Flexible electrode array, system and method of manufacturing for closed-loop neuromodulation

Abstract

The application discloses a flexible electrode array, a system and a manufacturing method for closed-loop neuromodulation, and relates to the technical fields of neural engineering, medical devices and biosensors. The flexible electrode array comprises a flexible biocompatible substrate, a recording electrode array and a stimulating electrode array. The recording sites are distributed in a matrix, and the stimulating sites are arranged in the same plane as the recording sites and between or within the rows of the recording electrode array, achieving a spatially co-located layout of recording and stimulation. The system further comprises an external control unit for receiving neural signals collected by the recording electrode array and dynamically adjusting stimulation parameters applied to the stimulating electrode array based on the neural signals. The application can improve biocompatibility, achieve high-resolution signal mapping, and realize efficient closed-loop neuromodulation by shortening the spatiotemporal distance between stimulation and monitoring.

Description

Technical Field

[0001] This invention relates to the fields of neural engineering, medical devices, and biosensor technology, specifically to a flexible electrode array, system, and manufacturing method for closed-loop neural modulation. Background Technology

[0002] Implantable neural electrodes are key devices for monitoring and modulating neural function, and have wide applications in basic neuroscience research and clinical disease treatment. To better adapt to soft biological tissues (such as the spinal cord), electrode arrays based on flexible substrates have been developed in the prior art. Some designs integrate electrodes for signal recording and electrodes for applying electrical stimulation on the same flexible substrate, achieving integration of recording and stimulation functions.

[0003] However, existing flexible electrode arrays still have shortcomings. First, while many flexible electrodes possess both recording and stimulation functions, their materials, dimensions, and spatial layout are not specifically optimized for high-resolution recording and efficient closed-loop feedback, resulting in insufficient spatial resolution of the recorded signals and difficulty in accurately mapping neural activity. Second, existing designs often have significant spatial distances or unreasonable layouts between stimulation and recording sites, leading not only to severe stimulation artifacts but also introducing significant spatiotemporal lag between stimulation and monitoring, greatly limiting the realization of real-time, precise closed-loop neuromodulation. Furthermore, long-term implantation biocompatibility and stability are also challenges that urgently need to be addressed. Inappropriate material and structural designs can easily induce tissue scarring, thereby affecting the long-term functional effectiveness of the device. Summary of the Invention

[0004] The purpose of this invention is to provide a flexible electrode array, system, and manufacturing method for closed-loop neuromodulation, aiming to solve the technical problems of existing implantable electrodes, such as mechanical mismatch with biological tissues, low recording resolution, and inability to achieve efficient closed-loop modulation due to spatiotemporal lag between stimulation and recording sites.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0006] A flexible electrode array for closed-loop neural modulation, comprising:

[0007] Flexible biocompatible substrate;

[0008] An encapsulation layer is applied to the flexible biocompatible substrate;

[0009] A recording electrode array is disposed on the flexible biocompatible substrate, the recording electrode array comprising a plurality of recording sites arranged in a matrix, the recording sites passing through the encapsulation layer and being exposed;

[0010] A stimulation electrode array is disposed on the flexible biocompatible substrate. The stimulation electrode array includes multiple stimulation sites that pass through the encapsulation layer and are exposed, and the stimulation sites are arranged coplanarly with the recording sites.

[0011] The stimulation sites are located between or within rows of the recording electrode array to achieve a spatial co-location of the recording sites and the stimulation sites.

[0012] As a further aspect of the present invention: the flexible biocompatible substrate is a polyimide film, and the encapsulation layer is a bio-inert parylene film.

[0013] As a further aspect of the present invention: the recording site is made of platinum-iridium alloy, and the diameter of the recording site is 5 μm to 15 μm; the diameter of the stimulation site is 50 μm to 80 μm.

[0014] As a further aspect of the present invention: the recording electrode array is distributed in M ​​rows × N columns, where M and N are both integers greater than 1; the spacing between adjacent recording sites is 0.5 mm to 1.5 mm.

[0015] As a further aspect of the present invention: the flexible biocompatible substrate has a multilayer metal interconnect circuit embedded inside, and the metal interconnect circuit is electrically connected to the recording site and the stimulation site.

