Multifunctional neural electrode for intracranial pressure detection and closed-loop nerve regulation

Abstract

The invention discloses a multifunctional neural electrode for intracranial pressure detection and closed-loop nerve regulation, the multifunctional electrode sequentially comprises a PMUT electrode for intracranial pressure detection and nerve regulation and a macro-micro electrode for electroencephalogram signal detection from top to bottom, and the PMUT electrode is bonded on the macro-micro electrode. The PMUT electrode is bonded to the macro-micro electrode to serve as a multifunctional electrode, the PMUT electrode can serve as a pressure sensor and can also serve as an ultrasonic transducer, the dual functions of intracranial pressure detection and fixed-point ultrasonic nerve stimulation are achieved, the macro-micro electrode can achieve detection of local field potential and peak potential, and the ultrasonic nerve stimulation function is achieved. Therefore, a detection-feedback-regulation closed-loop system is realized.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation. Background Technology

[0002] With the development of brain science and neural engineering technology, implantable neural electrodes are playing an increasingly important role in neural signal acquisition, brain disease treatment, and closed-loop neuromodulation. Currently, neural electrodes are mainly used to acquire electroencephalogram (EEG) signals (such as LFP, ECoG, or Spike) to study neural circuit activity patterns or to achieve electrical stimulation therapy for neurological diseases. However, traditional electrode systems are usually single-function and cannot simultaneously achieve multimodal information acquisition and modulation capabilities, limiting the precise intervention of complex neural dynamics. In recent years, ultrasound neuromodulation technology has become an important development direction in the field of neuromodulation due to its characteristics of no electrode damage, non-contact, and deep focusing. Studies have shown that low-intensity focused ultrasound (LIFU) can reversibly modulate the activity of neurons in specific brain regions through mechanical effects or acoustic membrane potential changes. However, existing ultrasound neuromodulation is generally transcranial nerve stimulation. While LIFU can focus on the deep brain with millimeter-level spatial resolution, transcranial focused ultrasound stimulation requires penetration of the skull. Due to the high acoustic impedance of the skull, severe scattering and refraction occur, and the treatment effect varies due to individual differences. In addition, most traditional ultrasonic transducers are made of rigid piezoelectric ceramic materials such as PZT or KNN, which limits their application in multifunctional neural interface systems.

[0003] Piezoelectric materials based on the piezoelectric effect can effectively realize the mutual conversion of mechanical energy and electrical energy, and have wide applications in actuators, sensors, medical monitoring, energy harvesting and other fields. Among them, polyvinylidene fluoride (PVDF) and its derivatives, as a classic piezoelectric polymer, have good flexibility, light weight, processability and biocompatibility, and show broad application prospects in miniaturized, multifunctional and self-powered flexible electronic devices.

[0004] On the other hand, intracranial pressure (ICP), as an important physiological parameter reflecting cerebral hemodynamics and the metabolic state of brain tissue, has extraordinary significance in pathology. Clinically, changes in ICP are closely related to the occurrence and progression of various neurological diseases (such as traumatic brain injury, cerebral hemorrhage, and cerebral edema). Existing methods for detecting ICP mainly rely on invasive means such as ventricular catheters and subdural probes (e.g., Chinese patent CN115607813A discloses a split drainage catheter based on angle tracking for self-detection of intracranial pressure, which measures intracranial pressure through ventricular drainage tube intervention; and Chinese patent CN116236172A discloses an intracranial pressure detection device, including an implanted probe and a signal repeater, wherein the implanted probe is used to implant in the cranium of a target object to detect intracranial pressure). These methods not only have the problems of high infection risk and poor long-term stability, but also cannot be synchronously recorded with neural electrical signals, making it difficult to achieve spatiotemporal correlation analysis between brain activity and cerebrospinal dynamics.

[0005] Therefore, there is an urgent need for a multifunctional neural electrode that integrates intracranial pressure detection and closed-loop neuromodulation to achieve multidimensional monitoring and regulation of brain nerve activity, providing new technical means for the diagnosis and treatment of neurological diseases (such as Parkinson's disease, epilepsy, and traumatic brain injury). Summary of the Invention

[0006] The purpose of this invention is to provide a multifunctional neural electrode for intracranial pressure detection and closed-loop neuromodulation. This invention uses a PMUT electrode bonded to a macro-micro electrode to form a multifunctional electrode. The PMUT electrode can be used as both a pressure sensor and an ultrasonic transducer, and has the dual functions of intracranial pressure detection and targeted ultrasonic neurostimulation. The macro-micro electrode can realize the detection of local field potential and peak potential, thereby realizing a closed-loop system of detection-feedback-modulation.

