CN110180047A - It is a kind of to capture, handle and feed back circulating tumor cell to excite immune device and its application - Google Patents

Abstract

A device for capturing, processing and reinfusing circulating tumor cell CTCs to stimulate immunity and its application, the device includes a blood transfusion unit, a CTCs capture and processing unit, a monitoring unit and an energy supply unit; the blood transfusion unit injects the user's blood In the device, the processed blood is returned to form a blood circuit; the blood circuit is connected with a CTCs capture and processing unit and a monitoring unit; the energy supply unit is connected with other units by wires. The device captures and processes CTCs and infuses the processed CTCs back into the human body to stimulate an immune response, achieve the effect of adjuvant treatment of tumors, and also prevent tumors from spreading 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 greatly reduces the cost compared with existing immunotherapy.

Description

A device for capturing, processing and reinfusing circulating tumor cells to stimulate immunity and its application

technical field

The invention belongs to the field of tumor immunotherapy, and specifically relates to a device for capturing, processing and transfusing circulating tumor cell CTCs to stimulate immunity and its application.

Background technique

Every year, more than 14 million people worldwide are diagnosed with cancer, and about 8.2 million of them will eventually die of cancer, and the death toll is expected to double by 2030. It can be seen that cancer has become one of the main killers of modern humans. This long-standing difficulty in the medical field has gradually developed into the sword of Damocles hanging over people's heads, threatening everyone's life safety at all times.

At present, the main treatment methods for cancer are surgery, radiotherapy and chemotherapy. As a mechanical method, surgery is a thorough local treatment, but since cancer cells will proliferate or metastasize to the surrounding and distant places, the recurrence or metastasis rate is as high as 90% after five years of surgery, and the cancer cannot be cured. Radiation therapy is effective for some regionally sensitive cancers, but it is difficult to deal with the whole body. Chemotherapy is a systemic treatment that can treat both primary and metastatic lesions. However, while traditional chemotherapy and radiotherapy kill tumors, they also damage normal cells, leading to a general decline in the quality of life of patients, and even being forced to stop treatment due to intolerance.

Despite the continuous improvement of cancer surgery methods and the continuous introduction of new chemotherapy drugs, the problem of eradicating residual cancer cells has not been 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 immunoediting and immune escape. There are still a large number of immune cells in many late-stage cancer patients, but they cannot effectively recognize and eliminate tumor cells with low immunogenicity after mutation. Therefore, improving the immunogenicity of tumors is the key to the successful treatment of tumors.

Existing immunotherapies include CAR-T, T-CRT, TIL, DC-CTL, etc. Most of these therapies focus on transforming or expanding human immune cells to achieve immune efficacy. For example, CAR-T is to add a chimeric antibody that can recognize tumor cells and activate immunity to T cells through genetic engineering technology, cultivate them in vitro, expand them in large quantities, and reinfuse the expanded chimeric T cells back into the patient. in vivo. However, such immunotherapy technology is costly, has a high recurrence rate, and has a small scope of application, and has not fundamentally solved the problem of tumor cell immune escape.

Contents of the invention

Technical problem to be solved: the present invention overcomes the deficiencies of the above-mentioned prior art, and is committed to solving the "four major problems" of a large number of cancer patients, high medical consumption for cancer patients, a high probability of cancer recurrence, and more pain suffered by patients, and provides a method of capturing, processing And reinfuse CTCs to stimulate immune device and its application. Based on CTCs sorting technology and related research on tumor cell immunogenic death, the device realizes the miniaturization and integration of cancer immunotherapy equipment, and provides a way to crack immune escape from the perspective of tumor cells. At the same time, the versatility and reusability of the device also greatly reduces the cost compared with existing immunotherapy.

Technical solution: a device for capturing, processing and reinfusing circulating tumor cell CTCs to stimulate immunity, the device includes a housing, a blood transfusion unit, a CTCs capture and processing unit, and an energy supply unit;

The blood transfusion unit includes an indwelling needle, a transfusion tube, a hemostatic clip, an air bubble detector, a blood pump, and a heparin pump; the indwelling needle, an air bubble detector, a blood pump, and a heparin pump are sequentially connected through a transfusion tube; the hemostatic clip is set on Between the indwelling needle and the air bubble detector, it is fixed on the transfusion vessel; the indwelling needle is airtight, and there is one at the blood extraction site and one at the blood reinfusion site; each of the two indwelling needles is attached with a bandage , the strap is made of cotton and linen;

