A blood fishing system, methods of use and purposes thereof

Abstract

The application discloses a blood fishing system, a method for using the same and an application. Taking blood magnetic fishing as an example, the system comprises a magnetic enhancer and a catcher for capturing a target object, wherein the catcher at least comprises a target object catcher I and a target object catcher II, the target object catcher I comprises a sleeve assembly and a first magnetic attraction assembly, the sleeve assembly comprises an outer sleeve and an attached sleeve arranged in the outer sleeve, a groove is arranged on the outer surface of the attached sleeve, and the first magnetic attraction assembly is arranged in the attached sleeve; and the target object catcher II comprises a magnetic separation tube and a second magnetic attraction assembly. The blood fishing system has universality and can also be used for enrichment and capture of other target objects such as microorganisms, proteins, nucleic acids and the like, and can be applied to the fields of medicine, biology, industrial pipeline fluids or gases and the like, so that the fast and efficient fishing and filtering effect can be achieved, the application is wide, and the system has high market value.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to a blood retrieval system, its usage method, and its applications. Background Technology

[0002] Finding and capturing rare targets in the blood, such as circulating tumor cells, has always been a challenge.

[0003] Cancer has long been the leading threat to human health, killing nearly ten million people worldwide each year. A major reason for cancer treatment failure is its tendency to metastasize, especially through the bloodstream; the vast majority of cancer patients ultimately die from metastasis. Recent research has increasingly focused on a key player: circulating tumor cells (CTCs). These are tumor cells that detach from the primary tumor site and enter the peripheral blood, where they can easily breach blood vessel walls and metastasize to other tissues. Numerous studies have shown that CTC detection has significant clinical implications for early cancer screening and diagnosis, recurrence monitoring, drug selection, efficacy evaluation, and prognostic assessment. Furthermore, further molecular biological analysis of captured CTCs or cultured CTC cell lines is an important direction in cancer research.

[0004] However, the concentration of CTCs in whole blood is extremely low (10 red blood cells per mL of whole blood). 9 10 white blood cells 7 (There are only one CTC). Currently, the enrichment methods for CTCs at home and abroad are not ideal. (1) The amount of blood sample collected is too small, resulting in extremely low enrichment efficiency of CTCs, but it is obviously unrealistic to "bleed out" a lot of blood for detection; (2) In vitro induction detection cannot obtain live CTCs; (3) The effective contact area for antibody-antigen contact capture in vivo is very small, and the contact probability is too low. This makes the progress of "liquid biopsy" targeting CTCs slow.

[0005] Therefore, there is an urgent need for a system and method that can retrieve targets from the bloodstream throughout the body, enabling the capture of large quantities of targets. Summary of the Invention

[0006] The purpose of this invention is to overcome the limitations of existing detection methods, such as small blood sample volume, false negative results, inability to capture target substances from non-ex vivo flowing blood with sample volume hundreds or tens of thousands of times larger, inability of target substances to reflect the overall condition, and poor reflection of tumor heterogeneity.

[0007] To achieve the above objectives, the present invention provides a blood retrieval system comprising: a magnetic enhancer for magnetically labeling target objects in a sample, wherein the magnetic enhancer is selected from immunomagnetic nanoparticles; and a capture device for capturing the magnetically labeled target objects; wherein the capture device comprises at least a target object capture device one and a target object capture device two, the target object capture device one comprising a sleeve assembly and a first magnetic attraction assembly, the sleeve assembly comprising an outer sleeve and an attachment sleeve disposed within the outer sleeve, the outer surface of the attachment sleeve having a groove, and the first magnetic attraction assembly disposed within the attachment sleeve for adsorbing and capturing the magnetically labeled target objects; the target object capture device two comprising a magnetic separation tube and a second magnetic attraction assembly, the magnetic separation tube being sandwiched between the second magnetic attraction assemblies, the second magnetic attraction assembly being used to adsorb and capture the magnetically labeled target objects.

[0008] Preferably, the first magnetic attraction component includes a chain of magnetic beads composed of a plurality of magnetic beads arranged in sequence, and a metal wire connected in series with the chain of magnetic beads; the adjacent magnetic poles of two adjacent magnetic beads have the same polarity, so that there is a gap between the two adjacent magnetic beads.

