) or Parylene polymer (Parylene C), and the electrode is relatively flexible, has good biocompatibility, is not easy to generate scar tissue, and can effectively stimulate and record nerve cell activity for a long time.

In a preferred embodiment, the thickness of the insulating layer 3 is 5 to 30 μm.

Specifically, in order to solve the problems related to scars and the like in the prior art, in the embodiment of the present invention, a thin film of a carbon-based conductive material (such as graphene, carbon nanotubes, and the like) is formed on a surface of a quartz glass fiber or an optical fiber, an electrode lead 22 and an electrode stimulation contact 21 are formed by laser segmentation, and a high molecular material is coated on the surface of the electrode lead 22 to serve as an insulating layer 3, so that a flexible probe with a single multi-electrode contact and small influence of nuclear magnetic resonance and the like is formed.

Further, in order to facilitate electrical connection with external electrode leads, the electrode leads 22 in the middle region of the probe body are covered with the insulating layer 3, and the insulating layer 3 at the tail part of the probe body 1 is removed.

Furthermore, a high-density electrode array such as an ECoG can also be realized by the plurality of probes through the plurality of electrode stimulation contacts 21.

In the above preferred embodiment, the tail portion (i.e. the end opposite to the electrode head 13) of the probe body 1 may be a cylinder, or may be a flattened structure that presses the tail portion of the probe body in a direction perpendicular to the probe body. The electrode external leads need to be connected to the electrode leads 22 in the tail region of the probe by soldering or anisotropic conductive material, and connected to an external device such as a pulse stimulator or a signal detector through the electrode external leads. As shown in fig. 5 and 6, the flattened structure can facilitate Wire Bond or connection with an ACF (anisotropic conductive paste) to an FPC (flexible circuit board).

The present invention also provides a method for preparing a biological neuromodulation probe for a multi-electrode contact, which is used for preparing the biological neuromodulation probe for a multi-electrode contact, as shown in fig. 7, and comprises the following steps:

step S1, carrying out plasma cleaning on a probe body 1;

in particular, the probe body may be a quartz glass fiber, or may also be an optical fiber.

S2, forming a carbon-based conductive thin film layer on the surface of the probe body 1;

specifically, the carbon-based conductive thin film layer may be made of a carbon-based conductive material, and the carbon-based conductive material may be Graphene (RGO). Furthermore, the surface of the glass can be melted first, and then the graphene can be grown by directly carrying out a Chemical Vapor Deposition (CVD) process to form a carbon-based conductive thin film layer; the Graphene oxide GO (Graphene oxide) can also be formed by a film forming mode of spraying, evaporating and overheating Graphene (RGO), or spraying Graphene oxide GO (Graphene oxide) dispersion liquid to prepare a GO film, or forming Graphene (RGO) through thermal reduction. The growth thickness of the carbon-based conductive thin film layer can be determined according to the actual required conductivity.

Step S3, carrying out laser etching on the carbon-based conductive film layer, and forming a plurality of electrode stimulation contacts 21 and corresponding electrode leads 22 after the laser etching, wherein the electrode stimulation contacts 21 and the electrode leads 22 are positioned on the surface of the probe body except the electrode head 13 and are distributed at intervals along the circumferential direction of the probe body 1, each electrode lead 22 extends to the tail part of the probe body 1 from the corresponding electrode stimulation contact 21, a lead welding point 221 is arranged on each electrode lead 22, and the lead welding point 221 is connected to an external device through an electrode external lead;

specifically, an ultrashort pulse picosecond laser etching light source (355 nm) is used for performing laser etching on the carbon-based conductive film on the surface to form a plurality of electrode leads 22 and electrode stimulation contacts 21, the number of the electrode stimulation contacts 21 may be multiple, the number of the electrode stimulation contacts 21 is the same as that of the electrode leads 22, for example, the number of the electrode stimulation contacts 21 is 4, 6 or 8, or more electrode stimulation contacts are designed according to actual needs, and the gap between the electrode leads 22 is 5 micrometers to 15 micrometers.

S4, forming a high polymer material layer on the surface to serve as an insulating layer 3, and etching the insulating layer 3 to expose windows of corresponding areas of the electrode stimulation contact 21 and the electrode lead 22 in the tail area of the probe;

specifically, the surface is coated with a polymer material by a process such as spray coating or dip coating, and the thickness of the polymer material may be set according to practical requirements, for example, 5 μm or more is coated, and then local exposure, development and hardening are performed by 365nm ultraviolet light to form windows of the corresponding regions of the electrode stimulation contacts 21 and the electrode leads 22.

Step S5, heating the electrode head 13 to form the electrode head 13 with a predetermined shape, as shown in fig. 8a and 8b, which are biological nerve modulation probes with multiple electrode contacts of electrode heads 13 with different predetermined shapes, respectively, wherein the electrode head 13 is arrowed as shown in fig. 8 a; as shown in fig. 8b, the electrode head 13 is hemispherical.

Further, after step S3 and before step S4, the method further includes: the quality of the pattern is automatically checked through automatic pattern software systems such as AOI (automatic Optical Inspection, AOI) and the like, the coating thickness (total diameter change) of protective insulation and biocompatible layers such as PI and the like is monitored and controlled, the shapes of electrode leads and electrode stimulation contacts 21 can be detected, and the laser etching condition is automatically adjusted.