The CTCs capture and processing unit includes an operation pool, a capture module and a processing module; the operation pool is a U-shaped blood circulation pipeline, and two ends are respectively provided with a blood inlet and a blood outlet; the blood inlet and the blood outlet are both connected to the The blood transfusion tube is connected; the capture module is arranged under the operation pool, including a magnetic bead tank, a magnetic bead replenishment device and a return pipe; the magnetic bead tank is provided with an immune sorting system; the magnetic bead tank passes through the first filter It communicates with the operating pool, and communicates with the return pipe through the second filter screen; the return pipe communicates with the blood outlet; the magnetic bead tank is provided with a replenishment port; the replenishment port is provided with a check valve; The magnetic bead replenishment device includes a magnetic bead tank and a delivery device; the magnetic bead tank is filled with an isotonic solution of suspended immune magnetic beads; the delivery device is a peristaltic pump, and the solution and the magnetic beads are input into the magnetic bead tank through the supplementary port The processing module includes a first magnetic pole for adsorption, a second magnetic pole for adsorption, a first thermal vibration pole, and a second thermal vibration pole; both the thermal vibration pole and the magnetic pole for adsorption are electromagnets; the first magnetic pole for adsorption is set at the operation In the U-shaped groove of the 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 both sides of the U-shaped groove of the operation pool;

The energy supply unit is connected with the CTCs capture and processing unit and the blood transfusion unit by wires.

Preferably, a monitoring unit is provided above the device, and the monitoring unit includes a monitoring module and a control module, and the monitoring module includes a temperature sensing element, a blood sensor, an external interactive system, a buzzing 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 transfusion vessel; the external interactive system and the data analysis system are connected in parallel inside the monitoring unit; The external interactive system is connected with wires, the control module includes a start switch and a stop switch, and both the monitoring module and the control module are connected with other units by data wires.

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

Preferably, there is at least one each of the first magnetic attraction pole, the second magnetic attraction pole, the first thermal vibration pole, and the second thermal vibration pole.

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

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

Preferably, the pore size of the first filter screen is not greater than 6 μm.

Preferably, the casing is a waterproof bag container.

Preferably, the energy supply unit contains an energy storage element, and the energy storage element is a storage battery, a solar cell or a hybrid energy battery; the energy storage element is connected with an energy indicator light.

The application of the above-mentioned device for capturing, processing and reinfusing CTCs to stimulate immunity in the treatment or adjuvant treatment of tumors.

Beneficial effect:

1. This device is based on the theory of tumor immunotherapy and is based on stimulating the patient's own immune function. CTCs are captured by immunomagnetic beads and subjected to magnetic thermal ablation to enhance their immunogenicity and then infuse them back into the patient's body to stimulate the immune response. At the same time, this process also prevents the tumor from spreading through the peripheral blood to a certain extent, thereby reducing the risk of cancer cell metastasis, and breaking through the limitations of the prior art that the immune editing and immune escape of the tumor greatly reduce the curative effect.

2. The device is highly integrated, has strong mobility and portability, and has wide applicability; it is convenient for different patients to wear and use for a long time without affecting normal life.

3. This device takes into account the patient's user experience, fully considers the development space of patient-friendly instruments, increases real-time monitoring of various blood indicators, and can effectively feed back to the platform and relevant professionals, and can also facilitate patients to learn their own treatment status Control the frequency and intensity of use of the instrument according to the signs.

4. This device exports the tumor cells that were originally in the patient's body to the outside of the body for treatment, making the treatment process more convenient and greatly reducing the damage to the patient's body.

5. This device takes full advantage of the high specificity of immunological methods, realizes the uninterrupted loop of extraction-capture-processing-reinfusion, and can maintain a relatively stable curative effect on most mutations of tumor cells.

Description of drawings

Fig. 1 is a schematic structural diagram of a device for capturing, processing and reinfusing CTCs to stimulate immunity according to the present invention.

Fig. 2 is a schematic structural diagram of the CTCs capture and processing unit of the present invention.

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

Fig. 4 is a schematic diagram of the three-dimensional structure of the device for capturing, processing and reinfusing CTCs to stimulate immunity according to the present invention.

Explanation of reference signs:

1. Heparin pump, 2. Blood sensor, 3. Blood pump, 4. Monitoring unit, 5. CTCs capture and processing unit, 6. Bubble detector, 7. Hemostatic clip, 8. Bandage, 9. Indwelling needle, 10 , energy supply unit, 11, operation pool, 12, first thermal vibration pole, 13, blood inlet, 14, first adsorption magnetic pole, 15, blood outlet, 16, second thermal vibration magnetic pole, 17, return pipe, 18, The second filter screen, 19, the first filter screen, 20, the second adsorption magnetic pole, 21, the magnetic bead tank, 22, the replenishment port, 23, the magnetic bead replenishment device, 24, the external interactive system, 25, the buzzer element, 26 . Data analysis system, 27. Data line, 28. Start switch, 29. Stop switch, 30. Transfusion tube, 31. Housing.

