CN117618789A - Wearable photodynamic wound treatment experimental system based on wireless power transmission system - Google Patents

Abstract

The invention provides a wearable photodynamic wound treatment experimental system based on a wireless electric energy transmission system, which can not anesthetize or fix a white mouse, so that the white mouse can be subjected to a photodynamic wound healing experiment in a free state, the illumination is uniform, and the adjustability of the light source intensity can be realized. The energy-saving device comprises an energy transmitting module, a wireless coupling module, an energy receiving module, a movable box and a wearing part; the wireless coupling module consists 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 movable box, the wearing part comprises a medical dressing, a flexible substrate attached to the adhesive surface of the dressing, a receiving coil attached to the flexible substrate, an energy receiving module and a plurality of LED lamps arranged in the receiving coil, the LED lamps are electrically connected with the energy receiving module, the medical dressing is further provided with a transparent packaging layer for packaging the receiving coil, the energy receiving module and the LED lamps, and a microneedle sheet is attached to the packaging layer.

Description

Wearable photodynamic wound treatment experimental system based on wireless power transmission system

Technical field

The invention relates to the technical fields of biomedicine and wireless energy transmission, and in particular, to a flexible experimental microsystem for diagnosis and treatment based on magnetic resonance wireless energy transmission.

Background technique

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

Yang T et al. (Yang T, Tan Y, Zhang W, et al. Effects of ALA-PDT on thehealing of mouse skin wounds infected with Pseudomonas aeruginosa and its related mechanisms[J]. Frontiers in Cell and Developmental Biology, 2020,8: 585132.) The study explored the effect of 5-aminolevulinic acid photodynamic therapy on skin wound healing in mice infected with Pseudomonas aeruginosa and its related mechanisms. It used laser to excite the photosensitizer, confirming the photodynamic therapy. Importance of wound testing.

Zhang X P et al. (Zhang Biodegradable microneedle roller for dermal drug delivery. A method for rapid transdermal drug delivery using degradable microneedle roller is explored. The article discusses the characteristics and effects of this technology, particularly its application in drug delivery.

Zhu J et al. (Zhu J, Dong L, Du H, et al. 5-Aminolevulinic acid-loadedhyluronic acid dissolving microneedles for effective photodynamic therapy ofsuperficial tumors with enhanced long-term stability[J]. Advanced healthcarematerials, 2019, 8(22 ):1900896.), titled: 5-Aminolevulinic Acid Loaded Hyaluronic Acid Dissolving Microneedles for Effective Photodynamic Therapy of Superficial Tumors with Enhanced Long-term Stability, study introduces a method using hyaluronic acid Degradable microneedles loaded with 5-aminolevulinic acid enable photodynamic therapy of superficial tumors via a laser light source, highlighting the advantages of this technology in improving long-term stability.

Huang J, et al. therapy, 2020,30:101748.), titled: The efficacy of single-shot photodynamic therapy with 5-aminolevulinic acid on wounds in diabetic mice infected with methicillin-resistant Staphylococcus aureus, this study reports the use of topical administration 5-ALA is used for antimicrobial photodynamic therapy to treat infected wounds in diabetic mice induced by methicillin-resistant Staphylococcus aureus (MRSA). It mainly demonstrates the bactericidal effect of 5-ALA in the mouse epidermal model, regardless of the epidermis. The feasibility of photodynamic therapy for MRSA infection was demonstrated by both healing and quantitative data curves, in which mice were kept immobilized by gas anesthesia.

From the above background technology, it can be seen that the treatment method using photodynamic drug delivery is also relatively common now. Most of the existing technologies use laser to irradiate the wound coated with medicine, or use microneedle tablets to administer the drug. When treating small children, When conducting photodynamic microneedle experiments on wound healing on white mice, the mice are usually anesthetized to prevent them from moving, and then the microneedle is attached to the wound of the mouse and treated through laser irradiation. However, this experimental device cannot realize the experiment of healing the wounds of the mice while they are moving freely.

Contents of the invention

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 conduct photodynamic wound healing experiments in a free state without anesthetizing or immobilizing them, and can illuminate the The light source is uniform, the light source is stable, and the light source intensity can be adjusted. It can realize the adjustment of the output strobe and the output power, and the output state of the transmitting coil can be controlled on the computer software through Bluetooth communication.

In order to achieve the above objects, the present invention provides the following technical solution: a wearable photodynamic wound treatment experimental system based on a wireless power transmission system, including an energy transmitting module, a wireless coupling module and an energy receiving module, which is characterized in that it also includes an activity boxes and wearing parts;

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 around the movable 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 receiving The plurality of LED lights in the coil 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 packaging layer.

