Antibacterial neural electrode based on high surface potential zirconium oxide layer and preparation method thereof

Abstract

The application provides an antibacterial neural electrode based on a high-surface-potential zirconium oxide layer and a preparation method thereof. The electrode comprises, from bottom to top, a bottom zirconium oxide film layer, a first insulating layer, a metal layer, a second insulating layer, a top zirconium oxide film layer and an electrode modification layer. A distal end of the metal layer is partially exposed to form an electrode point, and the electrode modification layer covers the electrode point. The bottom zirconium oxide film layer and the top zirconium oxide film layer are subjected to high-surface-potential treatment and exhibit a positive surface potential in a physiological environment. The positive surface potential can destroy the cell membranes of bacteria with negative charges through electrostatic action after the neural electrode is implanted in vivo, and inhibit the formation of microglial cells and astrocytes. The damage to the membranes of mammalian cells (such as neurons) with neutral electricity is extremely small. The application realizes active antibacterial function through the high-surface-potential zirconium oxide film layer, ensures long-term effective contact between the electrode and neurons, and thus realizes high-quality, long-term stable electrophysiological recording and stimulation function of the neural electrode.

Description

Technical Field

[0001] This application relates to the field of neural electrodes, specifically to an antibacterial neural electrode based on a high surface potential zirconia layer and its preparation method. Background Technology

[0002] Neural electrode technology is a core foundation for brain-computer interfaces, neural circuit research, and neurorepair medicine. Traditional neural electrode insulating substrates face two major challenges in terms of biocompatibility and long-term stability: bacterial infection and chronic foreign body reactions. The material itself is still recognized as a foreign body by the immune system, triggering continuous activation of microglia and astrocytes, ultimately leading to dense glial scarring that encapsulates the electrode. This scar layer not only physically isolates the electrode from electrical communication with the target neuron, causing a sharp decline in signal recording quality, but is also a major cause of long-term implantation failure. Therefore, developing neural interfaces that combine excellent, long-term stable biocompatibility and active antibacterial capabilities has become an urgent need in this field. Summary of the Invention

[0003] In view of one of the defects in the prior art, the purpose of this application is to provide an antibacterial neural electrode based on a high surface potential zirconia layer and a method for preparing the same.

[0004] According to a first aspect of this application, an antibacterial neural electrode based on a high surface potential zirconia layer is provided, comprising, from bottom to top: a bottom zirconia thin film layer, a first insulating layer, a metal layer, a second insulating layer, a top zirconia thin film layer, and an electrode modification layer, wherein: The distal local area of ​​the metal layer is exposed to form electrode points, and the electrode modification layer covers the electrode points. The bottom and top zirconia thin film layers exhibit a positive surface potential in a physiological environment after being treated with high surface potential, thereby achieving antibacterial function.

[0005] Optionally, the thickness of the bottom zirconium oxide film layer and the top zirconium oxide film layer is 0.05~1 μm.

[0006] Optionally, the bottom zirconia thin film layer and the top zirconia thin film layer are prepared by any one of the following methods: sol-gel method, atomic layer deposition technology, or magnetron sputtering process.

[0007] Optionally, the method for treating the high surface potential is surface functionalization or element doping.

[0008] Optionally, the surface functionalization includes: grafting a self-assembled monolayer onto the surface of the zirconium oxide thin film layer through surface functionalization.

[0009] Optionally, the self-assembled monolayer is formed from a silane coupling agent terminated with a quaternary ammonium salt group or an amino group.

[0010] Optionally, the element doping includes: using a zirconium oxide thin film layer doped with low-valent cations. Low-valent cations replace Zr. 4+ To maintain the material's electrical neutrality, a large number of oxygen vacancies with effective positive charges are generated inside the zirconia lattice. These oxygen vacancies directly contribute to the surface potential as intrinsic positive charge sources. They can also increase the isoelectric point of zirconia to above 8.5 by preferentially adsorbing hydroxide ions and suppressing surface deprotonation.

[0011] Optionally, the low-valence cation is yttrium ion (Y³). + ), magnesium ions (Mg²) + ) or calcium ions (Ca²) + Any one of them.

[0012] According to a second aspect of this application, a method for preparing an antibacterial neural electrode based on a high surface potential zirconia layer as described in the first aspect is provided, comprising: A sacrificial layer is deposited on a substrate, and the sacrificial layer is patterned. A bottom zirconium oxide film is formed on the surface of a patterned sacrificial layer, and the bottom zirconium oxide film is patterned by reactive ion etching. A first insulating layer is spin-coated onto a patterned bottom zirconium oxide film and patterned to expose the connection area; Deposit a metal layer and pattern it to form electrode traces and electrode points; A second insulating layer is spin-coated and patterned so that the metal layer is encapsulated and embedded, exposing only the electrode points; A top zirconium oxide film is formed and patterned to cover the non-electrode areas while keeping the electrode points exposed; Selectively deposit electrode modification layers on exposed electrode sites; The wafer-level structure is diced, the sacrificial layer is removed, and the electrode structure is released from the substrate to obtain an independent flexible neural electrode. The flexible neural electrode was immersed in a silanization solution for post-treatment, forming a positively charged self-assembled monolayer on the zirconia surface. After cleaning and drying, an antibacterial neural electrode based on a high surface potential zirconia layer was obtained.

