CN110180047B

CN110180047B - Device for capturing, processing and infusing circulating tumor cells back to stimulate immunity and application thereof

Info

Publication number: CN110180047B
Application number: CN201910374137.6A
Authority: CN
Inventors: 夏侯博; 严东楠; 沈靖菲; 查可扬; 魏新若; 周若晨
Original assignee: Southeast University
Current assignee: Southeast University
Priority date: 2019-05-07
Filing date: 2019-05-07
Publication date: 2021-09-28
Anticipated expiration: 2039-05-07
Also published as: CN110180047A

Abstract

A device for capturing, processing and returning Circulating Tumor Cells (CTCs) to stimulate immunity and application thereof, wherein the device comprises a blood transfusion unit, a CTCs capturing and processing unit, a monitoring unit and an energy supply unit; the blood transfusion unit inputs the blood of the user into the device and returns the processed blood to form a blood circuit; the blood circuit is connected with a CTCs capturing and processing unit and a monitoring unit; the energy supply unit is connected with other units through wires. The device captures and processes CTCs and infuses the processed CTCs back to a human body to stimulate immune response, so as to achieve the effect of adjuvant therapy of tumors and prevent the tumors from diffusing through peripheral blood to a certain extent, thereby reducing the risk of cancer cell metastasis. The versatility and reusability of the device of the present invention also allows for a significant cost improvement over current immunotherapy.

Description

Device for capturing, processing and infusing circulating tumor cells back to stimulate immunity and application thereof

Technical Field

The invention belongs to the field of immunotherapy of tumors, and particularly relates to a device for capturing, processing and infusing Circulating Tumor Cells (CTCs) back to stimulate immunity and application thereof.

Background

Each year, over 1400 million people worldwide are diagnosed with cancer, of which about 820 million will eventually die of cancer, and by 2030, the number of deaths will be doubled. As can be seen, cancer has become one of the major killers in modern human beings. The persistent difficulty in the medical field has gradually developed into the sword of damolix hanging at the top of the head of people, which threatens the life safety of each person all the time.

At present, the main treatment means of cancer are surgery, radiotherapy and chemotherapy. The operation is used as a mechanical means, the local treatment is thorough, but cancer cells can proliferate or metastasize to the periphery and far away, and the recurrence rate or metastasis rate after five years of operation is up to more than 90 percent, so that the cancer cannot be radically treated. Radiotherapy has significant efficacy for certain regional sensitive cancers, but is difficult to treat systemically. Chemotherapy is a systemic treatment and has therapeutic effects on primary and metastatic foci. However, when traditional chemotherapy and radiotherapy are used to kill tumor, they can also damage normal cells, which leads to general deterioration of life quality of patients and even to treatment discontinuation due to intolerance.

Despite the continuous improvement of the surgical methods for cancer and the continuous aging of chemotherapy drugs, the problem of residual cancer cell clearance cannot be completely solved, and the recurrence rate and death rate of cancer are still quite high. The main factors causing tumor recurrence and metastasis are tumor immune editing and immune escape, and many cancer patients still have a large number of immune cells in vivo, but the immune cells cannot effectively recognize and eliminate the tumor cells with low immunogenicity after mutation. Therefore, increasing the immunogenicity of tumors is key to successful tumor treatment.

Existing immunotherapy approaches include CAR-T, T-CRT, TIL, DC-CTL, etc., which are mostly focused on the modification or expansion of human immune cells to achieve the immune effect. Such as CAR-T, by genetically engineering T cells with a chimeric antibody that recognizes tumor cells and simultaneously activates immunity, culturing in vitro, expanding the chimeric T cells in large amounts, and returning the expanded chimeric T cells to the patient. However, the immunotherapy has high technology cost, large recurrence rate and small application range, and does not fundamentally solve the problem of tumor cell immune escape.

Disclosure of Invention

The technical problem to be solved is as follows: the invention overcomes the defects of the prior art, aims to solve the four problems of large total amount of cancer patients, high medical consumption of cancer patients, high recurrence rate of cancer and more pain suffered by the patients, and provides a device for capturing, processing and returning CTCs to stimulate immunity and application thereof. The device realizes the miniaturization and integration of cancer immunotherapy equipment based on the CTCs sorting technology and the related research of tumor cell immunogenic death, and provides a thought for breaking immune escape from the perspective of tumor cells. At the same time, the versatility and reusability of the device also make its cost a great improvement over current immunotherapy.

