Multistage self-anchoring flexible deep brain electrical stimulation electrode and preparation method thereof

Abstract

The invention relates to a multistage self-anchoring flexible deep brain electrical stimulation electrode and a preparation method thereof, and relates to the technical field of medical instruments. A bionic root system-octopus whisker composite framework including a main electrode base, a second-stage fractal arm and a third-stage self-anchoring tail end is adopted, intelligent materials such as carbon nano tube / PDMS composite fibers, temperature-sensitive PNIPAAm hydrogel and a degradable PLGA-gelatin composite material are fused, and a mechanical lock catch and biological fusion dual-anchoring mechanism is constructed. The distributed electrode array comprises platinum-iridium alloy, graphene / PDMS and a titanium nitride nano electrode, and cross-scale stimulation from the nuclear group level to the single cell level is achieved. The intelligent regulation and control system solves the problems of brain tissue displacement and chronic inflammation through a pressure feedback degradation and flexible interconnection technology. Compared with a traditional product, the contact area of the electrode is increased by 5-8 times, the stimulation precision reaches the single cell level, and the electrode is suitable for long-term deep brain stimulation treatment of nerve diseases such as Parkinson's disease and epilepsy and has remarkable clinical application value.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical devices, in particular to a multi-level self-anchoring flexible deep brain stimulation electrode integrating bionics, smart materials and fractal topology, and a preparation method thereof, which is suitable for deep brain stimulation treatment of neurological diseases such as Parkinson's disease, epilepsy and depression. BACKGROUND

[0002] Deep brain stimulation (DBS) is an important means for treating neurodegenerative diseases and functional brain diseases. Traditional DBS electrodes mostly adopt rigid straight rod structures, which have the following technical bottlenecks:

[0003] Poor tissue compatibility: the elastic modulus of rigid materials (such as platinum-iridium alloy) does not match that of brain tissue, and long-term implantation can easily cause chronic inflammation and glial scar;

[0004] Insufficient anchoring stability: rigid fixation by skull fixation screws cannot adapt to the physiological displacement of brain tissue of ±0.5mm per minute, resulting in electrode displacement or poor contact;

[0005] Limited stimulation precision: the size of the traditional electrode site is greater than 500μm, which can only achieve nucleus group stimulation and is difficult to precisely regulate single cell activity;

[0006] Small contact area: the contact area of the straight rod structure with the neural tissue is about 0.01mm², resulting in low signal transmission efficiency and large energy consumption.

[0007] In the prior art, although flexible electrodes improve some biocompatibility, they lack effective self-anchoring mechanisms and have single stimulation sites, which cannot meet the cross-scale neural regulation requirements. Therefore, there is an urgent need for a new type of deep brain electrode that has the functions of flexible fitting, self-adaptive anchoring and multi-scale stimulation. SUMMARY

[0008] (I) Technical problems solved

[0009] Therefore, the present application aims to provide a multi-level self-anchoring flexible deep brain stimulation electrode and a preparation method thereof, which solves the problems of unstable anchoring, low stimulation precision and poor biocompatibility of traditional electrodes by bionic structure design and integration of smart materials, and realizes cross-scale electrical regulation from macroscopic nucleus group to microscopic neuron.

[0010] (II) Technical solutions

[0011] To achieve the above purpose, one of the present application is implemented by the following technical solutions:

[0012] The multi-level self-anchoring flexible deep brain stimulation electrode comprises a primary structure, a secondary structure, a tertiary structure and a distributed electrode array,

[0013] The primary structure includes a main electrode base, which is a disc-shaped flexible base with a diameter of 300 μm. The disc-shaped flexible base is composed of an inner layer of conductive PEDOT:PSS and an outer layer of hyaluronic acid-chitosan biogel, with a micro signal interface integrated in the center;

[0014] The secondary structure includes a secondary flexible fractal arm, which includes 8-12 fractal tree-like branch arms with a diameter of 50-80 μm and a length of 2-5 mm radiating from the main base. The skeleton of the fractal tree-like branch arm is a carbon nanotube / PDMS composite fiber, and the surface is coated with a thermosensitive PNIPAAm hydrogel;

[0015] The tertiary structure includes three self-anchoring ends, each of which includes 3-5 smart anchoring units derived from the secondary arm end. The smart anchoring units include type A anchoring units and type B anchoring units. The type A anchoring units are "barb + suction cup" composite structures, the barbs are degradable PLGA microhooks, and the suction cups are elastic pits with built-in vacuum cavities. The type B anchoring units are porous spherical nodes loaded with nerve regeneration inducing factors and hydroxyapatite microspheres.

