Antibacterial photodynamic therapy light-operated catheter system based on targeted delivery

Abstract

The invention relates to the technical field of medical apparatus and instruments, discloses an antibacterial photodynamic therapy light-operated catheter system based on targeted delivery, and solves the technical problems of insufficient light penetration depth and active oxygen non-targeted tissue damage when traditional aPDT is used for treating deep tissue infection. Comprises: a sterile flexible catheter body including at least an inflow lumen and an outflow lumen; the light source module is integrated in the catheter body and is used for providing excitation illumination in vitro or in a specific cavity; the photosensitive medicine storage and delivery module is communicated with the inflow cavity; the reaction cavity is arranged in the catheter body / at the near end, the photosensitive medicine is activated by the light source when flowing through the area, and a photochemical product with bactericidal activity is generated. Through a working mode of in-vivo targeted release of the photoactivated antibacterial solution, generation and delivery of antibacterial active substances in a deep infection focus are realized, non-targeted damage caused by direct irradiation of high-energy light to in-vivo tissues is avoided, and safety, effectiveness and clinical application range of aPDT in deep infection treatment are remarkably improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical devices and interventional catheter therapy, in particular to an antibacterial photodynamic therapy light-controlled catheter system based on targeted delivery. BACKGROUND

[0002] Antimicrobial Photodynamic Therapy (aPDT) is a treatment modality that utilizes the synergistic effect of photosensitizer (PS), specific wavelength visible or near-infrared light and endogenous oxygen to generate reactive oxygen species (ROS) in situ. Although the initial ROS (such as singlet oxygen) has a very short lifetime, it can be converted into secondary oxidants (such as hydrogen peroxide, lipid peroxide or long-lived free radical intermediates) with a longer half-life in a specific medium, thereby achieving sustained killing of pathogenic microorganisms. Unlike the single target mechanism of traditional antibiotics, the ROS generated by aPDT can simultaneously attack various biological macromolecules of bacteria such as cell membrane, protein and nucleic acid, causing irreversible oxidative damage. This multi-target attack feature makes aPDT have the significant advantages of broad-spectrum antibacterial, rapid bactericidal and less likely to induce bacterial resistance.

[0003] However, although aPDT shows good prospects in the treatment of superficial infections (such as skin and mucosal infections), its application in deep tissue infections, especially diffuse peritoneal infection and deep abscess, has long been limited by two core technical bottlenecks: First, the tissue light penetration depth is limited. Biological tissues have strong absorption and scattering effects on light. The visible light (wavelength 400-700 nm) that effectively excites most photosensitizers usually has a penetration depth of less than 1 centimeter in tissues. For complex intra-abdominal infection (cIAI) with a wide range and deep lesions, the light energy of surface irradiation has been attenuated to almost nothing when it reaches the core of deep infection, which cannot effectively activate the photosensitizer, resulting in treatment failure. Although there are studies in the prior art that attempt to improve penetration by developing near-infrared light-excited photosensitizers, their ROS quantum yield is often low, and there are problems such as complex synthesis, greater damage to normal tissues, and difficulty in clinical translation.

[0004] Secondly, there are safety problems in direct light irradiation in vivo. In order to deliver light energy to the deep part, an invasive optical fiber probe is used for inter-tissue irradiation in the prior art. However, the high-power-density light energy can cause significant thermal effects in the irradiation area, which can easily cause thermal burns to fragile normal tissues (such as intestinal serosa, peritoneum, large blood vessels, etc.). In addition, the metabolism of photosensitive drugs in the body needs time, and during this period, if non-specific light irradiation occurs, it will cause phototoxicity damage to normal tissues, which seriously restricts the safety of the application of PDT in sensitive body cavities (such as the abdominal cavity).

[0005] Therefore, there is an urgent need in the art for an innovative aPDT delivery system and scheme, which can fundamentally avoid the limitation of tissue light penetration depth and eliminate the safety risks brought by direct light irradiation in vivo, so as to realize efficient, accurate and safe treatment of deep drug-resistant bacterial infections. SUMMARY

[0006] The present application provides an antibacterial photodynamic therapy light-controlled catheter system based on targeted delivery, which overcomes the two fundamental technical defects of the existing antibacterial photodynamic therapy (aPDT) in clinical application, especially in the treatment of deep tissue infections (such as complex abdominal cavity infections and deep tissue abscesses): Insufficient tissue penetration depth: biological tissues have strong absorption and scattering effects on light, which results in a very limited penetration depth (usually <1 cm) of effective excitation light (usually visible light) in tissues, which cannot effectively irradiate deep and diffuse infection foci, resulting in the failure of aPDT.

[0007] Safety risks of direct light irradiation in vivo: The invasive in vivo light irradiation used to deliver light energy to the deep part can easily cause thermal damage and non-specific phototoxicity damage to the surrounding normal tissues (such as the intestine, blood vessels, and nerves), which poses a major safety hazard and severely limits the application of aPDT in body cavities.

[0008] Therefore, the present application fundamentally avoids the problem of light tissue penetration and eliminates the safety risks brought by in vivo light irradiation, while achieving efficient, accurate and controllable delivery of reactive oxygen species (ROS) to deep infection foci.

[0009] To achieve the above-mentioned purpose, the present application provides an antibacterial photodynamic therapy light-controlled catheter system based on targeted delivery, which innovatively separates the "generation" and "action" of ROS in space: high-concentration ROS is generated in a controllable environment outside or beside the body, and then delivered to the deep infection area in the body in real time and targeted through a precise pipeline system.

