Extracorporeal circulation magnetic cell separation system

Abstract

The invention discloses an extracorporeal circulation magnetic cell separation system, and relates to the technical field of medical instruments. Comprising a blood protection pump, a mixer, a magnetic cell separator and an immune factor capturing system which are sequentially communicated, the upstream of the blood protection pump is connected with a patient through a vein pipeline; the magnetic cell separator comprises an electromagnetic field device and a cell material recoverer and is used for adsorbing and separating tumor cells marked by magnetic nanoparticles, the cell material recoverer adopts a sleeve structure, an inner-layer pipe is provided with a pore passage, and an inlet end and an outlet end of the magnetic cell separator are respectively provided with a front valve and a rear valve. According to the system, leukemia tumor cells are labeled in a targeted mode through magnetic nanoparticles, separation of a large number of specific cells is achieved through extracorporeal circulation and electromagnetic adsorption, and meanwhile the system has the nano material recycling function, can be used for magnetic dialysis treatment of leukemia patients and has the advantages of being high in separation efficiency, good in biocompatibility, high in automation degree and the like.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to an extracorporeal circulation magnetic cell separation system. Background Technology

[0002] Leukemia is a malignant hematologic disorder with complex pathological types, and its treatment outcomes are far weaker than other types of tumors. Leukemia cells often exhibit highly specific expression of certain antigens on their cell membranes; the types and abundance of these antigens allow for diagnosis and precise treatment of leukemia cells. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, accounting for approximately 70% of adult leukemia cases. Its 5-year overall survival rate is only about 25%, with a relapse rate as high as 50%. This low survival rate and extremely high relapse rate underscore the urgent need for research into leukemia treatment, and leukemia is currently listed as one of the top ten malignant tumors in my country. Current leukemia treatment strategies mainly include chemotherapy, stem cell transplantation, and immunotherapy; however, their widespread use is limited by severe drug resistance, relapse, and cytokine storms. Therefore, exploring new, safe, and effective treatment systems remains crucial.

[0003] Existing technologies include studies on using antibodies or targeted peptide-labeled magnetic beads to bind tumor cells and then using permanent magnets to separate small numbers of circulating tumor cells. However, most of these studies can only separate a limited number of cells, suitable only for clinical diagnosis and not for therapeutic purposes. Furthermore, there are no reports on techniques for adhering to, separating, and purifying tumor cells using simple magnetic nanomaterials. Additionally, there are no reports on a "tumor magnetic dialysis" strategy that utilizes an extracorporeal circulation system coupled with an electromagnetic field for repeated, large-scale, and specific separation and purification of leukemia tumor cells, suitable for long-term leukemia treatment. Therefore, there is an urgent need to design an extracorporeal circulation magnetic cell separation system that can meet therapeutic needs. Summary of the Invention

[0004] The main objective of this invention is to provide an extracorporeal circulation magnetic cell separation system to overcome the problems existing in the prior art.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution: An extracorporeal circulation magnetic cell separation system includes a blood protection pump, a mixer, a magnetic cell separator, and an immune factor capture system connected in sequence. The upstream of the blood protection pump is connected to the patient via a venous line, which is used to draw blood from the patient's body and provide a stable, low-pulsating blood flow. The mixer is connected downstream of the blood protection pump via medical tubing and is used to mix the drawn blood with magnetic nanoparticle buffer solution to form a homogeneous mixture of blood, magnetic nanoparticles, and tumor cells labeled with magnetic nanoparticles. The magnetic cell separator includes an electromagnetic field device and a cell material recovery device for adsorbing and separating tumor cells labeled with magnetic nanoparticles. The cell material recovery device adopts a sleeve structure with channels on the inner tube. The channels allow magnetic nanoparticles to pass through while restricting the passage of micron-sized cells. The inlet and outlet ends of the magnetic cell separator are respectively equipped with a front valve and a rear valve for switching between normal circulation mode and cleaning and recovery mode, so as to realize the physical isolation and automated cleaning of the magnetic analysis module. The immune factor capture system is installed in the reinfusion line to remove free immune factors from the blood and then reinfuse the treated blood into the patient via a vein.

[0006] Furthermore, the blood protection pump includes a pump head and a pump tube. The pump head adopts a linear peristaltic structure, which includes rotating massage fingers arranged linearly on both sides of the pump tube. Each rotating massage finger is connected to a stepper motor, which is used to control the rotating massage fingers to squeeze the pump tube. The pump tube includes an inlet section, a main pump section, and an outlet section connected in sequence. The inlet section is connected to the patient through a venous line. The main pump section is located in the groove formed by the two rows of rotating massage fingers. The outlet section is connected to the mixer.

