A passive implantable biphasic brain stimulation device based on ultrasound drive

Abstract

The present invention relates to the field of implantable biomedical devices, and discloses a passive implantable biphasic brain stimulation device driven by ultrasound. The device comprises: a dual piezoelectric layer structure, which is used to generate high-frequency and low-frequency signals driven by an external dual-frequency ultrasound probe to generate a responsive output AC signal; a frequency control layer, which is an acoustic metamaterial that selectively passes different frequencies of ultrasound waves; a biphasic rectifier circuit, which converts the AC signals of the high-frequency and low-frequency piezoelectric layers into DC signals, respectively, and generates biphasic stimulation pulses through differential output. The rear end of the biphasic rectifier circuit is connected to stimulation electrodes to generate biphasic electrical pulses at specific locations in the brain. The present invention employs acoustic metamaterial selective filtering; the dual piezoelectric layer structure responds to dual-frequency ultrasound, and the stimulation electrodes generate biphasic pulse outputs, thereby reducing the tissue damage and electrolysis hazards caused by charge accumulation on the electrodes under continuous stimulation.

Description

Technical Field

[0001] The present invention relates to the field of implantable biomedical devices, and more particularly to an ultrasound-driven passive implantable biphasic brain stimulation device. Background Art

[0002] Effective treatment of Parkinson's disease (PD) is a major medical challenge. Deep brain stimulation (DBS), a neuromodulatory therapy, has been approved by the US Food and Drug Administration (FDA) and is widely used to treat patients with the disease. However, the power supply of the DBS device, the core component of DBS, has always been challenging. Traditional external power supply solutions based on percutaneous leads are prone to tissue infection, and the introduction of batteries requires secondary surgery due to the need for regular replacement. Furthermore, the effective electrical stimulation frequency for Parkinson's disease is between 100-200 Hz, a high-frequency "therapeutic frequency." Achieving this stimulation frequency is challenging. If the charge on the stimulating electrode does not dissipate between successive stimulation pulses, it can cause tissue damage and electrolysis. Therefore, traditional clinically approved neurostimulation therapies use a biphasic stimulation method with alternating charging and discharging to achieve "charge balance." Therefore, to achieve safe and effective treatment for Parkinson's disease, it is crucial to overcome the key technical challenges of wireless power supply and stimulation frequency. The development of an ultrasound-driven, passive, implantable biphasic stimulator is of great significance.

[0003] In recent years, wireless energy transmission technology based on ultrasound drive has attracted much attention due to the many advantages of ultrasound, such as strong penetration, easy energy concentration, no electromagnetic interference, good directionality and biosafety.

[0004] For example, in the existing literature Zhang T, Liang H, Wang Z, et al. Piezoelectric ultrasound energy–harvesting device for deep brain stimulation and analgesia applications [J]. Science advances, 2022, 8(15): eabk0159., Zhu et al. reported a brain stimulator based on ultrasound drive. Although this technology improves the energy supply problem of the stimulator, there is also the problem that the device can only output single-phase pulses and cannot achieve high-frequency stimulation above 100 Hz. Summary of the Invention

[0005] In order to overcome or alleviate one or more of the above technical problems, the purpose of the present invention is to provide a passive implantable biphasic brain stimulation device based on ultrasound drive, which adopts external dual-frequency ultrasound drive to simultaneously output biphasic pulses. On the basis of improving the energy supply problem, it also improves the electrolysis problem under high-frequency stimulation, and electrolysis will not occur at a high stimulation frequency of 100-250Hz.

[0006] The present invention provides the following technical solutions:

[0007] A passive implantable biphasic brain stimulation device based on ultrasound drive, comprising:

[0008] A dual piezoelectric layer structure is used to generate a response output AC signal driven by a high-frequency and low-frequency signal generated by an external dual-frequency ultrasonic probe; the dual piezoelectric layer structure comprises a high-frequency piezoelectric layer (11) and a low-frequency piezoelectric layer (12);

[0009] The frequency control layer (2) is a diffraction grating type single-layer acoustic metamaterial (21) that selectively has high transmittance for low-frequency ultrasonic signals. The acoustic metamaterial (21) is a copper plate with a periodic cylindrical groove structure and is arranged between the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12);