[0010] The antibacterial photodynamic therapy light-controlled catheter system based on targeted delivery provided by the present application is used for targeted delivery of reactive oxygen species to deep infection foci in the body cavity of a patient, and the system comprises: A sterile flexible catheter body for implantation or insertion into a body cavity, the sterile flexible catheter body having a distal portion and a proximal portion, and having at least one inflow cavity and at least one outflow cavity internally; the inflow cavity is used to deliver a photosensitizing drug or antibacterial drug fluid to the site of infection, and the outflow cavity is used to drain fluid accumulated in the body cavity from the site of infection; wherein, the distal portion of the sterile flexible catheter body has one or more irrigation openings in fluid communication with the inflow cavity, and one or more drainage openings in fluid communication with the outflow cavity; A light source module is used to generate specific wavelengths of light that can efficiently excite photosensitive drug molecules with different properties. The light source module is integrated into the distal part of the sterile flexible catheter or optically coupled to the distal part of the sterile flexible catheter through an optical transmission component to ensure that the light it generates can irradiate the photosensitive drug solution flowing through the predetermined area. A photosensitive drug storage and delivery module includes a light-shielding container for storing a photosensitive drug solution and a fluid pump (precision fluid pump) connected to the light-shielding container; the fluid pump is operatively connected to the inlet of the inflow cavity of the proximal portion of the sterile flexible catheter via a fluid conduit, for pumping the photosensitive drug solution into the inflow cavity at a controlled flow rate; The reaction chamber, as a closed cavity or flow channel area, is located inside the sterile flexible catheter or adjacent to the distal portion of the sterile flexible catheter, such that the photosensitive drug solution flowing through the inflow channel must pass through the reaction chamber; the reaction chamber is used to receive sufficient irradiation from the light source module when the photosensitive drug solution flows through it, so as to activate the photosensitive drug in vitro or in situ and generate reactive oxygen species in situ before the photosensitive drug solution leaves the perfusion opening of the sterile flexible catheter; The control unit, comprising a microprocessor and operating software, is connected via wired or wireless means to the fluid pump in the light source module and the photosensitive drug storage and delivery module. It is used to independently or collaboratively control the operating parameters of the light source module and the delivery flow rate of the fluid pump. Specifically, all operating parameters controlled by the control unit include: The system includes the on / off state of the light source module, emission wavelength, light power density, and illumination duration; the on / off state and delivery flow rate of the precision fluid pump; the self-cleaning and sterilization of the sterile flexible catheter body; and the self-detection of abnormal signals.

[0011] Furthermore, the sterile flexible catheter is integrally molded from a biocompatible medical-grade polymer material using additive manufacturing technology. The medical-grade polymer material is thermoplastic polyurethane, silicone rubber, or polyethylene. The proximal portion of the sterile flexible catheter is provided with a standardized Luer connector or threaded interface for rapid and sterile connection with a standard abdominal drainage tube or infusion line. Furthermore, the light source module includes a miniaturized, high-density array of light-emitting diodes (LEDs) and a wavelength selection element. The LED array is disposed at the distal end of the sterile flexible catheter, surrounding the outer periphery of the reaction chamber, or embedded in the wall constituting the reaction chamber. The LED array is capable of emitting monochromatic or composite light with wavelengths in the visible or near-infrared bands. The wavelength selection element is a replaceable filter or a wavelength switching device that can be electrically controlled by the control unit to adapt to a variety of photosensitive drugs with different optimal excitation wavelengths.

[0012] Furthermore, the geometry of the reaction chamber is optimized through computational fluid dynamics simulation. The geometry can guide the photosensitive drug solution through in a preset flow pattern and ensure that the average residence time of the solution in the chamber is greater than or equal to the minimum illumination time required for the photosensitive drug to be fully activated. The inner surface of the reaction chamber is covered with a high reflectivity material layer, which is one of barium sulfate, titanium dioxide or metal coating, used to reflect the irradiated light back into the reaction chamber to maximize the light energy utilization and ensure that the photosensitive drug solution is irradiated uniformly. The cross-sectional shape of the reaction chamber is circular, elliptical, or asymmetrical with an internal turbulence structure. The internal turbulence structure is a spiral guide vane or a serrated texture, which is used to enhance the turbulence of the photosensitive drug solution as it flows through, so as to promote its mixing and interaction with light.

[0013] Furthermore, the control unit is used to implement closed-loop control, dynamically adjusting the operating parameters of the light source module and / or the fluid pump by receiving feedback signals from one or more sensors; the sensors include: A flow rate sensor installed in the fluid pipeline or reaction chamber is used to monitor the flow rate of reactive oxygen species, photosensitive drugs, and outflowing liquid in real time and to perform manual / automatic real-time control. A pressure sensor installed at the distal end of the sterile flexible catheter body is used to monitor the intracavitary pressure in real time and perform manual / automatic real-time adjustment. An optical sensor installed at the outlet of the reaction chamber is used to indirectly monitor the concentration of generated reactive oxygen species through quantitative fluorescence intensity analysis or chemical spectrophotometry, and to perform manual / automatic real-time control. The closed-loop control is configured as follows: when the pressure value detected by the pressure sensor exceeds a preset safety threshold, the fluid pump is controlled to reduce its flow rate or stop working; when the active oxygen concentration detected by the optical sensor is lower than a preset effective threshold, the light source module is controlled to increase its light power density or the fluid pump is controlled to reduce its flow rate.

[0014] Furthermore, the light-shielding container in the photosensitizing drug storage and delivery module is a disposable, pre-filled syringe or flexible bag, which is pre-packaged with a photosensitizing drug solution of a specific concentration. The photosensitizing drug is one of hematoporphyrin monomethyl ether, tarapofen sodium, or methylene blue, selected according to the type of pathogen to be killed, and can be combined with corresponding antibacterial drugs for synergistic effect.

[0015] Furthermore, it also includes an integrated monitoring module, which comprises: Diagnostic light sources are used to emit beams of light at specific wavelengths that can excite photosensitive drugs to produce characteristic fluorescence. A fluorescence detector is used to detect the intensity of the fluorescence signal reflected from the infection site; the control unit identifies the boundary of the infected area based on the spatial distribution or intensity change of the fluorescence signal, so as to plan or adjust the irradiation parameters of the light source module and / or the perfusion path of the fluid pump; A bioluminescent detector or a rapid adenosine triphosphate (ATP) concentration detection unit is used to analyze the fluid drained from the outflow cavity in real time, quantitatively assess the sterilization efficiency by monitoring the decay rate of ATP concentration, and provide closed-loop feedback on the treatment effect to the control unit.

[0016] The present invention also provides an antibacterial photodynamic therapy device comprising the targeted delivery-based antibacterial photodynamic therapy light-controlled catheter system as described above. The device includes a main unit housing that carries the control unit and a photosensitizing drug storage and delivery module (the photosensitizing drug is stored in a sterile dark environment at room temperature / 4°C), and a human-machine interface connected to the control unit. The human-machine interface is used to display system status, treatment parameters and alarm information, and to receive user operation commands.