[0016] The distributed electrode array includes 8 platinum-iridium alloy stimulation sites with a diameter of 10 μm set on the edge of the main base, 2-3 graphene / PDMS flexible thin film electrodes with a thickness of <2 μm set in the middle section of the secondary flexible fractal arm, and a titanium nitride nanoelectrode with a diameter of 500 nm set in the tertiary self-anchoring end.

[0017] Furthermore, the fractal topology parameters of the secondary flexible fractal arm are: branch angle 45°-60°, and the end gradually becomes thinner.

[0018] Furthermore, the curvature radius of the barb tip of the A-type anchoring unit is less than 5 μm, the porous sphere of the B-type anchoring unit has a porosity of ≥60%, a pore size of 5-10 μm, is made of a PLGA-gelatin composite material, and has a degradation period of 3-6 months.

[0019] Furthermore, it also includes an intelligent control system. The B-type anchoring unit has a built-in flexible piezoresistive sensor, which triggers local degradation of the PLGA shell when the tissue pressure exceeds 10kPa.

[0020] Furthermore, the anchoring mechanism of the electrode is as follows: mechanical anchoring by type A units dominates 0-2 weeks after surgery, biological anchoring by type B units is formed and type A barbs degrade in 2-12 weeks, and stable anchoring is achieved through glial cell wrapping and integration with bone tissue in >12 weeks.

[0021] Furthermore, the anti-motion interference structure of the electrode includes a spiral carbon nanotube wire, and the outer layer of the carbon nanotube wire is wrapped with a liquid metal-hydrogel composite layer.

[0022] The second aspect of the present invention is achieved through the following technical solutions:

[0023] A method for preparing the multi-stage self-anchoring flexible deep brain electrical stimulation electrode as described above comprises the following steps:

[0024] S1, microfluidic preparation of a double-layer composite hydrogel structure of the main electrode base with an integrated micro signal interface;

[0025] S2, 3D printing carbon nanotube / PDMS composite fiber skeleton, constructing fractal tree-like secondary arms, and coating the surface with PNIPAAm hydrogel;

[0026] S3, using soft lithography and emulsion-solvent evaporation method to prepare type A and type B three-level anchoring units and integrate pressure sensors;

[0027] S4, using electron beam evaporation, transfer printing and focused ion beam technology to prepare distributed electrode arrays;

[0028] S5. Use micro-encapsulation technology to prepare spiral carbon nanotube wires and liquid metal-hydrogel composite outer layers.

[0029] Furthermore, the porous sphere of the B-type anchoring unit achieves biological anchoring induction by loading nerve regeneration inducing factor (NGF) and hydroxyapatite microspheres.

[0030] Furthermore, the tertiary self-anchoring end and the secondary flexible fractal arm are integrated into one piece through micro-nano processing technology to ensure structural stability and functional synergy.

[0031] (3) Beneficial effects

[0032] The present invention provides a multi-stage self-anchoring flexible deep brain electrical stimulation electrode and a method for preparing the same. It has the following beneficial effects:

[0033] 1. The present invention provides a fixed foundation for the electrode through the primary structure of the main electrode base. The secondary flexible fractal arm provides a strong fractal ability, which is dispersed in multiple directions and has the same fixing ability in any direction, preventing uneven vibration or impact. At the same time, the tertiary structure achieves mechanical and biological dual dynamic anchoring, significantly increasing the contact area and adapting to brain tissue displacement, thus fundamentally solving the problem of unstable anchoring.

[0034] 2. The present invention achieves signal acquisition at multiple different spatial locations by using a distributed electrode array with eight 10μm diameter platinum-iridium alloy stimulation sites on the edge of the main base, 2-3 graphene / PDMS flexible thin film electrodes in the middle section of the secondary flexible fractal arms, and titanium nitride nanoelectrodes at the tertiary self-anchoring ends. This achieves breakthroughs in stimulation precision and improves the accuracy of signal analysis.

[0035] 3. All electrodes achieve single-cell level stimulation accuracy, and use biodegradable materials to integrate with tissues, thereby reducing the risk of chronic inflammation and improving biocompatibility; in addition, nanoelectrodes lower the current threshold and reduce energy consumption. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 It is a structural schematic diagram of the present invention;

[0037] Figure 2 This is a schematic diagram of the present invention with the introduction sleeve removed;

[0038] Figure 3 Schematic diagram of the electrode holder in a non-working state;

[0039] Figure 4 Schematic diagram of the electrode holder in working state;

[0040] Figure 5 for Figure 4 A schematic diagram of the other direction;

[0041] Figure 6 Schematic diagram of type B anchoring unit;

[0042] Figure 7 Schematic diagram of type A anchoring unit.

