CN116492525A - Blood salvaging system, use method and application thereof - Google Patents

Blood salvaging system, use method and application thereof Download PDF

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Publication number
CN116492525A
CN116492525A CN202310059513.9A CN202310059513A CN116492525A CN 116492525 A CN116492525 A CN 116492525A CN 202310059513 A CN202310059513 A CN 202310059513A CN 116492525 A CN116492525 A CN 116492525A
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magnetic
magnet
sleeve
blood
capturing
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蒋霆辉
陆珺
沈天皓
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Shanghai Xinguang Layer Biomedical Technology Co ltd
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Shanghai Xinguang Layer Biomedical Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3618—Magnetic separation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
    • A61B10/02—Instruments for taking cell samples or for biopsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/362—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits changing physical properties of target cells by binding them to added particles to facilitate their subsequent separation from other cells, e.g. immunoaffinity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • External Artificial Organs (AREA)

Abstract

The invention discloses a blood salvage system, a use method and application thereof. Taking blood magnetic salvage as an example, the method comprises the following steps: a magnetic enhancer, a catcher for catching a target object; the capture device at least comprises a first target object capture device and a second target object capture device, wherein the first target object capture device comprises a sleeve assembly and a first magnetic attraction assembly, the sleeve assembly comprises an outer sleeve and an attachment sleeve arranged in the outer sleeve, a groove is formed in the outer surface of the attachment sleeve, and the first magnetic attraction assembly is arranged in the attachment sleeve; the target object catcher comprises a magnetic separation tube and a second magnetic attraction component. The blood salvaging system has universality, can be also used for enriching and capturing other targets such as microorganisms, proteins, nucleic acids and the like, can be applied to the industrial fields such as medicine, biology, industrial pipeline fluid or gas and the like, can achieve the effects of rapid and efficient capturing and filtering, has wide application and has market value.

Description

Blood salvaging system, use method and application thereof
Technical Field
The invention belongs to the field of biomedicine, and particularly relates to a blood salvage system, a use method and application thereof.
Background
The search for and capture of rare targets in blood has been a challenge, such as circulating tumor cells.
Cancer has long been the first threat to human health, with nearly millions of people dying from cancer every year worldwide. The main reason for failure of cancer treatment is that cancer is susceptible to metastasis, particularly hematogenous metastasis, and most cancer patients eventually die from metastasis. The research hotspots in recent years are focusing more and more on a key role: circulating tumor cells (Circulating Tumor Cells, CTCs). It is a tumor cell which falls off from the primary tumor site, enters peripheral blood and cruises in the blood, and can possibly break through the inner wall of a blood vessel at any time and transfer to other tissues. A large number of researches show that the detection of CTCs has very important clinical significance for early screening and early diagnosis of tumors, recurrence monitoring, drug selection, curative effect evaluation, prognosis evaluation and the like. Furthermore, further molecular biological analysis of captured CTCs or cultured CTCs cell lines is also an important direction in tumor research.
However, CTCs were found to be very low in whole blood (1 mL of whole blood had red blood cells 10) 9 Individual, white blood cells 10 7 And only one CTC). At present, the enrichment method of CTCs at home and abroad is not ideal. (1) The blood sampling amount is too small, so that the enrichment efficiency of CTCs is extremely low, but the large bleeding for detection is obviously unrealistic; (2) in vitro induction detection fails to obtain CTCs viable cells; (3) The effective contact surface of in vivo antibody antigen contact capture is small, and the contact probability is too low. This makes current "liquid biopsies" targeting CTCs slow.
Thus, there is a need for a system and method that can salvage objects in whole body blood so that the objects can be captured in large amounts.
Disclosure of Invention
The invention aims to overcome the defects that the existing detection method has the defects of small blood sampling sample size, false negative detection result, incapability of capturing target objects from non-in-vitro flowing blood with the sample size of hundreds or tens of thousands of times, incapability of reflecting the whole body condition of the target objects and poor tumor heterogeneity reflection.