[0017] The present invention also provides a control method for the targeted delivery-based antibacterial photodynamic therapy light-controlled catheter system as described above, the control method comprising the following steps: (1) The control unit starts the fluid pump, so that the photosensitive drug solution flows through the inflow cavity at a preset initial flow rate; (2) When the photosensitive drug solution flows through the reaction chamber, the control unit activates the light source module, causing the light source module to emit excitation light according to preset parameters, activating the photosensitive drug solution before it flows out of the infusion opening, and generating a high concentration of active oxygen. (3) During operation, key parameters are monitored in real time through the control unit and sensors, and the flow rate and / or illumination parameters are dynamically adjusted using a closed-loop control algorithm.

[0018] Furthermore, when the light source module is started, the flow rate of the fluid pump is controlled within the range of 0.1 mL / min to 5 mL / min, and the light power density of the light source module is controlled within the range of 10 mW / cm² to 200 mW / cm², so as to ensure that the concentration of reactive oxygen species generated in the reaction chamber reaches the micromolar level and minimizes potential damage to normal tissues.

[0019] The photodynamic therapy catheter system for targeted delivery of antibacterial agents provided by this invention can be widely used in the treatment of various deep tissue infections. The following example of treating deep abdominal infections illustrates the usage and procedures of this system to verify its targeted delivery and real-time monitoring capabilities in complex environments: 1) Catheter placement: Under imaging guidance, the distal portion of the catheter is inserted and positioned in the target infected area within the patient's body cavity; 2) System initialization: Connect the light-shielding container pre-filled with photosensitizing drug solution to the precision fluid pump, and connect the fluid line to the inlet of the catheter body; set the initial treatment parameters in the system control unit, including photosensitizing drug concentration, target flow rate, light wavelength, light power density, and expected total light dose; 3) Treatment cycle start-up: Start the precision fluid pump to allow the photosensitive drug solution to flow through the inflow cavity at a preset initial flow rate; 4) In-situ activation and delivery: When the photosensitive drug solution flows through the reaction chamber, the light source module is activated to emit excitation light according to preset parameters, activating the photosensitive drug solution before it flows out of the perfusion opening, generating a high concentration of reactive oxygen species, thereby directly and immediately perfusing the treatment solution rich in reactive oxygen species into the target infection site. 5) Drainage: During or alternate with irrigation, the treated or excess fluid in the body cavity is drained out of the body through the outflow channel of the catheter body to maintain the pressure and fluid balance in the cavity; 6) Process monitoring and parameter adjustment: During the treatment process, key parameters are monitored in real time through the system control unit and related sensors, and the flow rate and / or light parameters are dynamically adjusted using a closed-loop control algorithm to optimize the generation efficiency of reactive oxygen species and the therapeutic effect, and ensure the safety of the treatment. 7) Treatment termination and flushing: After completing the preset treatment cycle, stop the irradiation of the light source module and the delivery of the precision fluid pump, switch the fluid source, and flush the fluid tubing and the catheter body with sterile saline or buffer solution.

[0020] 8) Synergistic treatment: One or more antibacterial drugs are infused or injected into the target infection site through the inflow channel of the catheter body; wherein, the selection of the antibacterial drugs is determined based on the drug sensitivity test results of pathogens isolated from the drainage fluid before and after treatment by the photo-controlled catheter delivery system, so as to achieve sequential synergistic treatment of antibacterial photodynamic therapy and antibacterial drug therapy.

[0021] The beneficial effects of this invention are as follows: 1. Breakthrough in tissue penetration depth limitation: Through the "extracorporeal pre-activation, in vivo ROS release" mode, the problem of light penetration is transformed into the problem of fluid transport. The fluid can be evenly diffused throughout the body cavity, thereby achieving comprehensive treatment of deep and diffuse infectious lesions without dead angles, solving the fundamental problem that traditional aPDT cannot treat deep infections.

[0022] 2. Improved treatment safety: Since high-energy light does not directly contact the patient's internal tissues, it fundamentally eliminates the photothermal damage and non-targeted phototoxicity that may be caused by internal light irradiation, making aPDT extremely safe for use in sensitive body cavities such as the abdominal cavity, and greatly expanding its clinical application scope.

[0023] 3. Achieving efficient and precise targeted therapy: ROS is generated and used immediately within a closed tubing system, minimizing the attenuation and loss of reactive oxygen species during delivery, as well as the non-specific distribution and metabolic consumption of photosensitizers in the body. This allows high concentrations of ROS to precisely target the infection site, significantly improving bactericidal efficiency while reducing the risk of systemic side effects.

[0024] 4. Ensure the controllability and stability of the treatment process: The reaction chamber optimized by CFD ensures the efficient and stable generation of ROS; the precise closed-loop feedback control system realizes real-time monitoring and dynamic optimization of key parameters (flow rate, light intensity, ROS concentration, pressure), ensuring the consistency, reliability and repeatability of treatment quality.

[0025] 5. Provides an intelligent integrated diagnosis and treatment platform: The integrated new monitoring functions (fluorescence localization, ATP efficacy assessment) integrate diagnosis and treatment, making the treatment process move from experience-based to digital, intelligent and personalized, providing a powerful tool for precision medicine.

[0026] 6. Strong clinical applicability and translational potential: The catheter design is compatible with existing clinical standard interfaces, requiring no changes to routine surgical procedures, resulting in a gentle learning curve for physicians. This system can not only be used to treat ESLD combined with cIAI, but can also be widely applied to various deep drug-resistant bacterial infections such as pleural abscesses, complex soft tissue infections, and osteomyelitis lavage, demonstrating extremely high clinical translational value and broad market prospects.

[0027] 7. Pioneering a new paradigm of synergistic treatment: The method provided by this invention naturally constitutes a synergistic treatment strategy of "aPDT + antibacterial drugs", providing a new and powerful weapon to deal with the antibacterial drug resistance crisis and extending the clinical lifespan of existing antibacterial drugs. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the overall structure of the photodynamic therapy light-controlled catheter system for targeted delivery of antibacterial drugs according to the present invention.

[0029] Figure 2 This is an enlarged cross-sectional structural diagram of the distal portion of the catheter body (including components such as the reaction chamber, LED array, and perfusion micropores) in this invention.

[0030] Figure 3 This is a block diagram illustrating the closed-loop control and detection principle of the system in this invention.

[0031] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0032] It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. Furthermore, it should be understood that the illustrative drawings are not drawn to scale. The flowcharts used in this application illustrate operations implemented according to some embodiments of this application. It should be understood that the operations in the flowcharts may not be implemented in sequence, and steps without logical contextual relationships may be reversed or performed simultaneously. Moreover, those skilled in the art, guided by the content of this application, may add one or more other operations to the flowcharts, or remove one or more operations from the flowcharts.