[0016] As a further aspect of the present invention: the flexible biocompatible substrate forms a recessed region in the area where the stimulation site is located, such that the upper surface of the stimulation site is coplanar with the upper surface of the recording site.

[0017] The present invention also provides a system for closed-loop neural modulation, comprising:

[0018] Any of the above-mentioned flexible electrode arrays for closed-loop neural modulation, and

[0019] An external control unit electrically connected to the flexible electrode array;

[0020] The external control unit is configured to receive neural signals acquired by the recording electrode array and dynamically adjust the stimulation parameters applied to the stimulation electrode array based on the neural signals.

[0021] As a further aspect of the present invention, the external control unit includes a data acquisition module, a closed-loop processing module, and a pulse generation module.

[0022] A method for manufacturing a flexible electrode array for closed-loop neural modulation includes the following steps:

[0023] Conductive structures for forming recording and stimulation sites are fabricated on a flexible biocompatible substrate;

[0024] An encapsulation layer is formed on the conductive structure; and

[0025] The encapsulation layer is selectively removed to expose portions of the conductive structure, which constitute the recording site and the stimulation site.

[0026] Compared with the prior art, the present invention has at least the following beneficial effects:

[0027] The flexible electrode array in this application utilizes a flexible biocompatible substrate, enabling excellent mechanical matching with soft biological tissues. This significantly reduces tissue scarring and foreign body reactions caused by mechanical mismatch, thus improving biocompatibility and long-term stability. Secondly, by optimizing the material and size of the recording sites and arranging them in a high-density matrix, the spatial sampling density is increased, allowing for high spatial resolution mapping of neurophysiological signals and providing a foundation for precise analysis of neural function. More importantly, by using a coplanar and staggered co-location of stimulation sites and high-density recording sites, the spatiotemporal distance between stimulation and monitoring is shortened. This allows the system to capture the neural responses induced by stimulation in real time and accurately, providing the hardware foundation for precise closed-loop neural modulation based on immediate feedback. This enables dynamic adjustment of stimulation strategies according to individualized neural signals. Attached Figure Description

[0028] The invention will now be further described with reference to the accompanying drawings.

[0029] Figure 1 This is a schematic diagram of the layering of the flexible electrode array provided in the embodiments of this application;

[0030] Figure 2 A top view schematic diagram of a flexible electrode array (excluding the encapsulation layer) provided in an embodiment of this application;

[0031] Figure 3 Schematic diagram of different electrode arrangements for the flexible electrode array provided in the embodiments of this application;

[0032] Figure 4 A schematic diagram of the architecture of a system for closed-loop neural modulation provided in an embodiment of this application;

[0033] Figure 5 This is a schematic diagram of the manufacturing process of the flexible electrode array provided in the embodiments of this application.

[0034] Figure 6 This is a flowchart illustrating a method for closed-loop neural modulation provided in an embodiment of this application.

[0035] In the figure: 100, flexible biocompatible substrate; 110, recording site; 120, stimulation site; 220, metal interconnect; 240, encapsulation layer; 250, electrode exposure window; 320, standard connector. Detailed Implementation

[0036] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] Example 1

[0038] Please see Figure 1 and Figure 2 As shown, this embodiment provides a specific structure, manufacturing process, and working principle of a flexible electrode array for closed-loop neuromodulation. This flexible electrode array aims to solve the problems of mechanical mismatch between implanted electrodes and biological tissues, low recording resolution, and low efficiency of synergistic stimulation and recording functions in existing technologies.

[0039] The flexible electrode array includes a flexible biocompatible substrate 100, and a recording electrode array and a stimulation electrode array disposed on the flexible biocompatible substrate 100. In one embodiment of this application, the flexible biocompatible substrate 100 is preferably a polyimide film with excellent biocompatibility and mechanical flexibility. Specifically, its thickness can be 50 μm. This thickness and material selection ensure that the entire flexible electrode array can flexibly conform to irregular biological tissue surfaces (e.g., the epidural surface of the spinal cord), thereby significantly reducing tissue inflammation caused by mechanical stiffness mismatch and scar tissue formation after long-term implantation, thus improving the long-term stability and biocompatibility of the device.