In order to achieve the above object, the present invention provides a blood salvage system comprising: a magnetic enhancer for magnetically labeling a target in a sample, the magnetic enhancer selecting immunomagnetic nanoparticles; a capturer for capturing the magnetically labeled target; the capture device at least comprises a first target object capture device and a second target object capture device, wherein the first target object capture device comprises a sleeve assembly and a first magnetic attraction assembly, the sleeve assembly comprises an outer sleeve and an attachment sleeve arranged in the outer sleeve, a groove is formed in the outer surface of the attachment sleeve, and the first magnetic attraction assembly is arranged in the attachment sleeve and is used for adsorbing and capturing a target object subjected to magnetic marking; the target object capturing device comprises a magnetic separation tube and a second magnetic attraction assembly, wherein the magnetic separation tube is arranged between the second magnetic attraction assemblies, and the second magnetic attraction assembly is used for adsorbing and capturing a target object marked by magnetism.
Preferably, the first magnetic component comprises a magnetic bead chain formed by a plurality of magnetic beads which are sequentially arranged, and a metal wire connected with the magnetic bead chain in series; the polarities of the adjacent magnetic poles of the two adjacent magnetic beads are the same, so that a gap exists between the two adjacent magnetic beads.
Preferably, the second magnetic component at least comprises a first magnet matrix and a second magnet matrix, and the first magnet matrix and the second magnet matrix are arranged in parallel and opposite directions.
Preferably, the first magnet matrix is composed of an even number of first magnet blocks, wherein the magnetic pole direction of one half of the first magnet blocks is opposite to the magnetic pole direction of the other half of the first magnet blocks; the second magnet blocks are composed of an even number of second magnet blocks.
Preferably, the blood salvage system further comprises a guide wire for guiding the outer sleeve.
Preferably, the blood salvage system further comprises radionuclide iodine-131 for killing the captured target object by ultra-short-range irradiation.
The invention also provides a use method of the blood salvage system, which comprises the following steps:
step 1, magnetically labeling a target in a sample by using a magnetic enhancer;
step 2, placing the first object capturing device at a first capturing position, backing the outer sleeve, sliding the outer sleeve and the attaching sleeve relatively to expose a groove of the attaching sleeve, and absorbing and capturing the object into the groove through the first magnetic component;
step 3, placing a second object capturing device at a second capturing position, clamping the magnetic separation tube between the second magnetic attraction components, and absorbing and capturing the object combined by the magnetic reinforcing agent to the inner wall of the magnetic separation tube under the strong magnetic field formed by the second magnetic attraction components;
the steps 2 and 3 can be alternately performed, and the steps 2 to 3 can be circularly performed for several times, so that the target objects can be captured.
Preferably, the time for capturing the target is 20-60 min.
Preferably, in step 2, radionuclide iodine-131 is added into the first object capturing device for ultra-short-range irradiation killing of the captured object.
The invention also provides an application of the blood salvage system, which can be used for salvaging any one or more than two of tumor cells, microorganisms, proteins and nucleic acids.
The invention has the beneficial effects that:
(1) The blood salvaging system comprises a magnetic enhancer and a capturer, wherein the capturer at least comprises a first target object capturer and a second target object capturer, the first target object capturer can be left in the body to salvage the target object through the combined intervention technology, and the second target object capturer can be placed in the body to salvage the target object. For salvaging the target object in the body, the capturer adopts a target object capturing device, the target object capturing device is provided with a groove and a magnetic device, the groove provides an accommodating space for the target object, the original state and activity of the target object can be maintained, and the magnetic device can enhance the adsorption effect of the target object; for the salvaging of the target object placed outside the body, the capturer adopts a circulating feedback type circulating tumor cell in-vitro magnetic filtering device, so that the target object can be enriched and captured, and compared with other biopsy tests, the traumability of the capturing process and the false negative rate of the result can be reduced; compared with the traditional blood sampling test, the circulating feedback of the flowing blood sample can obviously improve the sample quantity, does not need operation, and is suitable for repeated tests or periodic tests.
(2) The application adopts the magnetic enhancer, can target and combine the label and magnetize the target in the blood or body fluid, then trace, capture, filter or kill the target in a huge amount of flowing blood or body fluid, and has higher capture efficiency.