[0007] Furthermore, both the inlet and outlet sections are equipped with pressure sensors, and the outlet section is also equipped with a blood filter, which uses a 100-150μm filter screen to intercept tiny clots.

[0008] Furthermore, the pump tube is made of medical-grade flexible silicone tubing, with a coating covalently bonded to heparin or phosphocholine polymers to reduce protein adsorption and platelet adhesion.

[0009] Furthermore, the mixer includes an elliptical cylindrical mixer shell made of a biocompatible material, with a blood inlet and a magnetic nanoparticle inlet at one end, and a blood outlet at the other end, wherein the direction of the blood inlet is at 30° to the direction of the magnetic nanoparticle inlet.

[0010] Furthermore, the cell material recycling device includes an inner tube and an outer tube. The outer tube is sleeved on the outside of the inner tube, and the gap between the two is 1 mm. The inner tube (33) has a wall thickness of 0.1 mm, an inner diameter of 10 mm at the outlet, and an inner diameter of 50 nm for the channel, allowing nanoparticles with an outer diameter of 10-30 nm to pass through.

[0011] Furthermore, an electromagnetic field device is disposed on the outside of the outer tube, and its magnetic field strength ranges from 0.5 to 1T.

[0012] Furthermore, a magnetic nanoparticle filling pump is connected to the inlet of the magnetic nanoparticles. The magnetic nanoparticle filling pump is used to pump the magnetic nanoparticle buffer solution in the storage tank into the mixer. The return port of the outer tube is connected to the storage tank.

[0013] Furthermore, both the front valve and the rear valve are three-way solenoid valves, which are interconnected through a synchronous communication link and simultaneously connected to the system main controller. The three-way solenoid valve includes a valve body, a valve core, and a circulation pipe. The valve body is provided with a pipe groove to accommodate the circulation pipe. The valve core is located in the circulation pipe. The valve core is provided with a knob. The knob is connected to a dual-coil rotary electromagnetic driver. The two coils control the knob to rotate clockwise and counterclockwise, respectively. The first port of the front valve is connected to the main circulation blood inlet, the second port is connected to the inlet of the magnetic cell separator, and the third port is connected to the cell washing solution inlet pipeline. The first port of the rear valve is connected to the outlet of the magnetic cell separator, the second port is connected to the main circulation reinfusion pathway, and the third port is connected to the tumor cell washing solution waste outlet.

[0014] Furthermore, the immune factor capture system includes a blood filtration vessel containing magnetic beads conjugated with antibodies for removing free immune factors.

[0015] Compared with the prior art, the present invention has the following beneficial effects: This invention proposes a "tumor magnetic dialysis" treatment strategy for the first time, which achieves large-scale and specific separation of leukemia tumor cells through an extracorporeal circulation system. It can be used for long-term treatment and has clinical translational potential. The system utilizes magnetic nanoparticles to target and label leukemia tumor cells, achieving large-scale and specific cell separation through in vitro circulation and electromagnetic adsorption, with high separation specificity. The system integrates automated cleaning and recycling functions, which can recover magnetic nanomaterials while separating tumor cells, thereby improving material utilization and reducing treatment costs. The blood protection pump and low-shear flow channel design minimize blood cell damage, the mixer ensures gentle and efficient mixing, and the three-way solenoid valve enables safe and seamless mode switching, making the overall system safe and reliable. It can achieve cyclic processing, continuously reduce the tumor burden in the peripheral blood of patients, and provide a new method with low toxicity and high efficiency for the treatment of leukemia. It is used for magnetic dialysis treatment of leukemia patients and has the advantages of high separation efficiency, good biocompatibility and high degree of automation. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the overall system of the present invention.

[0017] Figure 2This is a schematic diagram of the blood protection pump structure of the present invention.

[0018] Figure 3 This is a schematic diagram of the mixer structure of the present invention.

[0019] Figure 4 This is a schematic diagram of the magnetic cell separator of the present invention.

[0020] Figure 5 This is a schematic diagram of the cell material recovery device of the present invention.

[0021] Figure 6 This is a schematic diagram of the V1 mode A state when the system of the present invention is in normal cycle.

[0022] Figure 7 For the present invention Figure 6 A schematic diagram of a three-way solenoid valve from another angle.

[0023] Figure 8 This is a schematic diagram of the system of the present invention in V1 mode B.

