Ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation

Abstract

The application discloses an ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation, which comprises a base microtube, a PMUT electrode for deep brain ultrasonic stimulation and a 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 strong support for future closed-loop nerve stimulation, and has the advantages of simple preparation process and low manufacturing cost.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to an ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation. BACKGROUND

[0002] Stereo-electroencephalography (SEEG) is an invasive technique used for the diagnosis and treatment of neurological diseases. The core function of SEEG electrodes is to record the neural electrical activity of deep and subcutaneous layers, and its high spatial resolution can effectively capture the synchronous or asynchronous discharge phenomena of different brain regions. The advantages of SEEG technology include: (1) accurate positioning, individualized surgical path according to the patient's clinical condition, each contact of the electrode corresponds to a different lesion site; (2) minimal surgical trauma, only a small hole about 3mm in the skull under anesthesia can be completed, and the patient can walk after surgery; (3) dynamic long-term monitoring, the patient can remain awake after electrode implantation to carry out daily activities, while performing long-term electroencephalogram monitoring, such as the Chinese patent with publication number CN116849609A discloses that by analyzing long-term SEEG monitoring and obtaining the position of the target electrode, automatic and accurate positioning of the epileptogenic zone is realized. However, the current commercialized SEEG electrodes can only record neural electrical activity and cannot intervene and treat the lesion area in a timely manner, and cannot form a closed loop.

[0003] Ultrasound, as a mechanical vibration wave, has wave effect, mechanical effect and thermal effect, and has great application value in clinical practice, which can be used for imaging diagnosis, auxiliary drug delivery, neural regulation and thermal ablation treatment, etc. Ultrasound technology has been applied to Parkinson's disease, obsessive-compulsive disorder, depression, Alzheimer's disease and other neurological diseases, and has a wide application prospect in the diagnosis and treatment of neurological diseases. For example, the immunotherapy device disclosed in Chinese patent CN112473026A generates specific ultrasound waves and guides them to the target neural nucleus of the nervous system, stimulates the central or peripheral system, and produces an activation or inhibition effect, achieving the purpose of immunotherapy for diseases. However, the existing ultrasonic transducer is mainly made of rigid piezoelectric ceramic material, which is difficult to integrate with flexible electrodes flexibly, thereby limiting its application in multifunctional neural interface systems.

[0004] Therefore, there is a need in the clinic for electrodes with more diversified functions, smaller size, higher safety and better biocompatibility. SUMMARY

[0005] The purpose of the present application is to provide an ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation, which can realize point deep brain ultrasonic stimulation and in-situ synchronous detection of electroencephalogram signal changes, and provides a feasible scheme for realizing a closed-loop neural regulation system.

[0006] In order to achieve the above-mentioned purpose, the specific technical scheme of the present application is as follows:

[0007] An ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation, which comprises, from inside to outside, a base microtube, a PMUT electrode for deep brain ultrasonic stimulation, and a SEEG electrode for electroencephalogram signal detection.

[0008] The present application proposes a new idea of integrating a flexible piezoelectric micromachined ultrasonic transducer (PMUT) with a SEEG electrode: the SEEG electrode has the function of neural signal detection, and a micromachined ultrasonic transducer PMUT with ultrasonic stimulation is innovatively added on the SEEG electrode through structural design. Compared with traditional ultrasonic transducers, the PMUT has the advantages of small size, light weight, low power consumption, low cost, high sensitivity, and easy integration with circuits and realization of intelligence. Secondly, the PMUT is manufactured based on microfabrication technology and has high customizability, and can be produced into a flexible matrix structure, which is convenient for integration with the SEEG electrode and realization of point deep brain ultrasonic stimulation. This integrated SEEG-PMUT system not only can monitor the brain in real time, but also can realize precise neural regulation through ultrasonic stimulation. It can be implanted in the lesion area of the brain to stimulate specific parts, and is used for treating brain diseases such as Parkinson's disease, primary tremor and dystonia, and provides a new multifunctional platform for the diagnosis and treatment of neurological diseases.

[0009] The base microtube is in the form of a circular tube and is made of any one of flexible polyurethane, epoxy resin or polydimethylsiloxane, preferably a biocompatible polyurethane tube.

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

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

[0012] The material of the upper electrode and the lower electrode is gold, silver, copper or platinum, etc. which has excellent electrical conductivity. The material of the piezoelectric film is PVDF, PZT or KNN, etc. which is a piezoelectric material, preferably a PVDF film with excellent flexibility. The material of the flexible substrate is 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 with a diameter of 100-1000 um. The thickness of the piezoelectric film is 5-500 um. The diameter of the cavity structure is 200-1500 um.

[0014] Further, 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 engraved on the flexible substrate by laser cutting technology.