(3) The blood salvage system has universality. Specifically, the method can be used for all tumor patients and tumor high-risk groups, can be repeatedly used, can be used for promoting radical cure and evaluating recurrence risk in early stage, can be used for filtering a net bag in operation, can be used for testing drug sensitivity and evaluating curative effect in middle and late stage, can be used for enriching and capturing other markable targets such as microorganisms, proteins, nucleic acids and the like besides CTCs, can be widely applied to the industrial fields such as medicine, biology, industrial pipeline fluid or gas and the like, and has great market value.
Drawings
FIG. 1 is a flow chart of a method of using the blood salvage system of the present invention.
Fig. 2 is a schematic structural view of the object capturing device according to the present invention.
FIG. 3 is a schematic diagram showing the operation of the extracorporeal magnetic filtration device for circulating tumor cells in a circulating and feedback manner.
FIG. 4 is a schematic diagram of a part of the structure of the extracorporeal magnetic filtration device for circulating tumor cells of the present invention.
FIG. 5 is a schematic diagram of the structure of the magnetic separation tube and magnet matrix of the extracorporeal magnetic filtration device for circulating tumor cells of the present invention.
The device comprises a 1-outer sleeve, a 2-attaching sleeve, a 20-groove, a 3-magnetic separation tube, a 4-first magnet matrix, a 41-first magnet block, a 5-second magnet matrix, a 51-second magnet block, a 6-first three-way valve, a 7-second three-way valve, an 8-peristaltic pump, a 9-first infusion tube and a 10-second infusion tube.
Detailed Description
The following description of the embodiments of the present invention will be made apparent and fully in view of the accompanying drawings, in which some, but not all embodiments of the invention are shown. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In the description of the present invention, it should be noted that the positional or positional relationship indicated by the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. are based on the positional or positional relationship shown in the drawings, are merely for convenience of describing the present invention and simplifying the description, and do not indicate or imply that the apparatus or elements referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as limiting the present invention. Furthermore, the terms "first," "second," "third," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
In the description of the present invention, it should be noted that, unless explicitly specified and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; may be a mechanical connection; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.
The invention provides a blood salvaging system, which comprises a magnetic enhancer combined with a target object, a capturer for capturing the target object combined with the magnetic enhancer and an auxiliary intervention technology, wherein the magnetic enhancer consists of high molecular nano particles, magnetic nano particles and specific antibodies. Wherein the magnetic nanoparticles can be Fe 3 O 4 Nanoparticles due to Fe 3 O 4 The nanoparticle itself cannot be combined with the specific antibody, and the nanoparticle needs to be combined with the polymer nanoparticle, while the liposome is a polymer nanoparticle, and Fe is added 3 O 4 The nanometer particles are encapsulated in the liposome, the specific antibody modifies the surface of the liposome, and the magnetic enhancer can be combined with the specific antigen on the surface of the abnormal cells (target objects) through the specific antibody, so that the abnormal cells have paramagnetism and can be attracted by a magnetic field.
The trap at least comprises a first target object trap and a second target object trap, so that the target object can be trapped and salvaged. The target objects of the invention are unified as unlabeled target objects before being marked by the magnetic enhancer, and are unified as magnetically marked target objects after being marked by the magnetic enhancer. The blood salvaging system can salvage the target object by using the mode that the target object catcher is left in the body, and the mode has the advantages that the attachment sleeve of the target object catcher is provided with the groove, so that an accommodating space can be provided for the target object, the original state and activity of the target object can be kept, the magnetic device comprises magnetic bead chains formed by magnetic beads which are sequentially arranged, the adjacent ends of the adjacent magnetic beads have the same polarity and repel each other, the magnetic field can be uniformly distributed in the whole length of the magnetic bead chains, and the surrounding 360-degree magnetic field is uniformly distributed without blind areas, so that the adsorption effect of the magnetic bead chains is enhanced. The method has the advantages that after a strong magnetic field is formed between the first magnet square matrix and the second magnet square matrix, the target object can be adsorbed and captured to two sides of the magnetic separation tube when passing through the magnetic separation tube; the circulation feedback way can filter blood in a large flow rate, can not cause a large amount of blood loss, does not need operation, avoids hurting patients and increasing economic burden, and is suitable for repeatedly salvaging target objects.