[0043] Description of reference numerals:

[0044] 1-Main electrode base; 2-Secondary flexible fractal arm; 3-Third-level self-anchoring end; 4-Distributed electrode array; 5-Signal interface; 6-Type A anchoring unit; 7-Barb; 8-Suction cup; 9-Type B anchoring unit; 10-Porous spherical node; 11-Hydroxyapatite microsphere; 12-Platinum-iridium alloy stimulation site; 13-Flexible thin film electrode; 14-Titanium nitride nanoelectrode; 15-Electrode rod; 16-Introduction sleeve; 17-Introduction cone; 18-Scale value; 19-Texture; 20-Electrode holder; 21-Operating handle. DETAILED DESCRIPTION

[0045] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0046] like Figure 1-7 As shown, an embodiment of the present invention provides a multi-stage self-anchoring flexible deep brain stimulation electrode, including an electrode rod 15 and an electrode base 20 electrically connected to the electrode rod. The electrode base 20 includes a three-stage gradient structure: a main electrode base 1 (a primary structure), a secondary flexible fractal arm 2, a tertiary self-anchoring end 3, and a distributed electrode array 4. The specific structure is as follows:

[0047] The main electrode base (primary structure) in this embodiment supports the entire electrode. It is a flexible, disc-shaped base with a diameter of 250-350μm. A micro-signal interface 5 is integrated in the center for transmitting electrical signals. It is made of a double-layer composite hydrogel: an inner layer of conductive PEDOT:PSS and an outer layer of hyaluronic acid-chitosan biogel, which has good affinity with human muscle and skin.

[0048] The secondary flexible fractal arms (secondary structure) in this embodiment consist of 8-12 flexible branches radiating from the main base. These arms are 50-80μm in diameter and 2-5mm in length, arranged in a fractal tree-like pattern. Branching angles are 45°-60°, and the ends taper gradually, creating a multi-dimensional anchoring mechanism that transforms a single fixed axis into multiple fixed roots. The framework is constructed from a carbon nanotube / PDMS composite fiber (tensile strength 10MPa) coated with a thermosensitive PNIPAAm hydrogel. This structure increases the contact area (400% greater than conventional methods), and the interbranching gaps guide glial cells to form bio-anchors.

[0049] The tertiary self-anchoring end (tertiary structure) of this embodiment is composed of 3-5 intelligent anchoring units derived from the end of each secondary arm, which include: Type A anchoring unit 6 (mechanical locking type): a "barb 7 + suction cup 8" composite structure with a diameter of 20μm, the barb is a degradable PLGA microhook (tip curvature radius <5μm), and the suction cup is an elastic pit with a diameter of 50μm (built-in vacuum cavity); Type B anchoring unit 9 (biofusion type): a porous spherical node 10 with a diameter of 30μm, the pores are loaded with nerve regeneration inducing factors (such as NGF) and degradable hydroxyapatite microspheres 11; the barbs / spheres of this embodiment are all made of PLGA-gelatin composite materials with a degradation period of 3-6 months. The suction cup base is elastic silicone rubber, and the spheres have built-in micro pressure sensors.

[0050] The distributed electrode array of this embodiment is specifically arranged as follows: 6-10 10μm diameter platinum-iridium alloy stimulation sites 12 (coarse modulation nuclei) are located at the edge of the main base; 2-3 graphene / PDMS flexible thin film electrodes 13 (<2μm thick) are arranged in each arm in the middle of the secondary arms, achieving medium-precision stimulation; and a 500nm diameter titanium nitride nanoelectrode 14 is embedded in each tertiary anchor unit, achieving single-cell stimulation. This cross-scale electrical control achieves a current threshold of only one-tenth that of conventional nanoelectrodes, significantly improving stimulation precision.

[0051] The intelligent control mechanism of this embodiment is:

[0052] Self-anchoring dynamic regulation: The porous sphere of the B-type anchoring unit has a built-in flexible piezoresistive sensor, which triggers the local degradation of the PLGA shell when the pressure exceeds 10kPa;

[0053] Degradation-anchoring synergy: 0-2 weeks, mechanical anchoring dominates; 2-12 weeks, biological anchoring is formed while the A-type barbs degrade; >12 weeks, anchoring is stabilized by tissue integration;

[0054] Anti-motion interference: Helical carbon nanotube wires (stretching rate 800%) connect the electrode sites, and the outer layer is wrapped with a liquid metal-hydrogel composite layer (gallium indium tin alloy droplets dispersed in sodium alginate gel).

