Ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation

Abstract

The invention discloses an ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation. The multifunctional electrode sequentially comprises a matrix microtube, a PMUT electrode for deep brain ultrasonic stimulation and an SEEG electrode for electroencephalogram signal detection from inside to outside. The ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation has the functions of fixed-point ultrasonic nerve stimulation and in-situ electroencephalogram signal detection, provides powerful support for closed-loop nerve stimulation in the future, and meanwhile has the advantages of being simple in preparation process, low in manufacturing cost and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to an ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation. Background Art

[0002] Stereotactic electroencephalography (SEEG) is an invasive technique used to diagnose and treat neurological diseases. The core function of SEEG electrodes is to record deep and subcutaneous neural electrical activity. Its high spatial resolution can effectively capture synchronous or asynchronous discharge phenomena in different brain regions. The advantages of SEEG technology include: (1) precise positioning. There is an individualized surgical path based on the patient's clinical symptoms, and each electrode contact corresponds to a different lesion site; (2) minimal surgical trauma. It only requires a small hole of about 3 mm in the skull under anesthesia, and the patient can walk after surgery; (3) dynamic long-term monitoring. After the electrode is implanted, the patient can remain awake and carry out daily activities while undergoing long-term EEG monitoring. For example, the Chinese patent with publication number: CN116849609A discloses that the automatic and accurate positioning of the epileptogenic zone can be achieved by analyzing long-term SEEG monitoring and obtaining the position of the target electrode. However, the current commercial SEEG electrodes can only record neural electrical activity, and cannot provide timely intervention and treatment for the lesion area, and cannot form a closed loop.

[0003] As a mechanical vibration wave, ultrasound has wave effect, mechanical effect and thermal effect, and has great application value in clinical practice. It can be used for imaging diagnosis of diseases, auxiliary drug delivery, neuromodulation and thermal ablation therapy. Ultrasound technology has now been applied to neurological diseases such as Parkinson's disease, obsessive-compulsive disorder, depression, Alzheimer's disease, and has broad application prospects in the diagnosis and treatment of nervous system diseases. For example, the immunotherapy device disclosed in the Chinese patent with publication number CN112473026A targets different immune nervous systems, generates specific ultrasound waves and guides them to the neural nuclei of the target nervous system, stimulates the central or peripheral system, and produces activation or inhibition of the immune effect, thereby achieving the purpose of immunotherapy of diseases. However, the existing ultrasonic transducers are mainly made of rigid piezoelectric ceramic materials, which are difficult to flexibly integrate with flexible electrodes, thereby limiting their application in multifunctional neural interface systems.

[0004] Therefore, electrodes with more diversified functions, miniaturized size, higher safety and better biocompatibility are needed clinically. Summary of the invention

[0005] The purpose of the present invention is to provide an ultrasound-EEG multifunctional electrode for deep brain stimulation, which can realize fixed-point deep brain ultrasound stimulation and synchronously detect EEG signal changes in situ, providing a feasible solution for realizing a closed-loop neural regulation system.

[0006] In order to achieve the above object, the specific technical solution of the present invention is as follows:

[0007] A multifunctional ultrasound-electroencephalogram electrode for deep brain stimulation, wherein the multifunctional electrode comprises, from inside to outside, a matrix microtube, a PMUT electrode for deep brain ultrasound stimulation, and a SEEG electrode for electroencephalogram signal detection.

[0008] The present invention proposes a new idea of ​​integrating a flexible piezoelectric micromachined ultrasonic transducer (PMUT) with a SEEG electrode: the SEEG electrode has the function of detecting neural signals, and a micromachined ultrasonic transducer PMUT with ultrasonic stimulation is innovatively added to the SEEG electrode through structural design. Compared with traditional ultrasonic transducers, PMUT has the advantages of small size, light weight, low power consumption, low cost, high sensitivity, and easy integration with circuits and intelligentization; secondly, PMUT is manufactured based on micromachining technology and is highly customizable. It can be produced into a flexible matrix structure, which is convenient for integration with SEEG electrodes to achieve fixed-point deep brain ultrasonic stimulation; this integrated SEEG-PMUT system can not only monitor brain nerves in real time, but also achieve precise neural regulation through ultrasonic stimulation. It can be implanted in the brain lesion area to perform ultrasonic stimulation on specific parts, which is used to treat brain diseases such as Parkinson's disease, essential tremor and dystonia, providing a new multifunctional platform for the diagnosis and treatment of neurological diseases.

