Wearable photodynamic wound therapy experimental system based on wireless power transfer system

Abstract

The present invention provides a wearable photodynamic wound treatment experimental system based on a wireless power transmission system, which can be used to perform photodynamic wound healing experiments on mice in a free state without anesthetizing or fixing them, and the illumination is uniform, and the light source intensity can be adjusted. It includes an energy transmitting module, a wireless coupling module and an energy receiving module, and also includes an active box and a wearable component; the wireless coupling module is composed of a transmitting coil connected to the energy transmitting module and a receiving coil connected to the energy receiving module; the transmitting coil is horizontally wound on the active box, and the wearable component includes a medical dressing, a flexible substrate attached to the adhesive surface of the dressing, a receiving coil and an energy receiving module attached to the flexible substrate, and a plurality of LED lamps placed in the receiving coil, the LED lamp is electrically connected to the energy receiving module, and also includes a transparent packaging layer that encapsulates the receiving coil, the energy receiving module and the LED lamp, and a microneedle sheet is attached to the packaging layer.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine and wireless energy transmission technology, and in particular to a flexible experimental microsystem for diagnosis and treatment based on magnetic resonance wireless energy transmission. Background Art

[0002] With the in-depth development of the fields of microelectronics and optoelectronics, combining efficient optoelectronic information devices with biological systems has gradually become a research focus. These devices have shown great potential in solving complex problems in life sciences and have attracted the attention of many scholars and researchers. However, in traditional biomedical applications, the collection and stimulation of physiological signals often rely on wired metal electrodes or optical fiber connections. This wired method not only increases the risk of damage to tissues, but also limits the range of activities of experimental subjects, which undoubtedly limits the widespread application of optoelectronic devices in the biomedical field. At present, some existing wireless transmission devices used in the medical field have problems such as low output power, low transmission efficiency and unmodulatable output.

[0003] Yang T et al. (Yang T, Tan Y, Zhang W, et al. Effects of ALA-PDT on the healing of mouse skin wounds infected with Pseudomonas aeruginosa and its related mechanisms [J]. Frontiers in Cell and Developmental Biology, 2020, 8: 585132.) studied the effects of 5-aminolevulinic acid photodynamic therapy on the healing of mouse skin wounds infected with Pseudomonas aeruginosa and its related mechanisms. They used laser to excite the photosensitizer, confirming the importance of photodynamic therapy wound experiments.

[0004] Zhang XP et al. (Zhang XP, Zhang BL, Chen BZ, et al. Dissolving microneedle rollers for rapid transdermal drug delivery [J]. Drug Delivery and Translational Research, 2022, 12: 459-471.), entitled: Degradable microneedle roller for rapid transdermal drug delivery, explored a method for rapid transdermal drug delivery using a degradable microneedle roller. The article discussed the characteristics and effects of the technology, especially its application in drug delivery.

[0005] Zhu J et al. (Zhu J, Dong L, Du H, et al. 5-Aminolevulinic acid-loaded hyaluronic acid dissolving microneedles for effective photodynamic therapy of superficial tumors with enhanced long-term stability [J]. Advanced healthcare materials, 2019, 8 (22): 1900896.), entitled: 5-Aminolevulinic acid-loaded hyaluronic acid dissolving microneedles for effective photodynamic therapy of superficial tumors with enhanced long-term stability. The study introduced a method of using hyaluronic acid-degradable microneedles loaded with 5-aminolevulinic acid to perform photodynamic therapy of superficial tumors using a laser light source, emphasizing the advantages of this technology in improving long-term stability.

[0006] Huang J et al. (Huang J, Guo M, Wu M, et al. Effectiveness of a single treatment of photodynamic therapy using topical administration of 5-aminolevulinic acid on methicillin-resistant Staphylococcus aureus-infected wounds of diabetic mice[J]. Photodiagnosis and photodynamic therapy, 2020, 30: 101748.), entitled: Efficacy of single photodynamic therapy with 5-aminolevulinic acid on wounds of diabetic mice infected with methicillin-resistant Staphylococcus aureus, reported the use of topical administration of 5-ALA for the treatment of wounds infected in diabetic mice induced by methicillin-resistant Staphylococcus aureus (MRSA), mainly demonstrating the bactericidal effect of 5-ALA in a mouse epidermal model. Both the healing of the epidermis and the quantitative data curves proved the feasibility of photodynamic therapy for MRSA infection, in which the mice were kept fixed by air anesthesia.