Detailed ways

The following examples can enable those skilled in the art to understand the present invention more fully, but do not limit the present invention in any way.

Example 1

As shown in Figures 1-2 of the description, a device for capturing, processing and reinfusing circulating tumor cells to stimulate immunity includes a housing 31, a blood transfusion unit, a CTCs capture and processing unit 5, and an energy supply unit 10. The blood transfusion The unit includes two closed indwelling needles 9, which are respectively arranged at the blood extraction place and the blood reinfusion place; each of the two indwelling needles 9 is attached with a strap 8, and the strap 8 is made of cotton and linen; The rear part of the indwelling needle 9 is connected with a blood transfusion vessel 30, the indwelling needle 9, the air bubble detector 6, the blood pump 3 and the heparin pump 1 are connected in series in the blood transfusion vessel 30, and the hemostatic clip 7 is arranged on the indwelling needle 9 and the air bubble detector 6, fixed on the blood transfusion vessel 30, the heparin pump 1 is provided with a heparin pool, the bubble detector 6 is provided with an ultrasonic transmitter and receiver, and the blood sensor 2 is connected with the monitoring unit 4 by a data line 27; 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 pipe for blood circulation, and a blood inlet 13 and a blood outlet 15 are respectively provided on both sides. The blood inlet 13 and the blood outlet 15 are all communicated with the blood transfusion vessel 30; the capture module is arranged below the operating pool 11, and includes a magnetic bead tank 21, a magnetic bead replenishment device 23 and a return pipe 17, and in the magnetic bead tank 21 An immune sorting system is provided, and the particle size of the magnetic beads in the magnetic bead tank 21 is 1-4.5 μm, and the magnetic beads are HER2 immune magnetic beads, EGFR immune magnetic beads, EpCAM immune magnetic beads or MUC1 immune magnetic beads; The bottom of the operation pool 11 is connected to the magnetic bead tank 21 through the first filter screen 19, and the side of the magnetic bead tank 21 is connected to the return pipe 17 through the second filter screen 18, and the pore size of the first filter screen 19 is not smaller than the particle size of the magnetic beads , the pore size of the first filter screen 19 is not greater than 6 μm; the pore size of the second filter screen 18 is not greater than the particle size of the magnetic beads, the return pipe 17 is connected with the blood outlet 15, and at least one supplementary filter is provided at the bottom of the magnetic bead tank. Port 22, the replenishment port is provided with a check valve and is connected to the magnetic bead replenishment device 23, the magnetic bead replenishment device 23 includes a magnetic bead pool and a delivery device, and the magnetic bead pool is filled with an isotonic substance that suspends immune magnetic beads. Solution; the conveying device is a peristaltic pump, and the solution and magnetic beads are input into the magnetic bead tank 21 through the replenishment port 22; the first adsorption magnetic pole 14 is provided above the operation pool, and the magnetic beads tank 21 is provided below The second adsorption magnetic pole 20, the first thermal vibration magnetic pole 12 and the second thermal vibration magnetic pole 16 are arranged on both sides of the operation pool, the first thermal vibration magnetic pole 14, the second adsorption magnetic pole 20 and the first thermal vibration magnetic pole 12, the second thermal vibration magnetic pole Each magnetic pole 16 is provided with at least one; the monitoring unit 4 includes a monitoring module and a control module, and the control module includes a start switch 28 and a stop switch 29, and the monitoring module and the control module are all connected to other units with a data line 27, The energy supply unit 10 contains an energy storage element, and the energy storage element is a storage battery, a solar cell or a hybrid energy battery; the energy storage element is connected with an energy indicator light, and the energy supply unit 10 is connected with other units by wires, The housing 31 is a waterproof bag-like container.

The energy supply unit 10 includes two sets of storage batteries, which are connected to the first magnetic pole 14, the second magnetic pole 20, the first thermal vibration pole 12, the second thermal vibration magnetic pole 16 and other electrical components through wires. The energy supply unit 10 is connected with a power line leading to the outside of the device to ensure the efficient operation of the device under various conditions.