[0013] Optionally, the temperature in the step of forming the bottom zirconia film and / or the top zirconia film is not greater than 200°C.

[0014] Optionally, the bottom zirconia film is patterned by reactive ion etching, wherein the reactive ion etching uses a Cl2 / BCl3 mixed gas and is combined with a metal hard mask to achieve high-precision patterning of the zirconia film.

[0015] Optionally, the post-treatment of immersing the flexible neural electrode in a silanization solution to form a positively charged self-assembled monolayer on the zirconium oxide surface includes: Method 1: Quaternary ammonium silane treatment: The flexible neural electrode is placed in an anhydrous ethanol solution of quaternary ammonium silane coupling agent with a concentration of 1-10 mM and reacted at 60-80°C for 2-12 h to form a stable positive potential self-assembled monolayer on the zirconium oxide surface.

[0016] Method 2: Aminosilane treatment: The flexible neural electrode is placed in an anhydrous ethanol solution of aminosilane coupling agent with a concentration of 1-10 mM and reacted at 50-70°C for 4-12 h. Then it is cured at 100-120°C for 30-60 min, so that the amino group is exposed on the surface and protonated to form a positive potential under physiological pH conditions.

[0017] According to a third aspect of this application, a method for preparing an antibacterial neural electrode based on a high surface potential zirconia layer as described in the first aspect is provided, comprising: A sacrificial layer is deposited on a substrate, and the sacrificial layer is patterned. A bottom zirconium oxide film is formed on the surface of a patterned sacrificial layer. The bottom zirconium oxide film is an element-doped zirconium oxide film layer. The bottom zirconium oxide film is patterned by reactive ion etching. A first insulating layer is spin-coated onto a patterned bottom zirconium oxide film and patterned to expose the connection area; Deposit a metal layer and pattern it to form electrode traces and electrode points; A second insulating layer is spin-coated and patterned so that the metal layer is encapsulated and embedded, exposing only the electrode points; A top zirconium oxide film with elemental doping is formed and patterned to cover the non-electrode areas while keeping the electrode points exposed. Selectively deposit electrode modification layers on exposed electrode sites; The wafer-level structure is diced to remove the sacrificial layer and release the electrode structure from the substrate, resulting in an independent flexible neural electrode, namely an antibacterial neural electrode based on a high surface potential zirconia layer.

[0018] The antibacterial neural electrode based on a high surface potential zirconia layer provided in this application achieves a stable high surface potential through high surface potential treatment of the bottom and top zirconia thin film layers, endowing the electrode surface with active antibacterial capabilities. This high surface potential can effectively repel and kill negatively charged bacteria, greatly reducing secondary inflammation and tissue damage caused by infection. At the same time, the zirconia material itself has excellent bioinertness, excellent biocompatibility, and chemical stability, which can reduce the recognition and activation of the immune system, actively creating an immune-tolerant microenvironment, further inhibiting microglial activation and astrocyte overgrowth, significantly reducing the formation of glial scars at the neural interface, and ensuring continuous and effective contact between the electrode and surrounding neurons. Through the synergistic effect of the above-mentioned antibacterial and immunomodulatory mechanisms, the immune response capacity is effectively reduced, jointly improving the long-term stability of the implant-tissue interface, ensuring continuous and efficient electrical signal interaction between the electrode and neurons, thereby achieving high-quality, long-term stable electrophysiological recording and stimulation functions of the neural electrode.

[0019] Other technical effects resulting from the additional features will be further illustrated in the corresponding embodiments. Attached Figure Description

[0020] Other features, objects, and advantages of this application will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings: Figure 1 This is a schematic diagram of the structure of an antibacterial nerve electrode according to an exemplary embodiment; Figure 2 This is a schematic flowchart illustrating a method for preparing an antibacterial nerve electrode according to an exemplary embodiment; Figure 3 This is a schematic diagram illustrating a method for forming a high surface potential according to an exemplary embodiment; In the figure: 1 is the antibacterial nerve electrode, 101 is the bottom zirconia thin film layer, 102 is the first insulating layer, 103 is the metal layer, 104 is the second insulating layer, 105 is the top zirconia thin film layer, 106 is the electrode modification layer, 2 is the nerve electrode, and 3 is the electrode impregnation solution. Detailed Implementation

[0021] The present application will now be described in detail with reference to specific embodiments. These embodiments will help those skilled in the art to further understand the present application, but do not limit the present application in any way. It should be noted that those skilled in the art can make several modifications and improvements without departing from the concept of the present application, and these all fall within the protection scope of the present application. Parts not described in detail in the following embodiments can be implemented using existing technology.

[0022] Traditional polymer electrodes, once implanted, gradually lead to bacterial infection and chronic foreign body reactions in biological tissues, causing glial scarring and probe failure, thus hindering long-term stable signal recording. Existing technologies have demonstrated that positively charged interfaces can achieve good antibacterial effects and biocompatibility. In 2019, Jiaul Hoque et al. disclosed a charge-switchable polymer coating ("Kills Bacteria and Prevents Biofilm Formation in Vivo") that efficiently kills bacteria and inhibits biofilm formation in vivo under a positively charged state, while exhibiting extremely low cytotoxicity to mammalian cells, validating the excellent cell selectivity and compatibility of the positively charged surface antibacterial strategy. In 2020, Ke Liu et al. reported on the antibacterial and biocompatibility of high-surface-potential zirconia ceramics. Applying this high-surface-potential zirconia material to dental implants demonstrated significant antibacterial effects, with little likelihood of inducing bacterial resistance. It also exhibited high structural strength and good biocompatibility, proving its excellent application potential and feasibility in the field of implant antibacterial modification. Therefore, this application abandons the traditional passive resistance strategy of neural electrodes and innovatively proposes introducing a high-surface-potential zirconia film into the neural electrode system. The aim is to utilize its excellent biocompatibility and antibacterial capabilities to solve the problems of long-term implantation failure and resulting immune infections associated with traditional electrodes.

