Battery-free flexible implantable deep brain stimulator, system and method of manufacture

Abstract

The application discloses a battery-free flexible implantable deep brain stimulator, a system and a preparation method, and belongs to the field of implantable biomedical devices. The application comprises: the piezoelectric device is used for receiving a pulse ultrasonic signal with a fundamental frequency of 1MHz emitted by an extracorporeal ultrasonic generator, and generating an alternating current signal consistent with the stimulation frequency and stimulation duration of the pulse ultrasonic signal through a piezoelectric effect; the rectifier circuit is used for converting the alternating current signal into a direct current signal; the stimulation electrode is used for acting the direct current signal on a target brain area; and the piezoelectric device is composed of a piezoelectric array of a plurality of square Sm-doped PMN-PT piezoelectric single crystal bulk materials with a center frequency of 1MHz. The application adopts the square Sm-doped PMN-PT piezoelectric single crystal bulk material with a center frequency of 1MHz to form the piezoelectric array, and due to the adoption of the Sm-doped PMN-PT array with a specific structure, the maximum output power can be obtained in the resonant state of the resonant frequency of 1MHz, so that wireless, battery-free and safe real-time deep brain stimulation is realized.

Description

Technical Field

[0001] This invention belongs to the field of implantable biomedical devices, and more specifically, relates to a battery-free flexible implantable deep brain stimulator, system, and preparation method. Background Technology

[0002] Implantable biomedical devices have demonstrated numerous advantages in improving patients' quality of life, but powering these devices remains a technological challenge. Traditional external power solutions require percutaneous or percutaneous leads, which are bulky and prone to infection, especially with long-term use. Integrating batteries with the implanted device is another option, but batteries must be replaced regularly due to their limited energy capacity, leading to postoperative pain and financial burden for patients. Achieving battery-free, wireless neurostimulation is of great significance in the biomedical field. Compared to existing wireless power delivery modes, ultrasound can achieve longer propagation depths and better spatial resolution within tissues, with a higher safety threshold.

[0003] Piezoelectric devices based on traditional piezoelectric materials (PMN-PT) have low direct electrical output power, which is insufficient to achieve deep brain stimulation. They need to be equipped with a charging capacitor / battery and a built-in controller. The piezoelectric device stores the electrical energy generated by ultrasound in the charging capacitor. The controller modulates the electrical energy in the charging capacitor by adjusting the stimulation frequency, duration and intensity, and outputs an electrical signal for deep brain stimulation.

[0004] Xu et al. proposed a novel material, Sm-PMNPT, which exhibits significantly improved piezoelectric properties compared to PMNPT. However, this new material is currently primarily used in ultrasonic imaging and signal detection, and its application in ultrasonic-driven wireless energy harvesting remains unexplored. The material's power output characteristics are highly dependent on its shape and size. Summary of the Invention

[0005] In response to the deficiencies and improvement needs of existing technologies, this invention provides a battery-free flexible implantable deep brain stimulator, system, and preparation method, with the aim of achieving wireless, battery-free, and safe real-time deep brain stimulation.

[0006] To achieve the above objectives, according to a first aspect of the present invention, a battery-free flexible implantable deep brain stimulator is provided. The implantable deep brain stimulator is ultrasonically driven and consists of piezoelectric devices, stimulation electrodes, and a rectifier circuit, all encapsulated within a biocompatible flexible organic shell.

[0007] The piezoelectric device is used to receive a pulsed ultrasound signal with a fundamental frequency of 1MHz emitted by an external ultrasound generator, and to generate an alternating current signal with the same stimulation frequency and duration as the pulsed ultrasound signal through the piezoelectric effect.

[0008] The rectifier circuit is used to convert AC signals into DC signals;

[0009] The stimulation electrode is used to apply a direct current signal to the target brain region;

[0010] The piezoelectric device is a piezoelectric array composed of multiple square Sm-doped PMN-PT piezoelectric single crystal blocks with a center frequency of 1MHz.