[0010] The biphasic rectifier circuit (3) is connected to the output electrodes of the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12), and converts the AC signals of the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12) into DC signals respectively, and generates biphasic stimulation pulses through differential output. The rear end of the biphasic rectifier circuit (3) is connected to the stimulation electrode (5) to generate biphasic electrical pulses at a specific position of the brain. The biphasic rectifier circuit (3) is located on one side of the high-frequency piezoelectric layer (11), the frequency control layer (2), and the low-frequency piezoelectric layer (12), and the biphasic piezoelectric layer structure, the frequency control layer (2), and the biphasic rectifier circuit (3) are encapsulated by an encapsulation layer.

[0011] In the above embodiment, the passive implantable biphasic brain stimulation device based on ultrasound drive adopts dual-frequency ultrasound drive. Ultrasound has the advantages of wireless energy transmission, strong penetration, easy energy concentration, no electromagnetic interference, good directionality and biosafety. The stimulation electrode outputs biphasic electrical pulses, which greatly reduces the hazards such as tissue damage and electrolysis caused by the accumulation of charge on the electrode under continuous stimulation, making it safer and more efficient. The dual piezoelectric layer structure responds to the dual-frequency ultrasound respectively, and by adjusting the timing of the ultrasonic transmission system, a biphasic pulse output is generated between the electrodes drawn from the upper and lower piezoelectric layers.

[0012] According to some embodiments, the acoustic metamaterial (21) includes an acoustic body (211) made of a copper plate, a plurality of cylindrical acoustic grooves (212) arranged in an array are provided on the upper surface of the acoustic body (211), and the acoustic grooves (212) are filled with water.

[0013] According to the above embodiment, the slotted structure of the acoustic metamaterial selectively transmits low-frequency signals and attenuates high-frequency signals.

[0014] According to some embodiments, the thickness of the acoustic body (211) is 2.2 mm; the diameter of a single acoustic groove (212) is 0.4 mm and the depth is 0.8 mm; the groove spacing between the acoustic grooves (212) is 0.5 mm.

[0015] In the above embodiment, a slotted acoustic metamaterial is added between the dual piezoelectric layers as a frequency control layer. This single-layer structure, with a thickness of only 2.2 mm, allows for a more compact device. The frequency control layer selectively transmits 1 MHz and 3 MHz ultrasound waves, exhibiting high permeability to 1 MHz ultrasound and high attenuation to 3 MHz and other frequencies. This effectively reduces interference with the low-frequency piezoelectric layer during high-frequency ultrasound application, while also providing good permeability to low-frequency ultrasound waves. This results in a purer biphasic electrical stimulation signal and improves output intensity.

[0016] According to some embodiments, the resonant frequency of the high-frequency piezoelectric layer (11) is 3 MHz, and the resonant frequency of the low-frequency piezoelectric layer (12) is 1 MHz.

[0017] According to some embodiments, the materials used to manufacture the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12) are both selected from Sm-PMNPT piezoelectric single crystals.

[0018] In the above embodiment, compared with the traditional piezoelectric devices made of ZnO, PZT ceramics, PZT 1-3 composite materials and KNN 1-3 composite materials, which show lower energy density, the Sm-PMNPT piezoelectric single crystal has excellent piezoelectric and dielectric properties. The saturated output power density of the piezoelectric device made of it has achieved a leap, reaching 1.1W / cm 2 .

[0019] According to some embodiments, the Sm-PMNPT piezoelectric single crystal is precisely cut and magnetron sputtered to form high-frequency and low-frequency piezoelectric array elements of specific sizes.

[0020] In the above embodiment, the ultrasonically driven passive implantable biphasic brain stimulation device is made more miniaturized and integrated, which is convenient for implantation, and can generate high-power output for the corresponding frequency.

[0021] According to some embodiments, the packaging layer is a biocompatible PDMS shell, the packaging layer includes a top PDMS packaging layer (41) and a bottom PDMS packaging layer (43), the matching layer (42) is used to improve the ultrasonic transmission efficiency, and the matching layer (42), the high-frequency piezoelectric layer (11), the frequency regulation layer (2), and the low-frequency piezoelectric layer (12) are packaged from top to bottom between the top PDMS packaging layer (41) and the bottom PDMS packaging layer (43).