[0007] From the above background technology, it can be seen that the treatment method of photodynamic drug delivery is also relatively common. Most of the existing technologies use laser irradiation to treat wounds coated with drugs, or use microneedle tablets to deliver drugs for treatment. When conducting photodynamic microneedle experiments on wound healing in mice, the mice are usually anesthetized to prevent them from moving, and then microneedles are attached to the wounds of the mice and treated by laser irradiation. However, this experimental device cannot realize the experiment of healing the wounds of mice while they are free to move. Summary of the invention

[0008] The purpose of the present invention is to provide a wearable photodynamic wound treatment experimental system based on a wireless power transmission system, which can allow mice to be anesthetized or fixed, and to perform photodynamic wound healing experiments on them in a free state, and the illumination is uniform, the light source is stable, and the light source intensity can be adjusted. The output strobe frequency and the output power can be adjusted, and the output state of the transmitting coil can be adjusted on the computer software side through Bluetooth communication.

[0009] In order to achieve the above-mentioned object, the present invention provides the following technical solutions: A wearable photodynamic wound treatment experimental system based on a wireless energy transmission system, comprising an energy transmitting module, a wireless coupling module and an energy receiving module, characterized in that it also comprises an active box and a wearable component;

[0010] The wireless coupling module is composed of a transmitting coil connected to the energy transmitting module and a receiving coil connected to the energy receiving module;

[0011] The transmitting coil is horizontally wound on the movable box, and the wearable parts include medical dressings, a flexible substrate attached to the adhesive surface of the dressing, a receiving coil and an energy receiving module attached to the flexible substrate, and multiple LED lights placed in the receiving coil, the LED lights are electrically connected to the energy receiving module, and also include a transparent packaging layer that encapsulates the receiving coil, the energy receiving module and the LED lights, and a microneedle sheet is attached to the transparent packaging layer. It also includes a main control microcontroller, which has the ability to adjust the input voltage and circuit of the transmitting coil through embedded development, and uses Bluetooth communication to design a control interface of Labview on the computer side, so that its output state can be remotely controlled; the energy transmitting module includes a transmitting source, and in order to ensure that the performance of the transmitting coil is optimal, a vector network analyzer is used to perform impedance matching debugging of the transmitting coil and the transmitting source.

[0012] Preferably, the microneedles in the microneedle sheet are mixed with photodynamic drugs, the microneedle sheet mixed with photodynamic drugs is attached to the wound of the mouse and fixed to the mouse by a dressing, and the mouse is placed in an activity box.

[0013] Preferably, the flexible substrate is a polyimide substrate.

[0014] Preferably, the transparent encapsulation layer is polydimethylsiloxane.

[0015] Preferably, a flexible LED bracket is fixed inside the receiving coil, the LED lamps are evenly distributed on the flexible LED bracket in a circular shape, and an LED lamp is fixed at the center position of the LED bracket.

[0016] Preferably, there are five LED lamps, one of which is located at the center of the LED bracket, and the other four LED lamps are evenly distributed in a circle around the center of the LED bracket.

[0017] Preferably, the purple LED lamp with a wavelength of 405 nm is located in the center of the LED bracket, and the red LED lamp with a wavelength of 630 nm is located around the LED bracket.

[0018] Preferably, the size of the microneedle sheet is 1 cm in length and width.

[0019] Preferably, the dimensions of the activity box are: 25 cm in length, 15 cm in width, and 15 cm in height.

[0020] The system described in the present invention utilizes magnetic resonance wireless energy transmission technology and is mainly composed of the following three parts: an energy transmitting system, a wireless coupling module, and an energy receiving module. The receiving module is mainly designed to provide a wearable LED patch for photodynamic wound therapy.

