Wireless micro-magnetic stimulation device based on magnetic coupling resonance

Abstract

The invention discloses a wireless micro-magnetic stimulation device based on magnetic coupling resonance, and belongs to the technical field of biomedical engineering. Aiming at the problems of limited application scene and inconvenient operation caused by wired power supply of a traditional micro-magnetic stimulation device, the invention designs a wireless micro-magnetic stimulation device by combining a magnetic coupling resonance wireless energy transmission technology and a micro-magnetic stimulation nerve regulation and control technology. According to the device, a magnetic coupling resonance model is established through theoretical analysis, the coil structure and the circuit design are optimized, and the wireless energy transmission efficiency and stability are improved. The device adopts a self-made transmitting terminal copper wire coil and a stimulation front end made of a flexible circuit board, and is suitable for in-vitro and short-term in-vivo experiments through waterproof and biocompatibility design. Simulation analysis and hippocampal brain slice in-vitro experiments prove that the device can accurately regulate and control deep nerve nuclei of the brain, has a remarkable promotion effect on LTP in a hippocampal Schaffer-CA1 region, and can be used for neuroscience research and nervous system disease treatment.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical engineering, and in particular relates to a wireless micro-magnetic stimulation device based on magnetic coupling resonance transmission technology. Background Art

[0002] In the field of neuroscience, magnetic stimulation technology is an important non-invasive neuromodulation method that can effectively regulate the activity of neurons in the cerebral cortex. This technology not only provides an effective tool for exploring the association mechanism between cognitive function and brain area activity, but also opens up new avenues for basic research and clinical treatment of neurological diseases. Although traditional transcranial magnetic stimulation (TMS) technology has achieved certain results in clinical treatment, its coil size is large (10-20cm), resulting in low spatial resolution of the magnetic field, making it difficult to accurately locate the target area deep in the brain, and may have unknown effects on other normal physiological activities in the brain area. With the rapid development of modern micromachining technology and vacuum surface treatment technology, a new type of micro-magnetic stimulation neuromodulation technology has emerged. This innovative technology uses cell-level micro-coils that can be precisely implanted near the target area, achieving precise positioning and regulation of neural structures deep in the brain, providing breakthrough technical support for neuroscience research and the treatment of neurological diseases.

[0003] However, due to the small size, low inductance, and high power consumption of micromagnetic coils, existing micromagnetic stimulation devices mostly use wired power supply methods, which not only limits the application scenarios of micromagnetic stimulation devices but also brings many inconveniences to experimental operations. The development of wireless power supply technology provides a possible solution to these problems. Magnetic coupling resonance wireless transmission technology has become an ideal solution due to its high efficiency, long-distance transmission capability, and good biocompatibility. This paper designs a micromagnetic stimulation device based on a magnetic coupling resonance wireless transmission system. It combines the advantages of magnetic coupling resonance wireless energy transmission technology and micromagnetic stimulation neural regulation technology to achieve wireless and precise magnetic stimulation of deep neural nuclei in the brain. Summary of the Invention

[0004] The present invention aims to design a wireless micro-magnetic stimulation device based on magnetic coupling resonance. The device uses wireless energy transmission technology to power the micro-magnetic stimulation device, which overcomes the limitations of the existing technology and optimizes the transmission efficiency and biocompatibility of the device. The technical solution of the invention is:

[0005] A wireless micro-magnetic stimulation device based on magnetic coupling resonance is characterized by theoretical analysis of magnetic coupling resonance, circuit analysis, device transmission efficiency analysis, device design, simulation analysis of magnetic stimulation threshold, and experimental verification. The method is as follows:

[0006] (1) Theoretical analysis of magnetic coupling resonance

[0007] A. Theoretical analysis of magnetic field distribution of toroidal coil

[0008] The geometric radius of the toroidal coil is R c , the effective value of the current passing through the coil is I RMS , establish a spatial rectangular coordinate system, assume that the magnetic field strength generated by the circular current at any point P (x, y, z) is B, and derive the expression of the magnetic induction intensity generated by the circular current as follows:

[0009]

[0010] B y =0 (2)

[0011]

[0012] in

[0013]

[0014] When considering the magnetic field distribution of a multi-turn (N) coil, the magnetic induction intensity components in the x-axis and z-axis directions at any position in the space of the coil can be calculated using the following expressions:

[0015]

[0016] Among them, B nx and B nz They represent the magnetic field components of the n-turn toroidal coil at point P along the x-axis and z-axis directions. Analysis shows that the magnetic field intensity at a certain point in the coil space changes linearly with the change of current intensity, that is, B c =f(I RMS ).

[0017] B. Theoretical analysis of double-coil magnetic field coupling

[0018] When the transmitting and receiving coils are coupled, the electromagnetic field distribution in the surrounding space is actually composed of the vector superposition of the electromagnetic fields generated by the two coils. This characteristic conforms to the superposition principle of electromagnetic fields. In a resonantly coupled wireless energy transmission system, the instantaneous magnetic induction intensity at any point in space is calculated using the transient superposition method. Assume that the time-varying current in the transmitting coil is expressed as:

[0019]

[0020] Then the time-varying current flowing through the receiving coil is

[0021]

[0022] The magnetic field B generated by the transmitting coil c1 The x, y, and z axis components are B c1x , Bc1y , B c1z , the magnetic field B generated by the receiving coil c2 The corresponding axial component is B c2x , B c2y , B c2z According to the superposition principle of time-varying electromagnetic fields, the instantaneous magnetic induction intensity vector at a spatial point P can be decomposed into the vector sum of the field intensity components generated by the transmitting coil and the receiving coil in the directions of each coordinate axis. The specific expression is as follows:

[0023] b x (t) = B x i(t) (8)

[0024] b y (t) = B y i(t) (9)

[0025] b z (t) = B z i(t) (10)

[0026] The total magnetic induction intensity generated along the x direction at a spatial point P is the instantaneous vector sum of the magnetic field components generated by the transmitting and receiving coils in that direction. The specific expression is:

[0027]

[0028] Solving for the root mean square value

[0029]

[0030] Then the effective value of the magnetic induction intensity in each direction generated by the two coupled coils at point P can be expressed as

[0031]

[0032] Theoretical modeling and analysis of the magnetic field strength in the coupling region of the toroidal coil show that the current in the transmitting and receiving coils is the key factor affecting the magnetic induction strength in the coupling region, B = f(I).

[0033] (2) Analysis of device transmission efficiency

[0034] The device adopts the SS type compensation topology circuit. After circuit analysis, the relationship between the system transmission efficiency and the operating frequency is obtained as follows:

[0035]

[0036] As the operating frequency increases from 4 MHz to 20 MHz, the system transmission efficiency η shows a continuous upward trend, and the rate of increase gradually accelerates, as shown by the gradual increase in the slope of the curve, with η increasing from 1.25% to 25%.

[0037] (3) Design of the device

[0038] A. Transmitter Design

[0039] The transmitting coil of the wireless micromagnetic stimulation device uses a homemade copper wire coil with 9 turns, a diameter of 2.6 cm, and a height of 0.6 cm. This coil size is just right for placement on the glass electrodes of the MEA electrophysiological platform, facilitating subsequent LTP in vitro experiments. First, an impedance analyzer was used to measure the inductance of the wound coil, which was 3.4 μH. Then, using the resonance equation at different operating frequencies (11 MHz, 8 MHz, and 5 MHz), the resonant capacitance values ​​were calculated to be 61.57 pF, 116.41 pF, and 298 pF, respectively. Finally, a capacitor with the corresponding capacitance value was selected and soldered to the wound coil to form a series resonant circuit, completing the transmitter.