In addition, the interventional technique, also called interventional therapy and interventional therapy, is the third major therapeutic discipline after internal medicine and surgery, and can make up the shortages of the internal and surgical techniques. The interventional technology is a minimally invasive treatment by applying modern high-tech means, and is characterized in that under the guidance of medical imaging equipment, special precise instruments such as a catheter, a guide wire and the like are introduced into a human body to diagnose and treat a focus in the body locally. The intravascular operation belongs to the technical field of intervention, and the subsequent operation can be performed by inserting a special catheter into a blood vessel without operating and only by a puncture needle eye which is not large in rice grains. Has the advantages of minimally invasive, high efficiency, quick recovery, good effect and the like. The interventional medical community has complete safety operation rules, so that the blood salvage system must be combined with an interventional technology to ensure safety. Even the "salvage" of the present invention is a continuation of the interventional technique.
The blood salvaging system is widely applied, all substances which can be magnetically marked can be captured by the system, the related field at least comprises medical science, biology, industrial field and the like, the blood salvaging system can be likened to 'net fishing' or 'remote fish attracting', the traditional inspection medicine belongs to 'net fishing', the sample size can be 10000 times when the target object catcher is in the body for salvaging, and the sample size can be more than 100 times when the target object catcher is in the body for salvaging in a circulating way. Therefore, the sample size of the blood salvage system is obviously higher than that of the traditional test medicine, and the positive capture rate is naturally higher than that of the traditional test medicine.
The invention is designed safely: (1) The target object capturing device uses an interventional catheter material and an existing blood transfusion pipeline material, so that the device is safe and reliable; (2) The magnetic component is not contacted with blood and human body, and is safe and reliable; (3) The head end of the target object capturing device is round and smooth, and the operation is guided by the ultra-smooth guide wire, so that the device is safer than the existing vein stent and other operations; (4) CTCs in vivo capture is only an interventional secondary operation, i.e. the resident can independently complete, and the academy will make special safety operation rules to ensure safety; (5) The extracorporeal magnetic filtration of the circulating tumor cells which are recycled does not involve arterial puncture, the operation is extremely simple, the risk is extremely low, and the necessary safe operation rules are customized according to the known standard in the field; (6) Aiming at thrombus problems possibly occurring in vascular operation and in-vitro magnetic filtration, the interventional and dialysis industries have complete heparinization operation procedures; (7) The immune magnetic nano-particles are currently internationally provided with an FDA approved preparation for a magnetic resonance contrast agent, and are safe and reliable.
The present embodiment is described in detail by taking capturing salvaged tumor cells in blood (i.e. blood magnetic salvaging):
examples
The invention provides a blood salvage system comprising a magnetic enhancer bound to an unlabeled target, a capturer for capturing the target bound with the magnetic enhancer, and an interventional technique. The target object capturing device comprises a target object capturing device and a target object capturing device, wherein the target object capturing device at least comprises a target object capturing device I and a target object capturing device II, and the target object capturing device II is a circulating feedback type circulating tumor cell in-vitro magnetic filtering device.
As shown in fig. 2, the target capturing device comprises a sleeve assembly and a first magnetic attraction assembly, the sleeve assembly comprises an outer sleeve 1 and an attaching sleeve 2 arranged in the outer sleeve 1, and a groove 20 is formed in the outer surface of the attaching sleeve 2. The outer sleeve 1 and the attaching sleeve 2 can slide relatively, so that at least part of the groove 20 is exposed out of the outer sleeve 1, and one end of the attaching sleeve 2 exposed out of the outer sleeve 1 is a closed end 21. The first magnetic component is arranged in the attaching sleeve 2. The end of the attachment sleeve 2 located in the outer sleeve 1 is an open end (rear end), and the first magnetic component is placed in the attachment sleeve 2 through the open end.