[0009] The matrix microtube is in the shape of a round tube and is made of any one of flexible polyurethane, epoxy resin or polydimethylsiloxane, preferably a polyurethane tube with biocompatibility.

[0010] The diameter of the matrix microtube is 0.5-2 mm, and the inner diameter of the matrix microtube is 200-1500 um.

[0011] The PMUT electrode is a piezoelectric micromechanical ultrasonic transducer, which includes, from top to bottom, an upper electrode, a piezoelectric film, a lower electrode and a flexible substrate with a cavity structure.

[0012] The upper electrode and the lower electrode are made of metals with excellent conductive properties such as gold, silver, copper or platinum; the piezoelectric film is made of piezoelectric materials such as PVDF, PZT or KNN, preferably a PVDF film with excellent flexibility; the flexible substrate is made of PI, PET, PVC or TPU, etc.

[0013] The width of the PMUT electrode is 1-5 mm, and the thickness is 50-500 um; the upper electrode and the lower electrode are circular electrodes, and the diameter is 100-1000 um; the thickness of the piezoelectric film is 5-500 um; and the diameter of the cavity structure is 200-1500 um.

[0014] Furthermore, the upper and lower electrodes are formed on the surface of the piezoelectric film by 3D printing technology, printing technology, plasma sputtering technology, etc. The cavity is carved on the flexible substrate by laser cutting technology.

[0015] Furthermore, the PMUT electrode is connected to the back-end circuit from the inside of the substrate microtube through an enameled wire.

[0016] Furthermore, the PMUT electrode has 1-8 channels.

[0017] The material of the electrode contacts in the SEEG electrode is selected from gold, silver, copper, stainless steel or platinum-iridium alloy, etc., preferably platinum-iridium alloy with higher conductivity and better biocompatibility.

[0018] The height of the electrode contacts in the SEEG electrode is 1000-1500 um, the distance between the electrode contacts in the SEEG electrode is 0.5-5 mm, and the number of the electrode contacts in the SEEG electrode is 4-20. The above parameters can be adjusted according to actual conditions.

[0019] Furthermore, the SEEG electrode is connected to the back-end circuit from the inside of the substrate microtube through enameled wire.

[0020] Furthermore, the SEEG electrode has 4-20 channels.

[0021] The multifunctional electrode further comprises an outermost packaging layer (such as parylene) and exposes the SEEG electrode contacts.

[0022] The preparation method of the ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation comprises:

[0023] (1) Curl the PMUT electrode onto the substrate microtube;

[0024] (2) Fix the SEEG electrode on the substrate microtube wrapped with the PMUT electrode;

[0025] (3) placing the substrate microtube in a state where the middle part of the substrate is suspended in the air into a chemical vapor deposition system for deposition to form an encapsulation layer;

[0026] (4) The electrode contacts of the SEEG electrode are exposed to form an ultrasound-EEG multifunctional electrode.

[0027] Specifically, the preparation method of the ultrasound stimulation-electroencephalogram multifunctional flexible DBS electrode comprises the following steps:

[0028] (1) preparing matrix microtubes of a predetermined length;

[0029] (2) Preparation of micromachined ultrasonic transducer stimulation electrodes: First, silver is plated on the PVDF film to form electrodes, then a laser cutter is used to form cavities on the Kapton tape, and finally, the PVDF piezoelectric layer and the Kapton cavity layer are stacked in sequence to form PMUT stimulation electrodes;

[0030] (3) curling the flexible PMUT stimulation electrode onto the matrix microtube;

[0031] (4) welding the enameled wire to the platinum-iridium ring electrode;

[0032] (5) The platinum-iridium electrode ring is fixed on the substrate microtube wrapped with the PMUT electrode, and the wire is connected from the inside of the substrate microtube to the back-end circuit to form the SEEG electrode;

[0033] (6) placing the substrate microtube in a suspended state in the middle into a chemical vapor deposition system to deposit a parylene film to form a protective layer on the outside of the tubular electrode body;

[0034] (7) The contact points of the platinum-iridium electrode are exposed to form an integrated ultrasound stimulation-electroencephalographic multifunctional DBS electrode.