The technical scheme is as follows: a device for capturing, processing and reinfusing circulating tumor cells CTCs for immunization, the device comprising a housing, a transfusion unit, a CTCs capture and processing unit and an energizing unit;

the blood transfusion unit comprises an indwelling needle, a blood transfusion tube, a hemostatic clamp, a bubble detector, a blood pump and a heparin pump; the indwelling needle, the bubble detector, the blood pump and the heparin pump are sequentially connected through a blood conveying pipe; the hemostatic clamp is arranged between the indwelling needle and the bubble detector and is fixed on the blood transfusion tube; the indwelling needle is closed, and 1 blood extraction part and 1 blood return part are respectively arranged; the 2 indwelling needles are respectively attached with 1 bandage which is made of cotton and hemp materials;

the CTCs capturing and processing unit comprises an operation pool, a capturing module and a processing module; the operation pool is a blood circulation pipeline with a U-shaped structure, and a blood inlet and a blood outlet are respectively arranged at two ends of the blood circulation pipeline; the blood inlet and the blood outlet are both communicated with a blood transfusion tube; the capture module is arranged below the operation pool and comprises a magnetic bead groove, a magnetic bead supplement device and a return pipe; an immune sorting system is arranged in the magnetic bead groove; the magnetic bead tank is communicated with the operation pool through a first filter screen and is communicated with the return pipe through a second filter screen; the return pipe is communicated with the blood outlet; a supplement port is arranged on the magnetic bead groove; the supplementing port is provided with a check valve; the magnetic bead supplementing device comprises a magnetic bead pool and a conveying device; an isotonic solution of suspended immunomagnetic beads is filled in the magnetic bead pool; the conveying device is a peristaltic pump, and the solution and the magnetic beads are input into the magnetic bead tank through a supplement port; the processing module comprises a first adsorption magnetic pole, a second adsorption magnetic pole, a first thermal vibration magnetic pole and a second thermal vibration magnetic pole; the thermal vibration magnetic pole and the adsorption magnetic pole are electromagnets; the first adsorption magnetic pole is arranged in the U-shaped groove of the operation pool; the second adsorption magnetic pole is arranged below the magnetic bead groove; the first thermal vibration magnetic pole and the second thermal vibration magnetic pole are respectively arranged on two side surfaces of the U-shaped groove of the operation pool;

the energy supply unit is connected with the CTCs capturing and processing unit and the blood transfusion unit through leads.

Preferably, a monitoring unit is further arranged above the device, the monitoring unit comprises a monitoring module and a control module, and the monitoring module comprises a temperature sensing element, a blood sensor, an external interaction system, a buzzer element and a data analysis system; the temperature sensing element is arranged on the inner wall of the operation pool; the blood sensor is arranged on the inner wall of the blood transfusion tube; the external interaction system and the data analysis system are connected in parallel inside the monitoring unit; the buzzer element is arranged above the outer side surface of the monitoring unit and is connected with an external interaction system through a lead, the control module comprises a starting switch and a stopping switch, and the monitoring module and the control module are connected with other units through data lines.

Preferably, the particle size of the magnetic bead in the magnetic bead tank is 1-4.5 μm, and the magnetic bead is HER2 immunomagnetic bead, EGFR immunomagnetic bead, EpCAM immunomagnetic bead or MUC1 immunomagnetic bead.

Preferably, the first and second attracting magnetic poles and the first and second thermal vibration magnetic poles are each provided at least 1.

Preferably, the magnetic bead tank is provided with at least one replenishment port.

Preferably, the pore size of the first filter screen is not smaller than the particle size of the magnetic beads; the diameter of the second filter screen is not more than the diameter of the magnetic beads.

Preferably, the first filter mesh size is not more than 6 μm.

Preferably, the housing is a waterproof bag-type container.

Preferably, the energy supply unit comprises an energy storage element, and the energy storage element is a storage battery, a solar battery or a hybrid energy battery; the energy storage element is connected with an energy indicating lamp.

Use of a device as described above for capturing, processing and reinfusing CTCs to stimulate immunity in the treatment or co-treatment of tumours.

