Nuclear magnetism compatible flexible stretchable multifunctional nerve probe and preparation method thereof

By developing a flexible stretchable multifunctional neural probe with nuclear magnetic compatibility and integrating electrophysiological and electrochemical detection functions, the problem of signal synchronization monitoring in the existing technology is solved, efficient and stable neural signal acquisition is achieved, and biocompatibility and nuclear magnetic compatibility are improved.

CN119867764APending Publication Date: 2025-04-25AEROSPACE INFORMATION RES INST CAS

Patent Information

Application Number
CN202510188540.5
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-02-20
Publication Date
2025-04-25

AI Technical Summary

Technical Problem

The prior art has multiple technical difficulties in achieving synchronous monitoring of neurotransmitter dopamine (DA), electroencephalography (EEG) and deep brain signal, including insufficient functionality, biocompatibility problems and lack of nuclear magnetic compatibility.

Method used

Develop a NM-compatible flexible stretchable multifunctional neural probe, using low magnetic materials such as Parylene and carbon-based films, integrate electrophysiological and electrochemical detection functions, reduce tissue damage through flexible design and improve stretchability through serpentine wire design.

Benefits of technology

A comprehensive recording of a variety of neural signals has been achieved, biocompatibility and nuclear magnetic compatibility have been improved, and the long-term stability of signal acquisition and data accuracy have been significantly improved, providing a new technical path for the comprehensive analysis of neural activities in the deep brain area.

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Abstract

The invention discloses a nuclear magnetism compatible flexible stretchable multifunctional nerve probe and a preparation method thereof, and belongs to the technical field of clinical nerve electrophysiological signal and neurotransmitter detection sensors, a bonding pad lead is connected with a deep brain nucleus electrophysiological lead, a neurotransmitter detection lead and a cortex electrophysiological lead; the electrophysiology detection site, the electrochemical reference electrode, the neurotransmitter detection site, the electrophysiology detection wire, the neurotransmitter detection wire, the bonding pad site, the bonding pad wire, the cortex electrophysiology detection site, the cortex electrophysiology detection wire, the electrophysiology reference electrode, the electrophysiology reference electrode wire and the electrochemical reference electrode wire are all arranged on the substrate. The probe integrates deep brain nucleus electrophysiological detection, neurotransmitter detection and cortex electrophysiological detection, integrates multi-modal detection, nuclear magnetic compatibility and flexible design, realizes comprehensive neural information recording with high temporal-spatial resolution, and provides an accurate and reliable tool for deep brain region and brain loop research.
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Description

Technical Field

[0001] The present invention belongs to the field of clinical neuroelectrophysiological signal and neurotransmitter detection sensors, and in particular relates to a nuclear magnetic resonance compatible flexible and stretchable multifunctional neural probe and a preparation method thereof. Background Art

[0002] In recent years, with the rapid development of neuroscience and brain-computer interface technology, researchers have deepened their research on the complex neural activities and dynamic changes of neurotransmitters in the brain. Especially in the study of emotion regulation, sleep-wake mechanism and neurological diseases, the synchronous monitoring of neurotransmitter dopamine (DA) and electroencephalogram (EEG) signals is of great significance for understanding the function and regulatory mechanism of deep neural circuits. DA is one of the key neurotransmitters in the central nervous system, which plays an important role in the process of emotion, motor control, reward mechanism, etc. The dynamic changes of DA levels in different regions of the brain are closely related to the neural activity pattern; and EEG provides a real-time reflection of the overall functional state of the brain by detecting changes in brain waves. Especially in the state of sleep, mood swings and neuropsychiatric diseases, there is a complex relationship between DA levels and EEG signals. Systematic synchronous monitoring of these signals will help reveal the intrinsic mechanism of neural activity in the brain. However, existing technical means still face multiple technical difficulties in realizing the synchronous monitoring of DA, EEG and deep brain area signals.

