CN117618789B

CN117618789B - Wearable photodynamic wound therapy experimental system based on wireless power transfer system

Info

Publication number: CN117618789B
Application number: CN202311633545.1A
Authority: CN
Inventors: 丁贺; 薛钊; 任雪纯
Original assignee: Beijing Institute of Technology BIT
Current assignee: Beijing Institute of Technology BIT
Priority date: 2023-12-01
Filing date: 2023-12-01
Publication date: 2025-04-04
Anticipated expiration: 2043-12-01
Also published as: CN117618789A

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 wireless coupling module comprises 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 a bonding surface of the dressing, a receiving coil attached to the flexible substrate, an energy receiving module, a plurality of LED lamps arranged in the receiving coil, the LED lamps are electrically connected with the energy receiving module, and the wireless coupling module further comprises 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 field of biomedicine and wireless energy transmission, in particular to a flexible experiment microsystem oriented to diagnosis and treatment based on magnetic resonance wireless energy transmission.

Background

With the intensive development of microelectronics and optoelectronics, the combination of highly efficient optoelectronic information devices with biological systems has become the focus of research. These devices have shown great potential in solving complex problems in life sciences, and have received attention from a wide range of scholars and researchers. However, in traditional biomedical applications, acquisition and stimulation of physiological signals often rely on wired metallic electrodes or fiber optic connections. This wired approach not only increases the risk of damage to the tissue, but also limits the range of motion of the subject, which clearly limits the wide application of optoelectronic devices in the biomedical field. Some existing wireless function transmitting devices applied to the medical field have the problems of low output power, low transmission efficiency, unmodulable output and the like.

The 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.) study explored the effect of 5-aminolevulinic acid photodynamic therapy on wound healing in pseudomonas aeruginosa infected mice and its associated mechanisms, which stimulated photosensitizers by means of lasers, confirming the importance of photodynamic therapy wound experiments.

Zhang X P et al (Zhang X P,Zhang B L,Chen B Z,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, discuss a method for rapid transdermal drug delivery using the degradable microneedle roller. The article discusses the features and effects of this technology, particularly in terms of drug delivery.

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, studied and introduced a photodynamic therapy of superficial tumors with a laser light source using hyaluronic acid-degradable microneedles loaded 5-aminolevulinic acid, underscores the advantages of this technique in terms of enhanced long-term stability.

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 5-aminolevulinic acid single photodynamic therapy for treatment of wounds in diabetic mice resistant to methicillin-resistant Staphylococcus aureus, reported treatment of wounds in methicillin-resistant Staphylococcus aureus (MRSA) -induced diabetic mice with topical 5-ALA photodynamic therapy, demonstrated primarily the degerming effect of 5-ALA in a mouse epidermis model, both in the healing case of the epidermis and in a quantified data curve demonstrating the feasibility of photodynamic therapy for MRSA infection, where mice were kept fixed by means of gas-anaesthesia.

As is clear from the background art described above, a treatment method using photodynamic therapy is also common, and in the prior art, treatment is generally performed by irradiating a wound coated with a drug with laser light or by administering a drug via a microneedle patch, and when a photodynamic microneedle test for wound healing is performed on a mouse, it is common to anesthetize the mouse to prevent movement of the mouse, and then apply the microneedle to the wound of the mouse and perform treatment by laser irradiation. However, this experimental device does not allow an experiment of healing the wound of the mice under the free movement of the mice.

Disclosure of Invention

The invention aims to provide a wearable photodynamic wound treatment experimental system based on a wireless electric energy transmission system, which can not be used for anesthetizing or fixing 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, the light source is stable, and the adjustability of the light source intensity can be realized. The adjustable output power of the output stroboscopic can be realized, and the output state of the transmitting coil can be regulated and controlled at a computer software end in a Bluetooth communication mode.

In order to achieve the aim, the invention provides the technical scheme that the wearable photodynamic wound treatment experiment system based on the wireless electric energy transmission system comprises an energy emission module, a wireless coupling module and an energy receiving module, and is characterized by further comprising 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 transmitting coil, the energy receiving module and a transparent packaging layer for packaging the LED lamps are further arranged, and a microneedle sheet is attached to the transparent packaging layer. The energy transmitting module comprises a transmitting source, and is used for carrying out impedance matching debugging on the transmitting coil and the transmitting source by adopting a vector network analyzer in order to ensure that the performance of the transmitting coil is optimal.