[0011] Preferably, the piezoelectric single crystal bulk material has a length of 1 mm, a width of 1 mm, and a thickness of 380 micrometers.

[0012] Beneficial effects: Compared with other sizes, the preferred size of the present invention can achieve high power output and miniaturization of the piezoelectric array while ensuring a center frequency of 1MHz. The specific analysis is as follows: At this size, the array elements of the piezoelectric array are square, the vibration mode is purer, and the center frequency of the array elements is 1MHz, which is consistent with the externally input ultrasonic frequency. Under the action of the external ultrasonic frequency of 1MHz, resonance occurs, and the maximum power output is achieved.

[0013] Preferably, the spacing between each piezoelectric single crystal block in the piezoelectric array is 1 / 2 of the side length of the piezoelectric single crystal block.

[0014] Beneficial effects: Compared with other spacing, the spacing of the present invention is preferably set to 1 / 2 of the side length. On the one hand, it facilitates the compression and stretching of the device. On the other hand, this compact approach also reduces the overall size of the device, realizing the flexibility and miniaturization of the device.

[0015] Preferably, the piezoelectric array is arranged in a 6×6 configuration.

[0016] Beneficial effects: The output power of the device increases with the number of array elements. If the number is too small, the output power will decrease; if the number is too large, the device size will increase. Compared with other array methods, the preferred array method of this invention can balance output power and device implantability, achieving high power output and miniaturization of the device.

[0017] Preferably, the piezoelectric single crystal bulk materials are connected in parallel electrical connections.

[0018] Beneficial effects: Compared with other connection methods, the present invention connects piezoelectric single crystal array elements in parallel, which increases the output current of the device and thus increases the output power of the device.

[0019] To achieve the above objectives, according to a second aspect of the present invention, a method for fabricating a battery-free, flexible implantable deep brain stimulator is provided, the method comprising the following steps:

[0020] S1. Preparation of intermediate layer: After the piezoelectric array is placed, it is directly wrapped with a biocompatible flexible organic material. The piezoelectric array is composed of multiple square Sm-doped PMN-PT piezoelectric single crystal blocks with a center frequency of 1MHz.

[0021] S2. Connect the upper piezoelectric array elements to the wave electrode and cast a biocompatible flexible organic material.

[0022] S3. Connect the lower piezoelectric array elements to the wave electrode and cast a biocompatible flexible organic material.

[0023] S4. After connecting the rectifier circuit and the stimulation electrode, cast a biocompatible flexible organic material.

[0024] Preferably, the array element and the wave electrode are connected in the following manner:

[0025] The prepared electrodes are attached to the tape by punching holes that correspond one-to-one with the piezoelectric elements. Then the tape is attached to the elements, and the elements and electrodes in the holes are fixed together by pouring conductive adhesive.

[0026] Beneficial effects: The present invention adopts the above-mentioned preferred hollow tape attachment method to achieve effective connection between the wave electrode (copper wire with a diameter of 100μm) and the array element, reducing the risk of the wave electrode and the array element falling off during the device fabrication process, and also facilitating electrical detection during the device fabrication process.

[0027] Preferably, the biocompatible flexible organic material is PDMS.

[0028] Beneficial effects: This invention preferably uses PDMS, which, as a commonly used biocompatible flexible organic material, does not cause toxic damage to tissues. Moreover, due to its flexibility, it can form non-rigid contact with tissues. This reduces the device's exposure to harsh chemical environments in tissues and prevents tissue damage caused by device-tissue contact, while also giving the device a certain degree of tissue adaptability for in vivo implantation.

[0029] To achieve the above objectives, according to a third aspect of the present invention, a deep brain stimulation system with adjustable stimulation parameters is provided, the system comprising:

[0030] An ultrasound generator is used to generate a pulsed ultrasound signal with a fundamental frequency of 1 MHz, which is applied to a battery-free, flexible implantable deep brain stimulator as described in the first aspect, wherein the stimulation frequency, stimulation duration, and stimulation intensity of the pulsed ultrasound signal are adjustable.

