A mouse liver fibrosis dosing and monitoring integrated device and methods of use thereof

Abstract

The application relates to a mouse liver fibrosis dosing and monitoring integrated device and a use method thereof, and belongs to the technical field of experimental animal automatic dosing and monitoring equipment. The mouse liver fibrosis dosing and monitoring integrated device and the use method thereof comprise a machine shell, a micro-injection pump module is fixedly installed at the top of the machine shell, and a central controller is fixedly installed in the machine shell. A valve shell, a valve core and a transition flow channel in a multi-drug switching actuator form a zero dead volume public flow channel, and a stepping drive motor is used for automatically switching different liquid channels, so that carbon tetrachloride liquid, calcitriol liquid and physiological saline flushing liquid can complete automatic low-residue switching on the same micro-injection pump module. The problems of complex operation, liquid residue and cross contamination in the background technology during long-term drug administration are solved, and the continuous stability of long-term liver fibrosis modeling experiments is improved.

Description

Technical Field

[0001] This invention relates to the field of automated drug delivery and monitoring equipment for laboratory animals, and in particular to an integrated device for drug delivery and monitoring of liver fibrosis in mice and its method of use. Background Technology

[0002] Mouse liver fibrosis models are typically induced by intraperitoneal injection of carbon tetrachloride (CCl4), and long-term intervention with drugs such as calcitriol is often performed during the modeling process. Current experimental procedures mostly employ manual intraperitoneal injection or conventional infusion pumps for drug delivery.

[0003] The above-mentioned administration methods have the following main problems in actual use: 1. Existing multi-drug intraperitoneal injection procedures usually require manual switching of syringes, three-way valves, or multiple independent injection pumps, which is not only complicated to operate, but also prone to drug residue in the common flow channel, and cross-contamination is likely to occur during long-term use. 2. Existing automated intraperitoneal injection equipment usually only has basic injection function and lacks the ability to identify in real time whether the needle tip has actually entered the peritoneal cavity. This can easily lead to problems such as accidental injection into subcutaneous tissue, intestinal lumen or solid organs, affecting experimental safety and model stability. 3. Existing drug delivery and monitoring systems are usually independent of each other, making it impossible to control the injection pump to stop in case of abnormal injection conditions. At the same time, there is a lack of dynamic auxiliary monitoring methods based on the injection process during long-term experiments, making it difficult to continuously analyze the state of the liver fibrosis model.

[0004] Therefore, it is necessary to provide an integrated device and method for administering and monitoring drug for mouse liver fibrosis based on dynamic pressure response closed-loop control, addressing the aforementioned problems in the prior art. Summary of the Invention

[0005] Therefore, it is necessary to address the problems in existing mouse liver fibrosis experiments, such as the risk of cross-contamination from long-term intraperitoneal injection of multiple drugs, the lack of real-time injection safety identification capabilities, and the inability to link the drug administration and monitoring systems for control. A device integrating drug administration and monitoring for mouse liver fibrosis, along with its usage method, should be provided.

[0006] An integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control includes a housing. A micro-injection pump module is fixedly installed on the top of the housing. A central controller is fixedly installed inside the housing. The output end of the micro-injection pump module is connected to a multi-drug switching actuator. The output end of the multi-drug switching actuator is connected to a dynamic pressure acquisition module. The output end of the dynamic pressure acquisition module is connected to an abdominal indwelling catheter system. The end of the abdominal indwelling catheter system is used to extend into the abdominal cavity of the experimental mouse. The dynamic pressure acquisition module is electrically connected to the central controller and is used to acquire the dynamic pressure waveform inside the abdominal indwelling catheter system in real time. The central controller has an injection status recognition system running inside. The injection status recognition system is used to identify the tissue space status of the needle tip based on the dynamic pressure waveform, and to control the injection status of the micro-injection pump module and the switching status of the multi-drug switching actuator according to the recognition result. The injection state recognition system includes a dynamic pressure waveform database, a rule threshold discrimination module, a machine learning-assisted correction module, and an injection state machine control module. The injection state machine control module includes the puncture establishment stage, the micro-injection stage, the dynamic response acquisition stage, the safety judgment stage, the formal injection stage, the aspiration verification stage, and the flushing and sealing stage.