[0023] Reference Figure 1 As shown, in one embodiment of this application, an antibacterial neural electrode based on a high surface potential zirconia layer is provided. The antibacterial neural electrode 1 includes, from bottom to top: a bottom zirconia thin film layer 101, a first insulating layer 102, a metal layer 103, a second insulating layer 104, a top zirconia thin film layer 105, and an electrode modification layer 106. The distal local area of ​​the metal layer 103 is exposed to form electrode points for recording nerve signals or electrical stimulation. The electrode modification layer 106 covers the electrode points. The bottom zirconia thin film layer 101 and the top zirconia thin film layer 105 are treated with high surface potential to present a stable positive surface potential in the physiological environment, thereby achieving antibacterial function.

[0024] Specifically, high surface potential refers to the electrical state in which the material surface stably exhibits a positive zeta potential under physiological pH conditions. The positive zeta potential needs to be maintained within the range of +30 mV to +70 mV. A positive zeta potential ≥ +30 mV on the surface of biomaterials provides electrostatic repulsion and contact disruption; if > 70 mV, it easily leads to non-specific protein adsorption and cytotoxicity risks. Physiological environment refers to the body fluid environment with pH ≈ 7.4. "Bottom" and "top" are defined relative to the substrate preparation direction.

[0025] A metal layer 103, composed of an electrochemically inert and biocompatible metal, is embedded between two insulating layers. An electrode modification layer 106 is used to reduce interfacial impedance and increase charge injection capacity. The electrode modification layer 106 is configured to enable efficient charge transfer between the electrode and nerve tissue and to withstand the liquid environment used in high surface potential treatments.

[0026] Due to the high surface potential treatment, the surfaces of the bottom zirconia film layer 101 and the top zirconia film layer 105 have a high positive surface potential. Most common pathogenic bacteria have surfaces rich in anionic groups such as lipopolysaccharides and teichoic acid, making them generally negatively charged. This application innovatively utilizes a zirconia film layer with a high positive surface potential to inhibit the initial approach and adhesion of bacteria through strong electrostatic repulsion, directly driving away negatively charged bacteria. Furthermore, it physically disrupts the bacterial cell membrane through a "contact-based" mechanism. When negatively charged bacteria come into contact with the zirconia film layer, the high positive potential on the electrode surface directly disrupts the integrity and permeability of the bacterial cell membrane through interfacial electrostatic interactions and a local electric field, leading to intracellular leakage, metabolic disorders, and ultimately bacterial death. This effectively inhibits the formation of protein conditioned membranes and bacterial biofilms from the source.

[0027] It should be noted that this neural electrode has minimal damaging effect on the membranes of electrically neutral mammalian cells (such as neurons).

[0028] Furthermore, the extremely high bioinertness, excellent biocompatibility, and chemical stability of zirconia materials make them less likely to be recognized as targets by the immune system, reducing its recognition and activation. This actively creates an immune-tolerant microenvironment, further inhibiting microglia activation and astrocyte overgrowth, significantly suppressing the formation of these two cell types. This effectively avoids secondary inflammation and excessive activation of the immune system caused by persistent infection, thereby significantly reducing chronic foreign body reactions and dense glial scarring. The weakened immune response indicates the formation of a thinner and more stable neural tissue-electrode interface, maintaining long-term stable interfacial impedance. In addition, neurons around the antibacterial electrode have a higher survival rate and can maintain long-term effective functional connections with the electrode. Therefore, foreign body reactions and glial scar proliferation can be suppressed at the source, ensuring continuous and effective contact between the electrode and surrounding neurons. This lays a solid foundation for establishing a stable and effective functional interface between the electrode and neurons, achieving biocompatibility in both the bulk material and surface function sense.

[0029] Through the synergistic effect of the antibacterial and immunomodulatory effects, the high positive potential surface of the zirconia film realizes the functional transformation from passively inhibiting bacterial adhesion to actively antibacterial, which greatly reduces secondary inflammation and tissue damage caused by infection, while effectively reducing the immune response capacity. Together, they improve the long-term stability of the implant-tissue interface, ensuring continuous and efficient electrical signal interaction between the electrode and the neuron, thereby achieving high-quality, long-term stable recording and stimulation of neurophysiological signals, effectively solving the core problem of signal attenuation or even failure during long-term implantation.

[0030] In order to ensure the overall flexibility of the electrode while providing reliable electrical insulation performance and preventing current leakage and mechanical fatigue during long-term implantation, in some specific embodiments of this application, the materials of the first insulating layer 102 and the second insulating layer 104 are any one of organic polymer, silicon oxide, silicon nitride and silicon carbide, and the thickness of the first insulating layer 102 and the second insulating layer 104 is 0.5~10 μm.