[0040] On the surface of a flexible biocompatible substrate 100, a recording electrode array and a stimulation electrode array are arranged coplanarly. The recording electrode array consists of multiple recording sites 110. For example... Figure 2As shown, these recording sites 110 are arranged in a high-density matrix. Specifically, in this embodiment, the recording electrode array is distributed in an 8-row × 4-column matrix, containing a total of 32 recording sites 110. This M-row × N-column matrix distribution (where M and N are both integers greater than 1) enables two-dimensional planar electrical signal sampling of the target neural region, thereby constructing an electrophysiological atlas of neural activity. To achieve high spatial resolution signal recording, the size of each recording site 110 is miniaturized. In this embodiment, the recording site 110 is made of a platinum-iridium alloy wire with excellent conductivity and corrosion resistance, and its diameter exposed to the tissue contact surface is preferably 10 μm. The center-to-center spacing of adjacent recording sites 110 is set to 1 mm. This spacing ensures sufficient spatial sampling density while avoiding signal crosstalk between channels. It should be noted that this spacing can be adjusted within the range of 0.5 mm to 1.5 mm according to specific application requirements.

[0041] The stimulation electrode array includes multiple stimulation sites 120. To achieve efficient coordination between stimulation and recording functions, i.e., to achieve a "spatial co-location layout," these stimulation sites 120 are integrated within the recording electrode array. Figure 1 As shown, in a preferred layout of this embodiment, the stimulation site 120 is located within a row of the recording electrode array. Specifically, one stimulation site 120 is provided in the central region of each row of recording electrodes. For example, in a row containing four recording sites 110, the stimulation site 120 may be located between the two middle recording sites 110. Thus, a total of eight rows of recording electrodes correspond to eight stimulation sites 120. The size of the stimulation site 120 is typically larger than that of the recording site 110 to deliver sufficient energy current to effectively activate or inhibit neuronal activity. In this embodiment, the diameter of the stimulation site 120 is preferably 60 μm, but this diameter can also be selected in the range of 50 μm to 80 μm. This co-located layout, embedding the stimulation site 120 in a high-density array of recording sites 110, greatly shortens the physical distance between the stimulation point and the response monitoring point, thereby allowing the neural electrical activity induced by the stimulus to be captured instantly and accurately by the adjacent recording site 110, laying the hardware foundation for achieving fast and precise closed-loop feedback control.

[0042] Further reference Figure 1 In one example, the flexible electrode array, from bottom to top, consists of: a flexible biocompatible substrate 100 as a support, specifically a polyimide substrate in this embodiment; a multilayer metal interconnect 220 embedded inside the flexible biocompatible substrate 100 or disposed on the substrate; a conductive structure for forming a recording site 110 or a stimulation site 120; and an encapsulation layer 240 covering the outermost layer.

[0043] Metal interconnects 220 are used to transmit electrical signals between electrode sites and external devices. These interconnects are typically made of highly conductive and chemically stable metals such as gold and platinum, and are formed on a flexible biocompatible substrate 100 using standard micro / nano fabrication processes (such as sputtering, photolithography, and lift-off). To accommodate the leads of all electrode sites within a limited area, the metal interconnects 220 can be designed as a multilayer structure, with layers isolated by insulating layers (such as another layer of polyimide) and interconnected vias. One end of each metal interconnect 220 is electrically connected to a specific recording site 110 or stimulation site 120, and the other end extends to the end of the flexible electrode array and converges in the flexible wiring area.

[0044] The encapsulation layer 240 protects the internal metal interconnects 220 from corrosive bodily fluids and provides electrical isolation to the biological tissue, ensuring that only electrode sites are exposed. In this embodiment, the encapsulation layer 240 is preferably a highly bioinert parylene film with a thickness of 10 μm. It is understood that parylene has excellent moisture resistance and biocompatibility, making it one of the ideal encapsulation materials for long-term implantable medical devices. After forming the encapsulation layer 240, a window, namely the electrode exposure window 250, is precisely opened directly above each recording site 110 and stimulation site 120 using a specific process, allowing the tip of the conductive platinum-iridium alloy wire to pass through the encapsulation layer 240 and be exposed, thereby forming a conductive contact with the nerve tissue.