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The passive implantable biphasic brain stimulation device based on ultrasound drive provided by the present invention adopts dual-frequency ultrasound drive. Ultrasound has the advantages of wireless energy transmission, strong penetration, easy energy concentration, no electromagnetic interference, good directionality and biosafety. The single-layer acoustic metamaterial has high transmittance only for a single frequency. It is a single-layer structure with the advantages of miniaturization and easy integration. By stimulating the electrodes to output biphasic electrical pulses, the hazards such as tissue damage and electrolysis caused by the accumulation of charges on the electrodes under continuous stimulation are greatly reduced, making it safer and more efficient. The dual piezoelectric layer structure responds to the dual-frequency ultrasound respectively, and by adjusting the timing of the ultrasonic emission system, a biphasic pulse output is generated between the electrodes drawn from the upper and lower piezoelectric layers. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Schematic diagram of an ultrasound-driven passive implantable biphasic brain stimulation device provided in an embodiment of the present invention.

[0025] Figure 2 This is a schematic diagram of a circuit for generating dual-phase pulses using differential output from a dual-phase rectifier circuit provided in an embodiment of the present invention.

[0026] Figure 3 This is a diagram of the simulation results of the frequency control layer provided by an embodiment of the present invention.

[0027] Figure 4 This is a comparison diagram of the output voltage of the low-frequency piezoelectric layer provided in an embodiment of the present invention under low-frequency ultrasound (1 MHz) and high-frequency ultrasound (3 MHz) driving.

[0028] Figure 5 This is a biphasic pulse diagram output by the biphasic brain stimulation device provided in an embodiment of the present invention.

[0029] Figure 6 This is a comparison chart of the maximum time of continuous stimulation without electrolysis of monophasic pulses and biphasic pulses at different frequencies provided by an embodiment of the present invention.

[0030] Figure 7Schematic diagram of the use of an ultrasound-driven passive implantable biphasic brain stimulation device provided in an embodiment of the present invention.

[0031] Figure 8 A schematic diagram of the structure of a frequency control layer provided in an embodiment of the present invention.

[0032] In the picture:

[0033] High-frequency piezoelectric layer 11; low-frequency piezoelectric layer 12; frequency control layer 2; acoustic metamaterial 21; acoustic body 211; acoustic groove 212; two-phase rectification circuit 3; first rectifier 31; second rectifier 32; top PDMS packaging layer 41; matching layer 42; bottom PDMS packaging layer 43; stimulation electrode 5. DETAILED DESCRIPTION

[0034] The present invention is described in detail below with reference to the embodiments and accompanying drawings. However, it should be understood that the embodiments and accompanying drawings are merely exemplary descriptions of the present invention and do not constitute any limitation on the scope of protection of the present invention. All reasonable variations and combinations within the scope of the inventive concept of the present invention fall within the scope of protection of the present invention.

[0035] The present invention utilizes a dual-piezoelectric layer structure to respond to dual-frequency ultrasound. By adjusting the timing of the ultrasonic transmission system, a biphasic pulse output is generated between the electrodes leading from the upper and lower piezoelectric layers. The frequency control layer utilizes acoustic metamaterials, a class of artificial materials that impart unique acoustic properties not possessed by natural materials by adding specific structures or by arranging and combining them in a specific manner.

[0036] The present invention will be further described below with reference to the accompanying drawings.