[0024] Figure 9 This is a schematic diagram of the V2 mode A state of the system of the present invention during cleaning and collection.

[0025] Figure 10 This is a schematic diagram of the system of the present invention in V2 mode B.

[0026] Explanation of reference numerals in the attached drawings: 1. Blood protection pump; 11. Rotary massage finger; 12. Stepper motor; 13. Inlet section; 14. Main pump section; 15. Outlet section; 16. Pressure sensor; 17. Blood filter; 2. Mixer; 21. Mixer housing; 22. Blood inlet; 23. Magnetic nanoparticle inlet; 24. Blood outlet; 35. Magnetic cell separator; 31. Electromagnetic field device; 32. Cell material recovery device; 33. Inner tube; 34. Channel; 35. Outer tube; 4. Immune factor capture system; 56. Front valve; 57. Valve body; 58. Valve core; 59. Circulation pipeline; 50. Knob; 51. Dual-coil rotary electromagnetic actuator; 52. Knob groove; 53. Rear valve; 6. Magnetic nanoparticle filling pump; 7. Storage tank; 8. Detailed Implementation

[0027] The technical solution of the present invention will be further described below with reference to the accompanying drawings and embodiments.

[0028] Combination Figures 1 to 9This embodiment provides an extracorporeal circulation magnetic cell separation system, including a blood protection pump 1, a mixer 2, a magnetic cell separator 3, and an immune factor capture system 4 connected in sequence. The upstream of the blood protection pump 1 is connected to the patient via a venous line to draw blood from the patient and provide a stable, low-pulsating blood flow. The mixer 2 is connected downstream of the blood protection pump 1 via a medical line to mix the drawn blood with a magnetic nanoparticle buffer solution to form a homogeneous mixture of blood, magnetic nanoparticles, and tumor cells labeled with magnetic nanoparticles. The magnetic cell separator 3 includes an electromagnetic field device 31 and a cell material collector 32, which are used to adsorb and separate tumor cells labeled with magnetic nanoparticles. The cell material collector 32 adopts a sleeve structure, and the inner tube 33 is provided with a channel 34. The channel 34 is used to allow magnetic nanoparticles to pass through and restrict the passage of micron-sized cells. The inlet and outlet ends of the magnetic cell separator 3 are respectively provided with a front valve 5 and a rear valve 6, which are used to switch between normal circulation mode and washing and recycling mode to realize physical isolation and automated cleaning of the magnetic analysis module. The immune factor capture system 4 is set in the reinfusion pipeline to remove free immune factors in the blood and reinfuse the processed blood into the patient via vein.

[0029] This approach utilizes the properties of carboxyl-based superparamagnetic iron oxide nanoparticles rich in complement and transferrin to induce specific adhesion and phagocytosis of nanoparticles by myeloid leukemia tumor cells that highly express complement and transferrin receptors. This dual-targeting mechanism actively "magnetizes" leukemia cells, while normal leukocytes rarely phagocytose them. For patients with high tumor burden, an extracorporeal circulation system can be used to mix blood with nanoparticles outside the body. Through the aforementioned dual-targeting effect, tumor cells are magnetized, and then an electromagnetic field is used to adsorb the magnetized tumor cells and unphagocytosed nanoparticles, while leukocytes and erythrocytes flow back into the body.

[0030] When a significant amount of tumor cells and nanoparticles accumulate, the inflow of blood is paused, and the remaining blood cells are flushed away with saline. Then, the outflow of blood is closed, and the magnetic field is shut off. This process flushes away tumor cells while simultaneously recovering the nanomaterials (the magnetic cell separator consists of a magnetic field, a cell and material recovery unit; the cell and material recovery unit is a sheath structure with 50nm-sized pores in the inner layer, allowing magnetic nanoparticles to pass through while blocking micron-sized cells). This cycle is repeated, using a strong magnetic field to adsorb and separate magnetized cells, thereby reducing the tumor burden in peripheral blood and achieving low-toxicity, high-efficiency magnetic dialysis treatment for leukemia.

[0031] like Figure 1As shown, the immune factor capture system 4 includes a blood filter tank containing magnetic beads coupled with antibodies to remove free immune factors.