[0045] Please see Figure 5As shown, the fabrication method of the flexible electrode array in this embodiment can employ microelectromechanical systems (MEMS) fabrication technology. A typical fabrication process may include: spin-coating and curing a first layer of polyimide film on a silicon wafer serving as a temporary carrier, as part of a flexible biocompatible substrate 100; subsequently, fabricating a first layer of metal interconnects on the polyimide film using metal sputtering and photolithography lift-off processes; based on this, spin-coating and curing a second layer of polyimide film to cover the first layer of interconnects, and etching vias for interlayer connections using reactive ion etching technology, repeating this process to fabricate the required multilayer metal interconnects 220; next, precisely etching microtrenches for accommodating platinum-iridium alloy wires on the top layer of polyimide using reactive ion etching; and then using high-precision... A robotic arm embeds a 10 μm diameter platinum-iridium alloy wire into a microgroove and ensures a reliable electrical connection between the wire and the end of the corresponding metal interconnect 220 using conductive adhesive or local welding. For larger diameter stimulation sites, a thicker wire can be embedded using a similar method, or the site can be thickened directly through electroplating. Then, a parylene film is uniformly deposited across the entire device surface as an encapsulation layer 240 using chemical vapor deposition. Finally, femtosecond laser or excimer laser is used for high-precision ablation to selectively remove the encapsulation layer 240 and a portion of the underlying polyimide, precisely forming an electrode exposure window 250 at the tip of each electrode site. Considering that the conductive structure of the stimulation site 120 (such as a thick wire) may be thicker than the platinum-iridium alloy wire of the recording site 110, to ensure the surface of the entire electrode array in contact with the tissue is as flat as possible, a pre-recessed treatment can be performed on the substrate region where the stimulation site 120 is located during the fabrication process. That is, before embedding the conductive structure of the stimulation site, a recessed region with a depth equivalent to the thickness of the stimulation site is etched into the polyimide substrate. Therefore, once the stimulation site 120 is formed, its upper surface can be roughly on the same plane as the upper surface of the surrounding recording sites 110, that is, coplanar, thereby avoiding additional mechanical compression of the underlying nerve tissue by the local protrusion.

[0046] like Figure 3 As shown, the overall dimensions of the flexible electrode array can be designed to be 14mm in length and 10mm in width. One end of the main body of the flexible electrode array extends integrally to form a flexible ribbon cable, and a standard connector 320 (e.g., a flexible printed circuit connector) is integrated at the end of the ribbon cable. Through this standard connector 320, the flexible electrode array can be conveniently electrically connected to an external control unit to transmit the acquired nerve signals and receive stimulation commands from the outside.

[0047] Example 2

[0048] This embodiment provides a variant design of a flexible electrode array for closed-loop neural modulation, mainly demonstrating the flexibility of the electrode array layout to adapt to different morphological neural targets or to achieve different modulation strategies.

[0049] Compared to the structure of Example 1, the electrode array in this embodiment can maintain the same material selection, hierarchical structure, and manufacturing process. For example, it also uses polyimide as the flexible biocompatible substrate 100, platinum-iridium alloy wire as the conductive material for the recording sites 110, and parylene as the encapsulation layer 240. The core difference lies in the spatial arrangement of the recording electrode array and the stimulating electrode array.

[0050] See Figure 3 As an optional implementation, in this embodiment, the matrix arrangement of the recording electrode array is adjusted to 16 rows × 2 columns. This longer and narrower array configuration is particularly suitable for applications that require monitoring and modulation along specific nerve bundles (such as ascending or descending conduction bundles in the spinal cord).

[0051] Furthermore, the layout of the stimulation sites 120 is also different. In Embodiment 1, the stimulation sites 120 are located within the rows of the recording electrodes; while in this embodiment, the stimulation sites 120 are arranged between two adjacent rows of the recording electrode array. Specifically, one stimulation site 120 may be located at the center between the first and second rows of the recording electrode array, another stimulation site 120 may be located at the center between the third and fourth rows, and so on. In this layout, a total of 16 rows of recording electrodes can be provided with 8 stimulation sites 120 located between the rows.