[0037] Example 1

[0038] like Figure 1As shown, the present invention provides a passive implantable biphasic brain stimulation device based on ultrasound drive, referred to as a biphasic brain stimulation device. The biphasic brain stimulation device is implanted in the brain as a whole and is ultrasonically driven by an external dual-frequency ultrasound probe to generate a pure and appropriately strong biphasic electrical stimulation signal. Its structure includes a dual piezoelectric layer structure for generating an AC signal in response to the dual-frequency ultrasound signal. The dual piezoelectric layer structure includes a high-frequency piezoelectric layer 11 and a low-frequency piezoelectric layer 12. The resonant frequency of the high-frequency piezoelectric layer 11 is 3MHz, and the resonant frequency of the low-frequency piezoelectric layer 12 is 1MHz. A frequency control layer 2 for selectively transmitting ultrasound waves of different frequencies is provided between the high-frequency piezoelectric layer 11 and the low-frequency piezoelectric layer 12, as well as a biphasic rectifier circuit 3 connected to the biphasic rectifier circuit 3. The biphasic rectifier circuit 3 outputs biphasic pulses. The rear end of the biphasic rectifier circuit 3 is connected to the stimulation electrode 5, which is precisely placed at the part of the brain to be stimulated to stimulate the corresponding part of the brain. The dual-phase rectifier circuit 3 is located on one side of the dual-piezoelectric cushion structure 1. The dual-piezoelectric layer structure and frequency control layer 2 are encapsulated within the encapsulation layer, which is a biocompatible PDMS shell. The PDMS shell contains, from top to bottom, a top PDMS encapsulation layer 41, a matching layer 42, a high-frequency piezoelectric layer 11, a frequency control layer 2, a low-frequency piezoelectric layer 12, and a bottom PDMS encapsulation layer 43. The dual-phase rectifier circuit 3 is located on one side of the high-frequency piezoelectric layer 11, the frequency control layer 2, and the low-frequency piezoelectric layer 12, and is encapsulated by the PDMS shell.

[0039] The dual-piezoelectric layer structure is formed by stacking high-frequency and low-frequency piezoelectric single crystals, wherein the high-frequency piezoelectric layer 11 is above the low-frequency piezoelectric layer 12, and can respond to the high-frequency and low-frequency signals in the dual-frequency ultrasound and output AC signals. The resonant frequencies of the high-frequency and low-frequency piezoelectric single crystals are 3MHz and 1MHz respectively, and the high-frequency and low-frequency ultrasound signals are 3MHz and 1MHz respectively;

[0040] The frequency control layer 2 is an acoustic metamaterial 21 with a grooved structure, located between the high-frequency piezoelectric layer 11 and the low-frequency piezoelectric layer 12. It includes an acoustic body 211, on the upper surface of which are arranged a plurality of acoustic grooves 212 arranged in an array. The acoustic grooves 212 are filled with water, which is highly selective for 1MHz and 3MHz ultrasound, highly transparent to 1MHz ultrasound, and highly attenuates 3MHz ultrasound, thereby eliminating interference of high-frequency ultrasonic signals on the low-frequency piezoelectric layer 12.

[0041] The matching layer 42 is used to reduce ultrasonic reflection caused by impedance mismatch and improve ultrasonic transmittance. This is a prior art and will not be described in detail here.

[0042] Figure 2This is a schematic diagram of a circuit for outputting biphasic pulses. Two rectifiers are used as a whole, namely the first rectifier 31 and the second rectifier 32. The models of the first and second rectifiers can be selected from LX10M MBCN. The two rectifiers are respectively connected to the output electrodes of the high-frequency piezoelectric layer 11 and the low-frequency piezoelectric layer 12, and the AC pulses output by the dual piezoelectric layer structure are rectified into DC pulses. Then the negative poles of the DC of the rectifiers are connected as a common ground, and the two positive poles of the rectifiers are respectively used as the positive and negative poles of the biphasic pulse to output the final biphasic pulse signal.

[0043] The manufacturing method of the biphasic brain stimulation device provided in this embodiment is described as follows:

[0044] Through dual piezoelectric simulation and experimental testing, the parameters of the dual-frequency piezoelectric array were precisely controlled to produce a high-frequency piezoelectric layer (3MHz) and a low-frequency piezoelectric layer (1MHz). The piezoelectric layer, also known as a piezoelectric sheet, is made of a material selected from Sm-PMNPT piezoelectric single crystals. The high-frequency and low-frequency piezoelectric layers have different thicknesses, and Au / Cr (150nm / 100nm) layers are magnetron sputtered on the surface of the piezoelectric sheet. Through precision cutting, high-frequency and low-frequency piezoelectric array elements of specific sizes are formed.