[0009] Preferably, the second magnetic attraction component includes at least a first magnet array and a second magnet array, wherein the first magnet array and the second magnet array are arranged in parallel and facing each other.

[0010] Preferably, the first magnet array consists of an even number of first magnet blocks, wherein the magnetic pole directions of half of the first magnet blocks are opposite to those of the remaining half of the first magnet blocks; the second magnet block consists of an even number of second magnet blocks.

[0011] Preferably, the blood retrieval system further includes a guide wire for guiding the outer sheath.

[0012] Preferably, the blood retrieval system further includes the radionuclide iodine-131 for ultra-short-range irradiation to kill the captured target.

[0013] The present invention also provides a method of using the blood retrieval system described in any one of the above claims, comprising the following steps:

[0014] Step 1: Use a magnetic enhancer to magnetically label the target object in the sample;

[0015] Step 2: Place the target object capture device one in the first capture position, retract the outer sleeve, and slide the outer sleeve relative to the attachment sleeve to expose the groove of the attachment sleeve. The target object is then attracted and captured into the groove by the first magnetic attraction component.

[0016] Step 3: Place the target capture device 2 in the second capture position, and clamp the magnetic separation tube between the second magnetic attraction components. Under the strong magnetic field formed by the second magnetic attraction components, the target object bound by the magnetic enhancer is adsorbed and captured to the inner wall of the magnetic separation tube.

[0017] Steps 2 and 3 can be performed alternately, and steps 2 to 3 can be repeated several times to ensure that all targets can be captured.

[0018] Ideally, the target capture time is 20–60 minutes.

[0019] Preferably, in step 2, radioactive nuclide iodine-131 is added to the target capture device to kill the captured target by ultra-short-range irradiation.

[0020] The present invention also provides an application of the blood retrieval system described in any one of the above claims, wherein the blood retrieval system can be used to retrieve any one or any combination of two or more of tumor cells, microorganisms, proteins, and nucleic acids.

[0021] The beneficial effects of this invention are:

[0022] (1) The blood retrieval system of the present invention includes a magnetic enhancer and a capture device. The capture device includes at least a target capture device one and a target capture device two. Through combined interventional techniques, the target capture device one can be left in the body to retrieve the target, and the target capture device two can be placed outside the body to retrieve the target. For retrieval of the target in the body, the capture device adopts a target capture device, which is provided with a groove and a magnetic device. The groove provides a space for the target to be contained, which helps to maintain the original state and activity of the target. The magnetic device can enhance the adsorption effect of the target. For retrieval of the target outside the body, the capture device adopts a circulating reinfusion type circulating tumor cell extracorporeal magnetic filtration device, which can enrich and capture the target. Compared with other biopsy tests, it can reduce the trauma of the capture process and the false negative rate of the results. Compared with traditional blood collection tests, the blood sample circulation reinfusion can significantly increase the sample volume, without the need for surgical operation, and is suitable for repeated or periodic tests.

[0023] (2) This application uses a magnetic enhancer, which can target and bind to the marker and magnetize the target in the blood or body fluid, and then trace, capture, filter or kill it from a huge amount of flowing blood or body fluid, with higher capture efficiency.

[0024] (3) The blood retrieval system of the present invention has universality. Specifically, it can be used for all cancer patients and high-risk groups of cancer, and can be used repeatedly. In the early stage, it can be used to promote radical cure and assess the risk of recurrence. It can also be used for intraoperative net filtration. In the middle and late stages, it can be used to test drug sensitivity and evaluate efficacy. In addition to enriching and capturing CTCs, it can also be used for enriching and capturing other labelable targets such as microorganisms, proteins, and nucleic acids. Its application can be extended to industrial fields such as medicine, biology, industrial pipeline fluids or gases. It has a wide range of applications and great market value. Attached Figure Description

[0025] Figure 1 This is a flowchart illustrating the usage method of the blood retrieval system of the present invention.

[0026] Figure 2 This is a schematic diagram of the target object capturing device of the present invention.

[0027] Figure 3 This is a schematic diagram of the operation of the circulating tumor cell extracorporeal magnetic filtration device of the present invention.

[0028] Figure 4 This is a partial structural schematic diagram of the circulating tumor cell extracorporeal magnetic filtration device of the present invention.