[0003] Traditional microelectrode arrays have made certain achievements in the field of neural signal recording and can provide neuroelectrophysiological information with high temporal and spatial resolution. However, microelectrode arrays are usually only suitable for recording electrical signals and lack sensitivity for detecting chemical signals of neurotransmitters such as DA. This single functionality limits the ability to synchronously collect multimodal information within neural circuits and cannot meet the monitoring needs of the simultaneous changes in brain neurotransmitters and electrical signals. Therefore, microelectrode arrays with insufficient functionality face major technical bottlenecks in achieving a comprehensive analysis of neural signals in deep brain areas. At the same time, traditional electrode materials often have biocompatibility issues with brain tissue, which may cause tissue inflammation or immune rejection after implantation, affecting the long-term stability of the experiment and data accuracy. In practical applications, physical contact between microelectrodes and brain tissue can cause irreversible tissue damage, especially during long-term monitoring. This effect is significant. The above problems not only limit the experimental application of microelectrode arrays, but also become a key factor hindering the development of brain-computer interfaces and neural regulation.

[0004] In order to solve these problems, flexible, MRI-compatible, multifunctional neural probes have become an important direction in the development of neuroscience instruments today. The key advantage of flexible probes is that they can effectively fit brain tissue, reduce tissue rejection, and significantly improve biocompatibility. Due to the soft nature of brain tissue itself, flexible probes can better adapt to the complex shape and structure of the brain during implantation, reduce mechanical damage, and increase the long-term stability of signal acquisition. In contrast, traditional rigid probes are prone to stress on surrounding tissues after implantation due to differences in material hardness, leading to inflammatory reactions, signal drift, and even early failure of the probe. The use of flexible probes makes it possible to record signals in the brain over a long period of time with high fidelity, thereby providing stable and reliable hardware support for the synchronous detection of neurotransmitters and electrophysiological signals.

[0005] The material design of flexible probes also needs to consider MRI compatibility to meet the needs of non-destructive imaging of brain structures in neuroscience. Magnetic resonance imaging (MRI) is a non-invasive, high-resolution brain imaging technology that is widely used to study brain anatomical structures and functional activities. However, the metal materials of conventional probes will produce artifacts and signal interference in the MRI environment, which not only affects the imaging quality, but also may bring potential safety hazards due to electromagnetic induction heating. To this end, the development of low-magnetic, flexible and MRI-compatible materials such as Parylene and carbon-based films can enable the probe to reduce the impact on MRI imaging while maintaining high-quality signal acquisition functions. This flexible, MRI-compatible probe can achieve synchronization of high-resolution imaging and neural signal recording in an MRI environment, significantly improving the ability to obtain multimodal brain information and providing a new technical path for the comprehensive analysis of neural activity in deep brain areas.

[0006] In addition, integrated multifunctional probes have also emerged to meet the needs of synchronous monitoring of DA and deep brain electrophysiological signals (including EEG and deep neuron discharge activity Spike). By integrating the three-electrode system with the electrochemical sensing function, this type of probe can realize real-time monitoring of DA concentration and synchronously capture brain electrophysiological activity, providing comprehensive data support for the dynamic changes of neurotransmitters and neural electrical activity in neural circuits. Especially in the study of emotions, sleep states and neuropsychiatric diseases, multimodal probes can reveal the synergistic mechanism of different signals in neural circuits. This type of probe can achieve reversible and precise coordinated monitoring of neurotransmitters and electrical signals without genetic modification, providing richer data and a deeper understanding of the functions of deep brain neural circuits.

[0007] The future development direction is to further improve the versatility, biocompatibility and data synchronization of the probe. The development of multifunctional probes will make it possible to synchronously detect more different types of neural information, which will not only help basic research in neuroscience, but will also play an important role in brain-computer interfaces, neural regulation, and the diagnosis and treatment of neurological diseases. While promoting the frontiers of brain science, this type of new probe also provides solid technical support for the advancement of brain-computer interface technology and the precision treatment of neurological diseases. Therefore, the development and application of flexible, MRI-compatible multifunctional neural probes will have a profound impact on neuroscience research and its clinical transformation. Summary of the invention

[0008] In view of the above technical problems, the present invention proposes a flexible, stretchable and multifunctional neural probe compatible with nuclear magnetic resonance and a preparation method thereof, which are used to at least partially solve the above technical problems.