Before capturing, the magnetic enhancer (containing Fe 3 O 4 CTCs in blood were magnetically labeled (the magnetic label in this example is a paramagnetic label). In the initial state, the attachment sleeve 2 is completely located within the outer sleeve 1. After the capturing device is left at the capturing position, the outer sleeve 1 is retracted, the outer sleeve 1 and the attaching sleeve 2 slide relatively, so that the groove of the attaching sleeve 2 is exposed outside the outer sleeve 1, and one end of the attaching sleeve 2 exposed outside the outer sleeve 1 is used as the front end of the attaching sleeve 2. The magnetic force of the magnetic assembly provided in the attachment sleeve 2 may penetrate the attachment sleeve 2 to radiate outward, attracting magnetically labeled CTCs to the outer circumference of the attachment sleeve 2. CTCs have a tendency to approach the magnetic assembly, the outer surface of the attachment sleeve 2 is provided with grooves 20, the bottoms of the grooves 20 are closer to the magnetic assembly 2, so the magnetic force at the bottoms of the grooves 20 is stronger, and thus, CTCs can be captured and stored in the grooves 20. The grooves 20 provide accommodation space for CTCs, which is beneficial to maintaining the original state of CTCs and protecting cell activity.
After the capturing is finished, the outer sleeve 1 is pushed forward, and the outer sleeve 1 and the attaching sleeve 2 slide relatively, so that the attaching sleeve 2 is completely positioned in the outer sleeve 1. Because CTCs can be attracted in the groove 20 all the time under the magnetic force action of the first magnetic component, the edge of the outer sleeve 1 can not scratch the CTCs and can not cause the CTCs to fall off in the process that the outer sleeve 1 and the attaching sleeve 2 slide relatively.
Finally, the target capturing device is entirely removed from the capturing position. When the CTCs are removed, the attaching sleeve 2 is completely positioned in the outer sleeve 1, CTCs stored in the groove 20 are protected by the outer sleeve 1, the CTCs cannot be scratched by the blood vessel wall or subcutaneous tissue to fall off, and all CTCs attracted and captured by the first magnetic component can be stored in the groove 20 through the target object capturing device and are completely taken out of the first capturing position.
As shown in fig. 3 to 5, the extracorporeal magnetic filtration device for circulating tumor cells in a circulating and feedback manner comprises a magnetic separation tube 3, wherein the magnetic separation tube 3 has a structure with a flat cylindrical middle part and a flat conical two ends and is provided with an opening; a first infusion tube 9 and a second infusion tube 10, wherein the first infusion tube 9 is communicated with one end opening of the magnetic separation tube 3, and the second infusion tube 10 is communicated with the other end opening of the magnetic separation tube 3. And a second magnetic attraction assembly comprising a first magnet matrix 4 and a second magnet matrix 5. When in working state, the first magnet matrix 4 and the second magnet matrix 5 are arranged in parallel and opposite directions, and the magnetic pole faces are opposite; the magnetic separation tube 3 is arranged between the first magnet square matrix 4 and the second magnet square matrix 5, and two large-area side surfaces of the magnetic separation tube 3 are respectively clung to or close to the magnetic pole surfaces of the first magnet square matrix 4 and the second magnet square matrix 5 which are opposite to each other, so that target objects CTCs flowing through the magnetic separation tube 3 are adsorbed and captured on two sides of the magnetic separation tube 3.
The first magnet matrix 4 consists of an even number of first magnet blocks 41, wherein the magnetic pole direction of one half of the first magnet blocks 41 is opposite to the magnetic pole direction of the other half of the first magnet blocks 41; the second magnet matrix 5 consists of an even number of second magnet blocks 51; the even number includes, but is not limited to, 2, 4, 6, and the number of the first magnet pieces 41 and the second magnet pieces 51 are equal. In the working state, each second magnet block 51 in the second magnet matrix 5 and each first magnet block 41 opposite to each second magnet block 4 are arranged in a different way, so that attractive force and repulsive force between the two groups of magnet matrixes are mutually counteracted or approximately counteracted to present weaker attractive force, and the two groups of magnet matrixes are in a natural folding state and do not influence the attractive force on paramagnetic objects, thereby not influencing the adsorption capture on CTCs; on the contrary, the attractive force or repulsive force between the two groups of magnet matrixes is too large, so that the operation is inconvenient, and the adsorption and capture efficiency of CTCs is affected.