[0029] Figure 5 This is a schematic diagram illustrating the working principle of the magnetic separation tube and magnet array of the circulating tumor cell extracorporeal magnetic filtration device of the present invention.

[0030] Among them, 1-outer sleeve, 2-attached sleeve, 20-groove, 3-magnetic separation tube, 4-first magnet array, 41-first magnet block, 5-second magnet array, 51-second magnet block, 6-first three-way valve, 7-second three-way valve, 8-peristaltic pump, 9-first infusion tube, 10-second infusion tube. Detailed Implementation

[0031] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. 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.

[0032] In the description of this invention, it should be noted that the terms "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0033] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0034] This invention provides a blood retrieval system comprising a magnetic enhancer that binds to a target, a capture device for capturing the target bound to the magnetic enhancer, and an auxiliary intervention technique. The magnetic enhancer is composed of polymeric nanoparticles, magnetic nanoparticles, and specific antibodies. The magnetic nanoparticles can be selected from Fe3O4 nanoparticles. Since Fe3O4 nanoparticles themselves cannot bind to specific antibodies, polymeric nanoparticles are needed to bind them together. Liposomes are a type of polymeric nanoparticle. The Fe3O4 nanoparticles are encapsulated within the liposomes, and the surface of the liposomes is modified with specific antibodies. The magnetic enhancer allows the specific antibodies to bind to specific antigens on the surface of abnormal cells (targets), making the abnormal cells paramagnetic and attractable by a magnetic field.

[0035] The capture device includes at least two target capture devices, namely Target Capture Device 1 and Target Capture Device 2, which can capture and retrieve target objects. Before being marked with the magnetic enhancer, all target objects in this invention are uniformly unmarked; after being marked with the magnetic enhancer, they are uniformly magnetically marked. This blood retrieval system can retrieve target objects by leaving Target Capture Device 1 inside the body. The advantage of this method is that the attachment sleeve of Target Capture Device 1 has grooves on its outside, providing space for the target object and helping to maintain its original state and activity. Furthermore, the magnetic device includes a chain of magnetic beads arranged sequentially, with adjacent ends of adjacent magnetic beads having the same polarity and repelling each other. This allows the magnetic field to be evenly distributed along the entire length of the chain, with a uniform 360° magnetic field distribution without blind spots, enhancing the adsorption effect of the magnetic bead chain. Alternatively, a target capture device can be placed externally and retrieved via a cyclic reinfusion method. The target capture device includes a magnetic separation tube and a first and second magnet array, which are arranged in parallel and facing each other. The advantage of this method is that after a strong magnetic field is formed between the first and second magnet arrays, the target will be attracted and captured to both sides of the magnetic separation tube when it passes through it. The cyclic reinfusion method can filter blood at a high flow rate without causing a large amount of blood loss, and it does not require surgical operation, avoiding injury to the patient and increasing the economic burden. It is suitable for repeated retrieval of target objects.

[0036] Furthermore, interventional techniques, also known as interventional therapy or interventional treatment, are the third major treatment discipline after internal medicine and surgery, capable of compensating for the shortcomings of internal and surgical techniques. Interventional techniques are minimally invasive treatments using modern high-tech methods. Guided by medical imaging equipment, specialized catheters, guidewires, and other precision instruments are introduced into the body to diagnose and treat lesions locally. Endovascular procedures fall under the field of interventional technology. They require no surgery, only a small puncture site (less than a grain of rice) to insert a specialized catheter into the blood vessel for subsequent procedures. They offer advantages such as being minimally invasive, highly efficient, having a rapid recovery time, and providing good results. The field of interventional medicine already has comprehensive safety operating procedures; therefore, blood retrieval systems must be combined with interventional techniques to ensure safety. In fact, the "retrieval" in this invention is a continuation of interventional techniques.

[0037] Blood retrieval systems have a wide range of applications; any substance that can be magnetically labeled can be captured by this system. Its applications include at least medicine, biology, and industry. The blood retrieval system can be likened to "casting a net to catch fish" or "remotely attracting fish," while traditional laboratory medicine is more like "scooping fish from the water." The target analyte capture device 1, which involves in-vivo retrieval, can increase the sample volume by 10,000 times, while the target analyte capture device 2, which involves extracorporeal circulation and reinfusion, can non-invasively increase the sample volume by more than 100 times. Therefore, the sample volume of the blood retrieval system is significantly higher than that of traditional laboratory medicine, and the positive capture rate is naturally also higher.