[0031] To ensure that the electrode has excellent conductivity, long-term electrochemical stability and good biocompatibility, and to meet the requirements of low-loss transmission of nerve signals and micro-nano fabrication precision, in some specific embodiments of this application, the metal layer 103 is made of any one of gold, platinum, or platinum-iridium alloy, and has a thickness of 0.05~1 μm.

[0032] In order to provide a dense and complete coverage while maintaining the ultra-thin and flexible properties of the electrode, and to ensure long-term mechanical wear resistance, structural integrity and stable high surface potential antibacterial function, in some specific embodiments of this application, the thickness of the bottom zirconia thin film layer 101 and the top zirconia thin film layer 105 is 0.05~1 μm, and can be prepared by any one of the following methods: sol-gel method, atomic layer deposition technology or magnetron sputtering process.

[0033] By combining an ultrathin zirconium oxide film with an insulating layer, the overall flexibility of the electrode is maintained while significantly improving the wear resistance, mechanical strength, and long-term durability of the electrode surface, effectively preventing damage to the electrode surface caused by long-term micro-movements.

[0034] In some specific embodiments of this application, the method for treating high surface potential is surface functionalization or element doping.

[0035] Specifically, surface functionalization includes: grafting self-assembled monolayers onto the surface of the zirconia thin film layer through surface functionalization.

[0036] In order to form a stable high surface potential of zirconia under physiological pH conditions and to enhance the dual antibacterial efficacy of electrostatic repulsion and contact sterilization through terminal cationic groups, in some specific embodiments of this application, the self-assembled monolayer is formed by a silane coupling agent with quaternary ammonium salt groups or amino groups at the end.

[0037] By treating with high surface potential, a monolayer is self-assembled on the surface of a zirconia thin film through surface functionalization grafting. After high surface potential treatment, the isoelectric point of the zirconia thin film is increased to above 8.5, so that it presents a positive Zeta potential in the range of +30 mV to +70 mV under physiological conditions. This inhibits bacterial biofilm formation through a dual mechanism of reducing initial bacterial adhesion through electrostatic repulsion and directly destroying the microbial membrane structure through high positive potential, while reducing the immune response of infection-related tissues.

[0038] Specifically, elemental doping includes: using low-valent cations to dope zirconium oxide thin films. Low-valent cations replace Zr. 4+ To maintain the material's electrical neutrality, a large number of oxygen vacancies with effective positive charges are generated inside the zirconia lattice. These oxygen vacancies directly contribute to the surface potential as intrinsic positive charge sources. They can also increase the isoelectric point of zirconia to above 8.5 by preferentially adsorbing hydroxide ions and suppressing surface deprotonation.

[0039] For example, the low-valent cation is any one of yttrium ions, magnesium ions, or calcium ions.

[0040] In order to effectively reduce the electrode-tissue interface impedance and significantly improve the charge injection capacity, thereby ensuring high signal-to-noise ratio recording of neural electrical signals and safe and efficient electrical stimulation function, in some specific embodiments of this application, the material of the electrode modification layer 106 is any one of porous iridium oxide, platinum black, platinum gray and titanium nitride.

[0041] Based on the same concept, another embodiment of this application provides a method for fabricating an antibacterial neural electrode based on a high surface potential zirconia layer as described in any of the above embodiments. The electrode is fabricated using standard micro / nano fabrication processes, referring to... Figure 2 The method specifically includes the following steps: S1. Sacrificial layer preparation: A sacrificial layer is deposited on the substrate and patterned. S2. Preparation of the bottom zirconia thin film layer: A bottom zirconia thin film is formed on the surface of the patterned sacrificial layer, and the bottom zirconia thin film is patterned by reactive ion etching; S3. Preparation of the first insulating layer: The first insulating layer is spin-coated onto the patterned bottom zirconium oxide film and patterned to expose the connection area; S4. Metal layer preparation: Deposit and pattern the metal layer to form electrode traces and electrode points; S5. Preparation of the second insulating layer: spin-coating and patterning the second insulating layer so that the metal layer is encapsulated and embedded, exposing only the electrode points; S6. Preparation of the top zirconia thin film layer: Form a top zirconia thin film and pattern it to cover the non-electrode areas while keeping the electrode points exposed; S7. Electrode modification layer preparation: Selectively deposit an electrode modification layer on the exposed electrode sites; S8. Remove the sacrificial layer and release the device: The wafer-level structure is diced to remove the sacrificial layer and release the electrode structure from the substrate to obtain an independent flexible neural electrode. S9. High surface potential post-treatment: The flexible neural electrode is immersed in a silanization solution for post-treatment, forming a positively charged self-assembled monolayer on the zirconia surface. After cleaning and drying, an antibacterial neural electrode based on a high surface potential zirconia layer is obtained.

[0042] Specifically, in step S1, a 4-inch silicon wafer is selected and ultrasonically cleaned in an acetone / ethanol / deionized water environment. The ultrasonic power is 100 W, the ultrasonic time is 10 min, and the cycle is repeated 3 times. On the cleaned silicon wafer, a 300 nm thick aluminum film is deposited by electron beam evaporation or sputtering. Then, photoresist is coated, and photolithography exposure and development are performed to define the desired pattern.