[0033] This invention provides a light-controlled catheter delivery system, which specifically includes the following components that work together in synergy: 1. Catheter body The catheter body is the end of the system and is made of a biocompatible flexible material (such as medical-grade thermoplastic polyurethane TPU or silicone rubber). It is preferably integrally molded using three-dimensional additive manufacturing (3D printing) technology to ensure the complex internal flow channel structure and adapt to the anatomical shape of the body cavity.

[0034] ① Multi-lumen structure: The catheter body has at least one inflow lumen and at least one outflow lumen. The two lumens are isolated from each other at the internal and external ends to avoid cross-contamination.

[0035] ② Infusion and drainage design: The distal end (implantation end) of the infusion cavity has multiple directional infusion micropores, the distribution of which has been optimized by hydrodynamics to ensure that the ROS solution can cover the target area. The distal end of the outflow cavity has a drainage opening for draining the fluid accumulated in the cavity and maintaining pressure balance.

[0036] ③ Standardized interface: The proximal end (external end) of the catheter is equipped with a standardized quick interface (such as a Luer connector or a universal threaded interface), which enables it to be quickly and aseptically connected to conventional abdominal drainage tubes or infusion lines, greatly improving clinical adaptability and ease of operation.

[0037] 2. Light source module This module is the activation source for the photosensitizer. Its key innovation lies in precisely and efficiently irradiating the photosensitizer solution flowing through a specific area, rather than directly irradiating human tissue. Specific implementation methods include: ① Integrated Light Source: A miniaturized, high-density array of light-emitting diodes (LEDs) is directly integrated and encapsulated within the distal wall of the conduit, surrounding the outer periphery of the reaction chamber. This LED array can be selected and customized according to the optimal absorption wavelength of the chosen photosensitizer (such as hematoporphyrin monomethyl ether (HMME), tarapofen sodium, methylene blue, etc.), and its optical power density can be precisely controlled within the range of 10 mW / cm² to 200 mW / cm².

[0038] ② Fiber-optic light source: An external high-intensity light source (such as a xenon lamp or semiconductor laser) is used to transmit the excitation light to the reaction chamber region at the distal end of the catheter body through a bundle of flexible quartz optical fibers.

[0039] ③ Wavelength adaptability: To improve the system's versatility, this module can be further integrated with a switchable filter device or a multi-wavelength composite LED chip, thereby enabling a single system to adapt to a variety of photosensitizers with different optical properties.

[0040] 3. Photosensitizer storage and delivery module This module is responsible for the safe storage and accurate delivery of photosensitizers.

[0041] ① Light-proof container: Utilizing disposable, pre-filled syringes or flexible storage bags wrapped in aluminum foil, ensuring complete light protection for the photosensitizer during storage and delivery to prevent pre-activation and degradation. The container is pre-sealed with a clinically approved, sterile solution of the photosensitizer at a specific concentration. The container can be set to storage temperatures, including room temperature (25°C) and refrigerated (4°C), for short-term storage requirements or long-term surgical treatment needs.

[0042] ② Precision fluid pump: A high-precision, low-pulsation syringe pump or peristaltic pump is used, with a wide flow rate control range (e.g., 0.1 mL / min to 5.0 mL / min) and a stability error of less than ±5%. This pump is one of the key actuators for achieving stable ROS output.

[0043] 4. Reaction chamber This is one of the core innovative components of the present invention, which is a miniaturized, high-efficiency photochemical reactor located inside the conduit through which the photosensitizer solution flows and is activated.

[0044] ① Computational Fluid Dynamics (CFD) Optimization Design: The three-dimensional geometry of the reaction chamber (such as a spherical, cylindrical, or irregularly shaped structure with internal turbulence ridges / spiral guide vanes) is simulated and optimized using CFD multiphysics simulation software (such as ANSYS Fluent) through flow-optic coupling simulation. The optimization objectives are: maximizing light energy utilization, ensuring uniform fluid illumination, and matching the average residence time of the photosensitizer in the chamber with the time required for full activation.

[0045] ② High reflectivity inner wall: The inner surface of the reaction chamber is coated with a high diffuse reflectivity coating (such as spectral grade barium sulfate, magnesium oxide or metal vacuum coating), which can efficiently reflect scattered light back to the center of the reaction chamber, significantly improving the light utilization efficiency, thereby generating a high concentration of ROS with a low input light power.

[0046] ③ Performance output: The optimized reaction chamber can continuously generate effective ROS concentrations at the micromolar (µM) to millimole (mM) level at its outlet, which is sufficient to rapidly kill various multidrug-resistant bacteria.

[0047] 5. Control Unit This unit is the "brain" of the system, enabling automated, intelligent, and highly safe treatment.

[0048] ① Central Processing and Coordination Control: The core is an embedded microprocessor (MCU) or programmable logic controller (PLC) running dedicated control software. It is responsible for receiving user instructions and coordinating the switching, wavelength, and power of the light source module, as well as the switching and flow rate of the precision fluid pump, to ensure precise synchronization between the two.

[0049] ② Closed-loop feedback control system: Integrates multiple sensors to form an intelligent closed-loop control loop, including: Pressure sensor: Monitors intracavitary pressure in real time. If the pressure exceeds a preset safety threshold, the system automatically reduces the perfusion flow rate or stops the pumping to prevent tissue damage.

[0050] Optical sensor: Located near the reaction chamber outlet, it utilizes a specific fluorescent probe (such as SOSG) to detect singlet oxygen. 1 The concentration of generated ROS can be monitored in real time using technologies such as 02 or electron spin resonance (ESR), and fed back to the control system to dynamically adjust the optical power or flow rate to ensure the stability and consistency of ROS output.

[0051] Temperature sensor: Monitors the temperature of the reaction chamber and the end of the conduit to prevent the solution from overheating due to photothermal effect.

[0052] ③ Intelligent Monitoring and Evaluation Subsystem (Advanced Functions): Infection boundary localization function: The system can emit low-power diagnostic light and detect the intensity and distribution differences of characteristic fluorescence signals of photosensitizers in infected and normal tissues to help define the precise boundary of the infected area, providing spatial navigation for precise targeted treatment.