[0035] The above simple preparation method will significantly reduce the preparation cost of traditional electrodes.

[0036] The beneficial effects of the present invention are as follows:

[0037] 1. The present invention realizes multifunctional neural regulation and detection by combining flexible PMUT electrodes with SEEG electrodes: on the one hand, a small-volume PMUT electrode is prepared by a simple low-temperature bonding technology, which greatly reduces the cost of preparing PMUT electrodes by traditional micro-nano processing; on the other hand, the size of the electrode is reduced by fixing the PMUT electrode on a flexible substrate.

[0038] 2. The present invention can be used to perform real-time targeted ultrasonic stimulation of brain lesions and simultaneously detect deep brain electroencephalogram signals in situ, thereby achieving precise neural regulation and detection deep in the brain, providing a feasible solution for achieving closed-loop neural regulation of electrodes, and is expected to play a significant role in the fields of brain science research and diagnosis and treatment of brain diseases.

[0039] 3. The ultrasound stimulation-EEG multifunctional electrode provided by the present invention can realize fixed-point deep brain ultrasound stimulation and synchronously detect EEG signal changes in situ. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 Schematic diagram of ultrasound-EEG multifunctional electrode for deep brain stimulation;

[0041] Figure 2 This is the preparation diagram and structural schematic diagram of the piezoelectric micromechanical ultrasonic transducer;

[0042] Figure 3 Flow chart for preparation of ultrasound-EEG multifunctional electrodes;

[0043] Figure 4 This is a photo of the ultrasound stimulation-EEG multifunctional electrode.

[0044] Figure 5 Output sound pressure map of ultrasound stimulation-EEG multifunctional electrode. DETAILED DESCRIPTION

[0045] The present invention will be further described below in conjunction with the accompanying drawings and embodiments. Here, the embodiments of the present invention and their descriptions are used to explain the present invention, but are not intended to limit the present invention.

[0046] Example

[0047] like Figure 1 As shown, this embodiment discloses an ultrasound-EEG multifunctional electrode device for deep brain stimulation, including: a SEEG electrode 3 for EEG signal detection, a PMUT electrode 2 for deep brain ultrasound stimulation: the PMUT electrode 2 is adhered to the base microtube 1, and then the platinum-iridium ring electrode (electrode contact) of the SEEG electrode 3 is fixed to the base microtube adhered with the PMUT electrode. For ease of understanding, refer to Figure 3 The method for preparing the ultrasound-EEG multifunctional electrode for deep brain stimulation provided in this embodiment includes steps S1 to S3:

[0048] S1: Prepare a PMUT electrode with ultrasonic stimulation function. The PMUT device is in the shape of a long strip, which is convenient for adhering to the substrate microtube: the PMUT electrode is a piezoelectric micromechanical ultrasonic transducer, which includes an upper electrode, a piezoelectric film 7, a lower electrode and a flexible substrate 5 with a cavity structure from top to bottom. The upper electrode and the lower electrode constitute an electrode 6.

[0049] In order to facilitate integration into the flexible substrate microtube, the PMUT electrode is flexible, and the piezoelectric element uses a PVDF film with excellent flexibility. Figure 2, PMUT electrodes were prepared by masking method. A single-sided silver-plated PVDF film was selected and cut into 3mm*5cm strips; the electrode wires were patterned on a 15um thick PI tape by a laser cutter to form a printed mask plate, and the circular electrode diameter was 750um; the printed mask was attached to the PVDF film, and a layer of conductive silver paste was applied on the mask, and the conductive silver paste was completely cured at room temperature. After removing the mask, silver wire electrodes were formed on the PVDF film, and the center spacing of the stimulation sites was 3.2mm; a 1mm circular hole was formed on the Kapton tape using a laser cutter, and then adhered to the PVDF. The PVDF film was suspended at the corresponding position to form a cavity structure. Finally, the flexible PMUT electrode was adhered to the flexible substrate base tube; the material of the substrate microtube 1 was polyurethane, with an outer diameter of 1mm, an inner diameter of 0.7mm, and a length of 10cm.