Has the advantages that:

1. the device is based on the tumor immunotherapy theory, is based on the aim of exciting the autoimmune function of a patient, captures CTCs through immunomagnetic beads and performs magnetic heat ablation, so that the immunogenicity of the CTCs is enhanced and then the CTCs is infused back into the body of the patient, and the aim of exciting immune response is fulfilled. Meanwhile, the process also prevents the tumor from diffusing through peripheral blood to a certain extent, thereby reducing the risk of cancer cell metastasis and breaking through the limitation that the curative effect is greatly reduced by immune editing and immune escape of the tumor in the prior art.

2. The device is highly integrated, has stronger mobility and portability, and has wider applicability; the convenient different patients wear the use for a long time, and can not influence normal life.

3. The device considers the user experience of the patient, fully considers the development space of the patient-friendly instrument, increases the monitoring of various real-time blood indexes, can effectively feed back to the platform and related professionals, and can also facilitate the patient to automatically control the use frequency and the intensity of the instrument according to the physical signs under the condition of learning the self treatment state.

4. The device outputs the original tumor cells in the body of the patient to the outside of the body for treatment, so that the treatment process is more convenient, and the harm to the body of the patient is greatly reduced.

5. The device gives full play to the high specificity advantage of the immunological method, realizes an uninterrupted loop of extraction-capture-treatment-feedback, and can maintain stable curative effect on most of mutation of tumor cells.

Drawings

FIG. 1 is a schematic diagram of the structure of the device for capturing, processing and returning CTCs to stimulate immunity according to the present invention.

FIG. 2 is a schematic diagram of a CTCs capture and processing unit according to the present invention.

Fig. 3 is a schematic structural diagram of a monitoring unit according to the present invention.

Fig. 4 is a schematic perspective view of the device for capturing, processing and returning CTCs to stimulate immunity according to the present invention.

Description of reference numerals:

1. heparin pump, 2, blood sensor, 3, blood pump, 4, monitoring unit, 5, CTCs capture and processing unit, 6, bubble detector, 7, hemostatic clamp, 8, bandage, 9, indwelling needle, 10, energy supply unit, 11, operation pool, 12, first thermal vibration magnetic pole, 13, blood inlet, 14, first adsorption magnetic pole, 15, blood outlet, 16, second thermal vibration magnetic pole, 17, reflux pipe, 18, second filter screen, 19, first filter screen, 20, second adsorption magnetic pole, 21, magnetic bead tank, 22, supplement port, 23, magnetic bead supplement device, 24, external interaction system, 25, buzzer element, 26, data analysis system, 27, data line, 28, start switch, 29, stop switch, 30, blood transfusion tube, 31, shell.

Detailed Description

The following examples are presented to enable one of ordinary skill in the art to more fully understand the present invention and are not intended to limit the invention in any way.

Example 1

1-2, an apparatus for capturing, treating and reinfusing circulating tumor cells for stimulating immunity, comprising a housing 31, a blood transfusion unit, a CTCs capturing and treating unit 5 and an energy supply unit 10, wherein the blood transfusion unit comprises 2 closed indwelling needles 9 respectively arranged at a blood drawing place and a blood reinfusion place; the 2 indwelling needles 9 are respectively attached with 1 binding belt 8, and the binding belts 8 are made of cotton and hemp materials; the back part of the indwelling needle 9 is connected with a blood conveying tube 30, the blood conveying tube 30 is connected with the indwelling needle 9, a bubble detector 6, a blood pump 3 and a heparin pump 1 in series, the hemostatic clamp 7 is arranged between the indwelling needle 9 and the bubble detector 6 and fixed on the blood conveying tube 30, the heparin pump 1 is provided with a heparin pool, the bubble detector 6 is provided with an ultrasonic transmitting and receiving device, and the blood sensor 2 is connected with the monitoring unit 4 through a data line 27; the CTCs capturing and processing unit 5 comprises an operation pool 11, a capturing module and a processing module, wherein the operation pool 11 is a U-shaped pipeline for circulation of blood, two side surfaces of the operation pool are respectively provided with 1