[0021] The transmitting module specifically includes: AC to DC power conversion module, programmable step-down unit, switch component, Bluetooth main control board, high-frequency transmitting source, impedance matching circuit and transmitting coil. The wearable LED patch designed for photodynamic therapy integrates a wireless power supply coil, LED array, biodegradable drug-containing microneedles, and a wireless coil wrapped with polydimethylsiloxane (PDMS).

[0022] In order to ensure efficient energy transmission, the resonant frequency of the transmitting coil and the receiving coil should be consistent and form a series-parallel resonant circuit. The transmitting coil controls its input power and the switch of the circuit through the main control board with Bluetooth function to achieve wireless operation and strobe power supply. At the same time, it is also equipped with a PC interface for wireless control. The impedance matching circuit achieves impedance matching and resonance through magnetic rings and dual capacitors to emit high-frequency electromagnetic waves. In addition, the entire transmitting system has been designed with a three-dimensional structure and the shell is customized using 3D modeling to ensure its high portability. The device also reserves adjustable interfaces for different modules to facilitate device debugging according to different application scenarios.

[0023] The beneficial effects of the present invention are as follows: by surrounding the transmitting coil outside the box where the mouse moves, a relatively balanced magnetic field is formed inside the box where the mouse moves, and the wireless receiving coil is worn on the mouse, so that the mouse can not only move freely inside the box, but also the magnetic field strength received by the receiving coil is relatively constant regardless of the position of the mouse in the active box. The photodynamic source of the microneedle patch with photodynamic drugs attached to the mouse wound is an LED lamp worn on the mouse, and the LED lamp is powered by an energy receiving module connected to the mouse, and the energy receiving module is powered by the receiving coil. Therefore, the stable and uniform magnetic field inside the active box provides stable energy to the energy receiving module, thereby making the LED lamp emit light evenly. The LED lamp is also worn on the mouse, and its position relative to the mouse wound will not change with the movement of the mouse. Then, when the LED lamp has stable illumination, it also has stable illumination for the microneedle patch on the mouse wound, so that the mouse can move freely in the active box to achieve stable illumination of the microneedle patch on its wound. A practical technical solution is provided for realizing photodynamic therapy for mice in an active state.

[0024] And we use a wireless power supply device. As we all know, wireless power supply can realize the adjustable control of the input voltage of the transmitting coil and the on-off of the circuit, and it can use the Bluetooth communication function to remotely control its output state. In this way, the output power of the transmitting coil can be adjusted, and the duty cycle and frequency of the LED can also be adjusted through the single-chip microcomputer combined with the Bluetooth communication mode. In this way, the brightness and on-off time of the LED can be adjusted, so as to adjust the temperature of the wearable device attached to the mouse surface, thereby avoiding further damage to the skin caused by the temperature rise of traditional light sources. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying any creative work.

[0026] Figure 1 .The overall framework of the magnetic resonance wireless energy transmission system;

[0027] Figure 2 .Schematic diagram of the wireless power supply transmitter module of the magnetic resonance coupling wireless energy transmission system;

[0028] Figure 3 .PC control interface of magnetic resonance coupling wireless energy transmission system;

[0029] Figure 4.Schematic diagram of the magnetic field simulation of the transmitting coil for wireless energy transmission;

[0030] Figure 5 .A wearable component of a battery-free light-emitting system for photodynamic therapy, wherein a is an exploded view of the wearable component, and b is a plan view and a schematic diagram of a bending state between a receiving coil and an LED light of the wearable component;

[0031] Figure 6 .Image of degradable drug-loaded microneedles for photodynamic therapy;

[0032] Figure 7 .Simulation of the light-guiding performance of degradable microneedles used in photodynamic therapy coils;

[0033] Figure 8 .Performance graph of wireless receiving coil for photodynamic therapy coil;

[0034] Fig. 9 .Image of the antibacterial and healing effects of photodynamic therapy coil on wounds.