[0007] To achieve the above objectives, the specific technical solution of the present invention is as follows: A multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation, comprising, from top to bottom, a PMUT electrode for intracranial pressure detection and neural modulation and a macro-microelectrode for electroencephalogram (EEG) signal detection, wherein the PMUT electrode is bonded to the macro-microelectrode.

[0008] This invention proposes a novel approach to integrating a flexible piezoelectric micromachined ultrasonic transducer (PMUT) with a flexible macro-microelectrode array. The flexible macro-microelectrode has neural signal detection capabilities, recording not only low-frequency local field potentials but also high-frequency EEG spike potentials. Through structural design, an implantable flexible PMUT is innovatively added to the flexible macro-microelectrode array. Compared to traditional ultrasonic transducers, it offers advantages such as smaller size, lighter weight, lower power consumption, lower cost, higher sensitivity, and ease of integration with circuits and intelligent implementation. Functionally, since the ultrasonic transducer can function as both an ultrasonic transmitter and receiver, when used as a transmitter, the inverse piezoelectric effect based on piezoelectric materials can be used for deep brain neural modulation; when used as a receiver, the direct piezoelectric effect based on piezoelectric materials can be used for intracranial pressure monitoring. In this invention, the same ultrasonic transducer can be used as both a pressure sensor and an ultrasonic transmitter to achieve neural modulation functions, thus realizing a closed-loop system of detection-feedback-modulation.

[0009] The PMUT electrode is a piezoelectric micromechanical ultrasonic transducer, which includes an upper electrode, a piezoelectric film, a lower electrode, and a flexible substrate with a cavity structure from top to bottom; the macro-micro electrodes with cavity structures serve as the flexible substrate with cavity structures in the PMUT electrode.

[0010] Furthermore, to reduce the spatial dimensions, circular openings are arranged on the macro-microelectrodes as backing cavities for the PMUT. Further, the circular cavity structure is cut into the macro-microelectrodes using laser cutting; the diameter of the cavity structure is 200-1500 μm.

[0011] The upper and lower electrodes of the PMUT electrode are made of metals with excellent electrical conductivity, such as gold, silver, copper, or platinum. The piezoelectric film is made of flexible piezoelectric materials such as PVDF or its copolymer (P(VDF-TrFE)), preferably PVDF film with excellent flexibility. The flexible substrate is made of PI, PET, PVC, or TPU.

[0012] The PMUT electrode has a width of 1-5 mm and a thickness of 50-500 μm; the upper and lower electrodes are circular electrodes with a diameter of 100-1000 μm; the piezoelectric film has a thickness of 5-500 μm; and the cavity structure has a diameter of 200-1500 μm.

[0013] Furthermore, the upper and lower electrodes are formed on the surface of the piezoelectric film using technologies such as 3D printing, printing, and plasma sputtering.

[0014] The macro- and micro-electrodes include a flexible substrate and multiple macro-electrode arrays and micro-electrode arrays of different sizes arranged on the flexible substrate.

[0015] The macro and micro electrodes are flexible electrode arrays. The macro and micro electrodes are made of gold, silver, copper, stainless steel or platinum-iridium alloy, and the flexible substrate used is PET, PI, PVC or TPU, etc.

[0016] The macroelectrodes in the macroelectrodes range in size from 500 to 2000 μm, while the microelectrodes range in size from 10 to 500 μm, with the electrode contacts arranged at equal intervals. The macroelectrodes are circular and equidistant along the axial direction, with the electrode spacing adjustable. The microelectrodes are also circular.

[0017] The macro-electrode array and the micro-electrode array form a conductive layer for detecting electroencephalogram (EEG) signals. To separate the wiring from the piezoelectric micromechanical ultrasonic transducer, a via-hole process is used to fabricate the macro-microelectrode array.

[0018] Furthermore, the macro-microelectrode also includes an encapsulation layer, which is Parylene-C, PI, PDMS, or SU-8, etc.

[0019] The multifunctional neural electrode includes an outermost encapsulation layer. Further, the encapsulation layer may be Parylene-C, PI, PDMS, SU-8, etc., ultimately exposing the contacts of the macro- and micro-electrodes for EEG signal acquisition.