[0053] Real-time efficacy assessment function: Real-time bioluminescent detection of adenosine triphosphate (ATP) in the fluid drained from the outflow cavity. By monitoring the dynamic decay rate of ATP concentration in the fluid, the bactericidal effect can be quantitatively assessed in near real-time, providing an objective and quantitative basis for determining the treatment endpoint (such as achieving a bactericidal rate of 99.9%).

[0054] This invention also provides an antibacterial photodynamic therapy device that integrates all the aforementioned system components and modularly integrates them into a portable or cart-type main unit. The device includes a human-machine interface (such as a touchscreen) for centrally displaying all status information and alarm information, and receiving operator commands, forming a complete and independent integrated medical device product.

[0055] In addition, the present invention also provides a typical workflow of the system, specifically including the following steps: (1) Catheter placement and positioning: Under the guidance of medical imaging (such as ultrasound or CT), the distal part of the sterile packaged catheter is percutaneously punctured or placed intraoperatively into the core area of ​​the target body cavity (such as the abdominal cavity, pleural cavity or abscess cavity) and properly fixed.

[0056] (2) System Connection and Initialization: Connect the proximal interface of the catheter to the external unit of the system. Install the light-shielding container pre-filled with photosensitizer. Based on the target pathogen species, infection severity, and characteristics of the selected photosensitizer, set individualized treatment parameters on the control unit touchscreen (e.g., photosensitizer concentration 20µg / mL, perfusion flow rate 1.2mL / min, illumination wavelength 530nm, light power density 150mW / cm², target ROS concentration >100μM).

[0057] (3) Start the treatment cycle: After confirming that the parameters are correct, start the system. The precision fluid pump starts working and pumps the photosensitizer solution into the inflow chamber at the set flow rate.

[0058] (4) In-situ activation and targeted delivery: When the photosensitizer solution flows through the CFD-optimized reaction chamber, the light source module instantly activates the photosensitizer according to preset parameters, efficiently generating a high concentration of ROS. This process is carried out entirely in a closed tubing system outside the body or near the body. Subsequently, the solution rich in highly active ROS is released directly and instantly to the deep infection site through the perfusion micropore at the distal end of the catheter within milliseconds after generation, achieving precise targeting of pathogens.

[0059] (5) Synchronous drainage and pressure management: While the treatment fluid is being infused, the original accumulated fluid and waste fluid after the reaction are continuously drained out of the body cavity through active negative pressure drainage or passive gravity drainage to maintain the stability of the cavity environment, and pressure sensors are used for real-time safety monitoring.

[0060] (6) Real-time monitoring and adaptive adjustment: Throughout the treatment process, the control system continuously receives feedback signals from ROS sensors, pressure sensors, etc. Based on the built-in intelligent algorithm, the system can dynamically fine-tune the light irradiation power and / or pump flow rate to cope with possible fluctuations and ensure stable and efficient ROS output throughout the treatment process.

[0061] (7) Treatment termination and system flushing: Once the preset treatment time is reached or satisfactory sterilization is confirmed by real-time ATP monitoring, the system will automatically or manually terminate the treatment. Subsequently, the system will automatically switch the fluid source and use sterile saline or buffer solution to thoroughly flush the entire fluid tubing and catheters to prevent residual photosensitizer or ROS from affecting subsequent operations.

[0062] (8) Sequential synergistic therapy: After PDT treatment, one or more conventional antibacterial drugs can be infused or injected into the lesion area immediately through the inflow lumen of the same catheter. Since aPDT has already disrupted the bacterial biofilm structure and reversed its drug resistance, low doses of antibacterial drugs can exert a powerful synergistic bactericidal effect, thereby significantly improving the overall efficacy and extending the lifespan of existing antibiotics.

[0063] To further illustrate the specific embodiments of the present invention in detail, specific examples are provided below.

[0064] Example 1: A light-controlled catheter delivery system for treating complicated intra-abdominal infections (cIAI) This embodiment provides a preferred implementation of the present invention, and the system is specifically optimized for complicated intra-abdominal infection (cIAI) caused by end-stage liver disease (ESLD) complicated by multidrug-resistant bacteria.

[0065] 1. System Overall Structure and Workflow Please see the appendix Figure 1 , 2 3. The system mainly consists of the following parts: a flexible multi-lumen catheter implanted in the body, an external control and delivery host, and fluid pipelines and electrical signal cables connecting the two.

[0066] The basic workflow is as follows: A precision fluid pump within the in vitro control and delivery unit pumps the photosensitive drug solution out and delivers it to the catheter via fluid tubing. As the solution flows through the reaction chamber at the distal end of the catheter, it is activated by a light source module integrated on the catheter, instantly generating reactive oxygen species (ROS). Subsequently, the activated, ROS-rich solution is directly infused into the abdominal cavity infection site, while simultaneously draining existing fluid accumulation in the abdominal cavity to maintain pressure balance. The entire process is automatically controlled and monitored in real time by the system control unit of the main unit.

[0067] 2. Detailed implementation methods of each component 1) Flexible multi-lumen catheter body: The catheter body is approximately 35cm in total length to accommodate percutaneous catheter placement. Its outer diameter is 4.0mm (approximately 12Fr), and it is internally divided into three independent channels: Inflow chamber (101) (approximately 1.2 mm in diameter, responsible for delivering the activated ROS solution); Outflow cavity (102) (approximately 1.5 mm in diameter, slightly larger than the inflow cavity to facilitate smooth drainage and prevent blockage); Cable cavity (103) (approximately 0.8 mm in diameter, used to accommodate a miniature wire connected to a remote light source).

[0068] The distal portion of the catheter body (104): the functional execution area, approximately 5 cm long. It is manufactured in one piece using medical-grade thermoplastic polyurethane (TPU, Shore hardness 85A) through high-precision fused deposition modeling (FDM) 3D printing technology, ensuring structural integrity and complex internal geometry.

[0069] On the distal sidewall: three sets of perfusion micropores (105) are spirally arranged axially, each set containing four micropores with a diameter of 100 μm, with the pore openings facing different directions to ensure that the ROS solution can diffuse in a vortex pattern, covering a larger infected area. At about 2 cm from the top, a drainage opening (106) is provided, which is embedded with an anti-backflow valve (such as a duckbill valve) to prevent tissue debris from clogging the opening.

[0070] The proximal portion of the catheter body is designed with a standardized three-way Luer lock connector, corresponding to the inflow cavity (101) and outflow cavity (102) interfaces, as well as a waterproof sealing interface reserved for cables.