[0032] like Figure 2 As shown, in this embodiment, the blood protection pump 1 includes a pump head and a pump tube. The pump head adopts a linear peristaltic structure, which includes rotating massage fingers 11 arranged linearly on both sides of the pump tube. Each rotating massage finger 11 is connected to a stepper motor 12. The stepper motor 12 is used to control the rotating massage fingers 11 to squeeze the pump tube. The pump tube includes an inlet section 13, a main pump section 14, and an outlet section 15 connected in sequence. The inlet section 13 is connected to the patient through a venous line. The main pump section 14 is located in the groove formed by the two rows of rotating massage fingers 11. The outlet section 15 is connected to the mixer 2. Both the inlet section 13 and the outlet section 15 are equipped with pressure sensors 16. The outlet section 15 is also equipped with a blood filter 17, which uses a 100-150μm filter screen to intercept microclots.

[0033] Unlike ordinary infusion pumps or dialysis pumps, the core objective of the blood protection pump 1 of this invention is to provide a stable and precise flow rate while absolutely minimizing mechanical damage (shear force) and physical trauma (squeezing, friction) to blood cells (especially fragile red blood cells and platelets), preventing hemolysis and cell activation, while ensuring sterility and biocompatibility.

[0034] Structurally, it employs a linear peristaltic design instead of the traditional rotary type. Eight linearly arranged, independently controlled rotary massage fingers 11 sequentially squeeze the pump tube. This design produces less pulsation, smoother blood flow, and less cell damage compared to rotating rollers.

[0035] The pump tube adopts a detachable, disposable, and sterile segmented structure. The inlet section 13 and outlet section 15 are equipped with pressure monitoring points to prevent the tube from collapsing. The main pump section 14 is located in the groove formed by two rows of rotating massage fingers 11. The tube wall thickness and elasticity have been optimized to ensure a gentle rebound while ensuring full compression and sealing.

[0036] The connection logic is as follows: patient vein → pump front-end pressure sensor → blood protection pump → pump rear-end pressure sensor → blood filter → mixer. When the system is about to switch to "cleaning mode", blood protection pump 1 will receive a "prepare to switch" command from the main controller and perform the action of "decelerating to maintain flow". It will only resume full-speed operation after receiving a signal from both the main controller and the valve system confirming that "circulation mode has been restored".

[0037] This invention employs a high-precision stepper motor as the drive unit to ensure stable and precisely adjustable flow rate. During operation, it features adaptive flow control, automatically adjusting the pump speed based on real-time monitored inlet and outlet pressures to maintain stable transmembrane pressure and flow rate, preventing hemolysis caused by excessive negative pressure. It also utilizes a pulsation suppression mode, further smoothing blood flow and reducing cell stress caused by pulsation by adjusting the motion waveform of the pressure finger. Furthermore, it can be linked with the pressure, bubble, and temperature sensors of the entire system; upon detecting any abnormality (such as a sudden pressure increase or bubbles), it immediately and safely shuts down and triggers an alarm.

[0038] In a further embodiment, the tubing connection after the pump adopts a streamlined, dead-cavity-free joint design to avoid turbulence and stagnation zones, thereby reducing platelet activation; the pump control system has a built-in intelligent pre-flush program to ensure that all tubing and pump sections are fully vented and filled with saline before connecting to the patient, achieving a "seamless connection".

[0039] In a further embodiment, the pump tubing is made of medical-grade flexible silicone tubing with a coating covalently bonded to heparin or phosphocholine polymers to reduce protein adsorption and platelet adhesion.

[0040] like Figure 3 As shown, in this embodiment, the mixer 2 includes an elliptical cylindrical mixer housing 21 made of biocompatible material. One end has a blood inlet 22 and a magnetic nanoparticle inlet 23, and the other end has a blood outlet 24. The direction of the blood inlet 22 is at a 30° angle to the direction of the magnetic nanoparticle inlet 23. This port design ensures that the buffer solution is injected tangentially at an acute angle (30°) to the blood flow direction to minimize fluid resistance and immediately initiate primary mixing. Subsequently, the blood and magnetic nanoparticles can be thoroughly mixed using an additional shaking device.

[0041] The core function of the mixer 2 of the present invention is to thoroughly, gently and efficiently mix the anticoagulated whole blood delivered from the blood protection pump 1 with the injected buffer solution containing magnetic nanoparticles specifically targeting tumor cells on its surface, forming a uniform mixture of blood, magnetic nanoparticles and tumor cells labeled by the magnetic nanoparticles, laying the foundation for efficient capture by the subsequent magnetoanalysis module.

[0042] The mixer plays a crucial role in the system logic, and its connection and operational logic are as follows: Input logic: Blood provides a stable, low-pulsation blood flow as the mixed main phase flow. Simultaneously, the system controller controls the precision injection device to inject a magnetic nanoparticle buffer solution through the blood and magnetic nanoparticles at a preset blood volume ratio.