[0052] This "row-to-row" layout also achieves spatial co-location of stimulation and recording, ensuring immediate capture of neural responses after stimulation. Compared to the in-row layout, in this layout, each stimulation site 120 is surrounded in a more symmetrical manner by four recording sites 110 in the two rows above and below it. When electrical stimulation is applied to the stimulation site 120, the four surrounding recording sites 110 can simultaneously record evoked potentials at different spatial locations. By analyzing the amplitude and delay differences of these four channels, the diffusion range and depth of influence of the stimulation current in neural tissue, as well as the spatial distribution pattern of activated neurons, can be more accurately inferred. This provides richer and more effective data support for optimizing stimulation parameters and establishing more accurate neural modulation models.

[0053] This embodiment demonstrates the high flexibility of the spatial co-location layout concept proposed in this application. Whether the stimulation site 120 is placed "within a row" or "between rows" of the recording electrode array, the technical objectives of this application can be achieved. Designers can flexibly choose the optimal layout scheme according to specific anatomical characteristics and research or clinical needs.

[0054] Example 3

[0055] This embodiment aims to illustrate that the core technical concept of this application is not limited to the specific combination of materials and manufacturing processes described in Embodiments 1 and 2. By adopting functionally equivalent alternative materials and manufacturing methods, a high-performance integrated flexible electrode array for closed-loop stimulation recording can also be achieved.

[0056] Regarding the material selection for the flexible biocompatible substrate 100, in addition to polyimide films, other biocompatible flexible polymers widely recognized in the art can also be used. For example, SU-8 photoresist can be used as the substrate material. SU-8 is a commonly used negative photoresist that exhibits good mechanical strength, chemical stability, and biocompatibility after curing, and can be directly molded into complex microstructures using standard photolithography processes. Alternatively, in another embodiment, polydimethylsiloxane can be selected. This is an elastomer material with extremely low Young's modulus, enabling better mechanical matching with biological soft tissues, and is particularly suitable for applications requiring devices with significant deformation capabilities.

[0057] Accordingly, there are various alternatives for the conductive materials and formation processes of the recording site 110 and the stimulation site 120. Example 1 uses an embedded platinum-iridium alloy wire, which is a reliable process. Alternatively, semiconductor microfabrication processes based on thin-film deposition can be used entirely. A specific process may include: depositing a conductive metal (such as gold or platinum) layer on a flexible biocompatible substrate 100 (such as polyimide or SU-8) by sputtering or electron beam evaporation; then patterning the metal thin film using photolithography and etching (wet or dry etching) processes to form the desired metal interconnects and the initial regions of the electrode sites. The recording site 110 can be patterned as a circular region with a diameter of approximately 10 μm, while the stimulation site 120 can be patterned as a circular region with a diameter of approximately 60 μm. To reduce electrode impedance and improve charge injection capability, a layer of platinum black can be further electroplated onto the gold or platinum surface, or it can be modified using a conductive polymer (such as PEDOT:PSS).

[0058] In addition to parylene, other materials with good biocompatibility and insulating properties can also be used for the encapsulation layer 240. For example, a medical-grade silicone film can be spin-coated, or a layer of SU-8 photoresist can be applied as the encapsulation layer. Subsequently, the encapsulation layer 240 covering the electrode sites is selectively removed using photolithography and etching techniques, or by laser ablation, to form the electrode exposure window 250.

[0059] In summary, this embodiment discloses an alternative fabrication method, which includes: fabricating a conductive structure (e.g., a thin film electrode of gold or platinum) for forming recording sites and stimulation sites on a flexible biocompatible substrate by deposition and patterning processes; subsequently, forming an encapsulation layer (e.g., SU-8 or silicone) on the conductive structure by spin coating or deposition; and finally, selectively removing the encapsulation layer by photolithography or laser ablation to expose a portion of the conductive structure to form the desired recording site 110 and stimulation site 120.

[0060] Although this embodiment differs from Embodiment 1 in the substrate material, conductive material, encapsulation material, and specific manufacturing process, the final device maintains the same core structure: a matrix-distributed recording electrode array and a spatially co-located stimulation electrode array are coplanarly integrated on a flexible substrate. This device also achieves high-resolution recording and efficient closed-loop modulation. Therefore, this embodiment demonstrates the universality of the technical solution of this application and provides multiple feasible technical paths for the large-scale, low-cost manufacturing of this electrode array.