[0007] In one embodiment, the multi-drug switching actuator includes a valve housing and a stepper motor. The valve housing is fixedly installed inside the housing, and the stepper motor is fixedly installed on one side of the valve housing. The output shaft of the stepper motor is connected to the drive end of the valve housing.

[0008] In one embodiment, the valve housing has multiple liquid inlet ports and a common liquid outlet port on its surface. A valve core is rotatably connected inside the valve housing. A through-type transition channel is provided inside the valve core. The stepper drive motor is used to drive the valve core to rotate, so that the transition channel is connected to different liquid inlet ports respectively, and is connected to the dynamic pressure acquisition module through the common liquid outlet port.

[0009] In one embodiment, the plurality of inlet ports are respectively connected to a carbon tetrachloride syringe, a calcitriol syringe, a saline syringe, and a spare syringe via infusion tubing.

[0010] In one embodiment, a zero-dead-volume common flow channel is formed between the transition channel and the common liquid outlet interface. The total volume of the common flow channel is no more than 5 μL, and the inner wall of the common flow channel adopts a rounded transition structure.

[0011] In one embodiment, the dynamic pressure acquisition module includes multiple pressure sensors, which are installed in parallel between the multi-drug switching actuator and the intraperitoneal catheter system. The pressure sensors are electrically connected to the central controller, and the range of the pressure sensors is 0-500 kPa, with a sampling frequency of not less than 100 Hz.

[0012] In one embodiment, the peritoneal catheter system includes a flexible silicone catheter, a subcutaneous fixation anchor, an anti-backflow check valve, and an anti-torsion buffer section. One end of the flexible silicone catheter is connected to a dynamic pressure acquisition module, and the other end of the flexible silicone catheter is used to extend into the peritoneal cavity of the experimental mouse. The subcutaneous fixation anchor is fixedly installed on the outside of the flexible silicone catheter. The anti-backflow check valve is installed in parallel inside the flexible silicone catheter, and the anti-torsion buffer section is located on the outside of the flexible silicone catheter.

[0013] In one embodiment, the dynamic pressure waveform database includes normal intra-abdominal pressure waveforms, subcutaneous tissue pressure waveforms, intestinal pressure waveforms, and solid organ pressure waveforms; the rule threshold discrimination module is used to make a preliminary judgment on the current injection state based on peak pressure, pressure rise rate, fluctuation frequency, and pressure integral area; the machine learning-assisted correction module is used to perform a secondary correction on the rule threshold discrimination results based on a support vector machine classification model or a convolutional neural network classification model.

[0014] In one embodiment, the micro-injection stage of the injection state machine control module is used to control the micro-injection pump module to inject 1-3 μL of test solution into the abdominal cavity; the dynamic response acquisition stage is used to control the dynamic pressure acquisition module to acquire the corresponding dynamic pressure waveform; the aspiration verification stage is used to control the micro-injection pump module to perform a 0.01-0.02 mL aspiration action, and the central controller evaluates the abdominal cavity compliance recovery status according to the pressure recovery curve; the central controller is used to record the long-term dynamic pressure change trend and generate auxiliary analysis results of the liver fibrosis model status.

[0015] A method for using an integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control includes the following steps: S1. Establishing an intraperitoneal catheter: The intraperitoneal catheter system was implanted into the peritoneal cavity of the experimental mice and fixed by a subcutaneous fixation anchor plate; S2. Set dosing parameters: Set the dosing cycle, injection flow rate, test volume and alarm threshold through the central controller; S3. Switching the target liquid: The central controller controls the stepper motor to drive the valve core to rotate, so that the transition channel is connected to the target liquid channel; S4. Perform micro-volume injection: The micro-volume injection pump module first injects 1-3μL of test solution into the abdominal cavity, and the dynamic pressure acquisition module simultaneously acquires the pressure waveform. S5. Execution Status Recognition: The rule threshold discrimination module first performs a preliminary analysis of the pressure waveform, and then the machine learning-assisted correction module further corrects the discrimination results; S6. Perform formal injection: When the judgment result is normal peritoneum, the micro-injection pump module performs formal drug injection. S7. Abnormal protection: When the judgment result is subcutaneous tissue, intestinal lumen or solid organ, the central controller immediately stops the injection and triggers an audible and visual alarm. S8. Perform compliance verification: After the formal injection is completed, perform aspiration. The central control unit assesses the abdominal cavity compliance recovery status based on the pressure recovery curve. S9. Perform flushing and tube sealing: The central controller switches the valve body to the saline flushing channel to perform common flow channel flushing and tube sealing. S10. Record trend data: The central controller records the long-term dynamic pressure change trend and generates auxiliary analysis results of the liver fibrosis model status.