blood inlet

13 and 1 blood outlet 15, and the blood inlet 13 and the blood outlet 15 are both communicated with a blood transfusion tube 30; the capture module is arranged below the operation pool 11 and comprises a magnetic bead tank 21, a magnetic bead supplementing device 23 and a return pipe 17, wherein an immune sorting system is arranged in the magnetic bead tank 21, the particle size of a magnetic bead in the magnetic bead tank 21 is 1-4.5 mu m, and the magnetic bead is HER2 immune magnetic bead, EGFR immune magnetic bead, EpCAM immune magnetic bead or MUC1 immune magnetic bead; the bottom of the operation pool 11 is connected with a magnetic bead tank 21 through a first filter screen 19, the side surface of the magnetic bead tank 21 is connected with a return pipe 17 through a second filter screen 18, the aperture of the first filter screen 19 is not smaller than the particle size of the magnetic beads, and the aperture of the first filter screen 19 is not larger than 6 μm; the pore diameter of the second filter screen 18 is not larger than the particle diameter of the magnetic beads, the return pipe 17 is communicated with the blood outlet 15, the bottom of the magnetic bead tank is provided with at least one supplement port 22, the supplement port is provided with a check valve and is connected with a magnetic bead supplement device 23, the magnetic bead supplement device 23 comprises a magnetic bead pool and a conveying device, and an isotonic solution of suspended immune magnetic beads is filled in the magnetic bead pool; the conveying device is a peristaltic pump, and the solution and the magnetic beads are input into the magnetic bead groove 21 through the supplement port 22; a first adsorption magnetic pole 14 is arranged above the operation pool, a second adsorption magnetic pole 20 is arranged below the magnetic bead groove 21, a first thermal vibration magnetic pole 12 and a second thermal vibration magnetic pole 16 are respectively arranged at two sides of the operation pool, and at least 1 first adsorption magnetic pole 14, at least 1 second adsorption magnetic pole 20, at least one first thermal vibration magnetic pole 12 and at least one second thermal vibration magnetic pole 16 are respectively arranged; the monitoring unit 4 comprises a monitoring module and a control module, the control module comprises a starting switch 28 and a stopping switch 29, the monitoring module and the control module are both connected with other units through data lines 27, the energy supply unit 10 comprises an energy storage element, and the energy storage element is a storage battery, a solar battery or a hybrid energy battery; the energy storage element is connected with an energy indicating lamp, the energy supply unit 10 is connected with other units through wires, and the shell 31 is a waterproof bag-type container.

The energy supply unit 10 comprises 2 groups of storage batteries, the storage batteries are connected with the first adsorption magnetic pole 14, the second adsorption magnetic pole 20, the first thermal vibration magnetic pole 12, the second thermal vibration magnetic pole 16 and other electric elements through wires, and the energy supply unit 10 is connected with a power line leading to the outside of the device, so that the efficient operation of the device under various conditions is ensured.

The working process of the device is as follows: 1. a preparation stage: when the start switch 28 is pressed, the power supply unit 10 starts operating, the indicator lights are turned on, and the indicator lights blink when the power is low. In the standby preparation phase, the patient has correctly punctured the indwelling needle 9 and tied the band 8. The start switch 28 is pressed again, the blood pump 3 is started, the venous blood of the patient is pumped out under negative pressure, the heparin pump 1 and the bubble detector 6 start to work, and the blood smoothly flows into the device.

2. And (3) treatment and feedback stages: the blood pump 3 continues to operate, blood flows into the operating reservoir 11, and the CTCs capture and processing unit 5 begins to operate. The magnetic bead supplementing device 23 delivers the magnetic bead suspension to the magnetic bead tank 21, the first magnetic absorption pole 14 starts to be energized, and the immunomagnetic beads in the tank start to diffuse into the operation pool 11 through the first filter screen 19 under the action of magnetic force. The second adsorption pole 20 is energized to prevent the immunomagnetic beads from being carried away by blood flow, and the CTCs begin to be enriched in the operation pool 11. After a period of time, the second adsorption magnetic pole 20 is energized with strong current, all immunomagnetic beads are settled by magnetic force, the immunomagnetic beads with CTCs are intercepted at the bottom of the operation pool 11 by the first filter screen 19, and the magnetic beads without CTCs are intercepted and recovered at the second filter screen 18 and prevented from entering the body of the user by passing through the first filter screen 19 and entering the magnetic bead tank 21. Then, alternating current is conducted to the first thermal vibration magnetic pole 12 and the second thermal vibration magnetic pole 16, the magnetic beads generate thermal effect under the action of the magnetic field, and the thermal vibration magnetic poles are powered off until the temperature sensed by the temperature sensing element on the inner wall of the operation pool 11 reaches 70 ℃. After 1.5min, the second adsorption magnetic pole 20 is powered off, the magnetic beads carry CTCs which are subjected to immunogenic death to be returned along with blood flow, and after the return, the CTCs which cannot activate immune response originally are exposed due to immunogenic death to reach the purpose of strengthening the immune effect of a user on tumors. The magnetic bead replenishment device 23 is operated again and a new cycle of CTCs capture and processing is started.