As shown in fig. 1, the blood salvage system of the present invention is used as follows:
s1: marking the target object by using a magnetic enhancer;
5-8 mg of magnetic enhancer (superparamagnetic particles) is injected intravenously 20-30 minutes before operation, and CTCs are marked.
S2: the first object capturing device and/or the second object capturing device capture the magnetically marked object;
in some embodiments, the first object capturing device may be used to capture the object in the body, and the second object capturing device may be used to capture the object in the body; in some embodiments, the second object capturing device may be used to capture the object in the body, and then the first object capturing device may be used to capture the object in the body;
in some embodiments, the first object capturing device and the second object capturing device may be alternately performed, and the steps may be repeated until the capturing is completed;
in some embodiments, the first object capturing device may be used to capture the object in the body separately, or the second object capturing device may be used to capture the object in the body separately.
S2.1, capturing a target object by adopting a target object capturing device, wherein the specific steps are as follows:
a: puncturing femoral vein in groin under local anesthesia, introducing catheter sheath, and establishing vein channel; and (3) performing inferior vena cava radiography to judge the capturing position of a first target object capturing device (target object capturing device) according to the morphology of the inferior vena cava, or selecting an aorta, an superior vena cava or a downstream tumor blood vessel and the like as required as capturing positions, and simultaneously injecting heparin to perform systemic heparinization so as to prevent coagulation and thrombosis.
b: the marker capture device is guided through the guide wire and enters the capture position of the inferior vena cava through the catheter sheath, the outer sleeve 1 is retracted, the groove 20 of the attachment sleeve 2 is exposed, the CTCs begin to be captured by adsorption, and the CTCs are captured as the attachment section of the attachment sleeve 2.
c: the target object capturing device is left for half an hour, human blood circulates once for 3min on average, half an hour is equivalent to 10 cycles, the total blood volume of the human body is calculated to be 5000mL, and the capturing half an hour is equivalent to filtering 50000mL of blood, which is 10000 times of the blood sampling volume of the traditional inspection medicine.
d: after the capturing of the target object capturing device is finished, the outer sleeve 1 is pushed forward, the attachment section of the attachment sleeve 2 is completely retracted into the outer sleeve 1, and then the whole target object capturing device is taken out.
e: the attachment section of the attachment sleeve 2 is pushed out from the front end of the outer sleeve 1 and placed in a test tube filled with a reagent, the first magnetic component is pulled out from the rear end of the attachment sleeve 2, the attachment section of the attachment sleeve 2 is sheared off and placed in the test tube filled with the reagent, and CTCs are obtained.
S2.2, capturing a target object by adopting a target object capturing device II, wherein the specific steps are as follows:
the specific steps are as follows:
a: target trap two (a circulating tumor cell in-vitro magnetic filter device) is used for adsorption and capture of CTCs. The first magnet square matrix 4 and the second magnet square matrix 5 are vertically upwards and parallelly placed in opposite directions, the magnetic pole faces are opposite, the magnetic separation tube 3 is vertically fixed between the two groups of magnet square matrices, the lower part is an inflow end, the upper part is an outflow end, and the magnetic separation tube is respectively connected with the first infusion tube 9 and the second infusion tube 10 through the first three-way valve 6 and the second three-way valve 7; binding an arterial tourniquet and/or a mercury sphygmomanometer at the elbow proximal segment of the patient's upper arm, adding pressure between the systolic pressure and the diastolic pressure, and resting at that pressure; puncturing a head vein at the upper arm of the near section of the sphygmomanometer, and opening a vein passage by the indwelling sleeve to be a feedback end; puncturing superficial veins at the forearm, and opening a vein passage by using an indwelling cannula as an output end; the first infusion tube 9 is connected with the sleeve at the output end, and the second infusion tube 10 is connected with the sleeve at the feedback end.
b: the first three-way valve 6 and the second three-way valve 7 are opened, blood flows out of a far-end vein, enters the first infusion tube 9, enters the magnetic separation tube 3 from the lower end of the magnetic separation tube 3 through the first three-way valve 6 after the speed is regulated by the peristaltic pump 8, at the moment, under a strong magnetic field formed between the first magnet array 4 and the second magnet array 5, CTCs combined by the magnetic reinforcing agent are adsorbed to the inner wall of the magnetic separation tube 3, the rest blood cells pass through the magnetic separation tube 3 without barriers, and then are input into the body from the second infusion tube 10 through the second three-way valve 7, and the filtering time is 20-30 min.