[0055] Preparation method of this embodiment

[0056] 1. Preparation of the main electrode base:

[0057] Microfluidic technology was used to prepare a disc-shaped substrate with a diameter of 300 μm. The inner layer was prepared with a PEDOT:PSS conductive layer by spin coating, the outer layer was cross-linked hyaluronic acid-chitosan biogel, and the center was integrated with a micro signal interface formed by SU-8 photolithography.

[0058] Second, secondary fractal arm forming:

[0059] The carbon nanotube / PDMS composite fiber skeleton was printed using 3D direct writing technology to control the fractal topological parameters (branching angle 45°-60°, end diameter 50μm), and the surface was coated with a PNIPAAm thermosensitive hydrogel layer using atomic layer deposition technology.

[0060] 3. Construction of three-level anchoring units:

[0061] Type A unit: A composite structure of PLGA microhook (tip curvature radius 3 μm) and silicone rubber suction cup (with built-in micro vacuum pump channel) was prepared by soft lithography;

[0062] Type B unit: PLGA-gelatin porous spheres (porosity 60%, pore size 5-10 μm) were prepared by emulsion-solvent evaporation method, loaded with NGF and hydroxyapatite microspheres, and then integrated with silicone rubber substrate to form a pressure sensor.

[0063] 4. Distributed Electrode Array Integration

[0064] The edge of the main base was prepared with platinum-iridium alloy stimulation sites (10 μm in diameter) by electron beam evaporation;

[0065] The graphene / PDMS flexible thin film electrode (thickness 1.5 μm) was prepared in the middle section of the secondary arm using transfer printing technology;

[0066] Titanium nitride nanoelectrodes (500 nm in diameter) were fabricated on the top of the tertiary anchoring unit using focused ion beam etching technology.

[0067] Flexible interconnection system preparation:

[0068] Spiral carbon nanotube wires (stretching rate 800%) are used to connect each electrode site to the main base, and the outer layer is wrapped with a gallium indium tin alloy droplet-sodium alginate gel composite layer through microencapsulation technology.

[0069] The specific implementation method of this embodiment is as follows:

[0070] During implementation, an introduction sleeve 16 can be removed and installed outside the electrode rod. An introduction cone 17 is provided at the front end of the introduction sleeve, so that the secondary fractal arm and the tertiary anchoring unit can be tightened, thereby facilitating the insertion of the entire electrode into the target brain area. In order to facilitate the observation of the implantation depth, a scale value 18 is set on the introduction sleeve.

[0071] In this embodiment, the barbs of the Type A anchoring unit penetrate the tissue using a thrusting force, and the suction cup automatically empties upon contact, creating negative pressure adsorption. Early (0-2 weeks): Mechanical anchoring (Type A unit) dominates fixation. The PNIPAAm hydrogel transitions from hydrophilic to hydrophobic at 37°C body temperature, enhancing physical adsorption. The conductive network between the main base and secondary arms begins to transmit electrical signals, enabling coarse nucleus-level stimulation. Mid-term (2-12 weeks): The hydroxyapatite of the Type B anchoring unit degrades to release calcium ions, inducing osteoblasts / glial cells to grow into the pores, forming biological anchor points. Simultaneously, the PLGA barbs of the Type A unit begin to degrade (at a rate of 5-10% per week), reducing foreign body stimulation. Long-term (>12 weeks): The electrode integrates with bone tissue through glial cell encapsulation, achieving stable anchoring. The pressure sensor of the Type B unit monitors tissue pressure in real time. When the pressure exceeds the threshold (10 kPa), the PLGA shell locally degrades, releasing a buffering space. The distributed electrode array switches between single-cell, medium-precision, and nucleus-level stimulation modes according to therapeutic needs.

[0072] To facilitate operation, an operating handle 21 is provided at the tail of the introduction sleeve of this embodiment, the diameter of which is larger than the diameter of the introduction sleeve, and a mesh 19 is provided on the operating handle to increase the stability of the support and make the operation more accurate and reliable.

[0073] This invention breaks through the technical bottleneck of traditional deep brain electrodes through the collaborative innovation of bionic root-octopus tentacle composite architecture, fractal topological branch design, mechanical-biological dual anchoring mechanism and multi-scale electrode array, and has the following significant advantages:

[0074] 1. Structural bionic innovation: Combining the multi-level diffusion of plant roots with the flexible adsorption characteristics of octopus tentacles, it achieves adaptive fit and anchoring in three-dimensional space;

[0075] 2. Intelligent material response: Integration of thermosensitive hydrogels, degradable polymers, and bioactive factors to achieve dynamic regulation and tissue integration after implantation;

[0076] 3. Functional cross-scale integration: Distributed electrode arrays from nanometer to micrometer scales support full-scale neural regulation from single cells to nuclei, combining high precision with low energy consumption;

[0077] 4. Improved safety mechanism: The pressure feedback degradation system and flexible interconnection technology effectively solve the problems of brain tissue displacement and chronic inflammation, and improve the safety of long-term implants.