Preferably, the microneedles in the microneedle sheet are mixed with a photodynamic drug. The microneedle sheet mixed with the photodynamic drug is attached to the wound of the mouse and fixed on the mouse through a dressing. The mouse is placed in the activity box.

Preferably, the flexible substrate is a polyimide substrate.

Preferably, the transparent encapsulation layer is polydimethylsiloxane.

Preferably, a flexible LED bracket is fixed in the receiving coil, the LED lights are evenly distributed on the flexible LED bracket in a circumferential shape, and an LED light is fixed at the center of the LED bracket.

Preferably, there are five LED lights, one LED light is located at the center of the LED bracket, and the other four LED lights are evenly distributed around the center of the LED bracket.

Preferably, the purple LED light with a wavelength of 405 nm is located in the center of the LED bracket, and the red LED lights with a wavelength of 630 nm are located around the LED bracket.

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

Preferably, the dimensions of the movable box are: 25cm long, 15cm wide, and 15cm high.

The system described in the present invention uses magnetic resonance wireless energy transmission technology and mainly consists 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 treatment. piece.

The transmitting module specifically includes: AC to DC power conversion module, programmable buck 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, an LED array, biodegradable medicated microneedles, and a wireless coil wrapped with polydimethylsiloxane (PDMS).

In order to ensure efficient energy transmission, the resonant frequencies 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 circuit switch through the Bluetooth-enabled main control board to achieve wireless operation and strobe energy 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 a magnetic ring and dual capacitors, thereby emitting high-frequency electromagnetic waves. In addition, the entire launch system has been designed with a three-dimensional structure and the shell is customized using 3D modeling, ensuring that it is highly portable. The device also reserves adjustable interfaces for different modules to facilitate device debugging according to different application scenarios.

The beneficial effects of the present invention are: by surrounding the transmitting coil outside the box where the mice move, a relatively balanced magnetic field is formed inside the box where the mice move, and by wearing the wireless receiving coil on the mouse, the mouse can not only It moves freely inside, and no matter where the mouse is in the activity box, the magnetic field intensity received by the receiving coil is relatively constant. For the microneedle patch with photodynamic drugs attached to the wound of the mouse, its photodynamic source It is an LED light worn on the mouse. The LED light is powered by the energy receiving module on the mouse. The energy receiving module is powered by the receiving coil. Therefore, the stable and uniform magnetic field inside the movable box supplies the energy receiving module. Provide stable energy, thereby making the LED light emit uniform light. The LED light is also worn on the mouse, and its position relative to the mouse's wound will not change with the movement of the mouse. In this case, the LED light has stable illumination. It also has stable illumination for the microneedle patch on the wound of the mouse, allowing the mouse to achieve stable illumination of the microneedle patch on the wound while the mouse can move freely in the activity box. It provides a practical technical solution for achieving photodynamic therapy in mice under active conditions.

And we use wireless power supply devices. As we all know, wireless power supply can already realize 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 status. Control, so that the output power of the transmitting coil can be adjusted through the microcontroller combined with the Bluetooth communication mode, and the duty cycle and frequency of the LED can also be adjusted. In this way, the brightness and on-off time of the LED can be controlled. To regulate the temperature of the wearable device attached to the surface of the mouse, thereby avoiding further damage to the skin caused by the temperature rise of traditional light sources.

Description of drawings

In order to explain the embodiments of the present invention more clearly, the drawings needed to be used in the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention. For ordinary people in the art, For technical personnel, other drawings can also be obtained based on these drawings without exerting creative work.

Figure 1. Overall framework of magnetic resonance wireless energy transmission system;

Figure 2. Schematic diagram of the wireless energy supply and transmission module of the magnetic resonance coupling wireless energy transmission system;

Figure 3. PC control interface of the magnetic resonance coupling wireless energy transmission system;

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

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

Figure 6. Diagram of degradable drug-loaded microneedles used for photodynamic therapy;

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

Figure 8. Performance diagram of the wireless receiving coil used in the photodynamic therapy coil;

Figure 9. Picture of the antibacterial and healing effects of photodynamic therapy coil on wounds.

In the figure, among them: movable box 1, wearable component 2, medical dressing 201, flexible substrate 202, LED light 203, encapsulation layer 204, microneedle sheet 205, mouse wound 206, LED bracket 207, transmitting coil 3, receiving coil 4.

Specific embodiments

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention.