[0009] The technical solution of the present invention is as follows:

[0010] A flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance includes: a substrate and sites, electrodes and pad wires arranged on the substrate;

[0011] The base includes three parts, namely a tip part, a side arm part and a base part; the tip part and the side arm part are respectively connected to the same side of the base part, and the side arm part is arranged on both sides of the tip part;

[0012] The sites include electrophysiological detection sites, neurotransmitter detection sites, pad sites, and cortical electrophysiological detection sites; the electrodes include electrochemical reference electrodes and electrophysiological reference electrodes; the pad wires include electrophysiological detection wires, neurotransmitter detection wires, cortical electrophysiological detection wires, electrophysiological reference electrode wires, and electrochemical reference electrode wires;

[0013] The electrophysiological detection site, neurotransmitter detection site, electrochemical reference electrode and electrophysiological reference electrode are arranged on the tip portion, the cortical electrophysiological detection site is arranged on the side arm portion, and the pad site is arranged on the base portion; the electrophysiological detection site is connected to the pad site through an electrophysiological detection wire, the neurotransmitter detection site is connected to the pad site through a neurotransmitter detection wire, the electrochemical reference electrode is connected to the pad site through an electrochemical reference electrode wire, the electrophysiological reference electrode is connected to the pad site through an electrophysiological reference electrode wire, and the cortical electrophysiological detection site is connected to the pad site through a cortical electrophysiological detection wire.

[0014] On the other hand, the present invention also provides a method for preparing a flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance, which is used to prepare the aforementioned neural probe, comprising the following steps:

[0015] Step 1: Layer 5 μm Parylene onto the cleaned silicon wafer;

[0016] Step 2, spin-coating photoresist S1813 on the Parylene layer;

[0017] Step 3: Photolithography of the conductive layer pattern;

[0018] Step 4: sputtering and stripping of the conductive layer C;

[0019] Step 5: Deposit a 2 μm Parylene layer;

[0020] Step 6: Use AZ4620 photolithography technology to carve patterns into the exposed area, and etch the film with oxygen plasma;

[0021] Step 7: Photolithography and etching of the shape of the neural probe outline is performed using AZ4903.

[0022] The present invention provides a nuclear magnetic resonance compatible flexible and stretchable multifunctional neural probe and a preparation method thereof, which has the following beneficial effects:

[0023] (1) The electrode of the present invention integrates the electrophysiological detection function and the electrochemical detection function of the three-electrode system, which can realize the comprehensive recording of various neural signals and provide the possibility for the comprehensive analysis of complex neural activities;

[0024] (2) The electrode of the present invention can simultaneously obtain electrophysiological signals from the cerebral cortex and deep brain regions, providing an effective tool for in-depth exploration of brain circuit activities and the multi-level structure of neural circuits;

[0025] (3) The electrodes are made of nuclear magnetic resonance compatible materials, which support the simultaneous detection of electrophysiological and neurotransmitter signals under magnetic resonance imaging, ensuring high-precision, multi-dimensional neural information acquisition under clinical conditions, and providing more accurate and comprehensive data support for neuroscience research;

[0026] (4) The electrodes are made of flexible materials, which are suitable for chronic animal experiments and long-term implantation, reducing tissue damage and signal drift, and significantly improving the stability of the electrodes in long-term experiments;

[0027] (5) Through the directional modification of nanocomposites, the electrodes significantly improve their biocompatibility with brain tissue, reduce the risk of immune response, and achieve high temporal and spatial resolution electrophysiological signal and neurotransmitter detection performance, providing accurate neural activity information for in-depth analysis of brain neural circuits;

[0028] (6) The conductors of cortical electrophysiological signals adopt a serpentine design, which gives the electrode good stretchability, enhances its adaptability in complex biological environments, and provides a flexible solution for signal acquisition under long-term and dynamic conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] For a more complete understanding of the present invention and its advantages, reference will now be made to the following description taken in conjunction with the accompanying drawings, which are incorporated herein and constitute a part of this specification, wherein:

[0030] Figure 1 It is a flexible, stretchable and multifunctional neural probe compatible with nuclear magnetic resonance.