[0040] B. Stimulate front-end design

[0041] The stimulation tip uses an MHQ1005PR51GT000 inductor in a 0402 package (1.0mm×0.5mm). Its inductance is 510nH, its rated current is 70mA, its DC resistance (DCR) is 8.44Ω, and its quality factor is 13 at 100MHz. Using the resonance equation, the resonant capacitor values ​​were calculated to be 410.47pF, 776.05pF, and 1.99nF at three different frequencies (11MHz, 8MHz, and 5MHz), respectively. Based on the resonant circuit design requirements, a suitable surface-mount capacitor was selected, ensuring that its capacitance met the design parameters and that the package size was suitable for subsequent soldering and debugging. Considering the subsequent implantation experiments, the stimulation tip was designed to be lightweight and flexible to minimize pain for the experimental animals. The stimulation tip was fabricated from a flexible printed circuit board (FPC), with a total length of 29.87mm (including the 14.73mm extended stimulator tip) and a width of 0.64mm.

[0042] C. Circuit connection design

[0043] The circuit connection includes a signal generator SDG1070, a power amplifier LYB-2025, a transmitting coil, and a stimulation front end. The signal generator is connected to the transmitting end, and the required frequency parameters are input. When the stimulation frequency is 11MHz, the current value is 0.25A; when the stimulation frequency is 8MHz, the current value is 0.34A; when the stimulation frequency is 5MHz, four different current values ​​are selected: 0.52A, 0.6A, 0.69A, and 0.74A. The power amplifier amplifies the input signal and transfers energy to the stimulation front end through the transmitting coil to generate the required magnetic field strength.

[0044] D. Waterproof and biocompatible design

[0045] To ensure water resistance and biocompatibility, the stimulation tip is coated with a double layer of UV photoresist (10-20μm thick) and Parylene-C (5-10μm thick), ensuring water resistance and biocompatibility, making it suitable for in vitro and short-term in vivo experiments. This double-layer structure enhances the stability and safety of the stimulation tip circuitry, providing reliable technical support for experiments.

[0046] (4) Simulation analysis of stimulation threshold

[0047] To verify the effectiveness of the wireless micromagnetic stimulation device, after selecting the magnetic stimulation frequency and current parameters, a simulation model of the device stimulating the rat hippocampus was constructed in COMSOL software. The model first defined the size parameters of the transmitting and receiving coils, then configured the material properties of air, ACSF, white matter, and hippocampus. The receiving coil was positioned in the CA1 region of the hippocampus to analyze the effective magnetic stimulation threshold of the device at the target site. The device was subjected to magnetic field simulation tests. The 10-turn transmitting coil and 49.8-turn receiving coil generated different magnetic field intensities under different operating parameters. The test results are as follows:

[0048] A. When the wireless micromagnetic stimulation device operates at 11 MHz / 0.25 A, the transmitting coil generates a magnetic field strength of 0.2 mT in the CA1 region of the hippocampus, and the receiving coil generates a magnetic field strength of 0.67 mT at the center.

[0049] B. When the wireless micromagnetic stimulation device was operating at 8 MHz / 0.34 A, the magnetic field strength generated by the transmitting coil in the CA1 region of the hippocampal slice was 0.23 mT, and the magnetic field strength at the center of the receiving coil was 0.67 mT.

[0050] C. When the wireless micromagnetic stimulation device operated at 5 MHz, the magnetic field strength generated by the two coils exhibited a gradient change as the current increased. When the current was 0.52 A, 0.6 A, 0.69 A, and 0.74 A, the magnetic field strength generated by the transmitting coil in the CA1 region of the hippocampal slice was 0.26 mT, 0.32 mT, 0.38 mT, and 0.43 mT, respectively, and the magnetic field strength at the center of the receiving coil was 0.67 mT, 0.74 mT, 0.82 mT, and 0.98 mT, respectively.