3. A device cleaning stage: after the whole set of device is used, the stop switch 29 is pressed, the blood pump 3 stops rotating, the hemostatic clamp 7 is clamped, and after the blood flow is stable, the blood drawing end indwelling needle is taken down. The blood drawing end pipe orifice is connected with a blood returning saline bottle, the stop switch 29 is pressed again, the hemostatic clamp 7 is opened, and the blood pump 3 is started again. After the blood in the tube completely flows back, the stop switch 29 is pressed for the third time, the blood return end remaining needle is taken down, and the tube is flushed and sealed. Finally, the brine bottle is taken down, and the residual liquid in the tube is emptied. For the used device, the pipeline is disinfected by using a disinfectant, and finally, the pipeline is flushed by reverse osmosis water for the next use.

It is recommended that the start and end steps be performed under doctor's supervision.

Example 2

The device is further improved on the basis of the device in the embodiment 1 as shown in the attached drawings 1-3 in the specification.

The monitoring module comprises a temperature sensing element arranged on the inner wall of the operation pool 11, a blood sensor 2 arranged on the inner wall of the blood transfusion tube 30, an external interaction system 24, a buzzer element 25 and a data analysis system 26, wherein the external interaction system 24 and the data analysis system 26 are connected in parallel inside the monitoring unit; the buzzer element 25 is arranged above the outer side surface of the monitoring unit 4 and is connected with the external interaction system 24 through a conducting wire, and the temperature sensing element is connected with the monitoring unit 4 through a data wire 27; the external interactive system 24 and the data analysis system 26 are connected with other units through data lines; the blood sensor 2 can analyze, compare and transmit the collected data in the body, and interact with a user through Bluetooth or WIFI; when the data analysis system 26 of the monitoring unit 4 finds that the information is abnormal, the external interactive system 24 controls the buzzer element 25 to give an alarm, and simultaneously gives a stop instruction to each unit, so as to ensure the safety of the user.

In the preparation stage, the monitoring unit 4 commands other units to be powered on for self-test, if the returned information is not abnormal, the standby preparation stage is started, and if the returned information is abnormal, the monitoring unit 4 sends out a buzzer to cut off the energy supply paths of other elements. In the feedback process, the blood passes through the blood sensor 2 of the monitoring unit 4 to obtain the conventional indexes of the blood of the user, the indexes such as alpha fetoprotein, carcinoembryonic antigen and the like are input into the data analysis system 26 by a data line, and the analysis result is sent to the designated equipment by the external interaction system 24 through Bluetooth or WIFI. The designated equipment is an information center of a patient treatment hospital.

Example 3

The device is practically designed on the basis of the device of the embodiment 2 as shown in the attached drawings 1-2 in the specification.

The device is integrated in a portable container, as shown in fig. 4, the housing 31 is a double-shoulder bag type container, and the units of the device are fixedly arranged in the inner space of the housing 31. The surface of the shell 31 is provided with a water-repellent coating, so that the influence of rainwater and the like on devices in the shell is prevented. The side of the shell 31 is provided with a hole for the blood transfusion tube 30 to penetrate in and out, the front end of the blood transfusion tube 30 is connected with an indwelling needle 9, the indwelling needle 9 is adhered to the adjustable-tightness wide waterproof bandage 8 through a medical adhesive tape, the bandage 8 is convenient for a user to fix a needle head and avoid infection, and the bandage 8 is made of a mixed textile material.

By adopting the portable design, the activity ability of the user can be furthest liberated, and the user can normally learn and work and even perform mild movement on the premise of permission of the physical condition, which has positive significance for the rehabilitation and the prevention of relapse of tumor patients.

Example 4

A device for capturing, processing and reinfusing circulating tumor cells for stimulating immunity, said device comprising a housing 31, a blood transfusion unit, a CTCs capturing and processing unit 5 and an energizing unit 10, said housing 31 being a waterproof bag-type container.