Preferably, the microneedles in the microneedle sheets are mixed with photodynamic medicaments, the microneedle sheets mixed with the photodynamic medicaments are attached to the wound of the mice, the mice are attached and fixed to the mice through dressing, and the mice are placed in the movable box.

Preferably, the flexible substrate is a polyimide substrate.

Preferably, the transparent encapsulation layer is polydimethylsiloxane.

Preferably, a flexible LED support is fixed in the receiving coil, the LED lamps are circumferentially and uniformly distributed on the flexible LED support, and an LED lamp is fixed at the center of the LED support.

Preferably, the LED lamps are five, one LED lamp is located at the center of the LED support, and the other four LED lamps are circumferentially and uniformly distributed around the center of the LED support.

Preferably, the ultraviolet LED lamp with the wavelength of 405nm is arranged in the center of the LED support, and the red LED lamp with the wavelength of 630nm is arranged around the LED support.

Preferably, the micro-needle pieces are 1cm long and wide.

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

The system described by the invention mainly comprises an energy transmitting system, a wireless coupling module and an energy receiving module by utilizing a magnetic resonance type wireless energy transmission technology, wherein the receiving module is mainly designed to be a wearable LED patch for photodynamic wound treatment.

The transmitting module comprises a power supply conversion module for converting alternating current into direct current, a programmable voltage reduction unit, a switch assembly, a Bluetooth main control board, a high-frequency transmitting source, an impedance matching circuit and a transmitting coil. In a wearable LED patch designed for photodynamic therapy, a wireless power coil, an LED array, biodegradable drug-containing microneedles, and a wireless coil wrapped with Polydimethylsiloxane (PDMS) are integrated.

To ensure efficient energy transfer, the resonant frequencies of the transmit and receive coils should be kept consistent and form a series-parallel resonant circuit. The transmitting coil controls the input power and the switch of the circuit through the main control board with the Bluetooth function, so that wireless operation and stroboscopic energy supply are realized. At the same time, a PC interface is also provided for wireless control. The impedance matching circuit achieves impedance matching and resonance through the magnetic ring and the double capacitors, so that high-frequency electromagnetic waves are emitted. In addition, the whole emission system is subjected to three-dimensional structural design, and the 3D modeling is utilized for customizing the shell, so that the high portability of the emission system is ensured. The device also reserves adjustable interfaces for different modules so as to facilitate device debugging according to different application scenes.

The micro-needle patch has the beneficial effects that the light emitting coil is surrounded outside the box of the mouse activity, so that a relatively balanced magnetic field is formed inside the box of the mouse activity, the wireless receiving coil is worn on the mouse body, the mouse can freely move in the box, the magnetic field intensity received by the receiving coil is relatively constant no matter the mouse is positioned at any position of the activity box, the micro-needle patch with photodynamic medicaments attached to the wound of the mouse, the photodynamic source of the micro-needle patch is an LED lamp worn on the mouse body, the LED lamp is powered by an energy receiving module on the mouse body, and the energy receiving module is powered by the receiving coil, so that the stable and uniform magnetic field inside the activity box provides stable energy for the energy receiving module, the LED lamp is uniformly luminous, the LED lamp is worn on the mouse body, the position of the LED lamp relative to the wound of the mouse is not changed along with the movement of the mouse, under the condition that the LED lamp has stable illumination, the micro-needle attached to the wound of the mouse also has stable illumination, and the micro-needle attached to the wound of the mouse can realize the stable illumination of the micro-needle patch in the activity box under the condition that the movement of the mouse can freely attach to the micro-needle. Provides a feasible technical scheme for realizing photodynamic therapy of mice in an active state.

And we use wireless energy supply's device, it is generally known that wireless energy supply can realize the control of the input voltage of transmitting coil and the break-make adjustable of circuit, and it can be with the help of bluetooth communication function, thereby carry out remote control to its output state, just so can combine the communication mode of bluetooth through the singlechip, it is adjustable to make transmitting coil's output, and LED's duty cycle and frequency also can be adjusted, can regulate and control LED's luminance and break-make time through this kind of mode, thereby regulate and control this wearing device and paste the temperature on mouse surface, thereby avoided traditional light source temperature to rise the further damage to skin.

Drawings

In order to more clearly illustrate the embodiments of the present invention, the drawings that are required for the description of the embodiments will be briefly described below, it being apparent that the drawings in the following description are only some embodiments of the present invention and that other drawings may be obtained from these drawings without inventive effort for a person of ordinary skill in the art.