[0043] In step S3, a polyimide (PI) precursor liquid is spin-coated onto the bottom zirconia thin film layer and soft-baked. Then, imidization is performed in a muffle furnace; next, photoresist is used as a mask, and electrode contours are formed by photolithography exposure and development. The non-electrode contour areas are then etched clean by a dry etching process to finally form the first insulating layer.

[0044] In step S4, a metal layer is deposited on the first insulating layer by sputtering, and then patterned by photolithography and etching processes (or lift-off processes) to form fine wires and electrode points.

[0045] In step S5, a polyimide (PI) precursor liquid is spin-coated onto the metal layer and soft-baked. Then, imidization is performed in a muffle furnace; next, photoresist is used as a mask, and electrode contours are formed by photolithography exposure and development. The non-electrode contour areas are then etched clean by a dry etching process to finally form the second insulating layer.

[0046] In step S7, porous iridium oxide (IrO) is selectively deposited on the exposed metal electrode sites by electroplating or electrochemical activation. x The process involves applying either platinum black or platinum black (Pt Black), and this step must be completed before surface treatment because subsequent silanization will damage the porous structure.

[0047] In step S8, the wafer that has completed the previous process is diced and separated into individual electrode devices; the individual devices are immersed in an aluminum-specific etching solution and wet etching is used to completely remove the aluminum sacrificial layer, so that the electrode devices are released from the silicon substrate to obtain independent flexible neural electrodes.

[0048] It should be noted that in some other embodiments, the zirconia thin film layer can also be prepared by sol-gel method or magnetron sputtering process.

[0049] To prevent high-temperature processing from damaging the underlying organic polymer insulating layer or causing film cracking and interface delamination due to thermal stress, and to ensure the process compatibility of the multilayer flexible structure, in some specific embodiments of this application, the zirconia film layer is formed using atomic layer deposition (ALD) technology at a temperature not exceeding 200°C during the steps of forming the bottom and / or top zirconia films. ALD enables sub-nanometer precision control of film thickness, resulting in precise, controllable, dense, and uniform thickness with strong adhesion to the substrate and high film structural stability. By setting the temperature, thermal damage to the organic polymer insulating substrate can be avoided, preventing thermal stress mismatch during the process and preventing film cracking or interface defects. Furthermore, a growth environment at 200°C or below results in a denser and more uniform zirconia film growth, which is beneficial for the stability of subsequent grafting processes.

[0050] To overcome the etching challenges posed by the high hardness and chemical inertness of zirconia materials, achieve micro / nano patterning with steep sidewalls and precise dimensions, and avoid etching damage to the underlying functional structure, in some specific embodiments of this application, reactive ion etching is used to pattern the bottom zirconia film. Specifically, reactive ion etching employs a Cl2 / BCl3 mixed gas and is combined with a metal hard mask to achieve high-precision patterning of the zirconia film.

[0051] Specifically, in step S2, an atomic layer deposition (ALD) technique is used to deposit a 200 nm thick zirconium oxide film on a patterned aluminum sacrificial layer at a process temperature below 200°C. After deposition, patterning is performed using a photoresist mask and reactive ion etching (RIE) with a Cl2 / BCl3 plasma gas combination. A chromium layer is used as a hard mask to achieve highly selective and anisotropic etching of the zirconium oxide, resulting in precise patterns.

[0052] In step S6, a second zirconium oxide film is deposited on the entire device surface again using low-temperature atomic layer deposition technology; then, zirconium oxide in the front pad and tail electrode area is precisely removed by photolithography and reactive ion etching to expose the underlying metal layer, while retaining zirconium oxide in other areas.

[0053] To promote the full hydrolysis of silane molecules and their efficient condensation with hydroxyl groups on the zirconium oxide surface under mild conditions, forming a dense, uniform, and strongly covalently bonded positively charged self-assembled monolayer, while avoiding structural damage to the flexible electrode caused by harsh environments, in some specific embodiments of this application, the flexible neural electrode is immersed in a silanization solution for post-treatment, forming a positively charged self-assembled monolayer on the zirconium oxide surface: Post-treatment method 1: Quaternary ammonium silane treatment: The flexible neural electrode is placed in an anhydrous ethanol solution of quaternary ammonium silane coupling agent with a concentration of 1-10 mM and reacted at 60-80°C for 2-12 h to form a stable positive potential self-assembled monolayer on the zirconium oxide surface.

[0054] Post-treatment method 2: Aminosilane treatment: The flexible neural electrode is placed in an anhydrous ethanol solution of aminosilane coupling agent with a concentration of 1-10 mM and reacted at 50-70°C for 4-12 h. Then it is cured at 100-120°C for 30-60 min, so that the amino group is exposed on the surface and protonated to form a positive potential under physiological pH conditions.