[0031] The implantable deep brain stimulator is used to be implanted between the scalp and the skull to generate deep brain stimulation electrical signals with the same frequency and duration as pulsed ultrasound signals, which are then applied to the target brain region.

[0032] In summary, the above-described technical solutions conceived in this invention can achieve the following beneficial effects:

[0033] (1) Compared with stimulators based on traditional piezoelectric materials (PMN-PT), the present invention uses square Sm-doped PMN-PT piezoelectric single crystal blocks with a center frequency of 1MHz to form a piezoelectric array. 1) The piezoelectric coefficient, electromechanical coupling coefficient and relative permittivity of the Sm-doped PMN-PT piezoelectric single crystal are as high as 4,000pC / N, 95% and 13,000 respectively. Based on the thickness tensile vibration theory of piezoelectric materials, the larger permittivity and the larger electromechanical coupling coefficient help to improve the output power. The present invention can obtain the maximum output power in the resonant state at a resonant frequency of 1MHz. Due to the inherent wireless energy transmission characteristics of ultrasound, the piezoelectric devices mentioned above exhibit high piezoelectric performance and can achieve high-power output in real time without the need for implanted batteries, thus achieving battery-free operation; 2) Under the piezoelectric effect, the stimulation frequency and duration of the electrical signal output by the ultrasound-driven piezoelectric device correspond one-to-one with the ultrasound signal. The parameters of the stimulation signal can be adjusted by regulating the external ultrasound signal, eliminating the need for implanted controllers and enabling wireless external control; 3) The elimination of the need for implanted batteries and controllers significantly reduces the size of the stimulator; 4) Compared to other structures, the square structure helps to achieve purer vibration modes of the array elements, thereby improving the energy conversion efficiency of the device; 5) The array elements of the array structure maintain parallel electrical connections, and the output current is positively correlated with the number of array elements, which can improve the electrical power output performance. In addition, the array structure can bend, increasing the flexibility of the stimulator; 6) Compared to the piezoelectric film, whose center frequency is too high to achieve resonance at 1MHz, and whose own strength is insufficient, making it prone to breakage under strong external ultrasound and exhibiting poor mechanical stability, the bulk structure has excellent mechanical properties.

[0034] (2) This invention proposes a layered fabrication process based on the principle of similar compatibility. After multiple castings of PDMS, it will still form a whole without delamination, eliminating the need for substrate transfer and making the device fabrication process simpler.

[0035] (3) This invention proposes a deep brain stimulation system with adjustable stimulation parameters. This system does not require an internal controller to modulate the stimulation parameters. The electrical stimulation parameters of the stimulator are entirely controlled by externally applied ultrasonic signals (including stimulation frequency, stimulation duration, and stimulation intensity), and can be adjusted in real time according to actual needs. Therefore, by adjusting the external ultrasonic parameters, the internal electrical stimulation parameters can be adjusted in real time. Attached Figure Description

[0036] Figure 1 This is a schematic diagram of the application of a battery-free flexible implantable brain nerve stimulation system in the potential deep brain stimulation of the human body, provided by an embodiment of the present invention.

[0037] Figure 2 This is a schematic diagram of a battery-free flexible implantable brain nerve stimulator provided in an embodiment of the present invention;

[0038] Figure 3 This is a schematic diagram of the manufacturing process of a battery-free flexible implantable brain nerve stimulator provided in an embodiment of the present invention;

[0039] Figure 4 This is a schematic diagram of the process flow for connecting the piezoelectric array and wave electrodes in a battery-free flexible implantable brain stimulator provided by an embodiment of the present invention. Detailed Implementation

[0040] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0041] like Figure 1 As shown, the present invention provides a battery-free flexible implantable neurostimulation system, comprising: an ultrasound generator (external) for providing ultrasound signals; and an implantable neurostimulator (in vivo) for receiving ultrasound signals and directly generating stimulation signals.