[0016] 1. The above-mentioned integrated drug delivery and monitoring device for mouse liver fibrosis and its usage method form a closed-loop linkage control between the injection status recognition system, the micro-injection pump module, and the multi-drug switching actuator. When the device detects an abnormal injection status, it can automatically stop the injection and switch to the flushing standby state. At the same time, the central controller can continuously record the long-term dynamic pressure change trend and generate auxiliary analysis results of the liver fibrosis model status. This solves the problems of the independent drug delivery system and monitoring system in the background technology and the lack of dynamic auxiliary monitoring capabilities in long-term experiments, and realizes integrated closed-loop control of drug delivery, monitoring and abnormal protection. 2. By forming a zero-dead-volume common flow channel through the valve body, valve core, and transition flow channel in the multi-drug switching actuator, and automatically switching different drug channels through a stepper drive motor, carbon tetrachloride solution, calcitriol solution, and physiological saline flushing solution can be automatically switched with low residue on the same micro-injection pump module. This solves the problems of complex operation, drug residue, and cross-contamination in the long-term administration of multiple drugs in the background technology, and improves the continuous stability of long-term liver fibrosis modeling experiments. 3. The dynamic pressure waveform inside the intraperitoneal catheter system is acquired in real time by the dynamic pressure acquisition module. The dynamic pressure waveform is then jointly analyzed by the rule threshold discrimination module and the machine learning-assisted correction module in the injection status recognition system. This enables the device to identify whether the needle tip is in the normal abdominal cavity, subcutaneous tissue, intestinal cavity or solid organ before the formal injection. This solves the problem of automatic intraperitoneal injection devices in the background technology lacking real-time tissue space recognition capability and being prone to mis-injection, thus improving the safety and recognition accuracy during the intraperitoneal injection process. Attached Figure Description

[0017] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0018] Figure 1 This is a schematic diagram of the overall structure of the present invention; Figure 2 This is a schematic diagram of the multi-drug switching actuator in this invention; Figure 3 This is a partial cross-sectional schematic diagram of the multi-drug switching actuator in this invention; Figure 4 This is a partial cutaway schematic diagram of the dynamic pressure acquisition module and the intraperitoneal indwelling catheter system in this invention; Figure 5 This is a system flowchart of the present invention; Figure 6 This is a schematic diagram of the structure and layout logic of the injection state recognition system in this invention; Figure 7 This is a schematic diagram of the operation steps of the present invention; Figure label: 100. Housing; 200. Micro-infusion pump module; 300. Central controller; 400. Multi-drug switching actuator; 410. Valve housing; 420. Stepper drive motor; 430. Inlet port; 440. Common outlet port; 450. Valve core; 460. Transition flow channel; 500. Dynamic pressure acquisition module; 510. Pressure sensor; 600. Abdominal indwelling catheter system; 610. Flexible silicone catheter; 620. Subcutaneous fixation anchor plate; 630. Anti-backflow check valve; 640. Anti-torsion buffer section; 700. Injection status recognition system; 710. Dynamic pressure waveform database; 720. Rule threshold discrimination module; 730. Machine learning-assisted correction module; 740. Injection state machine control module. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] It should be noted that when a component is referred to as being "fixed to" or "set on" another component, it can be directly on the other component or there may be an intermediate component. When a component is considered to be "connected to" another component, it can be directly connected to the other component or there may be an intermediate component present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used in this specification are for illustrative purposes only and do not represent the only possible implementation.

[0021] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this invention, "a plurality of" means at least two, such as two, three, etc., unless otherwise explicitly specified.

[0022] In this invention, unless otherwise explicitly specified and limited, "above" or "below" the second feature can mean that the first feature is in direct contact with the second feature, or that the first feature and the second feature are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0023] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used in this specification includes any and all combinations of one or more of the associated listed items.