[0055] Figure 3 A shows a flowchart of using surface functionalization to introduce a high surface potential into a neural electrode to form an antibacterial neural electrode. The specific process of step S9 is as follows: (1) Surface cleaning: The released neural electrodes are ultrasonically cleaned in acetone / ethanol / deionized water and dried with nitrogen or vacuum. (2) Surface activation: The electrode is placed in an oxygen plasma device for treatment with a power of 300 W, a gas flow rate of 100 sccm / min, and a treatment time of 1~10 min to increase the number of hydroxyl (-OH) on the zirconium oxide surface and improve the grafting activity. (3) Solution preparation: Dissolve the quaternary ammonium salt silane coupling agent in anhydrous ethanol solvent to prepare a 1-10 mM dilute silane coupling agent solution, i.e., electrode impregnation solution 3; It should be noted that the solution formed in this step is weakly acidic or near-neutral. Quaternary ammonium salts are themselves a source of positive charge and do not necessarily require an acidic environment to generate a positive charge; however, amino groups require an acidic environment to form a positive charge. (4) Silanization reaction: Immerse the activated neural electrode 2 (i.e., the independent flexible neural electrode obtained in step S8) in the dilute solution of the silane coupling agent prepared above; (5) Heating catalysis: The reaction system is placed in a constant temperature water bath at 60-80°C and reacted for 2-12 h. Heating can significantly accelerate the hydrolysis of silane molecules and the condensation reaction with -OH on the zirconium oxide surface. (6) Cleaning and drying: After the reaction is complete, the electrode is removed and ultrasonically cleaned in anhydrous ethanol and deionized water in sequence to completely remove the physically adsorbed and unreacted silane molecules, and then dried with nitrogen or vacuum. (7) High temperature curing: Heat the target electrode in a vacuum oven at 100-120°C for 30-60 min, or vacuum dry overnight at room temperature to strengthen the Si-O-Zr covalent bond.

[0056] Through the above-mentioned high surface potential post-treatment, the quaternary ammonium salt silane coupling agent is stably grafted onto the zirconium oxide surface via Si-O-Zr covalent bonds, thereby transferring the terminal quaternary ammonium cation (N... + It is densely fixed on the electrode surface, so that the electrode can obtain a stable and long-lasting high positive surface potential under physiological environment.

[0057] Based on the same concept, another embodiment of this application provides a method for preparing an antibacterial neural electrode based on a high surface potential zirconia layer as described in any of the above embodiments. The high positive surface potential of the zirconia film is formed in situ through elemental doping, eliminating the need for subsequent silanization post-treatment. The method includes the following steps: M1. Deposit a sacrificial layer on the substrate and pattern the sacrificial layer; M2. A bottom zirconia film is formed on the surface of the patterned sacrificial layer. The bottom zirconia film is an element-doped zirconia film layer. The bottom zirconia film is patterned by reactive ion etching. M3. Spin-coat the first insulating layer onto the patterned bottom zirconium oxide film and pattern it to expose the connection area; M4. Deposit a metal layer and pattern it to form electrode traces and electrode points; M5. Spin-coat the second insulating layer and pattern it so that the metal layer is encapsulated and embedded, exposing only the electrode points; M6. Form an element-doped top zirconium oxide film and pattern it to cover the non-electrode areas while keeping the electrode points exposed. M7. Selectively deposit electrode modification layers on exposed electrode sites; M8. The wafer-level structure is diced to remove the sacrificial layer and release the electrode structure from the substrate to obtain an independent flexible neural electrode, namely an antibacterial neural electrode based on a high surface potential zirconia layer.

[0058] It should be noted that the above steps M1, M3-M5, and M7-M8 can be performed with reference to the corresponding steps S1, S3-S5, and S7-S8 in the above embodiments.

[0059] Figure 3 B shows a flowchart illustrating the process of introducing a high surface potential during the electrode fabrication of a zirconia thin film. The principle of the elemental doping method is as follows: the zirconia thin film is in-situ doped with low-valent cations, replacing Zr with low-valent cations. 4+ To maintain the electrical neutrality of the material crystal, a large number of positively charged oxygen vacancies are spontaneously generated within the zirconium oxide lattice.

[0060] Low-valent cation doping is achieved through a super-cycle process using low-temperature atomic layer deposition technology, with Y³ + For example, the specific steps are as follows: place the substrate in the reaction chamber of the equipment, heat it to the deposition temperature (≤200℃), and evacuate the vacuum until the background vacuum level is below 10. -6 Torr; followed by supercycle deposition, each supercycle consisting of... m A ZrO2 deposition subcycle and n The composition of each Y2O3 depositional subcycle, according to ( m ×ZrO2cycles + n The combination of ×Y2O3 cycles) is regulated by adjusting... m and n The ratio to control Y³ + Doping concentration, the formula for calculating doping concentration is: Doping concentration (mol%) = n / ( m + n The process is repeated with a supercycle of 100% until the target thickness is reached, resulting in a doped zirconium oxide film.

[0061] The preferred features in the above embodiments can be used individually in any embodiment, or in any combination thereof, provided they do not conflict with each other. Furthermore, parts not described in detail in the embodiments can be implemented using existing technologies.

[0062] The present application will be further described below with reference to specific embodiments / comparative examples in order to better understand the above technical solutions of the present application. It should be understood that the following are only some examples and are not intended to limit the present application.

[0063] Example This embodiment provides a high surface potential antibacterial coating constructed by using polyimide PI-2610 as the insulating layer material, platinum-iridium alloy as the metal layer, and platinum black as the electrode modification layer, through surface silanization post-treatment. The specific preparation process is as follows: S1: Sacrificial Layer Preparation. A 4-inch silicon wafer was ultrasonically cleaned in an acetone / ethanol / deionized water environment at a power of 100 W for 10 min, repeated 3 times, and then dried with a nitrogen gun. SPR220-4.5 positive photoresist was coated onto the cleaned silicon wafer, and photolithography was performed to define the desired pattern. The photolithographically completed wafer was then subjected to oxygen plasma surface treatment (300 W, 100 sccm / min) for 2 min. A 30 nm thick chromium layer and a 300 nm thick aluminum layer were deposited by electron beam evaporation, and then stripped in acetone to obtain the patterned aluminum sacrificial layer.