[0051] (5) Experimental verification

[0052] After simulation analysis, it was determined that the device could achieve the required magnetic stimulation intensity for the experiment. Using this device, an in vitro experiment on hippocampal slices was conducted, recording a baseline of 10 minutes of field excitatory postsynaptic potentials (fEPSPs) from the Schaffer-CA1 region of the hippocampus. After successfully inducing LTP using high-frequency electrical stimulation, fEPSPs were recorded for another 15 minutes. After stabilization, magnetic stimulation was applied using the stimulation tip for 3 minutes. After the stimulation ended, fEPSPs were recorded for another 22 minutes. The experimental results are as follows:

[0053] A. At a magnetic stimulation intensity of 0.67 mT, after stimulation at frequencies of 11 MHz, 8 MHz, and 5 MHz, fEPSPs of LTP increased by 18.32%, 14.06%, and 2.48%, respectively, compared to pre-stimulation levels. The results indicate that at the same magnetic field intensity, the facilitation effect of magnetic stimulation at different frequencies on LTP in the Schaffer-CA1 region of the hippocampus increases with increasing frequency.

[0054] B. At a 5 MHz stimulation frequency, after stimulation with magnetic field intensities of 0.74 mT, 0.82 mT, and 0.98 mT, fEPSPs of LTP increased by 7.5%, 10.74%, and 17.5%, respectively, compared to pre-stimulation levels. These results indicate that the facilitatory effect of magnetic stimulation at different magnetic field intensities on LTP in the Schaffer-CA1 region of the hippocampus increases with increasing magnetic field intensity at the same stimulation frequency.

[0055] After the experiment, the experimental data were normalized and exported using LTP-analysis software. The data were then organized and plotted using Origin 2022 software, and statistical analysis and data processing were performed using Graphpad Prism 7. Statistical analysis included one-way analysis of variance and Tukey's multiple comparison test. The fEPSPs were expressed as mean ± standard deviation (mean ± SD).

[0056] The advantages and positive effects of the present invention are:

[0057] This paper designs a wireless micro-magnetic stimulation device based on magnetic coupling resonance. This device combines magnetic coupling resonance wireless energy transmission technology with micro-magnetic stimulation neuromodulation technology to achieve wireless, precise magnetic stimulation of deep brain nuclei. By designing a suitable resonant compensation circuit topology and optimizing the coil structure, the efficiency and stability of wireless energy transmission are improved, energy loss is reduced, and the stability and reliability of the device are ensured. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1 It is the overall flow chart of the present invention.

[0059] Figure 2Figure 3. The regulation of LTP in hippocampal CA1 synapses by stimulation at different frequencies under a magnetic field strength of 0.67 mT. A. Experimental results of 11 MHz stimulation frequency μMS stimulation of the hippocampal CA1 region. B. Experimental results of 8 MHz stimulation frequency μMS stimulation of the hippocampal CA1 region. C. Experimental results of 5 MHz stimulation frequency μMS stimulation of the hippocampal CA1 region. A1, B1, and C1 are box plots and variance analysis of fEPSPs between different experimental segments.

[0060] Figure 3 Figure 3. The regulation of LTP in hippocampal CA1 synapses by different magnetic field intensities at a stimulation frequency of 5 MHz. A. Experimental results of stimulating the CA1 region of the hippocampus with a magnetic field intensity of 0.74 mT. B. Experimental results of stimulating the CA1 region of the hippocampus with a magnetic field intensity of 0.82 mT. C. Experimental results of stimulating the CA1 region of the hippocampus with a magnetic field intensity of 0.98 mT. A1, B1, and C1 are box plots and variance analysis of fEPSPs between different experimental segments. DETAILED DESCRIPTION

[0061] The present invention is further described below with reference to the accompanying drawings and examples.

[0062] Step 1: Through theoretical analysis, a theoretical model of magnetic coupling resonance was established, and the expressions for the magnetic field distribution of the toroidal coil and the double coil were derived;

[0063] Step 2: After circuit analysis, the equivalent circuit model of the dual-coil series-series resonant compensation network is established, and the relationship between transmission efficiency and operating frequency is analyzed;

[0064] Step 3: Conduct hardware design for the wireless micromagnetic stimulation device, including coil fabrication for the transmitter and stimulation front end, circuit design, capacitor and inductor selection, front end fabrication, and waterproof coating design.