[0020] The front end of the macro-microelectrode is provided with a small hole for assisting implantation. Furthermore, the hole for assisting implantation is also prepared by laser cutting, and the pore diameter is 100 μm - 1 mm.

[0021] The method for preparing the multifunctional neural electrode includes: (1) Fabrication of flexible macro-microelectrode arrays using micro-nano fabrication technology; (2) A flexible PMUT electrode is bonded onto a macro-micro electrode to obtain a multifunctional electrode; (3) The multifunctional electrode is placed in a chemical vapor deposition system with its middle part suspended to deposit an encapsulation layer; (4) The back-end circuit is connected to form a multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation.

[0022] Furthermore, the method for preparing the multifunctional neural electrode includes: (1) Fabricate macro-microelectrodes using micro-nano fabrication technology; form cavities of PMUT electrodes on macro-microelectrodes by laser cutting; (2) A metal electrode is formed by plating silver on the PVDF film, and then a vibrating membrane is attached to the back of the PVDF film; (3) The PVDF film is bonded to the cavity of the macro-micro electrode by physical bonding to form the PMUT electrode; (4) A multifunctional electrode is obtained by connecting the electrode wires through hot pressing, electric welding, 3D printing or screen printing; (5) Place the multifunctional electrode in a chemical vapor deposition system with its middle part suspended to deposit a parylene film, forming a protective layer on the outside of the multifunctional electrode body; (6) Expose the contacts of macro-micro electrodes and connect them to the back-end FPCB board to form an integrated multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation provided by this invention combines a flexible PMUT electrode with a flexible macro-microelectrode array to achieve a closed-loop system of detection-feedback-modulation: On the one hand, based on the positive piezoelectric effect of the piezoelectric material in the PMUT electrode, changes in intracranial pressure can be easily detected, thus having advantages such as high sensitivity, low noise, and suitability for long-term implantation in monitoring changes in intracranial pressure; on the other hand, based on the inverse piezoelectric effect of the piezoelectric material in the PMUT electrode, targeted deep brain ultrasound stimulation can be achieved; furthermore, by detecting local field potentials and peak potentials in the deep brain in situ through macro-microelectrodes, a feasible solution for achieving closed-loop neural modulation is provided, which is expected to play a significant role in the fields of brain science research and diagnosis and treatment of brain diseases. 2. The multifunctional neural electrode provided by this invention is fabricated using a simple low-temperature bonding technique to create a small PMUT electrode, which significantly reduces the cost of fabricating PMUT electrodes using traditional micro-nano fabrication. In addition, by fixing the PMUT electrode onto a flexible substrate of macro-microelectrodes, the size of the electrode is reduced.

[0024] 3. The multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation provided by the present invention can realize targeted deep brain ultrasound stimulation and synchronously detect changes in electroencephalogram signals in situ. It has the functions of intracranial pressure detection, ultrasound neural modulation and electrophysiological recording, providing a feasible solution for realizing closed-loop neural modulation of electrodes. Attached Figure Description

[0025] Figure 1 A schematic diagram of macro-microelectrodes used for ultrasound neuromodulation and electroencephalogram (EEG) signal recording; Figure 2 This is a schematic diagram of the fabrication of an 8-channel macro-microelectrode; Figure 3 This is a schematic diagram of the fabrication of flexible PMUT and the assembly of multifunctional electrodes; Figure 4 Photographs of macro- and microelectrodes used for ultrasound neuromodulation and EEG signal recording. Figure 5 The sound pressure level of macro-microelectrodes used for ultrasound neuromodulation and electroencephalogram recording; Figure 6 The response time curve is used for intracranial pressure monitoring; Figure 7 Voltage output for monitoring intracranial pressure changes in rats. Detailed Implementation

[0026] The present invention will be further described below with reference to the accompanying drawings and embodiments. Here, the embodiments and descriptions of the present invention are used to explain the present invention, but are not intended to limit the present invention.