[0071] 2) Light source module: This embodiment employs an integrated light source solution. Inside the distal portion (104) of the catheter body, a ring-shaped micro-LED array (201) is encapsulated. This array consists of 24 surface-mount green LED chips (peak wavelength 532±5nm) soldered at equal intervals onto a flexible printed circuit board (FPC), the wavelength of which matches the absorption peak of the photosensitive drug hematoporphyrin monomethyl ether (HMME).

[0072] Optical performance: The LED array can provide a continuously adjustable optical power density of 5 to 150 mW / cm² in its surrounding central area at the rated operating current.

[0073] Heat dissipation and encapsulation: The LED array is completely encapsulated with medical-grade silicone potting compound with high thermal conductivity, which not only achieves electrical insulation and physical protection, but also rapidly conducts the generated heat to the flowing liquid and carries it away, ensuring that the local temperature is always below the safe threshold of 41°C.

[0074] Power supply and control: The LED array is connected to the constant current drive circuit inside the external host via an extremely thin coaxial cable passing through the cable cavity (103), which is precisely controlled by the system control unit.

[0075] 3) Photosensitizer storage and delivery module: This module is integrated into the in vitro host unit. The light-shielding container is a 50mL pre-filled, light-proof glass syringe, pre-sealed with 1.0mg / mL HMME sterile injection solution. The syringe barrel has graduation markings and is equipped with an electromagnetic shield to prevent external interference. The precision fluid pump is a new type of injection pump driven by a high-precision stepper motor, with a linear displacement resolution of 0.1µm and a corresponding flow rate adjustment accuracy of ±0.01mL / min. The flow rate control range of this pump is 0.2mL / min to 3.0mL / min, fully meeting the flow rate requirements for intraperitoneal perfusion.

[0076] 4) Reaction chamber (400): It is a cylindrical cavity located inside the distal portion (104) of the catheter body and surrounded by an LED array (201), with a length of 8 mm and a diameter of 2.0 mm.

[0077] CFD optimization design: The fluid dynamics and optical radiation transmission within the cylindrical cavity were coupled and simulated using ANSYS Fluent software. The simulation results show that at the set flow rate (1.0 mL / min), the fluid forms a stable laminar flow within the cavity, but its hydraulic residence time (τ) exceeds the theoretical time (approximately 0.5 seconds) required for the HMME to be fully activated at this optical power.

[0078] Inner wall treatment: The inner wall of the reaction chamber (400) is coated with a high-purity gold film of about 500 nm thick by magnetron sputtering. The gold film has extremely high reflectivity (>98%) near the wavelength of 532 nm, which can efficiently reuse the light that penetrates the liquid layer or is reflected from the inner wall, making the light field distribution in the entire chamber extremely uniform and without obvious irradiation dead angles.

[0079] Performance verification: In in vitro testing, when 20 µg / mL HMME solution was used, the flow rate was 1.0 mL / min, and the light power density was 100 mW / cm², the concentration of reactive oxygen species (ROS) at the outlet of the reaction chamber was stable at 85 ± 5 µM using the H2DCFDA fluorescent probe method, and the concentration fluctuation was less than 5% within 30 minutes of continuous operation.

[0080] 5) Control Unit (500) and Monitoring System: These are core boards embedded in the host computer.

[0081] Main control program: The control unit (500) runs a real-time operating system (RTOS) responsible for executing user instructions, coordinating the work of various modules, processing sensor data and running control algorithms.

[0082] Human-machine interface: The front of the main unit is equipped with a 7-inch color touch screen, which is used to display real-time parameters (current flow rate, light power, intracavitary pressure, real-time estimated ROS concentration, perfused volume, irradiated light energy), alarm information (pressure over-limit, abnormal ROS concentration, tubing blockage, excessive temperature, etc.) and treatment curves (real-time plotting of the trend of ROS concentration and intracavitary pressure over time).

[0083] Closed-loop feedback control system: including pressure monitoring and ROS concentration monitoring. Pressure monitoring: A miniature fiber optic pressure sensor is integrated near the drainage opening (106) of the catheter. Its measurement range is -10 to +50 mmHg, with an accuracy of ±1 mmHg. The control unit (500) sets the upper limit of pressure safety to 25 mmHg. Once the pressure exceeds this value, the system will immediately sound an audible and visual alarm and automatically reduce the perfusion flow rate to 0.5 mL / min. If the pressure does not decrease within 5 seconds, the perfusion will be paused. ROS concentration monitoring: A miniature fluorescence detection module is installed at the outlet of the reaction chamber (400). This module contains a miniature LED that emits a specific wavelength (e.g., 504 nm) and a photodiode that detects fluorescence at a specific wavelength (e.g., 525 nm). A low concentration of H2DCFDA probe is continuously injected into the system, and its fluorescence intensity is proportional to the ROS concentration. The control unit (500) converts the fluorescence signal into a real-time ROS concentration value through a calibration curve, and uses this feedback signal to dynamically fine-tune the drive current of the LED array (201) through a proportional-integral (PI) controller to stabilize the ROS concentration at the user-set target value (e.g., 50-150µM).

[0084] Intelligent Monitoring Subsystem (Advanced Functions): Includes infection boundary localization and real-time efficacy assessment. Infection Boundary Localization: Before treatment begins, the system can switch to "diagnostic mode." In this mode, the LED array (201) emits low-power (5mW / cm²) pulsed light, while the same fluorescence detection module detects the HMME fluorescence signal reflected from the tissue (peak value approximately 620nm). By generating a fluorescence intensity distribution map on the touchscreen, doctors can visually identify high-fluorescence areas (i.e., infection-rich areas), allowing for manual or automatic adjustment of catheter position or perfusion strategy for precise targeting. Real-time Efficacy Assessment: The system is externally connected to a miniaturized ATP bioluminescence detector, which is connected to the drainage tubing of the outflow chamber (102) via a three-way valve. During treatment, the system automatically collects a small amount of drainage fluid for ATP detection at regular intervals (every 5 minutes). The detection results are transmitted to the control unit (500) in real time, and an ATP decay curve is plotted. When the RLU value drops below 0.1% of the initial value and remains stable, the system can alert the operator that "the treatment endpoint may have been reached," providing important reference for clinical decision-making.

[0085] Example 2: This example describes in detail the typical workflow of the system in Example 1.