[0065] Step 4: Use COMSOL Multiphysics software to build a model of the wireless micromagnetic stimulation device to stimulate the hippocampus in rat brain slices. Observe the effects of different operating frequencies, coil turns, and transmitting coil current on the magnetic field intensity distribution to verify whether the wireless micromagnetic stimulation device can generate sufficient magnetic field intensity in the CA1 region of the rat hippocampus.

[0066] Step 5: Use the device to conduct in vitro experiments on hippocampal slices to study the regulation of LTP by the wireless micromagnetic stimulation device.

Claims

1. A wireless micro-magnetic stimulation device based on magnetic coupling resonance wireless transmission technology, characterized by Theoretical analysis of magnetic coupling resonance, device transmission efficiency analysis, device design, simulation analysis and experimental verification of magnetic stimulation threshold are as follows: (1) Theoretical analysis of magnetic coupling resonance A. The geometric radius of the toroidal coil is R c , the effective value of the current passing through the coil is I RMS , establish a spatial rectangular coordinate system, the magnetic field strength generated by the circular current at any point P (x, y, z) is B, when the coil is multi-turn, the magnetic field component (B) of the nth turn of the circular coil nx , B ny , B nz ) and calculate the magnetic field components (B) of the multi-turn coil along the x, y, and z axes cx , B cy , B cz ); The magnetic field strength at a certain point in the coil space changes linearly with the change of current intensity, that is, B c =f(I RMS ); B. Magnetic field B generated by the transmitting coil c1 The x, y, and z axis components are B c1x , B c1y , B c1z ,, the magnetic field B generated by the receiving coil c2 The corresponding axial component is B c2x , B c2y , B c2z ; When the double coils are coupled, the surrounding magnetic field B is composed of B c1 , B c2 The vector superposition is composed; calculate the root mean square value of each axis component of the two coils, and the effective value of the axial magnetic induction intensity corresponding to point P is B instx , B inst_y , B inst_z , and then calculate the effective value B of the magnetic induction intensity at point P inst ; (2) Analysis of device transmission efficiency An analysis of the transmission efficiency and operating frequency of the wireless micromagnetic stimulation device shows that as the operating frequency increases from 4 MHz to 20 MHz, the system transmission efficiency η shows a continuous upward trend, and the rate of increase gradually accelerates, as shown by the gradual increase in the slope of the curve, with η increasing from 1.25% to 25%. (3) Design of the device A. A homemade copper wire coil for the transmitter has nine turns, a diameter of 2.6 cm, and a height of 0.6 cm. Using an impedance analyzer, the coil's inductance is measured to be 3.4 μH. Using the resonance equation, the required resonant capacitance at 11 MHz, 8 MHz, and 5 MHz is calculated to be 61.57 pF, 116.41 pF, and 298 pF, respectively. B. The stimulation front end uses an MHQ1005PR51GT000 inductor in a 0402 package (1.0mm×0.5mm). Its inductance is 510nH, rated current is 70mA, DC resistance (DCR) is 8.44Ω, and quality factor is 13@100MHz. Using the resonance equation, the corresponding resonant capacitances at 11MHz, 8MHz, and 5MHz are calculated to be 410.47pF, 776.05pF, and 1.99nF, respectively. The stimulation front end is made of a flexible printed circuit board (FPC), with a total length of 29.87mm, including a 14.73mm extended stimulation tip, and a width of 0.64mm. C. Circuit connections include the SDG1070 signal generator, LYB-2025 power amplifier, transmitting coil, and stimulation front end. The signal generator is connected to the transmitting end, and the desired frequency parameters are input. When the stimulation frequency is 11 MHz, the current value is 0.25 A; when the stimulation frequency is 8 MHz, the current value is 0.34 A; when the stimulation frequency is 5 MHz, four different current values ​​are selected: 0.52 A, 0.6 A, 0.69 A, and 0.74 A. The power amplifier amplifies the input signal and transfers energy to the stimulation front end via the transmitting coil, generating the desired magnetic field strength. (4) Simulation analysis of magnetic stimulation threshold The device was tested for magnetic field simulation. The 10-turn transmitting coil and the 49.8-turn receiving coil generated different magnetic field intensities under different operating parameters. The test results are as follows: A. When the wireless micromagnetic stimulation device operates at 11 MHz / 0.25 A, the transmitting coil generates a magnetic field strength of 0.2 mT in the CA1 region of the hippocampus, and the receiving coil generates a magnetic field strength of 0.67 mT at the center. B. When the wireless micromagnetic stimulation device was operating at 8 MHz / 0.34 A, the magnetic field strength generated by the transmitting coil in the CA1 region of the hippocampal slice was 0.23 mT, and the magnetic field strength at the center of the receiving coil was 0.67 mT. C. When the wireless micromagnetic stimulation device operated at 5 MHz, the magnetic field strength generated by the two coils exhibited a gradient change as the current increased. When the current was 0.52 A, 0.6 A, 0.69 A, and 0.74 A, the magnetic field strength generated by the transmitting coil in the CA1 region of the hippocampal slice was 0.26 mT, 0.32 mT, 0.38 mT, and 0.43 mT, respectively, and the magnetic field strength at the center of the receiving coil was 0.67 mT, 0.74 mT, 0.82 mT, and 0.98 mT, respectively. (5) Experimental verification The device was used to conduct an in vitro hippocampal slice experiment, and the experimental results are as follows: A. At a magnetic stimulation intensity of 0.67 mT, after stimulation at frequencies of 11 MHz, 8 MHz, and 5 MHz, fEPSPs of LTP increased by 18.32%, 14.06%, and 2.48%, respectively, compared to pre-stimulation levels. The results indicate that at the same magnetic field intensity, the facilitation effect of magnetic stimulation at different frequencies on LTP in the Schaffer-CA1 region of the hippocampus increases with increasing frequency. B. At a stimulation frequency of 5MHz, after stimulation with magnetic field intensities of 0.74mT, 0.82mT and 0.98mT, the fEPSPs of LTP increased by 7.5%, 10.74% and 17.5% respectively compared with before stimulation; the results showed that the promoting effect of magnetic stimulation with different magnetic field intensities at the same stimulation frequency on LTP in the Schaffer-CA1 area of ​​the hippocampus increased with increasing magnetic field intensity.