[0043] Hybridization Logic: Within the mixer, blood and magnetic nanoparticles diffuse and mix in three dimensions within a very short flow channel, aided by mixing equipment such as a shaker. This simple mixing method is crucial, as it ensures sufficient contact and binding between the magnetic nanoparticles and target cells in the blood while minimizing mechanical damage or activation of blood cells.

[0044] Output logic: The homogeneous mixture of blood, magnetic nanoparticles, and tumor cells labeled with magnetic nanoparticles flows out through the blood outlet and is directly delivered to the inlet of the downstream magnetoanalysis module via tubing. The homogeneity of the mixture ensures the stability and maximization of the subsequent magnetic field capture efficiency.

[0045] The coordinated operation of mixer 2 with other components in the system produces technical effects that cannot be achieved by a single component: In conjunction with the blood protection pump 1: The stable flow rate provided by the blood protection pump is a prerequisite for the mixer 2 to achieve repeatable mixing. The cooperation between the two ensures the accuracy and consistency of the mixing ratio.

[0046] In conjunction with the magnetic cell separator 3: the output quality of the mixer 2 directly determines the capture efficiency of the magnetic separation module. Thorough and gentle mixing ensures: high utilization of magnetic nanoparticles; high binding saturation on the target cell surface; and reduced non-specific aggregation caused by uneven mixing, thereby improving the specificity and sensitivity of the magnetic separation module.

[0047] Regarding the regulation of the binding of nanoparticles to tumor cells: Leukemia tumor cells can actively engulf nanomaterials, so the mixing time can be appropriately extended to optimize the sensitivity and specificity of magnetized leukemia cell number (the effect of different incubation times on the type and number of magnetized cells).

[0048] like Figure 4-5 As shown, in this embodiment, the cell material recovery device 32 includes an inner tube 33 and an outer tube 35. The outer tube 35 is sleeved on the outside of the inner tube 33, with a gap of 1 mm between them. The wall thickness of the inner tube 33 is 0.1 mm, the inner diameter at the outlet is 10 mm, and the inner diameter of the channel is 50 nm, allowing nanoparticles with an outer diameter of 10-30 nm to pass through. An electromagnetic field device 31 is disposed on the outside of the outer tube 35, and its magnetic field strength ranges from 0.5 to 1 T. The strength of the magnetic field can be changed at any time by adjusting the current intensity, and the magnetic field can also be stopped at any time.

[0049] During operation, referring to routine hemodialysis, the total blood volume of the human body accounts for approximately 7-8% of body weight. For example, a 60 kg adult has a total blood volume of approximately 4.5 L. Generally, the extracorporeal circulation blood volume should not exceed 10% of the total blood volume (approximately 450 mL) to avoid adverse reactions such as hypotension. In this embodiment, the total circulating blood volume in the tubing is 300-350 mL. Running at a flow rate of 10 mL / min, the blood is mixed with the nanoparticles in vitro for approximately 30 minutes before passing through the magnetic field.

[0050] like Figure 1 and Figure 3 As shown, in this embodiment, a magnetic nanoparticle inlet 23 is externally connected to a magnetic nanoparticle filling pump 7. The magnetic nanoparticle filling pump 7 is used to pump the magnetic nanoparticle buffer solution in the storage tank 8 into the mixer 2. The return port of the outer tube 35 is connected to the storage tank 8. Figure 5 Specifically, the recovery rate of nanomaterials is approximately 60-70%.

[0051] like Figure 6-10 As shown, both the front valve 5 and the rear valve 6 are three-way solenoid valves. They are interconnected through a synchronous communication link and are simultaneously connected to the system main controller. The three-way solenoid valve includes a valve body 51, a valve core 52 and a circulation pipe 53. The valve body 51 is provided with a pipe groove to accommodate the circulation pipe 53. The valve core 52 is located in the circulation pipe 53. The valve core 52 is provided with a knob 54. The knob 54 is connected to a dual-coil rotary electromagnetic driver 55. The two coils control the knob 54 to rotate clockwise and counterclockwise respectively. The knob 54 is located in the knob groove 56. Among them, the first port of the front valve 5 is connected to the main circulation blood supply channel, the second port is connected to the inlet of the magnetic cell separator 3, and the third port is connected to the cell washing solution inlet pipeline. The first port of the rear valve 6 is connected to the outlet of the magnetic cell separator 3, the second port is connected to the main circulation reinfusion channel, and the third port is connected to the tumor cell washing solution waste outlet.