c: after the filtration is finished, the inflow channel is filled with normal saline to wash blood, after the blood in the magnetic separation tube 3 is basically washed clean, 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 removed through the disassembly valve, the two ends of the magnetic separation tube 3 are screwed by the heparin cap, the process is still carried out between the first magnet array 4 and the second magnet array 5, the magnetic separation tube 3 becomes a closed container, and then the closed container is taken out from the position between the first magnet array 4 and the second magnet array 5, so that a flat test tube is formed, and the flat test tube can be directly processed by a centrifugal machine and is subjected to subsequent detection, diagnosis and analysis experiments.
S3: capturing the magnetically marked target by adopting a second target capturing device and/or a first target capturing device;
the using method can firstly carry out the mode that the circulating feedback type circulating tumor cells are placed in vitro in the steps a to c in the step S2.2 to capture the target, and then carry out the mode that the target capturing device is left in vivo in the steps a to e in the step S2.1 to capture the target; the blood salvaging system can be repeatedly used, and when the capturing rate is low, the steps can be continuously circulated to capture more targets.
The blood salvaging system can realize diagnosis treatment and diagnosis detection at the same time:
(one) when the catcher in the blood salvage system selects the target object catching device: firstly, intravenous injection of a magnetic enhancer is carried out to mark CTCs; selecting a capturing position, reserving a target object capturing device at the capturing position, backing the outer sleeve, exposing a groove for attaching the sleeve, and starting to absorb and capture CTCs; ending the capturing after half an hour of capturing; and taking out the capturing device, collecting the captured CTCs, and performing medical diagnosis. Meanwhile, a target killing agent such as radionuclide iodine-131 can be added into the target capturing device for super-short-range irradiation killing of the captured CTCs, and it can be understood that other types of target killing agents can be added according to different targets, so that the treatment effect is realized.
(II) when the catcher in the blood salvaging system selects the circulating tumor cell in-vitro magnetic filtering device: human blood flows out through the first infusion tube and enters the magnetic separation tube, under the strong magnetic field formed between the first magnet matrix and the second magnet matrix, CTCs combined by the magnetic reinforcing agent are adsorbed to the inner wall of the magnetic separation tube, other blood cells pass through the magnetic separation tube without barriers, then flow back to the human body through the second infusion tube, and in the continuous blood circulation feedback process, the CTCs are continuously adsorbed to the inner wall of the magnetic separation tube, and the CTCs are obtained and then used for subsequent tumor diagnosis and detection.
The invention provides a blood salvaging system, which comprises a magnetic reinforcing agent, a first target object capturer, a second target object capturer and a combined intervention technology, so as to capture a target object. The groove of the first object catcher provides an accommodating space for the object, so that the original state and activity of the object can be kept, the magnetic beads are sequentially arranged, the polarities of the adjacent two ends of the adjacent magnetic beads are the same, the surrounding 360-degree magnetic field is uniformly distributed without blind areas, and the adsorption effect is enhanced; the second object capturing device comprises a magnetic separation tube, a first magnet matrix and a second magnet matrix, and blood is circulated and returned through the first infusion tube and the second infusion tube to absorb and capture the object to the inner wall of the magnetic separation tube under the strong magnetic field formed by the first magnet matrix and the second magnet matrix. The blood salvaging system can be applied to capturing any target in tumor cells, microorganisms, proteins and nucleic acids, and the number of cycles of use can be determined according to the capturing result of each time. Compared with the traditional inspection medicine, the sample size is greatly improved, the capturing efficiency is improved, the effects of rapid and efficient capturing and filtering can be achieved, the capturing aim is to obtain the target object, and the filtering aim is to purify the large environment where the target object is located. The blood salvaging system can be used in the scientific research and industrial fields and has a large market application prospect.