[0086] (1) Preoperative preparation and system self-test: Remove the catheter from the sterile packaging, ensuring it is intact. Install the light-shielded syringe pre-filled with HMME injection solution (1.0 mg / mL) into the slot of the precision fluid pump, and connect all fluid lines and electrical signal cables. Turn on the main unit power, and the system will perform a self-test program, including: checking the status of each sensor, calibrating the zero point and range of the fluorescence detection module, and testing the LED array (201) and the function of the precision fluid pump. After the self-test passes, the touch screen will display "System Ready".

[0087] (2) Image-guided catheter placement: Under ultrasound guidance, using the Seldinger technique, the distal portion (104) of the catheter body is percutaneously punctured and placed in the area with the most abundant peritoneal effusion or the most severe infection in the patient. After confirming the ideal catheter position, it is sutured and fixed at the skin inlet. The Luer lock connector at the proximal end of the catheter body is securely connected to the corresponding interface of the main unit.

[0088] (3) Individualized setting of treatment parameters: According to the specific situation of the patient's infection (such as the type of pathogen, the characteristics of ascites, and the extent of infection), the treatment parameters are set on the touch screen: the photosensitizer concentration is selected as "stock solution" (1.0 mg / mL) or diluted; the target ROS concentration is set to 100 µM (for common MDR ESKAPE pathogens); the perfusion flow rate is initially set to 1.0 mL / min; the light parameters are automatically locked at 532 nm wavelength and the light power density is initially set to 120 mW / cm²; the upper limit of pressure safety is set to 25 mmHg; the total treatment dose is set to the planned total perfusion volume, for example, 50 mL.

[0089] (4) Start Treatment and Real-time Monitoring: After confirming that all parameters are correct, click the "Start Treatment" button on the touchscreen. The system runs automatically according to the preset program: the precision fluid pump starts and pumps HMME solution at a flow rate of 1.0 mL / min. When the system detects that the reaction chamber (400) is full of liquid, the LED array (201) automatically lights up and irradiates the flowing solution at a power density of 120 mW / cm². The ROS-rich solution is then infused into the peritoneal cavity. At the same time, the outflow chamber (102) is connected to a negative pressure drainage device (pressure set to -5 mmHg) for continuous drainage. Throughout the treatment process, closely observe the real-time data displayed on the touchscreen: confirm that the ROS concentration is stable within the range of 100±10µM; confirm that the intraperitoneal pressure is maintained within the safe range of 10-15 mmHg; observe the ATP decay curve and evaluate the bactericidal effect.

[0090] (5) Closed-loop adaptive adjustment: If the system detects that the ROS concentration drops to 90µM, the PI controller in the control unit (500) will automatically and slightly increase the driving current of the LED array (201) to increase the light power density to 125mW / cm² until the ROS concentration returns to the target value. If the intraperitoneal pressure rises to 22mmHg (close to the safety threshold) due to slightly slower drainage, the system will issue an early warning and automatically reduce the perfusion flow rate slightly to 0.9mL / min until the pressure drops below 18mmHg.

[0091] (6) Treatment termination and tubing flushing: When the preset 50 mL volume of infusion is completed, or when ATP monitoring shows that the sterilization effect has reached the plateau phase, the system will automatically stop light exposure and infusion, and issue a "treatment complete" prompt. At this time, click the "fluid flushing" button, and the system will automatically switch the fluid source and use the pre-connected 500 mL sterile saline to flush the entire fluid tubing and catheter body at a high flow rate of 3.0 mL / min for about 3 minutes to ensure that there is no photosensitizer residue.

[0092] (7) Sequential antibiotic synergistic therapy (optional): After aPDT treatment and flushing, remove the HMME syringe and replace it with a syringe containing a sensitive antibiotic (selected based on drug sensitivity results). Through the inflow lumen (101) of the same catheter, slowly infuse the antibiotic solution into the abdominal infection foci that have been "pretreated" by aPDT, utilizing its synergistic effect to further eliminate residual bacteria.

[0093] Example 3: Another implementation of the system (fiber optic guide type). This example provides another implementation method, the main difference from Example 1 is the light source module.

[0094] In this embodiment, the light source module is no longer integrated onto the catheter body, but instead uses an external multi-wavelength laser (capable of outputting wavelengths of 405nm, 532nm, and 630nm). The laser is transmitted through a 400μm diameter multimode silica optical fiber. A miniature beam-shaping lens and a reflecting prism are located inside the distal end of the catheter body to deflect the collimated laser beam from the optical fiber by 90 degrees, transforming it into lateral illumination that uniformly covers a modified flattened circular reaction cavity (400°).

[0095] The advantages of this solution are that it allows for higher light source power and easier switching of treatment wavelengths, simply by switching the laser externally or using a tunable laser. It is particularly suitable for scientific research or scenarios requiring multiple photosensitizers.

[0096] In summary, through the specific embodiments described above, this invention provides a complete, detailed, and highly operable technical solution. This solution not only innovatively solves the challenge of aPDT treatment for deep infections, but also, through its highly integrated, intelligent, and automated design, makes it highly suitable for future clinical translation and commercial applications.

[0097] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, apparatus, article, or method that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, apparatus, article, or method. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, apparatus, article, or method that includes that element.

[0098] The above description is merely a preferred embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural or procedural transformations made based on the content of the present invention's specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of the present invention.

Claims

1. A light-controlled catheter system for targeted delivery of reactive oxygen species to a deep-seated infection site within a body cavity of a patient based on targeted delivery of antibacterial photodynamic therapy, characterized in that, The system comprises: a flexible catheter body for implantation or insertion into a body cavity, the flexible catheter body having a distal end portion and a proximal end portion, and internally provided with at least one inflow lumen for delivering photosensitive drug to a focus of infection and at least one outflow lumen for leading effusion in the body cavity away from the focus of infection; wherein the distal end portion of the flexible catheter body is provided with one or more perfusion openings in fluid communication with the inflow lumen, and one or more drainage openings in fluid communication with the outflow lumen; a light source module for generating light of specific wavelengths capable of exciting photosensitive drug molecules of different properties; the light source module is integrated in the distal end portion of the flexible catheter body, or is optically coupled with the distal end portion of the flexible catheter body through an optical transmission component, ensuring that the light generated thereby can irradiate the photosensitive drug solution flowing through the predetermined area; a photosensitive drug storage and delivery module, comprising a light-shielded container for storing photosensitive drug solution and a fluid pump in communication with the light-shielded container; the fluid pump is operably connected to the inflow lumen inlet of the proximal end portion of the flexible catheter body through a fluid pipeline, for pumping the photosensitive drug solution into the inflow lumen at a controlled flow rate; a reaction cavity, as a closed cavity or flow channel area, is provided in the distal end portion of the flexible catheter body, so that the photosensitive drug solution flowing through the inflow lumen must pass through the reaction cavity; the reaction cavity is used to receive irradiation from the light source module when the photosensitive drug solution flows through, to activate the photosensitive drug in situ and generate reactive oxygen in situ before the photosensitive drug solution exits the perfusion opening of the flexible catheter body; a control unit in signal connection with the light source module and the fluid pump in the photosensitive drug storage and delivery module, for independently or cooperatively controlling the operating parameters of the light source module and the delivery flow rate of the fluid pump.