[0038] Safety design of the present invention: (1) The target capture device uses interventional catheter materials and existing transfusion vascular materials, which are safe and reliable; (2) The magnetic suction component does not come into contact with blood and human body, which is safe and reliable; (3) The head of the target capture device is round and smooth, and the operation is guided by a super-slippery guidewire, which is much safer than existing venous stents and other surgeries; (4) The CTCs in vivo capture procedure is only a level 2 interventional procedure, which can be completed independently by resident physicians, and the academic community will formulate special safety operating procedures to ensure safety; (5) The circulating reinfusion type of circulating tumor cell extracorporeal magnetic filtration does not involve arterial puncture, the operation is extremely simple, the risk is minimal, and the necessary safety operating procedures are customized according to the standards known in the field; (6) In response to the thrombosis problem that may occur in vascular operation and extracorporeal magnetic filtration, the interventional and dialysis communities have complete heparinization operation procedures; (7) Immunomagnetic nanoparticles currently have FDA-approved formulations for use as magnetic resonance imaging contrast agents, which are safe and reliable.

[0039] This embodiment uses the capture and retrieval of circulating tumor cells in the blood (i.e., blood magnetic retrieval) as an example for detailed description:

[0040] Example

[0041] The present invention provides a blood retrieval system comprising a magnetic enhancer that binds to an unlabeled target, a capture device for capturing the target bound to the magnetic enhancer, and interventional technology. The capture device comprises at least a target capture device one and a target capture device two, wherein the target capture device one is a target capture apparatus, and the target capture device two is a circulating reinfusion type extracorporeal magnetic filtration device for tumor cells.

[0042] like Figure 2 As shown, the target acquisition device includes a sleeve assembly and a first magnetic attraction assembly. The sleeve assembly includes an outer sleeve 1 and an attachment sleeve 2 disposed within the outer sleeve 1. The outer surface of the attachment sleeve 2 has a groove 20. The outer sleeve 1 and the attachment sleeve 2 are slidable relative to each other, so that at least part of the groove 20 is exposed outside the outer sleeve 1. The end of the attachment sleeve 2 exposed outside the outer sleeve 1 is a closed end 21. The first magnetic attraction assembly is disposed within the attachment sleeve 2. The end of the attachment sleeve 2 located inside the outer sleeve 1 is an open end (rear end), and the first magnetic attraction assembly is placed in the attachment sleeve 2 through the open end.

[0043] Before capture, CTCs in the blood are magnetically labeled using a magnetic enhancer (immunomagnetic nanoliposomes containing Fe3O4) (in this embodiment, the magnetic label is a paramagnetic label). Initially, the attachment sleeve 2 is completely inside the outer sleeve 1. After the capture device is positioned in the capture position, the outer sleeve 1 is retracted, and the outer sleeve 1 slides relative to the attachment sleeve 2, exposing the groove of the attachment sleeve 2 outside the outer sleeve 1, with the end of the attachment sleeve 2 exposed outside the outer sleeve 1 serving as the front end of the attachment sleeve 2. The magnetic force of the magnetic component located inside the attachment sleeve 2 can penetrate the attachment sleeve 2 and radiate outward, attracting the magnetically labeled CTCs to the outer periphery of the attachment sleeve 2. CTCs tend to move closer to the magnetic component. The outer surface of the attachment sleeve 2 has a groove 20, and the bottom of the groove 20 is closer to the magnetic component 2, so the magnetic force at the bottom of the groove 20 is stronger. Therefore, CTCs can be captured and stored in the groove 20. The groove 20 provides space for CTCs, which helps maintain the original state of CTCs and protect cell activity.

[0044] After capture, push the outer sleeve 1 forward, and the outer sleeve 1 and the attachment sleeve 2 slide relative to each other, so that the attachment sleeve 2 is completely inside the outer sleeve 1. Because the CTCs can always be attracted within the groove 20 under the magnetic force of the first magnetic attraction component, the edge of the outer sleeve 1 will not scratch the CTCs during the relative sliding process of the outer sleeve 1 and the attachment sleeve 2, and the CTCs will not fall off.