The blood transfusion unit comprises an indwelling needle 9, a blood transfusion tube 30, a hemostatic clamp 7, a bubble detector 6, a blood pump 3 and a heparin pump 1; the indwelling needle 9, the bubble detector 6, the blood pump 3 and the heparin pump 1 are sequentially connected through a blood conveying pipe 30; the hemostatic clamp 7 is arranged between the indwelling needle 9 and the bubble detector 6 and fixed on the blood transfusion tube 30; the indwelling needle 9 is closed, and 1 blood extraction part and 1 blood return part are respectively arranged; the 2 remaining needles 9 are respectively attached with 1 bandage 8, and the bandage 8 is made of cotton and hemp.

The CTCs capturing and processing unit 5 comprises an operation pool 11, a capturing module and a processing module; the operation pool 11 is a blood circulation pipeline with a U-shaped structure, and two ends of the blood circulation pipeline are respectively provided with a blood inlet 13 and a blood outlet 15; the blood inlet 13 and the blood outlet 15 are both communicated with a blood transfusion tube 30; the capture module is arranged below the operation pool 11 and comprises a magnetic bead groove 21, a magnetic bead supplement device 23 and a return pipe 17; an immune sorting system is arranged in the magnetic bead groove 21; the magnetic bead groove 21 is communicated with the operation pool 11 through a first filter screen 19 and is communicated with the return pipe 17 through a second filter screen 18; the return tube 17 communicates with the blood outlet 15; a supplement port 22 is arranged on the magnetic bead groove 21; the supplement port 22 is provided with a check valve; the magnetic bead supplementing device 23 comprises a magnetic bead pool and a conveying device; an isotonic solution of suspended immunomagnetic beads is filled in the magnetic bead pool; the conveying device is a peristaltic pump, and the solution and the magnetic beads are input into the magnetic bead groove 21 through the supplement port 22; the processing module comprises a first adsorption magnetic pole 14, a second adsorption magnetic pole 20, a first thermal vibration magnetic pole 12 and a second thermal vibration magnetic pole 16; the thermal vibration magnetic pole and the adsorption magnetic pole are electromagnets; the first adsorption magnetic pole 14 is arranged in a U-shaped groove of the operation pool 11; the second adsorption magnetic pole 20 is arranged below the magnetic bead groove 21; the first thermal vibration magnetic pole 12 and the second thermal vibration magnetic pole 16 are respectively arranged on two side surfaces of a U-shaped groove of the operation pool 11; the energy supply unit 10 is connected with the CTCs capturing and processing unit 5 and the blood transfusion unit through leads, the monitoring unit 4 is further arranged above the device, the monitoring unit 4 comprises a monitoring module and a control module, and the monitoring module comprises a temperature sensing element, a blood sensor 2, an external interaction system 24, a buzzer element 25 and a data analysis system 26; the temperature sensing element is arranged on the inner wall of the operation pool 11; the blood sensor 2 is arranged on the inner wall of the blood transfusion tube 30; the external interaction system 24 and the data analysis system 26 are connected in parallel inside the monitoring unit; the buzzing element 25 is arranged above the outer side surface of the monitoring unit 4 and is connected with the external interaction system 24 through a lead, the control module comprises a starting switch 28 and a stopping switch 29, the monitoring module and the control module are both connected with other units through data lines 27, the blood sensor 2 can analyze, compare and transmit the collected data in the body, and interact with a user through Bluetooth or WIFI; when the data analysis system 26 of the monitoring unit 4 finds that the information is abnormal, the external interactive system 24 controls the buzzer element 25 to give an alarm, and simultaneously gives a stop instruction to each unit, so as to ensure the safety of the user.

The particle size of the magnetic beads in the magnetic bead groove 21 is 1-4.5 microns, and the magnetic beads are HER2 immunomagnetic beads, EGFR immunomagnetic beads, EpCAM immunomagnetic beads or MUC1 immunomagnetic beads; the number of the first adsorption magnetic pole 14, the second adsorption magnetic pole 20, the first thermal vibration magnetic pole 12 and the second thermal vibration magnetic pole 16 is at least 1; the magnetic bead groove 21 is provided with at least one supplement port 22; the aperture of the first filter screen 19 is not smaller than the particle size of the magnetic beads; the aperture of the second filter screen 18 is not larger than the particle size of the magnetic beads, and the aperture of the first filter screen 19 is not larger than 6 μm.