[0078] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the invention, and the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A multi-level self-anchoring flexible deep brain stimulation electrode, characterized in that: Including primary structure, secondary structure, tertiary structure and distributed electrode array, The primary structure includes a main electrode base, which is a disc-shaped flexible base with a diameter of 300 μm. The disc-shaped flexible base is composed of an inner layer of conductive PEDOT:PSS and an outer layer of hyaluronic acid-chitosan biogel, with a micro signal interface integrated in the center; The primary structure includes a secondary flexible fractal arm, which includes 8-12 fractal tree-like branch arms with a diameter of 50-80 μm and a length of 2-5 mm radiating from the main base. The skeleton of the fractal tree-like branch arm is a carbon nanotube / PDMS composite fiber, and the surface is coated with a thermosensitive PNIPAAm hydrogel; The tertiary structure includes three self-anchoring ends, each of which includes 3-5 smart anchoring units derived from the secondary arm end. The smart anchoring units include type A anchoring units and type B anchoring units. The type A anchoring units are "barb + suction cup" composite structures, where the barbs are degradable PLGA microhooks and the suction cups are elastic pits with built-in vacuum cavities. The type B anchoring units are porous spherical nodes loaded with nerve regeneration inducing factors and hydroxyapatite microspheres. The distributed electrode array includes 8 platinum-iridium alloy stimulation sites with a diameter of 10 μm set on the edge of the main base, 2-3 graphene / PDMS flexible thin film electrodes with a thickness of <2 μm set in the middle section of the secondary flexible fractal arm, and a titanium nitride nanoelectrode with a diameter of 500 nm set in the tertiary self-anchoring end.

2. The electrode according to claim 1, characterized in that The fractal topological parameters of the secondary flexible fractal arm are: a branch angle of 45°-60°, and a gradually tapering end.

3. The electrode according to claim 1, characterized in that The curvature radius of the barb tip of the A-type anchoring unit is less than 5 μm, the porous sphere of the B-type anchoring unit has a porosity of ≥60%, a pore size of 5-10 μm, is made of a PLGA-gelatin composite material, and has a degradation period of 3-6 months.

4. The electrode according to claim 1, characterized in that It also includes an intelligent control system. The B-type anchoring unit has a built-in flexible piezoresistive sensor, which triggers local degradation of the PLGA shell when the tissue pressure exceeds 10kPa.

5. The electrode according to claim 1, characterized in that The anchoring mechanism of the electrode is as follows: mechanical anchoring by type A units is dominant in 0-2 weeks after surgery, biological anchoring by type B units is formed and type A barbs are degraded in 2-12 weeks, and stable anchoring is achieved by glial cell wrapping and integration with bone tissue in >12 weeks.

6. The electrode according to claim 1, characterized in that The anti-motion interference structure of the electrode comprises a spiral carbon nanotube wire, and the outer layer of the carbon nanotube wire is wrapped with a liquid metal-hydrogel composite layer.

7. A method for preparing the multi-stage self-anchoring flexible deep brain electrical stimulation electrode according to any one of claims 1 to 6, characterized in that: The following steps are involved: S1, microfluidic preparation of a double-layer composite hydrogel structure of the main electrode base with an integrated micro signal interface; S2, 3D printing carbon nanotube / PDMS composite fiber skeleton, constructing fractal tree-like secondary arms, and coating the surface with PNIPAAm hydrogel; S3, using soft lithography and emulsion-solvent evaporation method to prepare type A and type B three-level anchoring units and integrate pressure sensors; S4, using electron beam evaporation, transfer printing and focused ion beam technology to prepare distributed electrode arrays; S5. Microencapsulation technology is used to prepare spiral carbon nanotube wires and liquid metal-hydrogel composite outer layers.

8. The preparation method according to claim 7, characterized in that The porous sphere of the B-type anchoring unit realizes biological anchoring induction by loading nerve regeneration inducing factor (NGF) and hydroxyapatite microspheres.

9. The preparation method according to claim 8, characterized in that The three-level self-anchoring end and the two-level flexible fractal arm are integrated into one piece through micro-nano processing technology to ensure structural stability and functional synergy.

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