[0024] The following is combined with Figures 1-7 This invention describes the integrated drug delivery and monitoring device for mouse liver fibrosis and its method of use.

[0025] In one embodiment, an integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control includes a housing 100. A micro-injection pump module 200 is fixedly installed on the top of the housing 100. A central controller 300 is fixedly installed inside the housing 100. The output end of the micro-injection pump module 200 is connected to a multi-drug switching actuator 400. The output end of the multi-drug switching actuator 400 is connected to a dynamic pressure acquisition module 500. The output end of the dynamic pressure acquisition module 500 is connected to an intraperitoneal catheter system 600. The end of the intraperitoneal catheter system 600 is used to extend into the abdominal cavity of the experimental mouse. The dynamic pressure acquisition module 500 is electrically connected to the central controller 300. An injection status recognition system 700 runs inside the central controller 300. The multi-drug switching actuator 400, the dynamic pressure acquisition module 500, and the injection status recognition system 700 form a closed-loop linkage control structure, enabling the device to simultaneously complete drug switching, dynamic pressure monitoring, and automatic protection against abnormal states during drug delivery.

[0026] like Figure 2 , Figure 3 , Figure 5 and Figure 6 As shown, the multi-drug switching actuator 400 includes a valve housing 410 and a stepper motor 420. The valve housing 410 is fixedly installed inside the housing 100, and the stepper motor 420 is fixedly installed on one side of the valve housing 410. The output shaft of the stepper motor 420 is connected to the drive end of the valve housing 410. The surface of the valve housing 410 has multiple liquid inlet ports 430 and a common liquid outlet port 440. A valve core 450 is rotatably connected inside the valve housing 410. The valve core 450 has a through-type transition flow channel 460 inside. Motor 420 drives valve core 450 to rotate, so that transition channel 460 is connected to different inlet ports 430 respectively, and connected to dynamic pressure acquisition module 500 through common outlet port 440. Multiple inlet ports 430 are connected to carbon tetrachloride injection syringe, calcitriol injection syringe, normal saline injection syringe and spare syringe respectively through infusion line. A zero dead volume common channel is formed between transition channel 460 and common outlet port 440. The total volume of common channel is not greater than 5μL. The inner wall of common channel adopts arc transition structure.

[0027] like Figure 4 , Figure 5 and Figure 6 As shown, the dynamic pressure acquisition module 500 includes multiple pressure sensors 510. The pressure sensors 510 are installed in parallel between the multi-drug switching actuator 400 and the intraperitoneal indwelling catheter system 600. The pressure sensors 510 are electrically connected to the central controller 300. The pressure sensors 510 are used to acquire the dynamic pressure waveform during the injection process in real time. The range of the pressure sensors 510 is 0-500 kPa, and the sampling frequency of the pressure sensors 510 is not less than 100 Hz.

[0028] like Figure 4 As shown, the intraperitoneal catheter system 600 includes a flexible silicone catheter 610, a subcutaneous fixation anchor plate 620, an anti-backflow check valve 630, and an anti-torsion buffer section 640. One end of the flexible silicone catheter 610 is connected to the dynamic pressure acquisition module 500, and the other end of the flexible silicone catheter 610 is used to extend into the intraperitoneal cavity of the experimental mouse. The subcutaneous fixation anchor plate 620 is fixedly installed on the outside of the flexible silicone catheter 610. The anti-backflow check valve 630 is installed in parallel inside the flexible silicone catheter 610. The anti-torsion buffer section 640 is located on the outside of the flexible silicone catheter 610.

[0029] like Figure 5 and Figure 6As shown, the injection state recognition system 700 includes a dynamic pressure waveform database 710, a rule threshold discrimination module 720, a machine learning-assisted correction module 730, and an injection state machine control module 740. The dynamic pressure waveform database 710 includes normal intra-abdominal pressure waveforms, subcutaneous tissue pressure waveforms, intestinal pressure waveforms, and solid organ pressure waveforms. The rule threshold discrimination module 720 is used to make a preliminary judgment on the current injection state based on peak pressure, pressure rise rate, fluctuation frequency, and pressure integral area. The machine learning-assisted correction module 730 is used to perform a secondary correction on the rule threshold discrimination results based on a support vector machine classification model or a convolutional neural network classification model. The injection state machine control module 740 includes a puncture establishment stage, a micro-injection stage, a dynamic response acquisition stage, a safety judgment stage, a formal injection stage, aspiration verification stage, and a flushing and sealing stage.