[0035] In the figure, there are: an active box 1, a wearable component 2, a medical dressing 201, a flexible substrate 202, an LED lamp 203, a transparent encapsulation layer 204, a microneedle sheet 205, a mouse wound 206, an LED bracket 207, a transmitting coil 3, and a receiving coil 4. Specific embodiments

[0036] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] A complete wireless power transmission system mainly consists of three core parts: energy transmission module, wireless coupling module and energy receiving module. Energy transmission module: The main components of this module include AC signal source and antenna tuner. Wireless coupling module: This module is mainly composed of primary resonant coil (ie, transmitting coil) and secondary resonant coil (ie, receiving coil). Energy receiving module: This part is mainly composed of high-frequency rectification and filtering circuit, voltage stabilization circuit and functional load designed for specific applications. The structure of these parts is as follows Figure 1 shown.

[0038] Working principle: First, the high-frequency signal source generates a high-frequency AC signal. In order to prevent excessive power from damaging the signal source, the echo detection module monitors the forward and reverse power in real time. The signal antenna tuning circuit performs impedance matching and resonance to ensure the best power transmission efficiency between the transmitting antenna and the output impedance of the transmitting source. At the receiving end, the receiving coil antenna and the transmitting coil antenna resonate at the same frequency, thereby achieving energy transmission between the two. Finally, the received energy is supplied to the DC load through the rectifier filter circuit and the voltage regulator circuit.

[0039] In addition, our specially designed magnetic resonance coupling wireless transmission system includes the following parts: programmable DC power supply: power supply for each module, switch module, Bluetooth main control board, high-frequency transmission source, impedance matching module. Customized transmission antenna: We use 3D modeling technology to print the overall model of the transmission system, such as Figure 2 As shown in Figure 1. This device is not only portable, but also has preset adjustable interfaces for each module, so that it can adapt to different application scenarios for device debugging. Figure 2 As shown in the figure, this is the schematic diagram of the wireless power supply transmitting device. This device adds a main control microcontroller on the basis of the AC signal source. Through embedded development, it is designed to have the function of adjusting the input voltage of the transmitting coil and the on-off of the circuit. With the help of Bluetooth communication, a computer-side Labview control interface is designed, so that its output status can be remotely controlled.

[0040] Compared with the traditional external power source, this invention firstly uses wireless power supply to free mice from the limitation of rigid wiring, so that mice can move freely. Secondly, the coil circuit is made of flexible materials, and the circuit is miniaturized, light and thin, avoiding the restraint of mice on the circuit. Finally, it is combined with degradable and transparent photodynamic therapy microneedles, which not only play the role of optical waveguide, but also serve as a carrier of drugs, solving the problems of light penetration and drug penetration. In addition, the wireless power supply module is developed through a single-chip microcomputer, combined with Bluetooth communication, so that the output power of the transmitting coil is adjustable, and the duty cycle and frequency of the LED are also adjustable. In this way, the temperature of the device attached to the mouse surface can be controlled, thereby avoiding further damage to the skin caused by the temperature rise of traditional light sources.

[0041] like Figure 3 As shown, we have designed a PC-side control interface for the present invention, through which the user can control the input voltage and frequency. Therefore, the device can provide wireless power supply for the customized receiving module in the transmitting coil.

[0042] Impedance matching between antenna and transmitting source In order to ensure the best performance of the transmitting antenna, this device mainly uses a vector network analyzer to debug the impedance matching between the transmitting antenna and the transmitting source. The specific steps are as follows: Use a vector network analyzer to measure the original impedance of the transmitting antenna at the transmitting frequency. By connecting different components in series or in parallel, such as inductors, capacitors or transformers, the impedance matching and resonance between the transmitting source and the output coil can be achieved. It is worth noting that the present invention specifically adopts the method of connecting two capacitors in series and in parallel and a transformer to achieve impedance matching.