[0031] Figure 2 This is a local enlarged image of the electrophysiological and neurotransmitter detection sites of deep brain nuclei of a flexible, stretchable, multifunctional neural probe compatible with nuclear magnetic resonance;

[0032] Figure 3 This is a local enlarged image of the cortical electrophysiological monitoring site of a nuclear magnetic resonance compatible flexible and stretchable multifunctional neural probe;

[0033] Figure 4 This is a flow chart of the preparation method of a flexible, stretchable and multifunctional neural probe that is compatible with nuclear magnetic resonance.

[0034] In the figure, 1-electrophysiological detection site, 2-electrochemical reference electrode, 3-neurotransmitter detection site, 4-electrophysiological detection wire, 5-neurotransmitter detection wire, 6-pad site, 7-pad wire, 8-substrate, 9-cortical electrophysiological detection site, 10-cortical electrophysiological detection wire, 11-electrophysiological reference electrode, 12-electrophysiological reference electrode wire, 13-electrochemical reference electrode wire, 14-snake wire bending radius, 15-cortical electrophysiological detection site window radius, 16-snake wire bending slope. DETAILED DESCRIPTION

[0035] Embodiments of the present invention will be described below with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present invention. In the following detailed description, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of embodiments of the present invention. However, it is apparent that one or more embodiments may also be implemented without these specific details. In addition, in the following description, descriptions of known structures and technologies are omitted to avoid unnecessary confusion of concepts of the present invention.

[0036] Example 1

[0037] like Figure 1 , Figure 2 and Figure 3As shown, the present embodiment discloses a flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance, which is used to detect electrophysiological signals of the cortex and deep brain nuclei during sleep under clinical nuclear magnetic resonance imaging, and synchronously detect neurotransmitter signals of deep brain nuclei, the multifunctional neural probe comprising: an electrophysiological detection site 1, an electrochemical reference electrode 2, a neurotransmitter detection site 3, an electrophysiological detection wire 4, a neurotransmitter detection wire 5, a pad site 6, a pad wire 7, a substrate 8, a cortical electrophysiological detection site 9, a cortical electrophysiological detection wire 10, an electrophysiological reference electrode 11, an electrophysiological reference electrode wire 12 and an electrochemical reference electrode wire 13; the neurotransmitter detection site 3, the electrochemical reference electrode 2, the electrophysiological detection wire 3, the electrophysiological detection wire 4, the neurotransmitter detection wire 5, the pad site 6, the pad wire 7, the substrate 8, the cortical electrophysiological detection site 9, the cortical electrophysiological detection wire 10, the electrophysiological reference electrode 11, the electrophysiological reference electrode wire 12 and the electrochemical reference electrode wire 13; the neurotransmitter detection site 3, the electrochemical reference electrode 2, the electrophysiological detection wire 3, the electrophysiological detection wire 4, the neurotransmitter detection wire 5, the electrochemical reference electrode 2, the electrophysiological detection wire 3, the electrochemical reference electrode wire 13, the electrophysiological detection wire 14, the electrochemical reference electrode wire 15, the electrophysiological detection wire 16, the electrophysiological reference electrode wire 17, the electrochemical reference electrode wire 18, the electrophysiological detection wire 19, the electrophysiological detection wire 20, the electrophysiological reference electrode wire 21, the electrophysiological reference electrode wire 22, and the electrochemical reference electrode wire 23. The electrode 2 and the electrophysiological reference electrode 11 are located between the electrophysiological detection site 1; the electrochemical reference electrode 2 surrounds the neurotransmitter detection site 3; the pad wire 7 is respectively connected to the electrophysiological detection wire 4, the neurotransmitter detection wire 5, the electrophysiological reference electrode 11 and the electrochemical reference electrode wire 13; the electrophysiological detection site 1, the electrochemical reference electrode 2, the neurotransmitter detection site 3, the electrophysiological detection wire 4, the neurotransmitter detection wire 5, the pad site 6, the pad wire 7, the cortical electrophysiological detection site 9, the cortical electrophysiological detection wire 10, the electrophysiological reference electrode 11, the electrophysiological reference electrode wire 12 and the electrochemical reference electrode wire 13 are all on the substrate 8.