[0042] like Figure 2 As shown, the implantable neurostimulator consists of a piezoelectric array, wave electrodes, and a rectifier circuit, all encapsulated within a biocompatible PDMS shell. Specifically: the innermost layer is an Sm-PMN-PT piezoelectric single-crystal array; the middle layer is a wave electrode; the middle PDMS filling layer; the outermost PDMS encapsulation layer; and the rectifier circuit and stimulation electrode components. The piezoelectric single crystal has a length of 1 mm, a width of 1 mm, a thickness of 380 micrometers, and a center frequency of 1 MHz.

[0043] When implanted between the scalp and skull, the piezoelectric array requires a center frequency of 1MHz to resonate with an external input of 1MHz. If the frequency is too high, the attenuation effect in the scalp layer increases, the energy transmission effect decreases, and the device cannot obtain a stable high power output. If the frequency is too low, it will penetrate the scalp, the device, and the skull, reaching the brain parenchyma directly, causing ultrasound biological effects and creating new interference.

[0044] The working process is as follows: First, the external pulse output circuit (with adjustable parameters: power, stimulation pulse width, stimulation pulse frequency, and stimulation duration) acts on the ultrasound generator to generate pulsed ultrasound; then, the pulsed ultrasound acts on the implantable neurostimulator (piezoelectric array, rectifier circuit, and stimulation electrodes, packaged in flexible PDMS). The entire device is miniaturized, biocompatible, and has high power output characteristics; it generates stimulation signals in real time (signal parameters include: intensity, stimulation frequency, and stimulation duration) to act on the brain region, ultimately achieving deep brain stimulation.

[0045] The piezoelectric arrays are electrically connected in parallel. The corrugated electrodes connecting the piezoelectric arrays are spaced 1.5 mm apart at the crests of adjacent corrugated electrodes.

[0046] The implantable neurostimulator of this invention employs a miniature, biocompatible package to achieve implantability, with device dimensions of 13.5 × 9.6 × 2.1 mm. 3 It can achieve wireless, battery-free, and high-power output. The piezoelectric array (6×6 array) utilizes high-performance Sm-PMNPT piezoelectric single crystals. The array element parameters (center frequency 1MHz, 1mm×1mm×380μm) achieve high-power output under 1MHz ultrasonic drive, which can directly realize deep brain stimulation.

[0047] like Figure 3 As shown, this invention proposes a method for fabricating a battery-free, flexible implantable deep brain stimulator, comprising: processing Sm-PMN-PT single crystal bulk material into a bulk material with a thickness of 380 micrometers, and sputtering electrodes on the upper and lower surfaces; cutting the Sm-PMN-PT piezoelectric single crystal bulk material with sputtered electrodes into array elements with a side length of 1 mm; casting the array in a designed 6×6 array pattern using PDMS, taking care not to cover the array elements; connecting the fabricated wave electrodes to the array elements on the upper surface one-to-one using E-Solder 3022 adhesive; and casting PDMS to cover the wave electrodes. Based on the principle of similarity and compatibility, the upper PDMS will fuse with the middle PDMS layer; similarly, the prepared wave electrode and the array elements on the lower surface are connected one-to-one using E-Solder 3022 adhesive; by covering the wave electrode with PDMS, the lower PDMS will fuse with the middle PDMS layer; the prepared rectifier circuit and stimulation electrode are placed in specific positions, and their continuity is checked; by covering the rectifier circuit and stimulation electrode with PDMS, the entire device is encapsulated in PDMS.