While the present invention has been described in detail through the foregoing description of the preferred embodiment, it should be understood that the foregoing description is not to be considered as limiting the invention. Many modifications and substitutions of the present invention will become apparent to those of ordinary skill in the art upon reading the foregoing. Accordingly, the scope of the invention should be limited only by the attached claims.

Claims (10)

1. A blood salvage system comprising:
a magnetic enhancer for magnetically labeling a target in a sample, the magnetic enhancer selecting immunomagnetic nanoparticles;
a capturer for capturing the magnetically labeled target;
the capture device at least comprises a first target object capture device and a second target object capture device, wherein the first target object capture device comprises a sleeve assembly and a first magnetic attraction assembly, the sleeve assembly comprises an outer sleeve and an attachment sleeve arranged in the outer sleeve, a groove is formed in the outer surface of the attachment sleeve, and the first magnetic attraction assembly is arranged in the attachment sleeve and is used for adsorbing and capturing a target object subjected to magnetic marking;
the target object capturing device comprises a magnetic separation tube and a second magnetic attraction assembly, wherein the magnetic separation tube is arranged between the second magnetic attraction assemblies, and the second magnetic attraction assembly is used for adsorbing and capturing a target object marked by magnetism.
2. The blood salvaging system of claim 1 wherein said first magnetic attraction assembly comprises a magnetic bead chain comprised of a plurality of magnetic beads arranged in sequence, and a wire connected in series with said magnetic bead chain; the polarities of the adjacent magnetic poles of the two adjacent magnetic beads are the same, so that a gap exists between the two adjacent magnetic beads.
3. The blood salvaging system of claim 1 wherein said second magnetic attraction assembly comprises at least a first magnet matrix and a second magnet matrix, said first magnet matrix and said second magnet matrix being disposed in parallel and opposite relation.
4. A blood salvaging system according to claim 3 wherein said first magnet matrix is comprised of an even number of first magnet blocks and said second magnet matrix is comprised of an even number of second magnet blocks, the number of first magnet blocks and second magnet blocks being equal; and the magnetic pole faces between half of the second magnet blocks in the second magnet square matrix and the first magnet blocks opposite to each other in the first magnet square matrix are arranged differently, and the magnetic pole faces between the rest half of the second magnet blocks and the first magnet blocks opposite to each other are arranged identically, so that attractive force and repulsive force between the two groups of magnet square matrixes are mutually offset or approximately offset.
5. The blood salvage system of claim 1 further comprising a guidewire for guiding said outer cannula.
6. The blood salvage system of claim 1 further comprising a radionuclide iodine-131 for ultra-short range radiation sterilization of captured objects.
7. A method of using a blood salvage system according to any one of claims 1-6, comprising the steps of:
step 1, magnetically labeling a target in a sample by using a magnetic enhancer;
step 2, placing the first object capturing device at a first capturing position, backing the outer sleeve, sliding the outer sleeve and the attaching sleeve relatively to expose a groove of the attaching sleeve, and absorbing and capturing the object into the groove through the first magnetic component;
step 3, placing a second object capturing device at a second capturing position, clamping the magnetic separation tube between the second magnetic attraction components, and absorbing and capturing the object combined by the magnetic reinforcing agent to the inner wall of the magnetic separation tube under the strong magnetic field formed by the second magnetic attraction components;
the steps 2 and 3 can be alternately performed, and the steps 2 to 3 can be circularly performed for several times, so that the target objects can be captured.
8. The method of claim 7, wherein the time to capture the target is 20 to 60 minutes.
9. The method of claim 7, wherein in step 2, the radionuclide iodine-131 is added to the first object capturing device for killing the captured object by ultra-short-range irradiation.
10. Use of a blood salvage system according to claims 1-6, characterized in that said blood salvage system can be used for salvaging any one or a combination of any two or more of tumor cells, microorganisms, proteins, nucleic acids.
CN202310059513.9A 2022-01-27 2023-01-18 Blood salvaging system, use method and application thereof Pending CN116492525A (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
CN2022202257000 2022-01-27
CN202220225700 2022-01-27
CN202220305105 2022-02-16
CN2022203051058 2022-02-16
CN202220603759 2022-03-20
CN2022206037599 2022-03-20

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CN116492525A true CN116492525A (en) 2023-07-28

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