[0052] Specifically, the valve core knob 54 is cubic in shape, and the valve body 51 has a matching cubic knob groove 56, which can be precisely rotated 90° clockwise or counterclockwise. The flow channel of the circulation pipe 53 adopts a T-shaped three-way layout, and all connections are smoothly transitioned to minimize turbulence, shear force, and blood residue.

[0053] In this embodiment, the front valve 5 is V1, the rear valve 6 is V2, the first port, the second port, and the third port of the front valve 5 are A1, B1, and C1, respectively, and the first port, the second port, and the third port of the rear valve 6 are A2, B2, and C2, respectively.

[0054] In the system cleaning and collection mode, V1: C1→B1, V2: A2→C2. The cleaning solution flows into and rinses the magnetic cell separator 3, and the waste liquid flows into the collection container. At this time, the main blood circulation pipeline is completely closed at port A1 of V1 and port B2 of V2.

[0055] In this embodiment, the dual-coil rotary electromagnetic actuator 55 adopts non-contact magnetic coupling rotary drive. The valve core has a built-in permanent magnet rotor, and the electromagnetic coil on the outer shell drives the rotor to rotate through the generated rotating magnetic field. This design achieves complete external dynamic sealing of the pipeline and eliminates the risk of wear and leakage at the traditional valve stem seal.

[0056] In this embodiment, each valve (V1, V2) and magnetic field (V3) has an independent drive motor and position feedback encoder. V1, V2, and V3 are interconnected via a communication link and connected to the system main controller. V1, V2, and V3 receive the "mode switching" command sent by the main controller. They exist in the following four states: State 1: Circulation Operation – The blood circulation path is A1→B1→Magnetic Cell Separator 3→A2→B2. The system continuously monitors the collection volume (differential pressure) or time of the magnetic separation device. When the collection conditions are met, the main controller issues a "Prepare for Cleaning" command, the blood protection pump stops rotating or flows back into the circuit via a short circuit to prevent clotting, and the main controller sends a pre-command to V1 via the synchronization link to "Switch to Mode B".

[0057] State 2: Blood cell recovery - V1 starts the valve core rotation, switches to mode B, starts the cleaning fluid pump, and according to the preset flow rate, pressure, and time program, the saline solution flows from C1 → B1 → magnetic cell separator 3 → A2 → B2.

[0058] State 3: Magnetic field cleaning and nanoparticle recovery - V1 maintains mode B, the main controller sends an "electromagnetic field shutdown" command to V3 and an "clean magnetic cell separator 3" command to V2. The saline solution flows from C1 → B1 → magnetic cell separator 3 → A2 → C2 → magnetized cell collection container and nanoparticle recovery device 8. The cleaning steps are programmable (e.g., rapid rinsing → soaking → slow rinsing).

[0059] State 4: Resumption of Circulation – Cleaning complete, cleaning fluid pump stops. The main controller sends a synchronization command to "switch back to mode A" again. V1 and V2 rotate synchronously to reset, and the V3 magnetic field is restored. After reset confirmation, the blood protection pump is notified to restore the set flow rate, and the system returns to normal operation.

[0060] Before and after each switchover, V1 and V2 not only report their own status to the master controller, but also exchange and verify each other's status via the communication link. Only when both parties confirm that the other has reached the target location will they send a final confirmation to the master controller, achieving the effect of "valve-valve" interlock verification.

[0061] In the event of a complete power outage, the built-in spring forces the valve core to reset to "Mode A" (i.e., A1→B1, A2→B2), ensuring that the blood circulation pathway is automatically restored in the event of any unexpected power failure. If one valve malfunctions (e.g., jamming, sensor failure), the other valve, upon receiving the fault signal, should refuse to execute any switching commands that may jeopardize the circuit and immediately sound an alarm.