A complete wireless power transmission system mainly contains three core parts: energy transmitting module, wireless coupling module and energy receiving module. Energy Transmission Module: The main components of this module include an AC signal source and an antenna tuner. Wireless coupling module: This module is mainly composed of a primary resonant coil (i.e., transmitting coil) and a secondary resonant coil (i.e., receiving coil). Energy receiving module: This part is mainly composed of high-frequency rectification and filtering circuits, voltage stabilizing circuits, and functional loads designed for specific applications. The structure of these parts is shown in Figure 1.

Working principle: First, a 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 forward and reverse power in real time. The signal antenna tuning circuit performs impedance matching and resonance to ensure optimal power transmission efficiency between the output impedance of the transmitting antenna and the transmitting source. At the receiving end, the receiving coil antenna and the transmitting coil antenna carry out resonant mutual inductance at the same frequency, thereby achieving energy transmission between the two. Finally, the received energy passes through the rectifier filter circuit and voltage stabilizing circuit and is supplied to the DC load.

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 emission source, and impedance matching module. Customized transmitting antenna: We used 3D modeling technology to print the overall model of the transmitting system, as shown in Figure 2. This device is not only portable, but also has adjustable interfaces preset for each module, allowing it to adapt to different application scenarios for device debugging. As shown in Figure 2, the schematic diagram of this wireless energy supply transmitting device is based on the AC signal source. This device adds a main control microcontroller. Through embedded development, a channel with input voltage and circuit for the transmitting coil is designed. With the adjustable function, and with the help of Bluetooth communication, the control interface of Labview on the computer side is designed, so that its output status can be controlled remotely.

Compared with the traditional external power supply light source, this invention first uses wireless power supply to free the mice from the restrictions of rigid wiring, allowing the mice to move freely. Secondly, the coil circuit is made of flexible materials, and the circuit is miniaturized, light, and It is thin and avoids the constraints of mice on the circuit. Finally, combined with degradable and transparent photodynamic therapy microneedles, it not only functions as an optical waveguide, but also serves as a drug carrier, solving the problems of light penetration and drug penetration. In addition, this device was developed through a microcontroller in the wireless power supply module, and combined with the Bluetooth communication method, 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 device can be adjusted and attached to The temperature of the surface of the mouse is thus avoided from further damage to the skin caused by the temperature rise of traditional light sources.

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

Impedance matching between the antenna and the transmitting source In order to ensure the best performance of the transmitting antenna, this equipment mainly uses a vector network analyzer to debug the impedance matching of 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 parallel, such as inductors, capacitors or transformers, etc., the impedance matching and resonance of the emission source and the output coil are achieved. It is worth noting that the present invention specifically adopts the method of connecting two capacitors and a transformer in series and parallel to achieve impedance matching.

As shown in Figure 4a, for biomedical research using mice as experimental models, we designed an acrylic material box with dimensions of 25cm × 15cm × 15cm as an movable box, and a transmitting coil was wound horizontally on the movable box. This design ensures that sufficient power is provided while the mice are 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 simulated the magnetic field distribution of the antenna within the transmitting coil using the finite element method. Simulation modeling: As shown in Figures 4b, 4c and 4d, the modeling and simulation of the transmitting coil is carried out through 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.

Figure 5a shows an exploded schematic diagram of the wireless wearable photodynamic therapy device on a mouse wound. This device mainly consists of the following modules: (i) Wireless power supply coil (receiving coil), which couples with external high-frequency electromagnetic waves (provided by the transmitting coil) to collect energy. The energy collected is then used to power LEDs. (ii) The LED group contains five LEDs symmetrically distributed at a distance of 0.5cm, ensuring that the wound surface can obtain approximately uniform illumination. The four corners are red LEDs with a wavelength of 630nm, and the other one in the center is a purple LED with a wavelength of 405nm. These LEDs are integrated on a flexible coil circuit on a polyimide (PI) substrate (Figure 5b). In order to ensure the safety and effectiveness of the device, we use polydimethylsiloxane (PDMS) to encapsulate the wireless power supply coil (receiver 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 set is 1cm × 1cm and is made of biocompatible and degradable materials. More importantly, these microneedles are mixed with photodynamic drugs (for example, 5-aminolevulinic acid). Microneedles not only serve as transdermal media but also as optical waveguide structures, ensuring that drugs and light can be effectively transmitted into deep tissues.