[0061] Example 4

[0062] Based on the electrode array described above, this embodiment further describes a complete closed-loop neuromodulation system and its working method to demonstrate its functional implementation in specific application scenarios.

[0063] Reference Figure 4 This figure is a schematic diagram of the overall architecture of the closed-loop neuromodulation system provided in this embodiment. The system mainly consists of two parts: a flexible electrode array implanted in the body, and an external control unit located outside the body.

[0064] The flexible electrode array can be any of the flexible electrode arrays for closed-loop neuromodulation described in Examples 1, 2, or 3. It acts as both a "sensor" and an "actuator" of the system, interacting directly with the target neural tissue.

[0065] The external control unit is the core control component of the system, responsible for signal processing, decision-making, and command generation. It is electrically connected to the flexible electrode array via a physical cable (through standard connector 320). Figure 4 As shown, the external control unit can be functionally divided into three core modules: a data acquisition module, a closed-loop processing module, and a pulse generation module.

[0066] The data acquisition module is connected to the recording electrode array of the flexible electrode array. Its main function is to receive and process the weak neural electrical signals acquired from all recording sites 110. The processing typically includes low-noise amplification, bandpass filtering (e.g., filtering out power frequency interference and DC drift), and analog-to-digital conversion. The processed multi-channel digital signal is transmitted to the closed-loop processing module in real time.

[0067] The closed-loop processing module is the core of intelligent control. It can be a computer running a specific algorithm, or an embedded system such as a dedicated digital signal processor or a field-programmable gate array (FPGA). Its core task is to analyze the neural signals received from the data acquisition module in real time. The analysis includes, but is not limited to: time-domain analysis (such as detecting neural impulses or evoked potentials of specific waveforms), frequency-domain analysis (such as calculating the power spectral density of specific frequency bands, for example, energy changes in the beta band related to motor intention or the gamma band related to pain), and spatial-domain analysis (such as constructing a spatial distribution map of neural activity based on multi-channel signals). Based on these analysis results, the closed-loop processing module makes decisions according to preset treatment logic or control algorithms. For example, when abnormal neural activity representing a pathological state is detected, the decision is to trigger an interventional stimulus; when the neural activity tends to normalize after stimulation, the decision is to maintain the current stimulation parameters; when the stimulation effect is unsatisfactory, the decision is to adjust the stimulation parameters.

[0068] The pulse generation module receives instructions from the closed-loop processing module and generates precise electrical stimulation pulses accordingly. These instructions specify a series of stimulation parameters, including the target stimulation site (i.e., which stimulation sites 120 to stimulate), the stimulation waveform (e.g., a biphasic square wave), the stimulation amplitude (current or voltage magnitude), the pulse width, and the stimulation frequency. The pulse generation module precisely applies the generated stimulation current or voltage to the designated stimulation sites 120 on the flexible electrode array via cables.

[0069] Taking a specific application scenario of chronic spinal pain management as an example, and combining it with... Figure 6 The flowchart shown below provides a detailed explanation of how the system works.

[0070] Step S401: Surgically implant a flexible electrode array into a specific segment of the patient's spinal cord, such as the epidural space in the dorsal horn region of the spinal cord corresponding to the area of ​​pain.

[0071] Step S402: After implantation, the system begins operation. The data acquisition module continuously acquires neurophysiological signals from the dorsal horn of the spinal cord via a recording electrode array.

[0072] Step S403: The acquired multi-channel analog signals are amplified, filtered, and digitized, and then transmitted in real time to the closed-loop processing module in the external control unit.

[0073] Step S404: The closed-loop processing module performs real-time analysis on the received digital signals. For example, the algorithm is configured to identify abnormal high-frequency oscillations in specific frequency bands (such as the gamma band) that are highly correlated with pain perception. When the closed-loop processing module detects that the power of this characteristic neural signal exceeds a preset threshold, the system determines that pain is about to occur or is occurring, and makes a decision that intervention is necessary.

[0074] Step S405: Based on the intervention decision, the closed-loop processing module immediately generates a set of stimulation parameters and sends them to the pulse generation module. This set of parameters can be a series of high-frequency (e.g., 100 Hz), low-amplitude (e.g., 100 microamps) biphasic pulses, designed to inhibit the transmission of pain signals to the brain through the principle of "gate control theory".