[0062] Using this approach, the three-way solenoid valve of this invention differs from conventional medical manual three-way valves. This "three-way solenoid valve" is the core actuator for the system to achieve automatic separation and collection of magnetic precipitation products, and its design can achieve the following effects: (1) Achieve physical isolation: In the cleaning mode, the two valves need to work together to completely and reliably physically isolate the magnetic analyzer from the main blood circulation circuit, ensuring that the cleaning process does not affect the safety and stability of the main circuit and prevent the cleaning solution from mixing into the blood; (2) Ensure process controllability: Precisely control the opening sequence of the inlet and outlet of the cleaning fluid, and cooperate with the cleaning fluid pump to achieve directional, efficient and repeatable rinsing and collection of the inside of the magnetic analysis device (captured tumor cells-nanomaterial complex); (3) Sterility and biocompatibility: All surfaces in contact with blood and cleaning fluid are highly smooth and free of dead space, and the materials meet medical-grade biocompatibility standards; (4) Intelligent triggering and linkage: It can receive multi-parameter fusion signals from the magnetic analysis device (such as pressure) and automatically and collaboratively start the collection process when the collection conditions are met; (5) Fail-safe: In the event of any unexpected power outage or system failure, it can automatically reset and lock in a safe state to ensure patient safety.

[0063] Working principle: Once nanomaterials enter the bloodstream, they rapidly combine with plasma proteins to form a protein corona, thereby acquiring novel and undesigned biological properties, which makes transformation difficult. Immune molecules are particularly important in this process.

[0064] Utilizing the properties of carboxyl-containing iron oxide and other magnetic nanoparticles rich in complement and transferrin, it is possible to induce myeloid leukemia tumor cells that highly express complement receptors and transferrin receptors to specifically adhere to and phagocytose the nanoparticles, while normal leukocytes rarely phagocytose them. Through this dual-targeting mechanism, leukemia cells actively phagocytose and magnetize the carboxyl-containing iron oxide and other nanoparticles. For patients with high tumor burden, an extracorporeal circulation system can be used to mix blood with the nanoparticles in vitro. Through the above dual-targeting effect, the tumor cells are magnetized. Then, an electromagnetic field is used to adsorb the magnetized tumor cells and the unphagocytosed nanoparticles into the magnetic field, while leukocytes and erythrocytes flow back into the body.

[0065] When a large number of tumor cells and nanoparticles accumulate, the inflow of circulation is paused, and the remaining blood cells are flushed away with saline. Then, the outflow of circulation is closed and the magnetic field is turned off. The nanomaterials are recovered while the tumor cells are flushed away (the magnetic cell separator is composed of a magnetic field and a cell and material recovery device. The cell and material recovery device is a sleeve structure with 50nm-sized pores in the inner layer, which can allow magnetic nanoparticles to pass through while blocking micron-sized cells).

[0066] This process is repeated, using a strong magnetic field to adsorb and separate magnetized cells, thereby reducing the tumor burden in peripheral blood and achieving low-toxicity, high-efficiency magnetic dialysis treatment for leukemia.

[0067] Specific operation: The blood circulation treatment process of this invention is based on hemodialysis technology. Blood is drawn out through the patient's arteriovenous fistula at a low flow rate (e.g., 10-20 mL / min). Simultaneously, magnetic nanomaterials are continuously added in proportion through an infusion three-way valve (flow rate 40 mL / h, concentration 1 mg / mL). The blood and nanomaterials enter the mixer together and are thoroughly mixed in the chamber (time 10-30 minutes; the design of the air-oxygen mixer in ECMO can be referenced to ensure uniform mixing). After the system is running stably, the blood flow rate is gradually adjusted to the target value. Treatment time (4-6 hours), temperature, and other parameters are set, and an anticoagulant (such as heparin) is continuously injected through a heparin pump to prevent blood clotting during extracorporeal circulation.

[0068] This invention is the first of its kind in the world to utilize an extracorporeal circulation device combined with an electromagnetic field to repeatedly, massively, and specifically separate and purify leukemia tumor cells, a strategy known as "tumor magnetic dialysis" that can be used for long-term treatment of leukemia.

[0069] The above description is merely a preferred embodiment of the present invention and does not constitute any limitation on the technical scope of the present invention. Therefore, any minor modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

1. An extracorporeal circulation magnetic cell separation system, characterized in that, It includes a blood protection pump (1), a mixer (2), a magnetic cell separator (3), and an immune factor capture system (4) connected in sequence. The upstream of the blood protection pump (1) is connected to the patient via a venous line, which is used to draw blood from the patient and provide a stable, low-pulsating blood flow. The mixer (2) is connected downstream of the blood protection pump (1) via a medical tubing and is used to mix the drawn blood with the magnetic nanoparticle buffer solution to form a uniform mixture of blood, magnetic nanoparticles and tumor cells labeled with magnetic nanoparticles. The magnetic cell separator (3) includes an electromagnetic field device (31) and a cell material collector (32) for adsorbing and separating tumor cells labeled with magnetic nanoparticles. The cell material collector (32) adopts a sleeve structure, and the inner tube (33) is provided with a channel (34). The channel (34) is used to allow magnetic nanoparticles to pass through and restrict the passage of micron-sized cells. The inlet and outlet ends of the magnetic cell separator (3) are respectively provided with a front valve (5) and a rear valve (6) for switching between normal circulation mode and cleaning and recycling mode to realize physical isolation and automated cleaning of the magnetic analysis module. The immune factor capture system (4) is installed in the reinfusion line to remove free immune factors in the blood and reinfuse the treated blood into the patient via a vein.