[0045] In order to achieve high frequency selectivity, an acoustic metamaterial 21 with a groove structure is designed. The structure is that a plurality of acoustic grooves 212 arranged in an array are provided on the upper surface of an acoustic body 211. Figure 8 The acoustic body 211 is made of copper with a thickness of 2.2 mm. A cylindrical acoustic groove 212 array with a diameter of 0.4 mm and a depth of 0.8 mm is formed on its upper surface using laser cutting technology. The groove spacing between the acoustic grooves 212 is 0.5 mm, which makes it have a greater attenuation for high-frequency (3 MHz) ultrasound and good permeability for low-frequency (1 MHz) ultrasound. It is placed between the high-frequency piezoelectric layer and the low-frequency piezoelectric layer to filter out high-frequency ultrasonic signals, so that the device has better frequency selectivity; in order to achieve the dual-phase output of the dual-frequency device, the dual-phase rectifier circuit 3 and the stimulation electrode 5 are connected to the high- and low-frequency piezoelectric layers, and PDMS is cast so that the dual piezoelectric layer structure, the frequency control layer 2 and the dual-phase rectifier circuit 3 are all wrapped in PDMS, and the outer shell is wrapped around it, and finally a highly integrated passive implantable biphasic brain stimulator is obtained.

[0046] The instructions for use of this embodiment are as follows:

[0047] like Figure 7First, a dual-frequency trigger signal is generated through the FPGA. This trigger signal is connected to the input of a power amplifier. The output of the power amplifier is connected to the signal input port of a dual-frequency ultrasound probe, which drives the probe to generate an ultrasound signal. Aligning the ultrasound probe with the biphasic brain stimulation device provided in this embodiment generates a biphasic pulse stimulation signal for neural stimulation. The parameters of the biphasic pulse include repetition frequency, pulse width, pulse interval, and pulse amplitude, which can be adjusted by adjusting the trigger signal of the FPGA.

[0048] Example 2

[0049] This embodiment is based on the experiment of the ultrasound-driven passive implantable biphasic brain stimulation device provided in Example 1. Figure 3 This is the comsol simulation result of the frequency control layer 2, which simulates the sound pressure transmission coefficient of the frequency control layer 2 under sound waves of different frequencies. From the simulation results, it can be obtained that the frequency control layer 2 is highly transparent to 1MHz sound waves (transmittance 89%), and highly attenuates 3MHz sound waves, with a transmittance of only 12%.

[0050] Example 3

[0051] This embodiment is based on the experiment of the ultrasound-driven passive implantable biphasic brain stimulation device provided in Example 1. Figure 4 This is a set of control experiment results. First, under 1MHz ultrasonic drive, the output voltage of the bottom low-frequency piezoelectric layer is 4.24V when there is a frequency control layer, and the output voltage is 4.89V when there is no frequency control layer. The 1MHz ultrasonic transmittance is 86.7%; under 3MHz ultrasonic drive, the output voltage is 0.25V when there is a frequency control layer, and the output voltage is 1.82V when there is no frequency control layer. The ultrasonic transmittance is 13.7%, which is consistent with the Figure 3 The simulation data are relatively consistent, and the experimental method further verifies that the frequency control layer is highly transparent to 1MHz ultrasound and highly attenuates 3MHz ultrasound.

[0052] Example 4

[0053] This embodiment is based on the experiment of the ultrasound-driven passive implantable biphasic brain stimulation device provided in Example 1. Figure 5 This is a set of biphasic stimulation pulse signals output by a biphasic brain stimulator (this product) measured in the experiment. The parameters of this biphasic pulse are positive phase pulse amplitude 2.5V, negative phase pulse amplitude 2.5V, pulse width 333us, pulse interval 500us, and pulse repetition frequency 100Hz.