Further, the formed probe may be cut into a desired length using a mechanical cutter using the formed quartz glass or the optical fiber.

Adopt above-mentioned technical scheme to have following advantage or beneficial effect:

1) Quartz glass fiber or optical fiber is used as a probe body, a carbon-based conductive film is formed on the surface of the probe body and used as an electrode lead and an electrode stimulation contact, and a biological nerve regulation probe with a multi-electrode contact is formed in a precise laser processing mode and the like, so that simultaneous stimulation and information measurement and extraction can be realized, stimulation with high density and different depths can be realized, and photoelectric multi-mode stimulation and information detection and extraction can also be realized;

2) The quartz glass fiber or the optical fiber is relatively flexible and thin, compared with a metal electrode, the quartz glass fiber or the optical fiber can reduce and reduce local scars of nerve tissues, has better magnetic and electric compatibility, is not easy to generate induced current, can reduce noise and improve the signal to noise ratio while avoiding damaging brain tissues and detecting and stimulating devices.

3) The carbon-based conductive film on the surface of the probe body is divided through a laser etching process to form the multi-electrode stimulating contact, the problem that a single probe electrode of single graphene can only form a single-electrode stimulating contact is solved, the preparation process is relatively simple and easy to control, and the method is suitable for machining and manufacturing and batch production of fine and tiny electrodes.

4) The combined stimulation of the multi-electrode stimulation contacts can be realized, the stimulation feedback signals are extracted at the same time, the combination of the multi-electrode stimulation contacts and the combination of a plurality of micro carbon-based materials can also form an ECoG array, and the high-density and high-resolution stimulation and recording are realized.

5) The arrowhead-shaped electrode tip may be used to assist in the implantation of a cannula for deep implantation (DBS).

While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.

Claims (10)

1. A multi-electrode contact fine carbon-based biological nerve regulation probe is characterized by comprising:

the probe comprises a probe body, wherein an electrode head part is formed at the head part of the probe body;

the carbon-based conductive film layer is arranged on the surface of the probe body except the head of the electrode, and is subjected to laser etching to form a plurality of electrode stimulation contacts and corresponding electrode leads, the electrode stimulation contacts and the electrode leads are distributed at intervals along the circumferential direction of the probe body respectively, each electrode lead extends to the tail of the probe body from the corresponding electrode stimulation contact, a lead welding point is arranged on each electrode lead, and the lead welding points are connected to external equipment through an electrode external lead;

and the insulating layer is arranged in the middle area of the probe body, covers the surfaces of the electrode leads and fills gaps among the electrode leads.

2. The multi-electrode contact fine carbon-based bio-neuromodulation probe of claim 1, wherein the probe body comprises an inner core and an outer core, the outer core wrapping an outer surface of the inner core.

3. The multi-electrode contact fine carbon-based biological nerve modulation probe according to claim 1, wherein the probe body is made of a non-metallic material, and the non-metallic material is one of quartz glass fiber and optical fiber.

4. The multi-electrode contact fine carbon-based bio-neuromodulation probe of claim 1, wherein the probe body has a diameter of 50-300 microns.

5. The multi-electrode contact fine carbon-based bio-neuromodulation probe of claim 1, wherein the insulating layer is made of a polymer material, and the polymer material at least comprises any one of polyimide or paraxylene polymer.

6. The multi-electrode contact fine carbon-based bio-neuromodulation probe of claim 1, wherein the insulating layer has a thickness of 5-30 microns.

7. The multi-electrode contact fine carbon-based bio-neuromodulation probe of claim 1, wherein the electrode head is any of arrow-shaped, hemispherical, or pseudo-tadpole shaped.

8. The multi-electrode contact fine carbon-based bio-neuromodulation probe of claim 1, wherein the lateral spacing between two adjacent electrode leads is in a range of 5-15 microns.

9. A multi-electrode contact fine carbon-based bio-neuromodulation probe as in claim 1, wherein the electrode stimulation contacts are of the same area.

10. A method for preparing a multi-electrode contact fine carbon-based bio-neuromodulation probe, which is used for preparing the multi-electrode contact bio-neuromodulation probe as claimed in any one of claims 1 to 9, comprising:

step S1, carrying out plasma cleaning on a probe body;

s2, forming a carbon-based conductive thin film layer on the surface of the probe body;

step S3, performing laser etching on the carbon-based conductive film layer to form a plurality of electrode stimulation contacts and corresponding electrode leads, wherein the plurality of electrode stimulation contacts and the plurality of electrode leads are positioned on the surface of the probe body except the head of the electrode and are distributed at intervals along the circumferential direction of the probe body, each electrode lead extends to the tail of the probe body from the corresponding electrode stimulation contact, a lead welding point is arranged on each electrode lead, and the lead welding points are connected to external equipment through an electrode external lead;

s4, forming a high polymer material layer on the surface to serve as an insulating layer, and etching the insulating layer to expose a window of a region corresponding to the electrode stimulation contact and a window corresponding to the electrode lead at the tail of the probe body;

and S5, heating the electrode head to form the electrode head in a preset shape.

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