[0050] S2: Use a spot welder to weld the enameled wire 4 to the platinum-iridium electrode, then put the platinum-iridium ring on the base microtube to form a SEEG electrode. The enameled wire 4 passes through the base microtube and is connected to the rear test end. The center spacing between the platinum-iridium rings is 3.4 mm.

[0051] S3: The outer end of the electrode includes an insulating layer. The substrate microtube is placed in a chemical vapor deposition system with the middle part suspended to deposit a parylene film to form a protective layer on the outside of the tubular electrode body, so that the flexible electrode is tightly fixed on the surface of the substrate microtube and insulated from the outside. Finally, the platinum-iridium ring is exposed to form the SEEG electrode contact.

[0052] The actual photo of the ultrasonic stimulation-EEG multifunctional electrode prepared in this example is shown in Figure 4 shown.

[0053] Application Examples

[0054] Figure 5 This is the sound pressure diagram output by the ultrasonic stimulation-EEG multifunctional electrode. The output performance of the electrode was characterized in a water tank. A five-cycle sine pulse was generated using a signal generator, the signal was amplified by a power amplifier and the PMUT device was driven. The signal was received by a hydrophone and finally displayed on an oscilloscope. The results are shown in Figure 5 As shown, the PMUT device can output a voltage of 34.4 mV, and the corresponding sound pressure is 11.8 kPa by conversion.

[0055] In summary, the present invention provides an ultrasound-EEG multifunctional electrode for deep brain stimulation. This electrode has a small size, a simple preparation process, and a low manufacturing cost. It can achieve precise ultrasound stimulation of brain lesions to achieve the purpose of treating neurological diseases. At the same time, since the multifunctional electrode integrates a SEEG electrode, it can record electrical signals of the brain while stimulating with ultrasound, providing strong support for future closed-loop neural stimulation.

[0056] It should be noted that the above is only an embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various changes and variations. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation, characterized in that: The multifunctional electrode includes, from the inside to the outside, a matrix microtube, a PMUT electrode for deep brain ultrasound stimulation, and a SEEG electrode for electroencephalogram signal detection.

2. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 1, characterized in that: The matrix microtube is in the shape of a round tube and is made of any one of flexible polyurethane, epoxy resin or polydimethylsiloxane.

3. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 1, characterized in that: The diameter of the matrix microtube is 0.5-2 mm, and the inner diameter of the matrix microtube is 200-1500 um.

4. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 1, characterized in that: The PMUT electrode is a piezoelectric micromechanical ultrasonic transducer, which includes, from top to bottom, an upper electrode, a piezoelectric film, a lower electrode and a flexible substrate with a cavity structure.

5. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 4, characterized in that: The material of the upper electrode and the lower electrode is gold, silver, copper or platinum, the material of the piezoelectric film is PVDF, PZT or KNN, and the material of the flexible substrate is PI, PET, PVC or TPU.

6. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 4, characterized in that: The width of the PMUT electrode is 1-1.5 mm, and the thickness is 50-500 um; the upper electrode and the lower electrode are circular electrodes with a diameter of 100-1000 um; the thickness of the piezoelectric film is 5-500 um; and the diameter of the cavity structure is 200-1500 um.

7. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 1, characterized in that: The material of the electrode contacts in the SEEG electrode is selected from gold, silver, copper, stainless steel or platinum-iridium alloy.

8. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 1, characterized in that: The height of the electrode contacts in the SEEG electrode is 1000-1500 um, the distance between the electrode contacts in the SEEG electrode is 0.5-5 mm, and the number of the electrode contacts in the SEEG electrode is 4-20.

9. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to claim 1, characterized in that: The multifunctional electrode further comprises an outermost packaging layer, and the SEEG electrode contacts are exposed.

10. The ultrasound-electroencephalogram multifunctional electrode for deep brain stimulation according to any one of claims 1 to 9, characterized in that: The preparation method of the multifunctional electrode comprises: (1) Curl the PMUT electrode onto the substrate microtube; (2) Fix the SEEG electrode on the substrate microtube wrapped with the PMUT electrode; (3) placing the substrate microtube in a state where the middle part of the substrate is suspended in the air into a chemical vapor deposition system for deposition to form an encapsulation layer; (4) The electrode contacts of the SEEG electrode are exposed to form an ultrasound-EEG multifunctional electrode.

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