[0045] Finally, the entire target capture device is removed from the capture position. During removal, the attachment sleeve 2 is completely inside the outer sleeve 1. The CTCs stored in the groove 20 are protected by the outer sleeve 1 and will not be scraped off by the blood vessel wall or subcutaneous tissue. All CTCs attracted and captured by the first magnetic component can be stored in the groove 20 by the target capture device and are completely removed from the first capture position.

[0046] like Figures 3-5 As shown, the circulating tumor cell extracorporeal magnetic filtration device includes a magnetic separation tube 3, which has a flattened cylindrical shape in the middle and flattened conical shapes at both ends with openings; a first infusion tube 9 and a second infusion tube 10, wherein the first infusion tube 9 is connected to one open end of the magnetic separation tube 3, and the second infusion tube 10 is connected to the other open end of the magnetic separation tube 3. A second magnetic attraction component includes a first magnet array 4 and a second magnet array 5. In operation, the first magnet array 4 and the second magnet array 5 are arranged parallel to each other with their magnetic pole faces facing each other; the magnetic separation tube 3 is placed between the first magnet array 4 and the second magnet array 5, with the two larger side surfaces of the magnetic separation tube 3 in close contact or near the magnetic pole faces of the opposing first magnet array 4 and second magnet array 5, so that the target CTCs flowing through the magnetic separation tube 3 are adsorbed and captured on both sides of the magnetic separation tube 3.

[0047] The first magnet array 4 consists of an even number of first magnet blocks 41, with half of the first magnet blocks 41 having their magnetic poles opposite to those of the remaining half. The second magnet array 5 consists of an even number of second magnet blocks 51, including but not limited to 2, 4, and 6, with the number of first magnet blocks 41 and second magnet blocks 51 being equal. In operation, the magnetic pole faces of each second magnet block 51 in the second magnet array 5 and its counterpart in the first magnet array 4 are opposite, causing the attractive and repulsive forces between the two magnet arrays to cancel each other out or nearly cancel each other out, resulting in a weaker attractive force. This allows the two magnet arrays to naturally close together without affecting the attraction to paramagnetic objects, thus maintaining the adsorption and capture of CTCs. Conversely, excessive attractive or repulsive forces between the two magnet arrays would not only cause operational inconvenience but also affect the adsorption and capture efficiency of CTCs.

[0048] like Figure 1 As shown, the method of using the blood retrieval system of the present invention is as follows:

[0049] S1: Marking the target object using a magnetic enhancer;

[0050] 5-8 mg of a magnetic enhancer (superparamagnetic particles) was injected intravenously 20-30 minutes before the procedure to mark CTCs.

[0051] S2: Target capture device one and / or target capture device two capture the magnetically marked target;

[0052] In some embodiments, a target object capture device can be used first to capture a target object inside the body, and then a target object capture device can be used to capture another target object inside the body; in some embodiments, a target object capture device can be used first to capture a target object inside the body, and then a target object capture device can be used first to capture another target object inside the body.

[0053] In some embodiments, target capture device one and target capture device two may be used alternately and repeatedly until the target is completely captured.

[0054] In some embodiments, a single target capture device can be used to capture targets within the body, or a single target capture device can be used to capture targets within the body.

[0055] S2.1 The specific steps for capturing a target object using a target object capture device are as follows:

[0056] a: Under local anesthesia, the femoral vein is punctured in the groin, a catheter sheath is introduced, and a venous access is established; inferior vena cava angiography is performed, and the capture position of the target capture device is determined according to the morphology of the inferior vena cava. Alternatively, the aorta, superior vena cava, or downstream vessels of the tumor can be selected as the capture position as needed. Heparin is injected at the same time to perform systemic heparinization to prevent coagulation and thrombosis.

[0057] b: Guided by a guidewire, the marker capture device enters the capture position in the inferior vena cava through the catheter sheath. The outer cannula 1 is withdrawn to expose the groove 20 of the attachment cannula 2, and the adsorption and capture of CTCs begins. The captured CTCs are the attachment segment of the attachment cannula 2.