[0038] The electrophysiological detection site 1, electrochemical reference electrode 2, neurotransmitter detection site 3 and electrophysiological reference electrode 11 are located at the front tip part of the micro-nano electrode array, and the pad site 6 is located at the rear of the micro-nano electrode array. The electrophysiological detection site 1 is connected to the pad site 6 through the electrophysiological detection wire 4, and the electrophysiological reference electrode 11 is connected to the pad site 6 through the electrophysiological reference electrode wire 12; preferably, the neurotransmitter detection site 3 is connected to the pad site 6 through the neurotransmitter detection wire 5, and the electrochemical reference electrode 2 is connected to the pad site 6 through the electrochemical reference electrode wire 13; preferably, the number of cortical electrophysiological detection wires 10 is two, and the cortical electrophysiological detection site 9 is connected to the pad site 6 through one cortical electrophysiological detection wire 10.

[0039] In this embodiment, the electrophysiological detection sites 1 are circular with a diameter of 20 microns, and there are 30 of them.

[0040] In this embodiment, the cortical electrophysiological detection sites 9 are hollow circles with a line width of 500 microns, and there are two of them.

[0041] In this embodiment, the line width of the electrochemical reference electrode 2 is 10 micrometers.

[0042] In this embodiment, the area of ​​the neurotransmitter detection site 3 is 28096 square micrometers.

[0043] In this embodiment, the electrophysiological detection wires 4 have a line width of 5 micrometers, and the number is equal to the electrophysiological detection sites 1.

[0044] In this embodiment, the cortical electrophysiological detection wires 10 have a line width of 50 micrometers and are two in number.

[0045] In this embodiment, the neurotransmitter detection wire 5 has a line width of 10 micrometers and is 1 in number.

[0046] In this embodiment, the electrophysiological reference electrode wire 12 has a line width of 5 microns.

[0047] In this embodiment, the electrochemical reference electrode wire 13 has a line width of 10 micrometers.

[0048] In this embodiment, the bending radius 14 of the serpentine wire is 225 microns.

[0049] In this embodiment, the window radius 15 of the cortical electrophysiological detection site is 500 microns.

[0050] In this embodiment, the serpentine wire bending slope 16 is -0.2.

[0051] In this embodiment, the pad sites 6 are square, and their number is equal to the number of electrophysiological detection sites 1, cortical electrophysiological detection sites 9, neurotransmitter detection sites 3, electrochemical reference electrodes 2 and electrophysiological reference electrodes 11, totaling 35, with a size of 200 microns.

[0052] In this embodiment, the electrophysiological detection site 1, electrochemical reference electrode 2, neurotransmitter detection site 3, electrophysiological detection wire 4, neurotransmitter detection wire 5, pad site 6, pad wire 7, cortical electrophysiological detection site 9, cortical electrophysiological detection wire 10, electrophysiological reference electrode 11, electrophysiological reference electrode wire 12, and electrochemical reference electrode wire 13 are all manufactured on a substrate 8 using microelectromechanical technology, and the material is single-polished Si.

[0053] In this embodiment, the electrophysiological detection site 1, electrochemical reference electrode 2, neurotransmitter detection site 3, electrophysiological reference electrode 11, electrophysiological detection wire 4, neurotransmitter detection wire 5, pad site 6, pad wire 7, cortical electrophysiological detection site 9 and cortical electrophysiological detection wire 10 are all made of platinum, and their thickness is 0.25 microns.