[0030] like Figure 5 , Figure 6 and Figure 7 As shown, the usage procedure of this integrated drug delivery and monitoring device for mouse liver fibrosis is as follows: In use, the abdominal indwelling catheter system 600 is first implanted into the abdominal cavity of the experimental mouse and fixed by the subcutaneous fixation anchor plate 620. Subsequently, the dosing cycle, injection flow rate, test injection volume, and alarm threshold are set via the central controller 300; The central controller 300 controls the stepper motor 420 to drive the valve core 450 to rotate, so that the transition channel 460 is connected to the target liquid channel; Before the formal switching of the medication, the central controller 300 prioritizes controlling the valve housing 410 to switch to the saline channel and controls the micro-injection pump module 200 to inject 5-10μL of saline to pre-flushing the common flow channel. Subsequently, the micro-injection pump module 200 first injects 1-3 μL of test solution into the abdominal cavity; The dynamic pressure acquisition module 500 synchronously acquires pressure waveforms; The rule threshold discrimination module 720 first performs a preliminary analysis of the pressure waveform; Subsequently, the machine learning-assisted correction module 730 further corrects the discrimination result; When the determination result is a normal abdominal cavity, the micro-injection pump module 200 performs the formal drug injection. When the determination result is subcutaneous tissue, intestinal lumen or solid organ, the central controller 300 immediately stops the injection and triggers an audible and visual alarm. At the same time, the central controller 300 controls the multi-drug switching actuator 400 to automatically switch to the saline flushing channel for standby. After the formal injection is completed, the micro-injection pump module 200 performs a back-pull action; The central controller 300 assesses the abdominal compliance recovery status based on the pressure recovery curve; Subsequently, the central controller 300 controls the valve housing 410 to switch to the saline flushing channel to perform common flow channel flushing and tube sealing; The central controller 300 continuously records the dynamic pressure change trend at the end of the formal injection and generates auxiliary analysis results of the liver fibrosis model status.

[0031] It should be noted that the physical model of the micro-injection pump module 200 is the Harvard Apparatus PHDUltra Multi-Rack multi-station micro-injection pump system. The core structure of the micro-injection pump module 200 consists of a multi-syringe synchronous mounting bracket, a high-precision stepper drive push rod, an independent linear propulsion mechanism, and a multi-channel linkage control unit, used to realize independent injection of multiple drug solutions, synchronous aspiration, and precise drug delivery control at multiple stations. The physical model of the central controller 300 is the Raspberry Pi Compute Module embedded medical experimental control platform. The core structure of the central controller 300 consists of an ARM embedded processor, a touch-screen human-machine interface, a high-speed data acquisition module, a multi-serial communication module, and a data storage module, used to complete dynamic pressure acquisition, status identification and analysis, closed-loop control calculation, and interactive setting of experimental parameters. The physical model of the stepper drive motor 420 is Oriental Motor. The PKP series two-phase stepper motor, specifically the stepper drive motor 420, comprises a permanent magnet rotor, a phase-splitting stator winding, a precision stepper drive shaft, and a microstepping control unit. It drives the stepper drive shaft to perform high-precision angular rotation via pulse signals, thereby causing the valve core 450 to perform fixed-point switching within the valve housing 410. This achieves precise flow channel communication control between different inlet ports 430 and the common outlet port 440. The pressure sensor 510 is a Honeywell Sensing Solutions TruStability HSC series pressure sensor. Its core structure includes a silicon piezoresistive diaphragm, a miniature pressure acquisition chamber, and a digital signal output unit, used for real-time acquisition of dynamic pressure waveforms within the abdominal cavity. The flexible silicone catheter 610 is an Instech Laboratories product. The SIL series of laboratory animal silicone catheters includes a flexible silicone catheter 610 whose core structure consists of a medical-grade flexible silicone tube and a PTFE low-friction inner liner, designed to reduce the risk of catheter bending and blockage during long-term implantation. The anti-backflow check valve 630 is a Cole-Parmer miniature check valve, whose core structure consists of an elastic valve diaphragm, a micro-pressure opening chamber, and a PEEK valve body, designed to prevent peritoneal fluid from flowing back into the common flow channel.