[0043] like Figure 4 As shown in Figure 1, for biomedical research using mice as experimental models, we designed an acrylic box with dimensions of 25cm×15cm×15cm as an activity box, on which a transmitting coil was horizontally wound. This design ensures that sufficient power can be provided while the mouse is able to move freely. In order to fully evaluate the performance of the transmitting coil, especially the magnetic field distribution inside it, we adopted the following methods: Simulation using finite element analysis: We used the finite element method to simulate the magnetic field distribution of the antenna inside the transmitting coil. Simulation modeling: As shown in Figure 1, Figure 4 As shown in Figures 4b, 4c and 4d, the transmitting coil is modeled and simulated using Ansys HFSS software. The simulation results show that the magnetic field distribution in the mouse activity area is uniform, which ensures that the mouse can obtain stable energy supply throughout the entire activity range.

[0044] Figure 5 a shows an exploded schematic diagram of the wireless wearable photodynamic therapy device on a mouse wound. The device mainly consists of the following modules: (i) a wireless power supply coil (receiving coil), which couples with external high-frequency electromagnetic waves (provided by the transmitting coil) to collect energy. The collected energy is then used to power the LED. (ii) The LED group contains five LEDs symmetrically distributed at a spacing of 0.5 cm, ensuring that the wound surface can receive approximately uniform illumination. The four corners are red LEDs with a wavelength of 630 nm, and the other one in the center is a purple LED with a wavelength of 405 nm. These LEDs are integrated on a flexible coil circuit on a polyimide (PI) substrate ( Figure 5 b). To ensure the safety and effectiveness of the device, we used polydimethylsiloxane (PDMS) to encapsulate the wireless power coil (receiving coil). This not only makes the coil electrically insulated, but also ensures the normal operation of the wearable device under various conditions. (iii) The size of the microneedle group is 1cm×1cm and is made of biocompatible and degradable materials. More importantly, these microneedles are mixed with photodynamic drugs (e.g., 5-aminolevulinic acid). The microneedles not only serve as transdermal media, but also act as optical waveguide structures, ensuring that drugs and light can be effectively transmitted to deep tissues.

[0045] Features and functions of microneedle modules The microneedle module is made of a biodegradable polymer mixed with hyaluronic acid (HA) and polyvinyl alcohol (PVA). This mixture ensures that the microneedle can maintain its overall framework while delivering sufficient drugs, thereby ensuring that the microneedle continues to function as an optical waveguide. Figure 6 Optical images showing the microneedle array clearly demonstrate their excellent flexibility, which allows the microneedles to fit tightly to the epidermis when applied to biological tissue. More importantly, the microneedles act as optical waveguides to transmit light from the surface to deep tissues, thereby enhancing the effect of photodynamic therapy. To gain a deeper understanding of this property of microneedles, we used a Monte Carlo numerical calculation method. We simulated the light transmission distribution of violet and red LEDs inside and outside the microneedles at different skin depths, taking into account the optical parameters that match human skin. Figure 7 a and 7b show the 2D profile of light distribution after passing through a single microneedle (light intensity is normalized). In the simulation, we ensured that the microneedle parameters used were exactly the same as the actual microneedles. The results show that after passing through the microneedle, the light is redistributed along the insertion depth of the microneedle and is delivered to the surrounding tissue through the side of the microneedle. Compared with other methods, microneedles provide a uniform and broad illumination pattern, ensuring that most of the light can be delivered to deep tissues.