[0054] In this embodiment, the surfaces of the electrophysiological detection wire 4, the neurotransmitter detection wire 5, the cortical electrophysiological detection wire 10 and the pad wire 7 are all covered with Parylene as an insulating layer, and the thickness of the insulating layer is 2 microns; preferably, the surfaces of the electrophysiological detection site 1, the electrophysiological reference electrode 11 and the cortical electrophysiological detection site 9 are modified by electroplating platinum nanoparticles, and the impedance after modification is less than 10 kiloohms; the surface of the neurotransmitter detection site 3 is electroplated with platinum and PEDOT:PSS nanoparticles, and coated with Nafion for modification, and the impedance after modification is less than 20 kiloohms; the surface of the electrochemical reference electrode 2 is modified by electroplating iridium oxide nanoparticles, and the impedance after modification is less than 10 kiloohms.

[0055] like Figure 4 As shown, the manufacturing process of the invention is as follows: step (1) laminating 5 μm Parylene on a cleaned silicon wafer; step (2) spin coating photoresist S1813 on the Parylene layer; step (3) photolithography of the conductive layer pattern; step (4) to step (5) sputtering and stripping of the conductive layer C (30 nm); step (6) depositing a 2 μm Parylene layer; step (7) to step (8) patterning the exposed area using AZ4620 photolithography technology and etching the film using oxygen plasma. Step (9) to step (10) photolithography and etching the shape of the neural probe outline using AZ4903.

[0056] Example 2

[0057] The method of using a nuclear magnetic resonance compatible flexible, stretchable, multifunctional neural probe described in Example 1 is as follows: PEG is coated on the tip of the electrode for curing and implanted into the deep brain nuclei, the electrophysiological detection site 1 provides electrophysiological signals of the deep brain nuclei, and the neurotransmitter detection site 3 provides electrochemical signals of the deep brain nuclei; the cortical electrophysiological detection wire 10 is stretched to a sufficient position of the skull nail in the prefrontal lobe, and the cortical electrophysiological detection site 9 is connected through silver paste and the skull nail and fixed to the left and right brains of the mouse prefrontal lobe for detecting cortical electrophysiological signals.

[0058] The detailed experimental steps are as follows:

[0059] After the mice were anesthetized with isoflurane and placed under magnetic resonance imaging, the microelectrode array was implanted into the sleep-related brain regions and cerebral cortex of the mice. After the mice recovered for 7 days, the experiments were conducted on the mice. Electrochemical reference electrode 2 and neurotransmitter detection site 3 were used to detect neurotransmitter signals, while electrophysiological detection site 1 and electrophysiological reference electrode 11 were used to detect the electrophysiological activity of the deep brain nuclei of the mice; cortical electrophysiological detection site 9 was used to detect cortical electrophysiological signals to distinguish different sleep stages, thereby discovering the neural information interaction between different brain regions in the loop, and achieving the purpose of clinically exploring brain regions.

[0060] It will be appreciated by those skilled in the art that, although the present invention has been shown and described with reference to specific exemplary embodiments of the present invention, it will be appreciated by those skilled in the art that, without departing from the spirit and scope of the present invention as defined by the appended claims and their equivalents, various changes in form and detail may be made to the present invention. Therefore, the scope of the present disclosure should not be limited to the above-described embodiments, but should be determined not only by the appended claims, but also by the equivalents of the appended claims.

Claims

1. A flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance, characterized in that: It includes: a substrate, and sites, electrodes and pad wires arranged on the substrate; The base includes three parts, namely a tip part, a side arm part and a base part; the tip part and the side arm part are respectively connected to the same side of the base part, and the side arm part is arranged on both sides of the tip part; The sites include electrophysiological detection sites, neurotransmitter detection sites, pad sites, and cortical electrophysiological detection sites; the electrodes include electrochemical reference electrodes and electrophysiological reference electrodes; the pad wires include electrophysiological detection wires, neurotransmitter detection wires, cortical electrophysiological detection wires, electrophysiological reference electrode wires, and electrochemical reference electrode wires; The electrophysiological detection site, neurotransmitter detection site, electrochemical reference electrode and electrophysiological reference electrode are arranged on the tip portion, the cortical electrophysiological detection site is arranged on the side arm portion, and the pad site is arranged on the base portion; The electrophysiological detection site is connected to the pad site via an electrophysiological detection wire, the neurotransmitter detection site is connected to the pad site via a neurotransmitter detection wire, the electrochemical reference electrode is connected to the pad site via an electrochemical reference electrode wire, the electrophysiological reference electrode is connected to the pad site via an electrophysiological reference electrode wire, and the cortical electrophysiological detection site is connected to the pad site via a cortical electrophysiological detection wire.