[0032] The subcutaneous fixation anchor plate 620 is a non-mature custom-made device. It is preferably integrally formed from medical-grade PEEK material, with an overall structure consisting of a disc-shaped fixation base and an annular suture fixation hole. A porous mesh tissue ingrowth zone is provided on the outer edge of the disc to improve long-term implantation stability. The anti-torsion buffer section 640 is also a non-mature custom-made device, preferably encapsulated in TPU flexible material. Its core structure consists of a spiral buffer sheath and a catheter limiting groove, used to reduce the bending stress on the flexible silicone catheter 610 during the activity of experimental mice. The transition channel 460 is a non-mature custom-made device. The microfluidic structure is fabricated such that the transition channel 460 is preferably formed by CNC machining of PEEK material with micropores, with an inner diameter of 0.2-0.35 mm and an overall length of no more than 8 mm. The inner wall adopts a rounded polished transition structure to ensure that the total volume of the common channel is no more than 5 μL. The pressure monitoring chamber inside the dynamic pressure acquisition module 500 is a non-mature customized structure. The pressure monitoring chamber is preferably formed by combining a PEEK cavity and a medical silicone sealing gasket. Its core structure is a straight-through microfluidic channel and a top pressure detection hole to reduce the influence of the additional dead volume on the dynamic pressure waveform during pressure detection.

[0033] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0034] The above-described embodiments are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the appended claims.

Claims

1. A mouse liver fibrosis drug delivery and monitoring integrated device based on dynamic pressure response closed-loop control, characterized in that, The device includes a housing (100), on the top of which a micro-injection pump module (200) is fixedly installed. A central controller (300) is fixedly installed inside the housing (100). The output end of the micro-injection pump module (200) is connected to a multi-drug switching actuator (400). The output end of the multi-drug switching actuator (400) is connected to a dynamic pressure acquisition module (500). The output end of the dynamic pressure acquisition module (500) is connected to an abdominal indwelling catheter system (600). The end of the abdominal indwelling catheter system (600) is used to extend into the abdominal cavity of the experimental mouse. The dynamic pressure acquisition module (500) is electrically connected to the central controller (300) and is used to acquire the dynamic pressure waveform inside the abdominal indwelling catheter system (600) in real time. The central controller (300) has an injection status recognition system (700) running inside. The injection status recognition system (700) is used to identify the tissue space status of the needle tip based on the dynamic pressure waveform, and to control the injection status of the micro-injection pump module (200) and the switching status of the multi-drug switching actuator (400) according to the recognition result. The injection state recognition system (700) includes a dynamic pressure waveform database (710), a rule threshold discrimination module (720), a machine learning-assisted correction module (730), and an injection state machine control module (740). The injection state machine control module (740) includes the puncture establishment stage, the micro-injection stage, the dynamic response acquisition stage, the safety judgment stage, the formal injection stage, the aspiration verification stage, and the flushing and sealing stage.

2. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 1, characterized in that: The multi-drug switching actuator (400) includes a valve housing (410) and a stepper motor (420). The valve housing (410) is fixedly installed inside the housing (100), and the stepper motor (420) is fixedly installed on one side of the valve housing (410). The output shaft of the stepper motor (420) is connected to the drive end of the valve housing (410).

3. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 2, characterized in that: The valve housing (410) has multiple liquid inlet ports (430) and a common liquid outlet port (440) on its surface. A valve core (450) is rotatably connected inside the valve housing (410). A through-type transition channel (460) is provided inside the valve core (450). The stepper drive motor (420) is used to drive the valve core (450) to rotate, so that the transition channel (460) is connected to different liquid inlet ports (430) respectively, and connected to the dynamic pressure acquisition module (500) through the common liquid outlet port (440).

4. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 3, characterized in that: The multiple inlet ports (430) are respectively connected to carbon tetrachloride injection syringe, calcitriol injection syringe, saline injection syringe and spare syringe via infusion tubing.

5. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 3, characterized in that: The transition channel (460) and the common outlet interface (440) form a zero dead volume common channel. The total volume of the common channel is no more than 5 μL, and the inner wall of the common channel adopts a rounded transition structure.

6. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 1, characterized in that: The dynamic pressure acquisition module (500) includes multiple pressure sensors (510), which are installed in parallel between the multi-drug switching actuator (400) and the intraperitoneal catheter system (600). The pressure sensors (510) are electrically connected to the central controller (300). The range of the pressure sensors (510) is 0-500 kPa, and the sampling frequency is not less than 100 Hz.

7. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 1, characterized in that: The peritoneal catheter system (600) includes a flexible silicone catheter (610), a subcutaneous fixation anchor plate (620), an anti-backflow check valve (630), and an anti-torsion buffer section (640). One end of the flexible silicone catheter (610) is connected to the dynamic pressure acquisition module (500), and the other end of the flexible silicone catheter (610) is used to extend into the peritoneal cavity of the experimental mouse. The subcutaneous fixation anchor plate (620) is fixedly installed on the outside of the flexible silicone catheter (610). The anti-backflow check valve (630) is installed in parallel inside the flexible silicone catheter (610). The anti-torsion buffer section (640) is located on the outside of the flexible silicone catheter (610).

8. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 1, characterized in that: The dynamic pressure waveform database (710) includes normal intra-abdominal pressure waveform, subcutaneous tissue pressure waveform, intestinal pressure waveform, and solid organ pressure waveform; the rule threshold discrimination module (720) is used to make a preliminary judgment on the current injection state based on peak pressure, pressure rise rate, fluctuation frequency, and pressure integral area; the machine learning auxiliary correction module (730) is used to perform a secondary correction on the rule threshold discrimination result based on the support vector machine classification model or the convolutional neural network classification model.

9. The integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control according to claim 1, characterized in that: The micro-injection stage of the injection state machine control module (740) is used to control the micro-injection pump module (200) to inject 1-3 μL of test solution into the abdominal cavity; the dynamic response acquisition stage is used to control the dynamic pressure acquisition module (500) to acquire the corresponding dynamic pressure waveform; the aspiration verification stage is used to control the micro-injection pump module (200) to perform a 0.01-0.02 mL aspiration action, and the central controller (300) evaluates the abdominal cavity compliance recovery status according to the pressure recovery curve; the central controller (300) is used to record the long-term dynamic pressure change trend and generate auxiliary analysis results of the liver fibrosis model status.

10. A method for using an integrated drug delivery and monitoring device for mouse liver fibrosis based on dynamic pressure response closed-loop control, characterized in that, Includes the following steps: S1. Establishing an intraperitoneal indwelling catheter: The intraperitoneal indwelling catheter system (600) is implanted into the intraperitoneal cavity of the experimental mice and fixed by a subcutaneous fixation anchor plate (620); S2. Set dosing parameters: Set the dosing cycle, injection flow rate, test volume and alarm threshold through the central controller (300); S3. Switching target liquid: The central controller (300) controls the stepper drive motor (420) to drive the valve core (450) to rotate, so that the transition channel (460) is connected to the target liquid channel; S4. Perform micro-volume injection: The micro-volume injection pump module (200) first injects 1-3 μL of test solution into the abdominal cavity, and the dynamic pressure acquisition module (500) simultaneously acquires the pressure waveform; S5. Execution status recognition: The rule threshold discrimination module (720) first performs a preliminary analysis of the pressure waveform, and then the machine learning-assisted correction module (730) further corrects the discrimination result; S6. Perform formal injection: When the judgment result is normal peritoneum, the micro-injection pump module (200) performs formal drug injection; S7. Execute abnormal protection: When the judgment result is subcutaneous tissue, intestinal lumen or solid organ, the central controller (300) immediately stops the injection and triggers an audible and visual alarm; S8. Perform compliance verification: After the formal injection is completed, perform aspiration. The central control unit (300) assesses the abdominal cavity compliance recovery status based on the pressure recovery curve. S9. Perform flushing and tube sealing: The central controller (300) controls the valve housing (410) to switch to the saline flushing channel to perform common flow channel flushing and tube sealing; S10. Record trend data: The central controller (300) records the long-term dynamic pressure change trend and generates auxiliary analysis results of the liver fibrosis model status.

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