Features and functions of the microneedle module The microneedle module is made of a degradable polymer mixed with hyaluronic acid (HA) and polyvinyl alcohol (PVA). This hybrid approach ensures that the microneedles can deliver enough drug while still maintaining their overall frame, ensuring that the microneedles can continue to function as optical waveguides. Figure 6 shows the optical image of the microneedle array clearly demonstrating its excellent flexibility, which allows the microneedles to adhere closely to the epidermis when applied to biological tissue. More importantly, microneedles act as optical waveguides that can transmit light from the surface to deep tissues, thereby enhancing the effect of photodynamic therapy. To gain insight into this property of microneedles, we used a Monte Carlo numerical calculation method. We simulated the light transmission distribution of purple and red LEDs inside and outside different skin depths after passing through microneedles, taking into account optical parameters that match human skin. Figures 7a and 7b show the two-dimensional profile of the light distribution after passing through a single microneedle (the light intensity is normalized). In the simulations, we ensured that the microneedle parameters used were completely consistent with the actually prepared microneedles. The results show that after passing through the microneedle, the light is redistributed along the insertion depth of the microneedle and is transmitted through the sides of the microneedle into the surrounding tissue. Compared to other methods, microneedling provides a uniform and broad illumination pattern, ensuring that most of the light is delivered into deep tissue.

LED stability in photodynamic therapy In photodynamic therapy, the continuity and stability of the light source are crucial. As shown in Figure 8a, although there are slight differences in light intensity at various locations in the animal cage, the LED can still maintain a relatively stable brightness in the mouse's free movement area. Considering that various postures of animals while walking may cause the device to deform, we ensure that the LED can still emit light normally when the deformation angle of the device is within 80° (the LED bracket is a flexible bracket, the substrate is a flexible substrate, and the packaging layer is also Flexible encapsulation layer). At the transmitter end, the luminous intensity of the LED will be affected by the transmit power. For example, when the emission 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 (as shown in Figure 8b). Under continuous illumination for 5 hours, purple light and red light can produce energy of 54J cm ^–2 and 32J cm ^–2 respectively, which is fully consistent with the "low light, long time" (beat) characteristics of photodynamic therapy. In addition, Figures 8c and 8d show the temperature distribution of the device in the working state. It can be clearly seen that the operating temperature of the device is within the normal body temperature range of the animal, ensuring the safety of the treatment. Evaluation of animal experimental effects In animal experiments, we placed the device on the wound on the back of mice to evaluate the antibacterial effect of the device composed of degradable microneedles and coiled light-emitting LEDs. As shown in Figure 9, 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 in wound healing (Figure 9c). Among them, Figure 9a: Representative photos of bacterial colonies collected from wound tissues with different treatments, Figure 9b: Statistical chart of bacterial counts in wound tissues with different treatments. Therefore, this unique design combining wireless light-emitting LEDs and drug-loaded microneedles has a significant therapeutic effect on mouse wounds under active conditions.

Claims (9)

1. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system, including an energy transmitting module, a wireless coupling module and an energy receiving module, characterized in that it also includes an movable 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 around the movable box (1), and the wearing part (2) includes a dressing (201), a flexible substrate (202) attached to the adhesive surface of the dressing (201), and a patch. A receiving coil (4) and an energy receiving module combined on a flexible substrate (202), as well as a plurality of LED lights (203) placed in the receiving coil (4), the LED lights (203) and the energy receiving module are electrically connected , also includes a transparent encapsulation layer (204) that encapsulates the receiving coil (4), the energy receiving module and the LED lamp (203), and a microneedle sheet (205) is attached to the encapsulating layer (204). 2. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 1, characterized in that the microneedles in the microneedle sheet (205) are mixed with photodynamic drugs, mixed with The microneedle sheet (205) of the photodynamic drug is attached to the wound (206) of the mouse, and is wrapped and fixed on the mouse through a medical dressing (201). The mouse is placed in the movable box (1). 3. 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. 4. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 1, characterized in that the transparent encapsulation layer (204) is polydimethylsiloxane. 5. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 1, characterized in that a flexible LED bracket (207) is fixed in the receiving coil (4), and the LED The lights (203) are evenly distributed around the flexible LED bracket (207), and an LED light (203) is fixed at 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 there are five LED lights (203), one of which is located at the LED The other four LED lights (203) are evenly distributed around the center of the LED bracket (207). 7. A wearable photodynamic wound treatment experimental system based on a wireless power transmission system according to claim 6, characterized in that, located in the center of the LED bracket (207) is a purple LED lamp with a wavelength of 405nm, located in the LED bracket (207) 207) Surrounded by red LED lights with a wavelength of 630nm. 8. 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 both length and width. 9. 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 movable box (1) are: 25cm long, 15cm wide, and 15cm high.