[0064] S2: Fabrication of the bottom zirconia thin film layer. A 200 nm thick zirconia thin film was deposited on a patterned aluminum sacrificial layer using atomic layer deposition (ALD) at a process temperature below 200°C. SPR220-4.5 positive photoresist was then coated onto the film, and photolithography exposure and development defined the desired pattern. A 50 nm chromium layer was evaporated as a hard mask, and the hard mask was patterned by a lift-off method. Then, reactive ion etching was performed using a Cl2 / BCl3 plasma gas combination (gas flow ratio: Cl2:BCl3 = 30:10, chamber pressure 10 mTorr). Finally, the chromium hard mask was removed using a selective chromium etchant to obtain the patterned bottom zirconia thin film layer.

[0065] S3: Preparation of the first insulating layer. PI-2610 was spin-coated onto the bottom zirconia thin film and pre-baked at 150°C for 2 min. Then, imidization was performed in a muffle furnace at 350°C for 30 min. Next, positive photoresist AZ4562 was used as an etching mask, and electrode contours were formed by photolithography exposure and development. The non-electrode contour areas were then etched clean using a dry etching process (etching gas: O2:SF6=90:10) to finally form the first insulating layer.

[0066] S4: Metal Layer Fabrication. The first insulating layer was surface-treated using oxygen plasma. Using magnetron sputtering in a high-vacuum argon atmosphere, a 20 nm thick tantalum adhesion layer and a 300 nm thick platinum-iridium alloy layer were sequentially deposited on the first insulating layer, with iridium comprising 15% of the total weight. The metal layer was patterned using photolithography and ion milling processes to form the designed fine conductive lines and electrode points.

[0067] S5: Fabrication of the second insulating layer. The fabrication parameters for the second insulating layer are the same as those for the first insulating layer. Note the photolithography windowing to expose the front-end pads and the rear-end electrode points.

[0068] S6: Fabrication of the top zirconia thin film layer. A second zirconia thin film layer is deposited again on the entire device surface using low-temperature atomic layer deposition (ALD). Then, the zirconia layer in the front pad and rear electrode area is precisely removed by photolithography and reactive ion etching to expose the underlying metal layer, while retaining the zirconia layer in other areas.

[0069] S7: Electrode Modification Layer Preparation. The electrode modification layer was prepared by electrodeposition of platinum black. Before electroplating, the platinum-iridium electrode surface was treated with O2 Plasma for 1-3 min to effectively clean and activate its surface. The electrode was used as the working electrode and placed in a 0.5 M H2SO4 solution at a temperature of -0.2 V to +1.2 V. vs. Cyclic voltammetry (CV) scans were performed between the reference electrode and the electrode until the CV curves stabilized to reduce surface oxides and remove adsorbates. Then, formal electroplating was performed using a plating solution containing 3 wt% hexachloroplatinic acid and 0.0015 wt% lead acetate, depositing a charge of 200 mC / cm² at a current density of 10 mA / cm² in constant current mode. After deposition, electrochemical cyclic voltammetry stabilization was performed in a 0.5 M sulfuric acid solution. Finally, the electrode surface was rinsed thoroughly with deionized water to remove residual plating solution.

[0070] S8: Remove the sacrificial layer and release the device. After dicing the entire wafer into individual devices using a precision wafer dicing machine, the devices are immersed in 10% dilute hydrochloric acid for wet chemical etching. The aluminum sacrificial layer is completely dissolved, yielding individual neural electrodes. Finally, the devices are sequentially rinsed with deionized water and critically dried to complete the device release.

[0071] S9: Post-treatment for high surface potential. The released neural electrodes were ultrasonically cleaned in acetone / ethanol / deionized water, each solution being cleaned for 10 min, and then dried with nitrogen or vacuum. Next, the electrodes were treated with oxygen plasma for 5 min, ensuring both the bottom and top zirconia film layers were treated. Then, a surface functionalization solution was prepared by dissolving a quaternary ammonium silane coupling agent in anhydrous ethanol to a 10 mM dilute solution. The electrodes were then immersed in this dilute silane coupling agent solution, and the entire reaction system was placed in an 80°C constant temperature water bath for 12 h. After the reaction, the electrodes were removed and ultrasonically cleaned sequentially in anhydrous ethanol and deionized water, then dried with nitrogen or vacuum. Finally, the electrodes were cured at 100°C under vacuum for 60 min to complete the high surface potential modification.

[0072] By following the above steps, the structural integrity of the device can be guaranteed, while ensuring the efficiency and uniformity of the surface modification process, ultimately resulting in an antibacterial flexible neural electrode with high surface potential.