[0058] c: The target capture device is left in place for half an hour. Human blood circulates once every 3 minutes on average. Half an hour is equivalent to 10 cycles. Based on a total human blood volume of 5000mL, capturing for half an hour is equivalent to filtering 50000mL of blood, which is 10000 times the blood sample volume of traditional laboratory medicine.

[0059] d: After the target capture device finishes capturing, push the outer sleeve 1 forward to completely retract the attachment section of the attachment sleeve 2 into the outer sleeve 1, and then take out the entire target capture device.

[0060] e: Push the attachment section of the attachment sleeve 2 out from the front end of the outer sleeve 1 and place it in a test tube containing reagents. Pull out the first magnetic suction component from the rear end of the attachment sleeve 2, cut off the attachment section of the attachment sleeve 2, and place it in a test tube containing reagents to obtain CTCs.

[0061] S2.2 The specific steps for capturing the target object using the target object capture device are as follows:

[0062] The details are as follows:

[0063] a: CTCs are adsorbed and captured using Target Capture Device II (Circulating Tumor Cell Extracorporeal Magnetic Filtering Device). The first magnet array 4 and the second magnet array 5 are placed vertically upwards, parallel to each other, with their magnetic poles facing each other. The magnetic separation tube 3 is vertically fixed between the two magnet arrays, with the lower end being the inflow end and the upper end the outflow end. It is connected to the first infusion tube 9 and the second infusion tube 10 via the first three-way valve 6 and the second three-way valve 7, respectively. An arterial tourniquet and / or a mercury sphygmomanometer are applied to the patient's upper arm near the elbow, and the pressure is increased to between the systolic and diastolic pressures and maintained at that pressure. A cephalic vein is punctured in the upper arm near the sphygmomanometer, and a cannula is inserted to open the venous access, which is the infusion end. A superficial vein is punctured in the forearm, and a cannula is inserted to open the venous access, which is the output end. The first infusion tube 9 is connected to the cannula at the output end, and the second infusion tube 10 is connected to the cannula at the infusion end.

[0064] b: Open the first three-way valve 6 and the second three-way valve 7. Blood flows out from the distal vein and enters the first infusion tube 9. After the peristaltic pump 8 adjusts the speed, it enters the magnetic separation tube 3 from the lower end through the first three-way valve 6. At this time, under the strong magnetic field formed between the first magnet array 4 and the second magnet array 5, CTCs bound by the magnetic enhancer are adsorbed onto the inner wall of the magnetic separation tube 3. The remaining blood cells pass through the magnetic separation tube 3 without hindrance and are then returned to the body through the second infusion tube 10 via the second three-way valve 7. The filtration time is 20-30 minutes.

[0065] c: After filtration, physiological saline is injected into the influent to flush the blood. After the blood in the magnetic separation tube 3 is basically cleaned, the first three-way valve 6 and the second three-way valve 7 are closed. The first three-way valve 6 and the second three-way valve 7 are then removed by disassembling the valves. Heparin caps are then tightened at both ends of the magnetic separation tube 3. This process is still carried out between the first magnet array 4 and the second magnet array 5. After this, the magnetic separation tube 3 becomes a sealed container. It is then taken out between the first magnet array 4 and the second magnet array 5, which becomes a flat test tube. It can be directly processed by a centrifuge and used for subsequent detection, diagnostic and analytical experiments.

[0066] S3: Capture magnetically marked targets using Target Collector II and / or Target Collector Pair;

[0067] The method of use can first perform steps a to c in S2.2 to capture the target by placing circulating tumor cells outside the body, and then perform steps a to e in S2.1 to capture the target by leaving the target capture device inside the body. The blood retrieval system can be used repeatedly. When the capture rate is low, the above steps can be repeated to capture more targets.

[0068] The blood retrieval system of this invention can simultaneously perform diagnosis and treatment, and diagnostic testing.

[0069] (I) When the target object capture device is selected in the blood retrieval system: First, a magnetic enhancer is injected intravenously to mark CTCs; a capture position is selected, the target object capture device is placed at that position, the outer sleeve is withdrawn to expose the groove of the attachment sleeve, and the adsorption and capture of CTCs begins; capture ends after half an hour; the capture device is removed, the captured CTCs are collected, and medical diagnosis is performed. Simultaneously, a target object killing agent, such as the radionuclide iodine-131, can be added to the target object capture device for ultra-short-range irradiation to kill the captured CTCs. It is understood that other types of target object killing agents can also be added depending on the target object to achieve a therapeutic effect.