[0027] Example like Figure 1 As shown, this embodiment discloses a multifunctional neural electrode for intracranial pressure detection and closed-loop neuromodulation, including: a through-hole 1 for assisting implantation; macro-microelectrodes for detecting electroencephalogram (EEG) signals (where 2 is a macroelectrode and 3 is a microelectrode); and a PMUT electrode 5 for deep brain ultrasound stimulation (where 4 is a circular electrode patterned on a flexible piezoelectric material PVDF, which also serves as a pressure sensor for monitoring changes in intracranial pressure). The PMUT electrode is adhered to the macro-microelectrode with a cavity structure 8, and 6 and 7 are electrode connection lines. For ease of understanding, the preparation method of the multifunctional electrode for intracranial pressure monitoring and closed-loop neuromodulation provided in this embodiment includes steps S1 to S3: S1, such as Figure 2 The macro-microelectrode array is fabricated as shown: To ensure electrode flexibility, a 25 μm thick PET film was selected and laser-cut to the appropriate size. To separate the PMUT electrode 5 from the macro / micro electrodes, vias were used to fabricate the electrodes. A 50 μm diameter via was formed on the PET substrate using a laser cutter, and the upper and lower copper layers were connected vias using a black hole process and copper electroplating. A 1 mm diameter cavity structure for the PMUT and a 1 mm via for auxiliary implantation were cut using a laser cutter. A uniform copper layer was formed on the PET film and the inner walls of the vias using photolithography, metal deposition, and lift-off processes. An insulating layer was fabricated on the conductor to protect the circuit pattern from short circuits and oxidation. The final fabricated macro / micro electrodes are shown below. Figure 1 As shown, it mainly includes a cavity structure 8 for fabricating PMUT electrode 5, a through hole 1 for assisting implantation, four macroelectrodes 2 with a diameter of 500 μm for recording local field potentials, and four microelectrodes 3 with a diameter of 250 μm for recording brain spike potentials.

[0028] S2, such as Figure 3 The PMUT electrode with ultrasound stimulation and intracranial pressure monitoring functions is shown in the figure. The PMUT device is elongated and easy to adhere to macro and micro electrodes: PMUT electrode 5 is a piezoelectric micromechanical ultrasonic transducer, which includes an upper electrode, a piezoelectric film 7, a lower electrode and a flexible substrate (macro and micro electrode) with a cavity structure 8 from top to bottom. The upper electrode and the lower electrode are circular electrodes 4.

[0029] To facilitate integration onto macro and micro electrodes, PMUT electrode 5 should be flexible, and the piezoelectric element within it uses a PVDF thin film with excellent flexibility. For example... Figure 2 PMUT electrodes 5 were fabricated using a masking method. A single-sided silver-plated PVDF film was cut into strips of 1 mm x 1 cm. Electrode wires were patterned on a 15 μm thick PI tape using a laser cutter to form a printed mask. The circular electrode diameter was 750 μm. The printed mask was then attached to the PVDF film, and a layer of conductive silver paste was applied to the mask. The conductive silver paste was allowed to fully cure at room temperature. After removing the mask, silver wire electrodes were formed on the PVDF film. Double-sided adhesive tape was attached to the back of the PVDF film and then adhered to the macro-microelectrode. The PVDF film was suspended at the corresponding positions, forming a cavity structure. Finally, conductive silver paste was used to connect the PMUT contacts to the back-end circuitry.

[0030] S3: The outer end of the electrode includes an insulating layer. The multifunctional electrode is connected to the back-end circuit using conductive silver paste. Then, it is placed in a chemical vapor deposition system with the middle part suspended to deposit a parylene film, forming a protective layer on the outside of the multifunctional electrode body.

[0031] A photograph of the physical sample of the multifunctional neural electrode prepared in this embodiment for intracranial pressure detection and closed-loop neuromodulation is shown below. Figure 4 As shown.

[0032] Application examples Figure 5 The image shows the sound pressure output of the PMUT electrode as an ultrasonic transmitter in water. The electrode's output performance was characterized in a water tank. A 20-cycle sinusoidal pulse was generated using a signal generator, amplified by a power amplifier, and used to drive the PMUT device. The signal was received using an NH-1000 hydrophone and finally displayed on an oscilloscope. The results are as follows: Figure 5 As shown, the PMUT device can output a voltage of 43.6 mV, which corresponds to a sound pressure level of 40.8 kPa.

[0033] Figure 6The response time and pressure output of the PMUT electrode as a pressure sensor were measured. A cyclic pressure of 5 N was applied to the multifunctional electrode using a universal testing machine, and its voltage output under external pressure was recorded using a source meter. The voltage output of this composite electrode was 25-50 mV, and its response time to pressure changes was 40 ms, demonstrating high sensitivity.

[0034] Figure 7 To detect intracranial pressure changes in SD rats, electrodes were implanted into the rat brain. External force was applied to the rat's abdomen to induce changes in intracranial cerebrospinal fluid pressure. This pressure was then output as a voltage change via a flexible piezoelectric patch on the PMUT. During the compression of the rat's abdominal cavity, the voltage change was approximately 0.10 V.