FIG. 1 is a schematic illustration of an overall frame of a magnetic resonance wireless energy transfer system;

Figure 2 is a schematic diagram of a wireless powered transmit module of a magnetic resonance coupled wireless energy transfer system;

FIG. 3 is a PC-side control interface of the magnetic resonance coupled wireless energy transfer system;

FIG. 4 is a schematic diagram of a simulation of a magnetic field of a transmitting coil for wireless energy transfer;

FIG. 5. Wearable component of a batteryless lighting system for photodynamic therapy, wherein a is an exploded view of the wear and b is a plan view and a schematic view of the state of bending between the receiving coil and the LED lights of the wearable component;

FIG. 6 is a diagram of a degradable drug-loaded microneedle for photodynamic therapy;

FIG. 7 is a graph of the light guiding performance simulation of a degradable microneedle for use in photodynamic therapy coils;

FIG. 8 is a graph of performance of a wireless receive coil for a photodynamic therapy coil;

Fig. 9 is a graph of the antimicrobial and healing effects of the photodynamic therapy coil on the wound.

In the figure, a movable box 1, a wearing part 2, a medical dressing 201, a flexible substrate 202, an LED lamp 203, a transparent packaging layer 204, a micro-needle 205, a mouse wound 206, an LED bracket 207, a transmitting coil 3 and a receiving coil 4 are shown.

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without any inventive effort, are intended to be within the scope of the invention.

A complete wireless power transmission system mainly comprises three core parts, namely an energy transmitting module, a wireless coupling module and an energy receiving module. The main components of the energy transmitting module comprise an alternating current signal source and an antenna tuner. The wireless coupling module mainly comprises a primary resonance coil (namely a transmitting coil) and a secondary resonance coil (namely a receiving coil). The energy receiving module mainly comprises a high-frequency rectifying and filtering circuit, a voltage stabilizing circuit and a functional load designed for specific application. The structure of these parts is shown in fig. 1.

The working principle is that firstly, a high-frequency signal source generates a high-frequency alternating current signal. 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 optimal power transmission efficiency between the output impedance of the transmitting antenna and the output impedance of the transmitting source. At the receiving end, the receiving coil antenna and the transmitting coil antenna carry out resonance mutual inductance under the same frequency, so that energy transmission is realized between the receiving coil antenna and the transmitting coil antenna. And finally, the received energy is supplied to a direct current load through a rectifying and filtering circuit and a voltage stabilizing circuit.

In addition, the magnetic resonance coupling wireless transmitting system specially designed by the user comprises a programmable direct current power supply, a switch module, a Bluetooth main control board, a high-frequency transmitting source and an impedance matching module. Customized transmit antenna we printed an overall model of the transmit system using 3D modeling techniques, as shown in fig. 2. The device is portable, and an adjustable interface is preset for each module, so that the device can adapt to different application scenes for device debugging. As shown in FIG. 2, the main control singlechip is added on the basis of an alternating current signal source, the function of adjusting the input voltage of a transmitting coil and the on-off state of a circuit is designed through embedded development, and a control interface of a computer terminal Labview is designed by means of Bluetooth communication, so that the output state of the control interface can be controlled remotely.

Compared with the traditional external power supply light source, the invention firstly gets rid of the limitation of rigid wiring by a wireless power supply mode, so that the mouse can move freely, secondly adopts flexible materials to manufacture a coil circuit, and the circuit is miniaturized, light and thin, avoids the constraint of the mouse to the circuit, and finally combines the degradable transparent photodynamic therapy microneedle, thereby not only playing the role of an optical waveguide, but also being used as a carrier of a medicine, and solving the problems of light permeation and medicine permeation. In addition, the wireless energy supply module develops the device through the singlechip, and combines the communication mode of Bluetooth, so that the output power of the transmitting coil is adjustable, the duty ratio and the frequency of the LED are also adjustable, and the temperature of the device attached to the surface of a mouse can be regulated and controlled in the mode, so that the further damage of the temperature rise of the traditional light source to the skin is avoided.

As shown in FIG. 3, a PC control interface is designed for the invention, through which a user can control the input voltage and frequency. Thus, the device is capable of providing wireless power to a customized receiving module within a transmitting coil.