[0073] To address the challenges of traditional neural electrodes, where surface protein adsorption induces bacterial infection and immune responses, ultimately leading to glial scarring and signal attenuation, this application proposes a novel neural electrode based on a high surface potential zirconia thin film. This electrode utilizes the stable positive charge of the zirconia surface to effectively kill bacteria and inhibit biofilm formation while significantly reducing immune responses and glial scar formation. Furthermore, it exhibits high safety for mammalian cells, thus establishing a stable electrode. A neural interface enables long-term, low-impedance, high-signal-to-noise ratio recording of neural signals. This neural electrode based on high surface potential zirconia successfully combines active antibacterial properties with excellent biocompatibility, providing a new path for the development of next-generation long-term stable neural interfaces.

[0074] In the description of the embodiments of this application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "bottom", "inner", "outer", "clockwise", "counterclockwise", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings. They are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application.

[0075] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined with "first" or "second" may explicitly or implicitly include one or more of that feature.

[0076] In the description of the embodiments in this application, "multiple" means two or more, unless otherwise explicitly specified. In this application, unless otherwise explicitly specified and limited, the terms "installed," "connected," "linked," "fixed," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances.

[0077] The terms "comprising" and "having," and any variations thereof, in the embodiments of this application are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or device that includes a series of steps or units is not limited to the steps or units listed, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to such processes, methods, products, or devices.

[0078] The foregoing has described some specific embodiments of this application. It should be understood that this application is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the substantive content of this application. The above-described preferred features can be used in any combination without conflict.

Claims

1. An antibacterial neural electrode based on a high surface potential zirconia layer, characterized in that, From bottom to top, it includes: a bottom zirconium oxide thin film layer, a first insulating layer, a metal layer, a second insulating layer, a top zirconium oxide thin film layer, and an electrode modification layer, wherein: The distal local area of ​​the metal layer is exposed to form electrode points, and the electrode modification layer covers the electrode points. The bottom and top zirconia thin film layers exhibit a positive surface potential in a physiological environment after being treated with high surface potential, thereby achieving antibacterial function.

2. The antibacterial neural electrode based on a high surface potential zirconia layer according to claim 1, characterized in that, The bottom zirconia thin film layer and the top zirconia thin film layer are prepared by any one of the following methods: sol-gel method, atomic layer deposition technology or magnetron sputtering process.

3. The antibacterial neural electrode based on a high surface potential zirconia layer according to claim 1, characterized in that, The thickness of the bottom zirconia thin film layer and the top zirconia thin film layer is 0.05~1 μm.

4. The antibacterial neural electrode based on a high surface potential zirconia layer according to claim 1, characterized in that, The method for treating high surface potential is surface functionalization or element doping.

5. The surface functionalization method according to claim 4, characterized in that, The surface functionalization includes: grafting a self-assembled monolayer onto the surface of the zirconium oxide thin film layer through surface functionalization.

6. The surface functionalization method according to claim 5, characterized in that, The self-assembled monolayer is formed by a silane coupling agent with a quaternary ammonium salt group or an amino group at the end.

7. The element doping method according to claim 4, characterized in that, The element doping includes: using a zirconium oxide thin film layer doped with low-valence cations.

8. The low-valent cation according to claim 7, characterized in that, The low-valent cation is any one of yttrium ions, magnesium ions, or calcium ions.

9. A method for preparing an antibacterial neural electrode based on a high surface potential zirconia layer as described in any one of claims 1 to 8, characterized in that, include: A sacrificial layer is deposited on a substrate, and the sacrificial layer is patterned. A bottom zirconium oxide film is formed on the surface of a patterned sacrificial layer, and the bottom zirconium oxide film is patterned by reactive ion etching. A first insulating layer is spin-coated onto a patterned bottom zirconium oxide film and patterned to expose the connection area; Deposit a metal layer and pattern it to form electrode traces and electrode points; A second insulating layer is spin-coated and patterned so that the metal layer is encapsulated and embedded, exposing only the electrode points; A top zirconium oxide film is formed and patterned to cover the non-electrode areas while keeping the electrode points exposed; Selectively deposit electrode modification layers on exposed electrode sites; The wafer-level structure is diced, the sacrificial layer is removed, and the electrode structure is released from the substrate to obtain an independent flexible neural electrode. The flexible neural electrode was immersed in a silanization solution for post-treatment, forming a positively charged self-assembled monolayer on the zirconia surface. After cleaning and drying, an antibacterial neural electrode based on a high surface potential zirconia layer was obtained.

10. A method for preparing an antibacterial neural electrode based on a high surface potential zirconia layer as described in any one of claims 1 to 8, characterized in that, include: A sacrificial layer is deposited on a substrate, and the sacrificial layer is patterned. A bottom zirconium oxide film is formed on the surface of a patterned sacrificial layer. The bottom zirconium oxide film is an element-doped zirconium oxide film layer. The bottom zirconium oxide film is patterned by reactive ion etching. A first insulating layer is spin-coated onto a patterned bottom zirconium oxide film and patterned to expose the connection area; Deposit a metal layer and pattern it to form electrode traces and electrode points; A second insulating layer is spin-coated and patterned so that the metal layer is encapsulated and embedded, exposing only the electrode points; A top zirconium oxide film with elemental doping is formed and patterned to cover the non-electrode areas while keeping the electrode points exposed. Selectively deposit electrode modification layers on exposed electrode sites; The wafer-level structure is diced to remove the sacrificial layer and release the electrode structure from the substrate, resulting in an independent flexible neural electrode, namely an antibacterial neural electrode based on a high surface potential zirconia layer.

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