[0035] In summary, this invention provides a multifunctional neural electrode for intracranial pressure detection and closed-loop neuromodulation. This electrode is small in size, simple in fabrication process, and low in manufacturing cost. It can detect signals of local field potentials and spike potentials in the brain. At the same time, since this multifunctional electrode integrates a flexible PMUT, it can precisely stimulate brain lesions through ultrasound to achieve the purpose of treating neurological diseases, providing strong support for future closed-loop neurostimulation. The piezoelectric element in the PMUT can be used as a sensitive pressure sensor for intracranial pressure detection, thereby realizing a closed-loop system of detection-feedback-modulation.

[0036] It should be noted that the above description is only one embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation, characterized in that, The multifunctional electrode, from top to bottom, includes a PMUT electrode for intracranial pressure detection and neuromodulation and a macro-micro electrode for electroencephalogram (EEG) signal detection, with the PMUT electrode bonded to the macro-micro electrode.

2. The multifunctional neural electrode according to claim 1, characterized in that, The PMUT electrode is a piezoelectric micromechanical ultrasonic transducer, which includes an upper electrode, a piezoelectric film, a lower electrode, and a flexible substrate with a cavity structure from top to bottom; the macro-micro electrodes with cavity structures serve as the flexible substrate with cavity structures in the PMUT electrode.

3. The multifunctional neural electrode according to claim 2, characterized in that, The upper and lower electrodes of the PMUT electrode are made of gold, silver, copper or platinum, the piezoelectric film is made of PVDF or its copolymer (P(VDF-TrFE)), and the flexible substrate is made of PI, PET, PVC or TPU.

4. The multifunctional neural electrode according to claim 2, characterized in that, The PMUT electrode has a width of 1-5 mm and a thickness of 50-500 μm; the upper electrode is a circular electrode with a diameter of 100-1000 μm; the piezoelectric film has a thickness of 5-500 μm; and the cavity structure has a diameter of 200-1500 μm.

5. The multifunctional neural electrode according to claim 1, characterized in that, The macro- and micro-electrodes include a flexible substrate and multiple macro-electrode arrays and micro-electrode arrays of different sizes arranged on the flexible substrate.

6. The multifunctional neural electrode according to claim 5, characterized in that, The macro and micro electrodes are flexible electrode arrays. The materials of the macro and micro electrodes are selected from gold, silver, copper, stainless steel or platinum-iridium alloy, and the flexible substrate used is PET, PI, PVC or TPU.

7. The multifunctional neural electrode according to claim 6, characterized in that, The macroelectrode has a size of 500-2000 μm, the microelectrode has a size of 10-500 μm, and the electrode contacts are arranged at equal intervals.

8. The multifunctional neural electrode according to claim 1, characterized in that, The multifunctional neural electrode includes an outermost encapsulation layer, and the front end of the macro-micro electrode has a small hole for assisting implantation.

9. The multifunctional neural electrode according to any one of claims 1-8, characterized in that, The method for preparing the multifunctional neural electrode includes: (1) Fabrication of flexible macro-microelectrodes using micro-nano fabrication technology; (2) A flexible PMUT electrode is bonded onto a macro-micro electrode to obtain a multifunctional electrode; (3) The multifunctional electrode is placed in a chemical vapor deposition system with its middle part suspended to deposit an encapsulation layer; (4) The back-end circuit is connected to form a multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation.

10. The multifunctional neural electrode according to claim 9, characterized in that, The method for preparing the multifunctional neural electrode includes: (1) Fabricate macro-microelectrodes using micro-nano fabrication technology; form cavities of PMUT electrodes on macro-microelectrodes by laser cutting; (2) A metal electrode is formed by plating silver on the PVDF film, and then a vibrating membrane is attached to the back of the PVDF film; (3) The PVDF film is bonded to the cavity of the macro-micro electrode by physical bonding to form the PMUT electrode; (4) A multifunctional electrode is obtained by connecting the electrode wires through hot pressing, electric welding, 3D printing or screen printing; (5) Place the multifunctional electrode in a chemical vapor deposition system with its middle part suspended to deposit a parylene film, forming a protective layer on the outside of the multifunctional electrode body; (6) Expose the contacts of macro-micro electrodes and connect them to the back-end FPCB board to form an integrated multifunctional neural electrode for intracranial pressure detection and closed-loop neural modulation.

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