Impedance matching of the antenna and the transmitting source in order to ensure that the performance of the transmitting antenna is optimal, the device mainly adopts a vector network analyzer to carry out impedance matching debugging of the transmitting antenna and the transmitting source. The method comprises the following specific steps of measuring the original impedance of a transmitting antenna at a transmitting frequency by using a vector network analyzer. Impedance matching and resonance of the emission source and the output coil are achieved through different components, such as an inductor, a capacitor or a transformer, connected in series or in parallel. It is noted that the invention particularly adopts a method of connecting two capacitors in series and parallel and a transformer to realize impedance matching.

As shown in fig. 4a, for biomedical research using mice as experimental models, we designed an acryl material box having a size of 25cm×15cm as a movable box on which a transmitting coil is horizontally wound. This design ensures that sufficient power can still be provided in the event that the mice are free to move. In order to fully evaluate the performance of the transmitting coil, and in particular its internal magnetic field distribution, we have adopted a method of simulation using finite element analysis, we have used a finite element method to simulate the magnetic field distribution of the antenna within the transmitting coil. Simulation modeling as shown in fig. 4b, 4c and 4d, modeling simulation of the transmit coil is performed by ANSYS HFSS software. Simulation results show that the magnetic field distribution in the active region of the mice is uniform, which ensures that the mice can be stably energized throughout the range of activity.

Fig. 5a shows an exploded schematic of a wireless wearable photodynamic therapy device on a mouse wound. The device is mainly composed of (i) a wireless power supply coil (receiving coil) coupled with external high frequency electromagnetic waves (provided by a transmitting coil) to collect energy. The collected energy is then used to power the LEDs. (ii) The LED group comprises five LEDs which are symmetrically distributed at intervals of 0.5cm, so that the surface of a wound can be ensured to obtain approximately uniform illumination. Four corners of the LED are red LEDs with the wavelength of 630nm, and the other corner is positioned at the center of the LED is a purple LED with the wavelength of 405 nm. These LEDs are integrated on a flexible coil circuit on a Polyimide (PI) substrate (fig. 5 b). To ensure the safety and effectiveness of the device, we use Polydimethylsiloxane (PDMS) to encapsulate the wireless power coil (receive coil). This not only electrically insulates the coil, but also ensures proper operation of the wearable device under various conditions. (iii) The microneedle array was 1cm by 1cm in size and was fabricated from biocompatible and degradable materials. More importantly, these microneedles incorporate photodynamic drugs (e.g., 5-aminolevulinic acid). The microneedles act not only as a transdermal medium, but also as an optical waveguide structure, ensuring that the drug and light can be effectively transmitted into the deep tissues.

Characteristics of microneedle module and functional microneedle module are manufactured using a degradable polymer of Hyaluronic Acid (HA) and polyvinyl alcohol (PVA) mixed. This mixing ensures that the microneedle will maintain its overall frame while delivering enough drug to ensure that the microneedle continues to function as an optical waveguide. Fig. 6 shows that the optical image of the microneedle array clearly shows its excellent flexibility, which enables the microneedles to closely conform to the epidermis when applied to biological tissue. More importantly, the microneedles act as optical waveguides to transfer light from the surface to the deep tissues, thereby enhancing the effect of photodynamic therapy. To gain insight into this property of microneedles, we have used the monte carlo numerical calculation method. The light transmission distribution of the purple light and red light LEDs at different skin depths after passing through the microneedles is simulated, and optical parameters matched with human skin are considered during simulation. Fig. 7a and 7b show a two-dimensional profile of the light distribution after passing through a single microneedle (light intensity normalized). In the simulation, we ensure that the microneedle parameters used are exactly identical to those of the actual preparation. The results show that light will redistribute along the depth of insertion of the microneedles after passing through the microneedles and will be transmitted through the sides of the microneedles into the surrounding tissue. In contrast to other approaches, microneedles provide a uniform and broad illumination pattern, ensuring that most of the light is delivered into the deep tissue.