[0048] Adopting such Figure 4Steps (1)-(7) shown complete the connection between the array elements and the wave electrodes on the lower surface of the device: Prepare adhesive tape and cut out holes at specific positions, where the cut-out positions correspond to the positions of the array elements. To improve the adhesion of the wave electrodes to the adhesive tape, the cut-out positions are left untreated; Arrange the prepared wave-shaped copper wire electrodes reasonably according to the positions of the array elements. Ensure that the electrodes on the top are conductive throughout the process; Flip the adhesive tape with wave electrodes in (2); Adhere the flipped adhesive tape to the array elements and PDMS on which the PDMS intermediate layer is cast, and ensure that the holes of the adhesive tape correspond one-to-one with the array elements; At the cut-out holes, use E-Solder conductive adhesive to connect the wave electrodes and array elements together, and then cure them by heating in an oven; Remove the adhesive tape.

[0049] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A battery-free flexible implantable deep brain stimulator, wherein the implantable deep brain stimulator is ultrasonically driven and consists of piezoelectric devices, stimulation electrodes, and a rectifier circuit, all encapsulated within a biocompatible flexible organic shell, characterized in that... The piezoelectric device is used to receive a pulsed ultrasound signal with a fundamental frequency of 1MHz emitted by an external ultrasound generator, and to generate an alternating current signal with the same stimulation frequency and duration as the pulsed ultrasound signal through the piezoelectric effect. The rectifier circuit is used to convert AC signals into DC signals; The stimulation electrode is used to apply a direct current signal to the target brain region; The piezoelectric device is a piezoelectric array composed of multiple square Sm-doped PMN-PT piezoelectric single crystal blocks with a center frequency of 1MHz; the piezoelectric single crystal blocks are 1 mm long, 1 mm wide, and 380 μm thick; the piezoelectric single crystal blocks are electrically connected in parallel.

2. The implantable deep brain stimulator as described in claim 1, characterized in that, The spacing between each piezoelectric single crystal block in the piezoelectric array is 1 / 2 of the side length of the piezoelectric single crystal block.

3. The implantable deep brain stimulator as described in claim 1, characterized in that, The piezoelectric array is arranged in a 6×6 configuration.

4. A method for fabricating a battery-free, flexible implantable deep brain stimulator, characterized in that, The method includes the following steps: S1. Preparation of the intermediate layer: After the piezoelectric array is placed, it is directly wrapped with a biocompatible flexible organic material. The piezoelectric array is composed of multiple square Sm-doped PMN-PT piezoelectric single crystal blocks with a center frequency of 1MHz. The piezoelectric single crystal blocks are 1 mm long, 1 mm wide, and 380 μm thick. The piezoelectric single crystal blocks are connected in parallel by electrical connections. S2. Connect the upper piezoelectric array elements to the wave electrode and cast a biocompatible flexible organic material. S3. Connect the lower piezoelectric array elements to the wave electrode and cast a biocompatible flexible organic material. S4. After connecting the rectifier circuit and the stimulation electrode, cast a biocompatible flexible organic material.

5. The preparation method according to claim 4, characterized in that, The array element is connected to the wave electrode in the following manner: The prepared electrodes are attached to the tape by punching holes that correspond one-to-one with the piezoelectric elements. Then the tape is attached to the elements, and the elements and electrodes in the holes are fixed together by pouring conductive adhesive.

6. The preparation method according to claim 4 or 5, characterized in that, The biocompatible flexible organic material is PDMS.

7. A deep brain stimulation system with adjustable stimulation parameters, characterized in that, The system includes: an ultrasound generator and a battery-free, flexible implantable deep brain stimulator as described in any one of claims 1 to 3; An ultrasound generator is used to generate pulsed ultrasound signals with a fundamental frequency of 1MHz, which are applied to an implantable deep brain stimulator. The stimulation frequency, stimulation duration, and stimulation intensity of the pulsed ultrasound signals are adjustable. The implantable deep brain stimulator is used to be implanted between the scalp and the skull to generate deep brain stimulation electrical signals with the same frequency and duration as pulsed ultrasound signals, which are then applied to the target brain region.

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