[0075] Step S406: The pulse generation module applies precise electrical stimulation to the spinal cord tissue through the stimulation site 120 closest to the location of the abnormal signal source, based on the received parameters.

[0076] Subsequently, the process forms a closed loop. After the electrical stimulation is applied, its effect on neural activity is immediately captured by recording sites 110 on the same electrode array. These new neural signals re-enter step S402 and are analyzed by the closed-loop processing module in step S404. If the analysis finds that the original abnormal high-frequency oscillations have been successfully suppressed, the closed-loop processing module decides to maintain the current stimulation parameters; if the suppression effect is not significant, the module automatically fine-tunes the stimulation parameters in step S405 (e.g., slightly increasing the stimulation frequency or amplitude) according to a preset optimization algorithm, and then applies new stimulation in step S406. This "record-analysis-decision-stimulation-re-re-record" cycle continues on a millisecond timescale, thereby achieving adaptive, personalized, and precise closed-loop control of neural activity, ultimately achieving the best analgesic effect while minimizing unnecessary electrical stimulation and potential side effects.

[0077] The preferred embodiments of the present invention have been described in detail above and should not be construed as limiting the scope of the invention. All equivalent variations and modifications made within the scope of the claims of this invention should still fall within the patent coverage of this invention.

Claims

1. A flexible electrode array for closed-loop neural modulation, characterized in that, include: Flexible biocompatible substrate; An encapsulation layer is applied to the flexible biocompatible substrate; A recording electrode array is disposed on the flexible biocompatible substrate, the recording electrode array comprising a plurality of recording sites arranged in a matrix, the recording sites passing through the encapsulation layer and being exposed; A stimulation electrode array is disposed on the flexible biocompatible substrate. The stimulation electrode array includes multiple stimulation sites that pass through the encapsulation layer and are exposed, and the stimulation sites are arranged coplanarly with the recording sites. The stimulation sites are located between or within rows of the recording electrode array to achieve a spatial co-location of the recording sites and the stimulation sites. The flexible biocompatible substrate forms a recessed region in the area where the stimulation site is located, such that the upper surface of the stimulation site is coplanar with the upper surface of the recording site.

2. The flexible electrode array for closed-loop neural modulation according to claim 1, characterized in that: The flexible biocompatible substrate is a polyimide film, and the encapsulation layer is a bio-inert parylene film.

3. The flexible electrode array for closed-loop neural modulation according to claim 1, characterized in that, The recording site is made of platinum-iridium alloy and has a diameter of 5 μm to 15 μm; the stimulation site has a diameter of 50 μm to 80 μm.

4. A flexible electrode array for closed-loop neural modulation according to claim 1, characterized in that, The recording electrode array is arranged in M ​​rows × N columns, where M and N are both integers greater than 1; the spacing between adjacent recording sites is 0.5 mm to 1.5 mm.

5. A flexible electrode array for closed-loop neural modulation according to claim 1, characterized in that, The flexible biocompatible substrate has multiple layers of metal interconnects embedded inside, which are electrically connected to the recording site and the stimulation site.

6. A system for closed-loop neural modulation, characterized in that, include: The flexible electrode array for closed-loop neural modulation as described in any one of claims 1-5, and the external control unit electrically connected to the flexible electrode array; The external control unit is configured to receive neural signals acquired by the recording electrode array and dynamically adjust the stimulation parameters applied to the stimulation electrode array based on the neural signals.

7. A system for closed-loop neural modulation according to claim 6, characterized in that, The external control unit includes a data acquisition module, a closed-loop processing module, and a pulse generation module.

8. A method for manufacturing a flexible electrode array for closed-loop neural modulation as described in any one of claims 1-5, characterized in that, Includes the following steps: On a flexible biocompatible substrate, a recessed area is formed in the region used to form stimulation sites; Conductive structures for forming recording and stimulation sites are fabricated on a flexible biocompatible substrate; An encapsulation layer is formed on the conductive structure; And selectively removing portions of the encapsulation layer to expose portions of the conductive structure, the exposed portions constituting the recording sites and the stimulation sites.

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