LED stability in photodynamic therapy the persistence and stability of the light source is of paramount importance. As shown in fig. 8a, the LEDs maintain a relatively stable brightness in the free active area of the mice, despite slight differences in light intensity at various locations within the animal cage. Considering that various postures of animals during walking can cause deformation of the device, the LED can still normally emit light when the deformation angle of the device is within 80 degrees (the LED support is a flexible support, the substrate is a flexible substrate, and the transparent packaging layer is also a flexible packaging layer). At the emission end, the luminous intensity of the LED may be affected by the emission power. For example, when the emission power is 8W, the light power of the violet LED may reach 3mW, while the light power of the red LED is about 1.8mW (as shown in fig. 8 b). Under illumination lasting 5 hours, the purple light and the red light can respectively generate energy of 54J cm ^–2 and 32J cm ^–2, which completely accords with the characteristics of low illumination and long time (beat) in photodynamic therapy. In addition, fig. 8c and 8d show the temperature distribution of the device in the working state, and it can be clearly seen that the working temperature of the device is within the normal body temperature range of the animal, so that the safety of treatment is ensured. Animal experiment effect evaluation in an animal experiment, we placed the device at the wound of the back of a mouse to evaluate the antibacterial effect of the device composed of degradable microneedles combined with coil light emitting LEDs. As shown in fig. 9, the bacterial inactivation effect of the experimental and control groups was compared, and we found that the bacterial count of the treated 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 pseudomonas aeruginosa growth in skin wounds and wound healing (fig. 9 c). Wherein FIG. 9a is a representative photograph of bacterial colonies collected from different treated wound tissues and FIG. 9b is a statistical plot of the counts of colonies in different treated wound tissues. Therefore, the unique design combining the wireless light-emitting LED and the drug-loaded microneedle has remarkable treatment effect on the wounds of mice in an active state.

Claims

1. The wearable photodynamic wound treatment experiment system based on the wireless electric energy transmission system comprises an energy emission module, a wireless coupling module and an energy receiving module, and is characterized by further comprising a movable box (1) and a wearing part (2);

the wireless coupling module consists 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 wearing part (2) comprises a dressing (201), a flexible substrate (202) attached to the bonding surface of the dressing (201), a receiving coil (4) attached to the flexible substrate (202), an energy receiving module and a plurality of LED lamps (203) arranged in the receiving coil (4), the LED lamps (203) are electrically connected with the energy receiving module, the energy receiving module further comprises a transparent packaging layer (204) for packaging the receiving coil (4), the energy receiving module and the LED lamps (203), and a micro-needle (205) is attached to the transparent packaging layer (204);

The micro-needles in the micro-needle sheet (205) are mixed with photodynamic medicaments, the micro-needle sheet (205) mixed with the photodynamic medicaments is attached to a wound (206) of a mouse and is wound and fixed on the mouse through a medical dressing (201), and the mouse is placed in a movable box (1);

the duty ratio and the frequency of the LED lamp are adjustable;

The control interface of the Labview of the computer terminal is designed by means of Bluetooth communication, so that the output state of the control interface can be controlled remotely;

The energy transmitting module comprises a transmitting source, and in order to ensure that the performance of the transmitting coil (3) is optimal, a vector network analyzer is adopted to carry out impedance matching debugging on the transmitting coil (3) and the transmitting source.

2. The wearable photodynamic wound therapy experiment system based on a wireless power transmission system according to claim 1, wherein the flexible substrate (202) is a polyimide substrate.

3. The wearable photodynamic wound therapy experiment system based on a wireless power transmission system according to claim 1, wherein the transparent encapsulation layer (204) is polydimethylsiloxane.

4. The wearable photodynamic wound therapy experiment system based on the wireless power transmission system according to claim 1, wherein a flexible LED support (207) is fixed in the receiving coil (4), the LED lamps (203) are circumferentially and uniformly distributed on the flexible LED support (207), and an LED lamp (203) is fixed at the central position of the LED support (207).

5. The wearable photodynamic wound therapy experiment system based on the wireless power transmission system according to claim 4, wherein the number of the LED lamps (203) is five, one LED lamp (203) is located at the center of the LED support (207), and the other four LED lamps (203) are uniformly distributed circumferentially around the center of the LED support (207).

6. The wearable photodynamic wound therapy experiment system based on the wireless power transmission system according to claim 5, wherein the ultraviolet LED lamp with the wavelength of 405nm is positioned at the center of the LED bracket (207), and the red LED lamps with the wavelength of 630nm are positioned around the LED bracket (207).

7. The wearable photodynamic wound therapy experiment system based on the wireless power transmission system according to claim 1, wherein the micro-needle (205) has a size of 1cm in length and width.

8. The wearable photodynamic wound therapy experiment system based on the wireless power transmission system according to claim 1, wherein the dimensions of the movable box (1) are 25cm long, 15cm wide and 15cm high.