2. The light-controlled targeted delivery based antibacterial photodynamic therapy catheter system according to claim 1, wherein, The flexible catheter body is integrally formed by additive manufacturing technology from biocompatible medical-grade polymer materials, such as thermoplastic polyurethane, silicone rubber or polyethylene; the proximal end portion of the flexible catheter body is provided with a standardized luer connector or threaded interface for connection with a standard abdominal drainage tube or infusion pipeline.

3. The light-controlled targeted delivery based antibacterial photodynamic therapy catheter system according to claim 1, wherein, The light source module comprises a light-emitting diode array and a wavelength selection element; the light-emitting diode array is arranged around the outer periphery of the reaction cavity in the distal end portion of the flexible catheter body, or is embedded in the tube wall constituting the reaction cavity; the light-emitting diode array can emit monochromatic light or composite light with wavelengths in the visible light band or near-infrared band; The wavelength selection element is a replaceable optical filter or a wavelength switching device that can be electrically controlled and adjusted by the control unit, to adapt to a variety of photosensitive drugs with different optimal excitation wavelengths.

4. The light activated catheter system for targeted delivery based antibacterial photodynamic therapy according to claim 1, wherein, The geometry of the reaction cavity can guide the photosensitive drug solution to pass through in a predetermined flow state, and ensure that the average residence time of the solution in the cavity is greater than or equal to the minimum illumination time required for the photosensitive drug to be fully activated; The inner surface of the reaction cavity is covered with a high reflectivity material layer, which is one of barium sulfate, titanium dioxide or a metal plating layer, for reflecting the irradiation light back into the reaction cavity to maximize the light energy utilization and ensure uniform illumination of the photosensitive drug solution; The cross-sectional shape of the reaction cavity is circular, elliptical or asymmetric with an internal turbulence structure, which is a spiral guide vane or a zigzag concave-convex pattern, for enhancing the turbulence level of the photosensitive drug solution when flowing through to promote its mixing and interaction with the light.

5. The light activated catheter system for targeted delivery based antibacterial photodynamic therapy according to claim 1, wherein, The control unit is configured to implement closed-loop control by receiving feedback signals from one or more sensors to dynamically adjust the operating parameters of the light source module and / or the fluid pump; the sensors include: a flow rate sensor arranged in the fluid conduit or the reaction cavity for real-time monitoring of the flow rates of active oxygen, photosensitive drug and effusion fluid; a pressure sensor arranged at the distal end of the flexible catheter body for real-time monitoring of the pressure in the body cavity; an optical sensor arranged at the outlet of the reaction cavity for indirect monitoring of the concentration of generated active oxygen by fluorescence quantitative intensity analysis or chemical spectrophotometry; The closed-loop control is configured to control the fluid pump to reduce the flow rate or pause when the pressure value monitored by the pressure sensor exceeds a preset safety threshold, and to control the light source module to increase the light power density or control the fluid pump to reduce the flow rate when the active oxygen concentration monitored by the optical sensor is below a preset effective threshold.

6. The light activated catheter system for targeted delivery based antibacterial photodynamic therapy according to claim 1, wherein, The light-shielded container in the photosensitive drug storage and delivery module is a disposable, pre-filled syringe or flexible bag, which is pre-packaged with a photosensitive drug solution, and the photosensitive drug is one of hematoporphyrin monomethyl ether, talaporfin sodium or methylene blue.

7. The light activated catheter system for targeted delivery based antibacterial photodynamic therapy according to claim 1, wherein, It also includes an integrated monitoring module, which includes: a diagnostic light source for emitting a specific wavelength light beam capable of exciting the photosensitive drug to produce characteristic fluorescence; a fluorescence detector for detecting the intensity of the fluorescence signal reflected back from the infection focus; the control unit identifies the boundary of the infected area according to the spatial distribution or intensity change of the fluorescence signal to plan or adjust the illumination parameters of the light source module and / or the perfusion path of the fluid pump; a bioluminescence detector or a rapid adenosine triphosphate concentration detection unit for real-time analysis of the effusion drained from the effusion channel, which quantitatively evaluates the sterilization efficiency by monitoring the decay rate of adenosine triphosphate concentration therein.

8. An antibacterial photodynamic therapy apparatus comprising the light-controlled catheter system for targeted delivery of antibacterial photodynamic therapy according to any one of claims 1 to 7, characterized in that, The device includes a main box body carrying the control unit, the photosensitive drug storage and delivery module, and a human-machine interaction interface connected with the control unit, which is used to display system status, treatment parameters and alarm information, and receive user's operation instructions.

9. A method of controlling a light-controlled catheter system for targeted delivery-based antimicrobial photodynamic therapy according to any one of claims 1 to 7, characterized in that The control method includes the following steps: (1) The control unit starts the fluid pump to make the photosensitive drug solution flow through the inflow channel at a preset initial flow rate; (2) When the photosensitive drug solution flows through the reaction cavity, the control unit starts the light source module, and the light source module emits excitation light according to the preset parameters to activate the photosensitive drug solution before it flows out of the perfusion opening, thereby generating reactive oxygen; (3) During operation, the control unit and the sensor monitor key parameters in real time, and use a closed-loop control algorithm to dynamically adjust the flow rate and / or light parameters.

10. The control method according to claim 9, characterized by, In step (2), when the light source module is started, the flow rate of the fluid pump is controlled in the range of 0.1 mL / min to 5 mL / min, and the light power density of the light source module is controlled in the range of 10 mW / cm² to 200 mW / cm², so as to ensure that the concentration of reactive oxygen generated in the reaction cavity reaches the micromolar level or above and the potential damage to normal tissues is minimized.

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