[0015] Further, the PMUT electrode is connected to the backend circuit from the inside of the base microtube by an enameled wire.

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

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

[0018] The height of the electrode contact 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 electrode contacts in the SEEG electrode is 4-20. The above parameters can be adjusted according to actual conditions.

[0019] Further, the SEEG electrode is connected to the backend circuit from the inside of the base microtube by an enameled wire.

[0020] Further, 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 contact.

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

[0023] (1) winding the PMUT electrode on the base microtube;

[0024] (2) fixing the SEEG electrode on the base microtube wound with the PMUT electrode;

[0025] (3) The base microtube is placed in a chemical vapor deposition system in a suspended middle posture to deposit a packaging layer;

[0026] (4) The electrode contact of the SEEG electrode is exposed to form an ultrasound-electroencephalogram multifunctional electrode.

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

[0028] (1) A base microtube with a preset length is prepared;

[0029] (2) A micro-mechanical ultrasound transducer stimulation electrode is prepared: silver is first plated on a PVDF film to form an electrode, then a laser cutting machine is used to form a cavity on a Kapton tape, and finally a PVDF piezoelectric layer and a Kapton cavity layer are sequentially stacked to form a PMUT stimulation electrode;

[0030] (3) The flexible PMUT stimulation electrode is rolled on the base microtube;

[0031] (4) An enameled wire is welded on the platinum-iridium ring electrode;

[0032] (5) The platinum-iridium electrode ring is fixed on the base microtube with the PMUT electrode wound thereon, and the lead wire is connected to the rear-end circuit from the inside of the base microtube to form a SEEG electrode;

[0033] (6) The base microtube is placed in a chemical vapor deposition system in a suspended middle posture to deposit a parylene film to form a protective layer on the outside of the tubular electrode main body;

[0034] (7) The contact of the platinum-iridium electrode is exposed to form an overall ultrasound stimulation-electroencephalogram multifunctional DBS electrode.

[0035] The above simple preparation method can greatly reduce the preparation cost of a traditional electrode.

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

[0037] 1. The present application realizes multifunctional neural regulation and detection by combining a flexible PMUT electrode with a SEEG electrode: on the one hand, a small-sized PMUT electrode is prepared by a simple low-temperature bonding technology, which greatly reduces the cost of a traditional micro-nano processing PMUT electrode; on the other hand, the PMUT electrode is fixed on a flexible base to reduce the size of the electrode.

[0038] 2. The present application can be used for real-time spot ultrasound stimulation of brain lesions and in-situ detection of deep brain electroencephalogram signals, so as to realize precise neural regulation and detection of the deep brain, and provide a feasible scheme for closed-loop neural regulation of the electrode, which is expected to play a major role in the field of brain science research and brain disease diagnosis and treatment.

[0039] 3. The ultrasound stimulation-EEG multifunctional electrode provided by this invention can realize targeted deep brain ultrasound stimulation and synchronously detect changes in EEG signals in situ. Attached Figure Description

[0040] Figure 1 A schematic diagram of an ultrasound-EEG multifunctional electrode used for deep brain stimulation;

[0041] Figure 2 The fabrication diagram and structural schematic diagram of a piezoelectric micromechanical ultrasonic transducer are shown.

[0042] Figure 3 This is a flowchart of the fabrication process for an ultrasound-EEG multifunctional electrode.

[0043] Figure 4 Photograph of an actual ultrasound stimulation-EEG multifunctional electrode;

[0044] Figure 5 This is the sound pressure level output of the ultrasound stimulation-EEG multifunctional electrode. Detailed Implementation

[0045] 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.

[0046] Example

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

[0048] S1: Fabricate a PMUT electrode with ultrasonic stimulation function. The PMUT device is long and strip-shaped, which is easy to adhere 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 form the electrode 6.

[0049] To facilitate integration onto flexible substrate microtubes, the PMUT electrodes are flexible, and the piezoelectric elements within them utilize a PVDF thin film with excellent flexibility. (See diagram) Figure 2The PMUT electrode is prepared by a mask method. A single-side silver-plated PVDF film is selected and cut into a 3mm*5cm strip; an electrode lead patterning is performed on a PI tape with a thickness of 15um by a laser cutting machine to form a printing mask plate, and the diameter of the circular electrode is 750um; the printing mask is attached to the PVDF film, and a layer of conductive silver paste is coated on the mask, and the conductive silver paste is completely cured at room temperature; after the mask plate is removed, the silver lead electrode is formed on the PVDF film, and the center distance of the stimulation site is 3.2mm; a 1mm circular hole is formed on the Kapton tape by a laser cutting machine, and then attached to the PVDF, and the PVDF film is in a suspended state at the corresponding position to form a cavity structure. Finally, the flexible PMUT electrode is attached to the flexible base pipe; the material of the base microtube 1 is polyurethane, the outer diameter is 1mm, the inner diameter is 0.7mm, and the length is 10cm.