The energy supply unit 10 comprises 2 groups of storage batteries, the storage batteries are connected with the first adsorption magnetic pole 14, the second adsorption magnetic pole 20, the first thermal vibration magnetic pole 12, the second thermal vibration magnetic pole 16 and other electric elements through wires, and the energy supply unit 10 is connected with a power line leading to the outside of the device, so that the efficient operation of the device under various conditions is ensured. The housing 31 is a backpack container, and the units of the device are fixedly arranged in the inner space of the housing 31. The surface of the shell 31 is provided with a water-repellent coating, so that the influence of rainwater and the like on devices in the shell is prevented. The side of the shell 31 is provided with a hole for the blood transfusion tube 30 to penetrate in and out, the front end of the blood transfusion tube 30 is connected with an indwelling needle 9, the indwelling needle 9 is adhered to the adjustable-tightness wide waterproof bandage 8 through a medical adhesive tape, the bandage 8 is convenient for a user to fix a needle head and avoid infection, and the bandage 8 is made of a mixed textile material.

As shown in tables 1 and 2, taking the specific arrangement and main function of the device in example 4 as an example, the device achieves the following effects after use:

a) dividing early cancer patients with intact immune system and considerable mobility into two groups, wherein experimental group patients use the device while giving conventional cancer treatment; the control group was given conventional cancer treatment only;

b) tracking and comparing in 16 months, and monitoring and recording the vital signs of the patient and various indexes of blood;

c) in 16 months, the survival quality and the psychological state of the patients in the experimental group are generally superior to those of the patients in the control group;

d) as shown in table 1, after 16 months, the survival rate of the patients in the experimental group is higher than that of the patients in the control group, which indicates that the capture feedback of the device can effectively control the transfer of CTCs and stimulate autoimmune response in the patients, and plays an auxiliary role in the conventional cancer treatment of the patients;

e) as shown in table 2, after 16 months, the number of CTCs contained in the mean unit volume blood of the patients in the experimental group was less than that in the control group, and the lesion metastasis tendency was lower than that in the control group;

f) the PFS progression-free survival and total OS survival of most of the experimental patients was improved within 1-2 years.

TABLE 1 survival rate comparison table

TABLE 2 CTC content per 7.5ml blood

Claims

1. A device for capturing, processing and returning circulating tumor cells to stimulate immunity, characterized in that the device comprises a housing (31), a blood transfusion unit, a CTCs capture and processing unit (5) and an energy supply unit (10) );

The blood transfusion unit comprises an indwelling needle (9), a blood transfusion tube (30), a hemostatic clip (7), an air bubble detector (6), a blood pump (3) and a heparin pump (1); the indwelling needle (9), The air bubble detector (6), the blood pump (3) and the heparin pump (1) are connected in sequence through the transfusion vessel (30); the hemostatic clip (7) is arranged between the indwelling needle (9) and the air bubble detector (6) , which is fixed on the transfusion vessel (30); the indwelling needle (9) is of a closed type, and one is provided at the blood extraction site and the blood return site; the two indwelling needles (9) are each attached with a binding a strap (8), the strap (8) is made of cotton and linen;

The CTCs capture and processing unit (5) includes an operation pool (11), a capture module and a processing module; the operation pool (11) is a U-shaped blood circulation pipeline with blood inlets (13) and The blood outlet (15); the blood inlet (13) and the blood outlet (15) are both communicated with the blood transfusion vessel (30); the capture module is arranged below the operation pool (11), and includes a magnetic bead groove (21), a magnetic The bead replenishing device (23) and the return pipe (17); the magnetic bead tank (21) is provided with an immune sorting system; the magnetic bead tank (21) passes through the first filter screen (19) and the operation pool (11) ) is communicated with the return pipe (17) through the second filter screen (18); the return pipe (17) is communicated with the blood outlet (15); the magnetic bead groove (21) is provided with a replenishment port (22); the replenishing port (22) is provided with a check valve; the magnetic bead replenishing device (23) includes a magnetic bead pool and a conveying device; the magnetic bead pool is filled with an isotonic solution of suspended immunomagnetic beads; The conveying device is a peristaltic pump, and the solution and the magnetic beads are input into the magnetic bead tank (21) through the replenishment port (22); the processing module comprises a first adsorption magnetic pole (14), a second adsorption magnetic pole (20) and The first thermal vibration magnetic pole (12) and the second thermal vibration magnetic pole (16); the thermal vibration magnetic pole and the adsorption magnetic pole are both electromagnets; the first adsorption magnetic pole (14) is arranged in the U-shaped recess of the operation pool (11). the second adsorption magnetic pole (20) is arranged below the magnetic bead slot (21); the first thermal vibration magnetic pole (12) and the second thermal vibration magnetic pole (16) are respectively arranged in the operation pool (11) The two sides of the U-shaped groove; the particle size of the magnetic beads in the magnetic bead groove (21) is 1-4.5 μm, and the magnetic beads are HER2 immunomagnetic beads, EGFR immunomagnetic beads, EpCAM immunomagnetic beads or MUC1 immunomagnetic beads beads; the aperture of the first filter screen (19) is not smaller than the particle size of the magnetic beads; the aperture of the second filter screen (18) is not larger than the particle size of the magnetic beads;