[0054] Example 5

[0055] This embodiment is based on the experiment of the ultrasound-driven passive implantable biphasic brain stimulation device provided in Example 1. Figure 6This is the result of an electrolysis experiment comparing a biphasic brain stimulation device and a monophasic brain stimulator. During the experiment, the electrodes were placed in normal saline. When bubbles were observed between the electrodes after the stimulation began, electrolysis was considered to have occurred. Figure 6 The left picture is the electrolysis experiment result of the monophasic brain stimulator, and the right picture is the experiment result of the biphasic brain stimulator. The right picture shows that electrolysis does not occur at a high stimulation frequency of 100-250Hz. The comparison shows that Example 1 has an improved ability to suppress electrolysis compared to traditional monophasic brain stimulators, and can be used in high-frequency stimulation scenarios.

[0056] The above embodiments are merely preferred embodiments of the present invention, and the scope of protection of the present invention is not limited to the above embodiments. All technical solutions that fall within the scope of protection of the present invention are within the scope of protection of the present invention. It should be noted that improvements and modifications that can be made by a person skilled in the art without departing from the principles of the present invention are also considered to be within the scope of protection of the present invention.

Claims

1. A passive implantable biphasic brain stimulation device based on ultrasound drive, comprising: A dual piezoelectric layer structure is used to generate a response output AC signal driven by high-frequency and low-frequency signals generated by an external dual-frequency ultrasonic probe; The dual piezoelectric layer structure comprises a high-frequency piezoelectric layer (11) and a low-frequency piezoelectric layer (12); The frequency control layer (2) is a diffraction grating type single-layer acoustic metamaterial (21) that selectively has high transmittance for low-frequency ultrasonic signals. The acoustic metamaterial (21) is a copper plate with a periodic cylindrical groove structure and is arranged between the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12); The biphasic rectifier circuit (3) is connected to the output electrodes of the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12), and converts the AC signals of the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12) into DC signals respectively, and generates biphasic stimulation pulses through differential output. The rear end of the biphasic rectifier circuit (3) is connected to the stimulation electrode (5) to generate biphasic electrical pulses at a specific position of the brain. The biphasic rectifier circuit (3) is located on one side of the high-frequency piezoelectric layer (11), the frequency control layer (2), and the low-frequency piezoelectric layer (12), and the biphasic piezoelectric layer structure, the frequency control layer (2), and the biphasic rectifier circuit (3) are encapsulated by an encapsulation layer.

2. The ultrasound-driven passive implantable biphasic brain stimulation device according to claim 1, characterized in that: The acoustic metamaterial (21) comprises an acoustic body (211) made of a copper plate, a plurality of cylindrical acoustic grooves (212) arranged in an array are provided on the upper surface of the acoustic body (211), and the acoustic grooves (212) are filled with water.

3. The ultrasound-driven passive implantable biphasic brain stimulation device according to claim 2, characterized in that: The acoustic body (211) has a thickness of 2.2 mm; the diameter of a single acoustic groove (212) is 0.4 mm and the depth is 0.8 mm; the groove spacing between the acoustic grooves (212) is 0.5 mm.

4. The ultrasound-driven passive implantable biphasic brain stimulation device according to claim 1, characterized in that: The resonant frequency of the high-frequency piezoelectric layer (11) is 3 MHz, and the resonant frequency of the low-frequency piezoelectric layer (12) is 1 MHz.

5. The ultrasound-driven passive implantable biphasic brain stimulation device according to claim 4, characterized in that: The materials used to manufacture the high-frequency piezoelectric layer (11) and the low-frequency piezoelectric layer (12) are both selected from Sm-PMNPT piezoelectric single crystals.

6. The ultrasound-driven passive implantable biphasic brain stimulation device according to claim 5, characterized in that: The Sm-PMNPT piezoelectric single crystal is precisely cut and magnetron sputtered to form high-frequency and low-frequency piezoelectric array elements of specific sizes.

7. The ultrasound-driven passive implantable biphasic brain stimulation device according to claim 1, characterized in that: The packaging layer is a biocompatible PDMS shell, comprising a top PDMS packaging layer (41) and a bottom PDMS packaging layer (43); a matching layer (42) is used to improve ultrasonic transmission efficiency; the matching layer (42), the high-frequency piezoelectric layer (11), the frequency regulation layer (2), and the low-frequency piezoelectric layer (12) are packaged from top to bottom between the top PDMS packaging layer (41) and the bottom PDMS packaging layer (43).

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