2. The method according to claim 1, characterized in that A wireless micro-magnetic stimulation device based on magnetic coupling resonance was designed. After selecting the magnetic stimulation frequency and current parameters, a simulation model of the device stimulating the rat hippocampus was constructed in COMSOL software. The model first defined the size parameters of the transmitting / receiving coils, then configured the material properties of air, cerebrospinal fluid (ACSF), white matter, and hippocampus, and positioned the receiving coil in the CA1 region of the hippocampus. The effective magnetic stimulation threshold of the device on the target point was analyzed.

3. The method according to claim 1, characterized in that To ensure waterproofness and biocompatibility, the stimulation tip is double-coated with UV photoresist (10-20 μm thickness) and polyparaxylene (Parylene-C, 5-10 μm thickness) to ensure waterproofness and biocompatibility, making it suitable for in vitro and short-term in vivo experiments.

4. The method according to claim 1, characterized in that After simulation analysis, it was found that the device can achieve the magnetic stimulation intensity required for the experiment. The device was used to conduct an in vitro experiment on hippocampal slices, recording the baseline of field excitatory postsynaptic potentials (fEPSPs) in the Schaffer-CA1 area of ​​the hippocampus for 10 minutes. After successfully inducing LTP using high-frequency electrical stimulation, fEPSPs were recorded for another 15 minutes. After stabilization, magnetic stimulation was performed using the stimulation front end for 3 minutes. After the stimulation ended, fEPSPs were recorded for another 22 minutes.

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