The energy supply unit (10) is connected with the CTCs capturing and processing unit (5) and the blood transfusion unit by a wire;

A monitoring unit (4) is further provided above the device, the monitoring unit (4) includes a monitoring module and a control module, and the monitoring module includes a temperature sensing element, a blood sensor (2), an external interaction system (24), A buzzer element (25) and a data analysis system (26); the temperature sensing element is arranged on the inner wall of the operation pool (11); the blood sensor (2) is arranged on the inner wall of the blood transfusion vessel (30); the external interaction system ( 24) is connected in parallel with the data analysis system (26) inside the monitoring unit; the buzzer element (25) is arranged above the outer side of the monitoring unit (4), and is connected with the external interaction system (24) by wires, and the control module Including a start switch (28) and a stop switch (29), the monitoring module and the control module are connected with other units by data lines (27);

During the working process of the device for capturing, processing and returning circulating tumor cells to stimulate immunity: the blood pump (3) continues to work, the blood flows into the operation pool (11), the CTCs capture and processing unit (5) ) starts to work, the magnetic bead replenishing device (23) sends the magnetic bead suspension to the magnetic bead groove (21), the first adsorption magnetic pole (14) starts to energize, and the immune magnetic beads in the groove pass through the first filter screen ( 19) Begin to diffuse into the operation cell (11), the second adsorption magnetic pole (20) is energized to prevent the immunomagnetic beads from being carried away by the bloodstream, and CTCs begin to be enriched in the operation cell (11). A strong current is applied to the adsorption magnetic pole (20), and all the immunomagnetic beads are settled by the magnetic force. The immunomagnetic beads adsorbed with CTCs are blocked by the first filter screen (19) at the bottom of the operation cell (11), while the magnetic beads without CTCs are blocked by the first filter screen (19). It can enter the magnetic bead groove (21) through the first filter screen (19), and be intercepted and recovered at the second filter screen (18) to prevent it from entering the user's body. Then the first thermal vibration magnetic pole (12) and the second The thermal vibration magnetic pole (16) is supplied with alternating current, and the magnetic beads generate thermal effects under the action of the magnetic field. When the temperature of the temperature sensing element on the inner wall of the operating pool (11) reaches 70°C, the thermal vibration magnetic pole is powered off. After 1.5 minutes, the second The adsorption magnetic pole (20) is powered off, and the magnetic beads carry the CTCs that have died of immunogenicity back into the bloodstream. After the reinfusion, the CTCs that could not activate the immune response are exposed to the antigen due to the death of the immunogenicity, which can strengthen the user's understanding of the immune system. For the purpose of tumor immune effect, the magnetic bead supplement device (23) worked again, and a new round of CTCs capture and processing began.

2. A device for capturing, processing and returning circulating tumor cells to stimulate immunity according to claim 1, characterized in that: the first adsorption magnetic pole (14), the second adsorption magnetic pole (20) and the first adsorption magnetic pole (20) There are at least one thermal vibration magnetic pole (12) and at least one second thermal vibration magnetic pole (16).

3 . The device for capturing, processing and returning circulating tumor cells to stimulate immunity according to claim 1 , wherein the magnetic bead groove ( 21 ) is provided with at least one supplementary port ( 22 ). 4 .

4 . The device for capturing, processing and returning circulating tumor cells to stimulate immunity according to claim 1 , wherein the pore size of the first filter screen ( 19 ) is not greater than 6 μm. 5 .

5 . The device for capturing, processing and returning circulating tumor cells to stimulate immunity according to claim 1 , wherein the casing ( 31 ) is a waterproof bag-type container. 6 .

The device for capturing, processing and returning circulating tumor cells to stimulate immunity according to claim 1, characterized in that: the energy supply unit (10) contains an energy storage element, and the energy storage element is a battery , a solar cell or a hybrid energy battery; the energy storage element is connected with an energy indicator light.