[0070] (II) When the capture device in the blood retrieval system is selected as the extracorporeal magnetic filtration device for circulating tumor cells: human blood flows out through the first infusion tube and enters the magnetic separation tube. Under the strong magnetic field formed between the first and second magnetic arrays, CTCs bound by the magnetic enhancer are adsorbed onto the inner wall of the magnetic separation tube. The remaining blood cells pass through the magnetic separation tube without obstruction and then flow back to the human body through the second infusion tube. During the continuous blood circulation and reinfusion process, CTCs are continuously adsorbed onto the inner wall of the magnetic separation tube. After obtaining CTCs, they are used for subsequent tumor diagnosis and detection.

[0071] This invention proposes a blood retrieval system comprising a magnetic enhancer, a first target analyte trap, and a second target analyte trap, combining interventional techniques to capture target analytes. The grooves in the first target analyte trap provide space for the target analyte, helping to maintain its original state and activity. Magnetic beads are arranged sequentially, with adjacent beads having the same polarity at their adjacent ends, and a uniform 360° magnetic field distribution without blind spots, enhancing the adsorption effect. The second target analyte trap contains a magnetic separation tube, a first magnetic array, and a second magnetic array. Under the strong magnetic field formed by the first and second magnetic arrays, blood is circulated back through the first and second infusion tubes, adsorbing and capturing the target analyte onto the inner wall of the magnetic separation tube. This blood retrieval system can be applied to capture any target analyte among tumor cells, microorganisms, proteins, and nucleic acids, and the number of cycles can be determined based on the capture results each time. Compared to traditional laboratory medicine, the sample volume is greatly increased, thus improving capture efficiency, achieving rapid and efficient capture and filtration. The purpose of capture is to obtain the target analyte, and the purpose of filtration is to purify the environment in which the target analyte resides. This blood retrieval system can be used in scientific research and industrial fields, and has great market application prospects.

[0072] Although the present invention has been described in detail through the preferred embodiments above, it should be understood that the above description should not be considered as a limitation of the present invention. Various modifications and substitutions to the present invention will be apparent to those skilled in the art after reading the above description. Therefore, the scope of protection of the present invention should be defined by the appended claims.