2. The extracorporeal circulation magnetic cell separation system as described in claim 1, characterized in that, The blood protection pump (1) includes a pump head and a pump tube. The pump head adopts a linear peristaltic structure and includes rotating massage fingers (11) arranged linearly on both sides of the pump tube. Each of the rotating massage fingers (11) is connected to a stepper motor (12). The stepper motor (12) is used to control the rotating massage fingers (11) to squeeze the pump tube. The pump tube includes an inlet section (13), a main pump section (14), and an outlet section (15) connected in sequence. The inlet section (13) is connected to the patient through a venous line. The main pump section (14) is located in the groove formed by the two rows of rotating massage fingers (11). The outlet section (15) is connected to the mixer (2).

3. The extracorporeal circulation magnetic cell separation system as described in claim 2, characterized in that, Both the inlet section (13) and the outlet section (15) are equipped with pressure sensors (16), and the outlet section (15) is also equipped with a blood filter (17), which uses a 100-150μm filter screen to intercept microclots.

4. The extracorporeal circulation magnetic cell separation system as described in claim 2, characterized in that, The pump tube is made of medical-grade flexible silicone tubing, with a coating covalently bonded to heparin or phosphocholine polymers to reduce protein adsorption and platelet adhesion.

5. The extracorporeal circulation magnetic cell separation system as described in claim 1, characterized in that, The mixer (2) includes an elliptical cylindrical mixer shell (21) made of biocompatible material, with a blood inlet (22) and a magnetic nanoparticle inlet (23) at one end and a blood outlet (24) at the other end. The direction of the blood inlet (22) is 30° to the direction of the magnetic nanoparticle inlet (23).

6. The extracorporeal circulation magnetic cell separation system as described in claim 5, characterized in that, The cell material recovery device (32) includes an inner tube (33) and an outer tube (35). The outer tube (35) is sleeved on the outside of the inner tube (33), with a gap of 1 mm between them. The inner tube (33) has a wall thickness of 0.1 mm and an inner diameter of 10 mm at the outlet. The channel (34) has an inner diameter of 50 nm, allowing nanoparticles with a diameter of 10-30 nm to pass through.

7. The extracorporeal circulation magnetic cell separation system as described in claim 6, characterized in that, An electromagnetic field device (31) is disposed on the outside of the outer tube (35), and its magnetic field strength ranges from 0.5 to 1T.

8. The extracorporeal circulation magnetic cell separation system as described in claim 6, characterized in that, The magnetic nanoparticle inlet (23) is connected to a magnetic nanoparticle filling pump (7), which is used to pump the magnetic nanoparticle buffer solution in the storage tank (8) into the mixer (2). The return port of the outer tube (35) is connected to the storage tank (8).

9. The extracorporeal circulation magnetic cell separation system as described in claim 1, characterized in that, Both the front valve (5) and the rear valve (6) are three-way solenoid valves. They are interconnected through a synchronous communication link and are simultaneously connected to the system main controller. The three-way solenoid valve includes a valve body (51), a valve core (52), and a circulation pipe (53). The valve body (51) is provided with a pipe groove to accommodate the circulation pipe (53). The valve core (52) is located in the circulation pipe (53). The valve core (52) is provided with a knob (54). The knob (54) is connected to a dual-coil rotary electromagnetic driver (55). The two coils control the knob (54) to rotate clockwise and counterclockwise, respectively. The first port of the front valve (5) is connected to the main circulation blood supply path, the second port is connected to the inlet of the magnetic cell separator (3), and the third port is connected to the cell washing solution inlet pipeline. The first port of the rear valve (6) is connected to the outlet of the magnetic cell separator (3), the second port is connected to the main circulation reinfusion path, and the third port is connected to the tumor cell washing solution waste outlet.

10. The extracorporeal circulation magnetic cell separation system as described in claim 1, characterized in that, The immune factor capture system (4) includes a blood filter tank containing magnetic beads coupled with antibodies for removing free immune factors.

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