2. A flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to claim 1, characterized in that: The electrophysiological detection sites are circular with a diameter of 20 microns, 30 in number, and are arranged along the edge of the tip.

3. The flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to claim 1, characterized in that: The cortical electrophysiological detection sites are two hollow circles with a line width of 500 microns.

4. The flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to claim 1, characterized in that: The cortical electrophysiological detection wires are arranged in a serpentine shape, with a serpentine bending radius of 225 microns and a serpentine bending slope of -0.

2.

5. The flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to claim 1, characterized in that: The window radius of the cortical electrophysiological detection site is 500 microns.

6. The flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to claim 1, characterized in that: The pad sites are square in shape, and their number is equal to the sum of the number of detection sites, cortical electrophysiological detection sites, neurotransmitter detection sites, electrochemical reference electrodes and electrophysiological reference electrodes, which is 35 in total and has a size of 200 microns.

7. The flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to claim 1, characterized in that: The electrophysiological detection sites, electrochemical reference electrodes, neurotransmitter detection sites, electrophysiological detection wires, neurotransmitter detection wires, pad sites, pad wires, cortical electrophysiological detection sites, cortical electrophysiological detection wires, electrophysiological reference electrodes, electrophysiological reference electrode wires, and electrochemical reference electrode wires are all manufactured on a substrate using micro-electromechanical technology, and their material is single-polished Si.

8. The flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to claim 1, characterized in that: The surfaces of the electrophysiological detection wire, neurotransmitter detection wire, cortical electrophysiological detection wire and pad wire are all covered with Parylene as an insulating layer, and the thickness of the insulating layer is 2 microns; the surfaces of the electrophysiological detection site, electrophysiological reference electrode and cortical electrophysiological detection site are modified by electroplating platinum nanoparticles, and the impedance after modification is less than 10 kiloohms; the surface of the neurotransmitter detection site is modified by electroplating platinum and PEDOT:PSS nanoparticles, and coated with Nafion, and the impedance after modification is less than 20 kiloohms; the surface of the electrochemical reference electrode 2 is modified by electroplating iridium oxide nanoparticles, and the impedance after modification is less than 10 kiloohms.

9. The NMR-compatible flexible and stretchable multifunctional neural probe according to claim 1, characterized in that: The surfaces of the electrophysiological detection wire, neurotransmitter detection wire, cortical electrophysiological detection wire and pad wire are all covered with Parylene as an insulating layer, and the thickness of the insulating layer is 2 microns; the surfaces of the electrophysiological detection site, electrophysiological reference electrode and cortical electrophysiological detection site are modified by electroplating platinum nanoparticles, and the impedance after modification is less than 10 kiloohms; the surface of the neurotransmitter detection site is modified by electroplating platinum and PEDOT:PSS nanoparticles, and coated with Nafion, and the impedance after modification is less than 20 kiloohms; the surface of the electrochemical reference electrode 2 is modified by electroplating iridium oxide nanoparticles, and the impedance after modification is less than 10 kiloohms.

10. A method for preparing a flexible and stretchable multifunctional neural probe compatible with nuclear magnetic resonance according to any one of claims 1 to 9, characterized in that: The steps include: Step 1: Layer 5 μm Parylene onto the cleaned silicon wafer; Step 2, spin-coating photoresist S1813 on the Parylene layer; Step 3: Photolithography of the conductive layer pattern; Step 4: sputtering and stripping of the conductive layer C; Step 5: deposit a 2 μm Parylene layer; Step 6: Use AZ4620 photolithography technology to pattern the exposed area and etch the film with oxygen plasma. Step 7: Photolithography and etching of the shape of the neural probe outline is performed using AZ4903.

Citation Information

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