[0046] LED stability in photodynamic therapy In photodynamic therapy, the continuity and stability of the light source are crucial. Figure 8 a shows that although there are slight differences in light intensity at different locations in the animal cage, the LED can still maintain a relatively stable brightness within the free activity area of ​​the mouse. Taking into account that the various postures of the animal when walking may cause the device to deform, we ensure that the LED can still emit light normally when the device deformation angle is within 80° (the LED bracket is a flexible bracket, the substrate is a flexible substrate, and the transparent packaging layer is also a flexible packaging layer). At the transmitting end, the luminous intensity of the LED will be affected by the transmitting power. For example, when the transmitting power is 8W, the optical power of the purple LED can reach 3mW, while the optical power of the red LED is about 1.8mW (such as Figure 8 b). Under 5 hours of continuous illumination, purple light and red light can generate 54 J cm –2 and 32J cm –2 energy, which is completely consistent with the characteristics of "low light, long time" (beat) in photodynamic therapy. In addition, Figure 8Figures c and 8d show the temperature distribution of the device in working state. It can be clearly seen that the working temperature of the device is within the normal body temperature range of the animal, ensuring the safety of the treatment. Animal experiment effect evaluation In the animal experiment, we placed the device on the wound on the back of the mouse to evaluate the antibacterial effect of the device composed of degradable microneedles and coil-light-emitting LEDs. Fig. 9 As shown in Figure 2, by comparing the bacterial inactivation effects of the experimental group and the control group, we found that the number of bacteria in the treatment group was significantly reduced, reaching 2.48log 10 CFU / mL (p<0.05). This result clearly shows the powerful effect of our device in inhibiting the growth of Pseudomonas aeruginosa in skin wounds and wound healing ( Fig. 9 c) Among them, Fig. 9 a: Representative photos of bacterial colonies collected from wound tissues with different treatments. Fig. 9 b: Statistical graph of bacterial colonies in wound tissues treated with different methods. Therefore, this unique design combining wireless light-emitting LEDs and drug-loaded microneedles has a significant therapeutic effect on wounds in active mice.

Claims

1. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system, comprising an energy transmitting module, a wireless coupling module and an energy receiving module, characterized in that: It also includes an activity box (1) and a wearable component (2); The wireless coupling module is composed of a transmitting coil (3) connected to the energy transmitting module and a receiving coil (4) connected to the energy receiving module; The transmitting coil (3) is horizontally wound on the movable box (1); the wearable component (2) comprises a dressing (201), a flexible substrate (202) attached to the adhesive surface of the dressing (201), a receiving coil (4) and an energy receiving module attached to the flexible substrate (202), and a plurality of LED lights (203) disposed in the receiving coil (4); the LED lights (203) are electrically connected to the energy receiving module; and the wearable component (2) comprises a transparent encapsulation layer (204) encapsulating the receiving coil (4), the energy receiving module and the LED lights (203); and a microneedle sheet (205) is attached to the transparent encapsulation layer (204); The microneedles in the microneedle sheet (205) are mixed with photodynamic drugs, and the microneedle sheet (205) mixed with photodynamic drugs is attached to the wound (206) of the mouse and fixed on the mouse by wrapping the medical dressing (201), and the mouse is placed in an activity box (1); The duty cycle and frequency of the LED lamp are adjustable; It also includes a main control microcontroller, which has the ability to adjust the input voltage of the transmitting coil and the on / off of the circuit through embedded development, and uses Bluetooth communication to design a control interface of Labview on the computer side, so that its output state can be remotely controlled; The energy transmission module comprises a transmission source. In order to ensure that the performance of the transmission coil (3) is optimal, a vector network analyzer is used to perform impedance matching debugging between the transmission coil (3) and the transmission source.

2. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 1, characterized in that: The flexible substrate (202) is a polyimide substrate.

3. According to claim 1, a wearable photodynamic wound treatment experimental system based on a wireless power transmission system is characterized in that: The transparent encapsulation layer (204) is polydimethylsiloxane.

4. According to claim 1, a wearable photodynamic wound treatment experimental system based on a wireless power transmission system is characterized in that: A flexible LED bracket (207) is fixed inside the receiving coil (4), the LED lamps (203) are evenly distributed on the flexible LED bracket (207) in a circular shape, and an LED lamp (203) is fixed at the center of the LED bracket (207).

5. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 4, characterized in that: There are five LED lamps (203), one of which is located at the center of the LED bracket (207), and the other four LED lamps (203) are evenly distributed in a circle around the center of the LED bracket (207).

6. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 5, characterized in that: Located at the center of the LED bracket (207) is a purple LED lamp with a wavelength of 405nm, and located around the LED bracket (207) are red LED lamps with a wavelength of 630nm.

7. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 1, characterized in that: The size of the microneedle sheet (205) is 1 cm in length and width.

8. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 1, characterized in that: The dimensions of the activity box (1) are: 25 cm in length, 15 cm in width, and 15 cm in height.

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