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

[0051] S3: The outer end of the electrode includes an insulating layer, the base microtube 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 tubular electrode body, so that the flexible electrode is tightly fixed on the surface of the base microtube and insulated from the outside. Finally, the platinum-iridium ring is exposed to form a SEEG electrode contact.

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

[0053] Application example

[0054] Figure 5 The ultrasonic stimulation-electroencephalogram multifunctional electrode outputs the sound pressure graph. The output performance of the electrode is characterized in a water tank, a signal generator is used to generate a sine pulse with five cycles, a power amplifier is used for signal amplification and driving the PMUT device, a hydrophone is used to receive the signal, and finally displayed on an oscilloscope. The results are shown in Figure 5 , the PMUT device can output a voltage of 34.4mV, and the corresponding sound pressure is 11.8kPa through conversion.

[0055] In conclusion, the application provides an ultrasonic-electroencephalogram multifunctional electrode for deep brain stimulation, which has small volume, simple preparation process, low manufacturing cost, can realize precise stimulation of brain lesions by ultrasonic waves to achieve the purpose of treating neurological diseases, and can record electrical signals of the brain while ultrasonic stimulation is performed due to the integrated SEEG electrode, thereby providing strong support for future closed-loop neural stimulation.

[0056] It should be noted that the above description is only one embodiment of the application and is not intended to limit the application. For those skilled in the art, the application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the application shall be included in the protection scope of the application.

Claims

1. An ultrasound-electroencephalography multifunctional electrode for deep brain stimulation, characterized in that, The multifunctional electrode comprises, from inside to outside, a base microtube, a PMUT electrode for deep brain ultrasound stimulation, and a SEEG electrode for brain electrical signal detection. The base microtube has a diameter of 0.5-2 mm and an inner diameter of 200-1500 um. The PMUT electrode is a piezoelectric micro-mechanical ultrasonic transducer comprising, from top to bottom, an upper electrode, a piezoelectric film, a lower electrode, and a flexible substrate with a cavity structure. The PMUT electrode has a width of 1-1.5 mm and a thickness of 50-500 um; the upper electrode and the lower electrode are circular electrodes with a diameter of 100-1000 um; the piezoelectric film has a thickness of 5-500 um; and the cavity structure has a diameter of 200-1500 um. The SEEG electrode has electrode contacts with a height of 1000-1500 um, a distance between the electrode contacts of 0.5-5 mm, and a number of 4-20 electrode contacts. The preparation method of the multifunctional electrode comprises: (1) preparing a base microtube with a predetermined length; (2) preparing a micro-mechanical ultrasonic transducer stimulation electrode: first, forming an electrode on a PVDF film by silver plating, then forming a cavity on a Kapton tape using a laser cutting machine, and finally stacking a PVDF piezoelectric layer and a Kapton cavity layer to form a PMUT stimulation electrode; (3) winding the flexible PMUT stimulation electrode on the base microtube; (4) welding an enameled wire on a platinum-iridium circular electrode; (5) fixing the platinum-iridium electrode ring on the base microtube with the PMUT electrode wound thereon, connecting the wire from the inside of the base microtube to the back-end circuit to form a SEEG electrode; (6) placing the base microtube in a chemical vapor deposition system with the middle part hanging to deposit a parylene film, forming a protective layer on the outside of the tubular electrode body; (7) exposing the contacts of the platinum-iridium electrode to form an overall ultrasonic stimulation-brain electrical multifunctional DBS electrode.

2. The ultrasonic-electroencephalographic multi-functional electrode for deep brain stimulation according to claim 1, characterized in that, The base microtube is in the form of a circular tube and is made of any one of flexible polyurethane, epoxy resin, or polydimethylsiloxane.

3. The ultrasonic-electroencephalographic multi-functional electrode for deep brain stimulation according to claim 1, characterized in that, The upper electrode and the lower electrode are made of gold, silver, copper, or platinum, the piezoelectric film is made of PVDF, PZT, or KNN, and the flexible substrate is made of PI, PET, PVC, or TPU.

4. The ultrasonic-electroencephalographic multi-functional electrode for deep brain stimulation according to claim 1, characterized in that, The electrode contacts of the SEEG electrode are made of gold, silver, copper, stainless steel, or platinum-iridium alloy.

5. The ultrasonic-electroencephalographic multi-functional electrode for deep brain stimulation according to claim 1, characterized in that, The multifunctional electrode further comprises an outermost encapsulation layer, and the SEEG electrode contacts are exposed.

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