Claims

1. A blood retrieval system, characterized in that, Include: A magnetic enhancer is used to magnetically label target substances in a sample, wherein the magnetic enhancer is selected from immunomagnetic nanoparticles; A capture device used to capture targets that have been magnetically marked; The capture device includes at least two target capture devices: a first target capture device and a second target capture device. The first target capture device includes a sleeve assembly and a first magnetic attraction assembly. The sleeve assembly includes an outer sleeve and an attachment sleeve disposed within the outer sleeve. The outer surface of the attachment sleeve has a groove. The outer sleeve and the attachment sleeve are slidable relative to each other, so that the groove on the outer surface of the attachment sleeve is exposed outside the outer sleeve or is contained therein. The first magnetic attraction assembly is disposed within the attachment sleeve and is used to attract and capture magnetically marked target objects. The first magnetic attraction assembly includes a chain of magnetic beads composed of a plurality of sequentially arranged magnetic beads and a metal wire connected in series with the chain of magnetic beads. The adjacent magnetic poles of two adjacent magnetic beads have the same polarity, so that there is a gap between two adjacent magnetic beads. The target capture device includes a magnetic separation tube and a second magnetic attraction component. The magnetic separation tube is sandwiched between the second magnetic attraction components, and the second magnetic attraction components are used to attract and capture magnetically marked target objects. The magnetic separation tube has a structure with a flat cylindrical shape in the middle and flat conical shapes at both ends with openings; The second magnetic attraction component includes at least a first magnet array and a second magnet array, wherein the first magnet array and the second magnet array are arranged in parallel and facing each other; The first magnet array consists of an even number of first magnet blocks, and the second magnet array consists of an even number of second magnet blocks, with the number of first magnet blocks and second magnet blocks being equal. In this case, half of the second magnet blocks in the second magnet array have opposite magnetic pole faces to the opposite first magnet blocks in the first magnet array, while the remaining half of the second magnet blocks have the same magnetic pole faces to the opposite first magnet blocks, so that the attractive and repulsive forces between the two sets of magnet arrays cancel each other out. The specific steps for capturing a target object using a target object capture device are as follows: a: Under local anesthesia, the femoral vein is punctured in the groin, a catheter sheath is introduced, and a venous access is established; inferior vena cava angiography is performed, and the capture position of the target capture device is determined based on the morphology of the inferior vena cava, or / as needed, the aorta, superior vena cava, or downstream vessels of the tumor are selected as the capture position, and heparin is injected simultaneously for systemic heparinization to prevent coagulation and thrombosis; b: Guided by a guidewire, the marker capture device enters the capture position in the inferior vena cava through the catheter sheath. The outer cannula is withdrawn to expose the groove of the attachment cannula, and the capture of circulating tumor cells (CTCs) begins. The captured CTCs become the attachment segment of the attachment cannula. c: The target capture device is left in place for half an hour. Human blood circulates once every 3 minutes on average. Half an hour is equivalent to 10 cycles. The calculation is based on a total human blood volume of 5000mL. d: After the target capture device finishes capturing, push the outer sleeve forward to completely retract the attachment section of the attachment sleeve into the outer sleeve, and then take out the entire target capture device. e: Push the attachment segment of the attachment sleeve out from the front end of the outer sleeve and place it in a test tube containing reagents. Pull out the first magnetic suction component from the rear end of the attachment sleeve, cut off the attachment segment of the attachment sleeve, and place it in a test tube containing reagents to obtain circulating tumor cells (CTCs). The specific steps for capturing the target object using the target object capture device are as follows: a: Target trap II (circulating tumor cell extracorporeal magnetic filtration device) is used to adsorb and capture circulating tumor cells (CTCs). The first and second magnet arrays are placed vertically upwards, parallel to each other, with their magnetic poles facing each other. The magnetic separation tube is vertically fixed between the two sets of magnet arrays, with the lower end being the inflow end and the upper end being the outflow end. The first and second infusion tubes are connected through the first and second three-way valves, respectively. An arterial tourniquet and / or a mercury sphygmomanometer are applied to the patient's upper arm near the elbow, and the pressure is increased to between the systolic and diastolic pressures and maintained at that pressure. A cephalic vein is punctured in the upper arm near the sphygmomanometer, and a cannula is inserted to open the venous access, which is the infusion end. A superficial vein is punctured in the forearm, and a cannula is inserted to open the venous access, which is the output end. The first infusion tube is connected to the cannula at the output end, and the second infusion tube is connected to the cannula at the infusion end. b: Open the first three-way valve and the second three-way valve. Blood flows out from the distal vein and enters the first infusion tube. After the peristaltic pump adjusts the speed, it enters the magnetic separation tube from the lower end through the first three-way valve. At this time, under the strong magnetic field formed between the first and second magnetic arrays, the circulating tumor cells (CTCs) bound by the magnetic enhancer are adsorbed onto the inner wall of the magnetic separation tube. The remaining blood cells pass through the magnetic separation tube without obstruction and are then returned to the body through the second infusion tube via the second three-way valve. The filtration time is 20-30 minutes. c: After filtration, physiological saline is injected to flush the blood. Once the blood in the magnetic separation tube is basically clean, the first and second three-way valves are closed. The first and second three-way valves are then removed by disassembling the valves. Heparin caps are then tightened at both ends of the magnetic separation tube. This process is still carried out between the first and second magnet arrays. After this, the magnetic separation tube becomes a sealed container. It is then removed from between the first and second magnet arrays and becomes a flat test tube, which can be directly processed by a centrifuge and used for subsequent detection, diagnostic, and analytical experiments.

2. The blood retrieval system as described in claim 1, characterized in that, The blood retrieval system also includes a guide wire for guiding the outer cannula.

3. The blood retrieval system as described in claim 1, characterized in that, The blood retrieval system also includes the radioactive nuclide iodine-131, which is used to kill captured targets by ultra-short-range irradiation.

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