The working process of the device is as follows: 1. Preparatory stage: press the start switch 28, the energy supply unit 10 starts to work, the indicator light is on, and will flicker if the battery is low. In the standby preparation stage, the patient has correctly punctured the indwelling needle 9 and fastened the bandage 8 at this time. Press the start switch 28 again, the blood pump 3 starts, the patient's venous blood 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. Processing and reinfusion stage: the blood pump 3 continues to work, the blood flows into the operation pool 11, and the CTCs capture and processing unit 5 starts to work. The magnetic bead replenishing device 23 transports the magnetic bead suspension to the magnetic bead tank 21, the first magnetic adsorption pole 14 starts to be energized, and the immune magnetic beads in the tank pass through the first filter screen 19 and start to diffuse into the operation pool 11 under the action of magnetic force. The second magnetic adsorption pole 20 is supplied with current so that the immunomagnetic beads are not carried away by the blood flow, and CTCs begin to accumulate in the operation pool 11 . After a period of time, the second adsorption magnetic pole 20 is supplied with a strong current, and all the immunomagnetic beads are subjected to magnetic sedimentation, and the immunomagnetic beads adsorbed with CTCs are blocked by the first filter screen 19 at the bottom of the operation pool 11, while the magnetic beads without adsorbed CTCs are It can pass through the first filter screen 19 and enter the magnetic bead tank 21, and be blocked and recovered at the second filter screen 18 to prevent it from entering the user's body. Then the first thermo-vibration pole 12 and the second thermo-vibration pole 16 are supplied with alternating current, and the magnetic beads generate heat effect under the action of the magnetic field until the temperature of the temperature sensing element on the inner wall of the operation pool 11 reaches 70°C, and the thermo-vibration pole is cut off. After 1.5 minutes, the second adsorption magnetic pole 20 was powered off, and the CTCs carrying the immunogenic death were reinfused with the blood flow. After the reinfusion, the CTCs that could not activate the immune response were exposed to the antigen due to immunogenic death, reaching The purpose of strengthening the user's immune effect on tumors. The magnetic bead replenishment device 23 operates again, and a new round of CTCs capture and processing begins.

3. Device cleaning stage: after the whole device is used, press the stop switch 29, the blood pump 3 stops, the hemostatic clip 7 is clamped dead, and after the blood flow is stabilized, the indwelling needle at the blood draw end is removed. The nozzle of the blood pumping port is connected with the blood return saline bottle, and the stop switch 29 is pressed again, then the hemostatic clamp 7 is opened, and the blood pump 3 starts again. After all the backflow of blood in the tube is completed, press the stop switch 29 for the third time, take off the indwelling needle at the blood return end, and flush and seal the tube. Finally, remove the saline bottle and empty the remaining liquid in the tube. For the used device, the pipeline should be disinfected with disinfectant, and finally rinsed with reverse osmosis water for the next use.

It is recommended to perform the starting and ending steps under the supervision of a physician.

Example 2

Shown in conjunction with accompanying drawings 1-3 of the description, the device is further improved on the basis of the device in embodiment 1.

The monitoring module includes a temperature sensing element placed on the inner wall of the operation pool 11, a blood sensor 2 placed on the inner wall of the blood transfusion vessel 30, an external interaction system 24, a buzzer element 25 and a data analysis system 26. The external interaction system 24 communicates with the data The analysis system 26 is connected in parallel inside the monitoring unit; the buzzer element 25 is located above the outer surface of the monitoring unit 4, and is connected to the external interactive system 24 with wires, and the temperature sensing element is connected to the monitoring unit 4 with a data line 27; The external interaction system 24 and the data analysis system 26 are connected to other units through data lines; the blood sensor 2 can analyze, compare and transmit the collected data inside the body, and communicate with the user through Bluetooth or WIFI. Interaction: When the data analysis system 26 of the monitoring unit 4 finds that the information is abnormal, the external interaction system 24 controls the buzzer element 25 to issue a warning, and at the same time sends a stop command to each unit to ensure the safety of the user.

In the preparation stage, the monitoring unit 4 commands other units to start self-checking. If there is no abnormality in the returned information, it will enter the standby preparation stage. If there is an abnormality, the monitoring unit 4 will beep to cut off the energy supply path of other components. During the reinfusion process, the blood passes through the blood sensor 2 of the monitoring unit 4 to obtain the user’s blood routine indicators, such as alpha-fetoprotein, carcinoembryonic antigen, etc., are input to the data analysis system 26 through the data line, and the analysis results are passed through the external interactive system 24. Bluetooth or WIFI to send to the specified device. The designated device is the information center of the hospital where the patient sees a doctor.

Example 3

Shown in conjunction with description accompanying drawing 1-2, on the basis of embodiment 2 device, this device is done practical design.

The device is integrated into a portable container. As shown in Figure 4 of the specification, the housing 31 is a backpack-style container, and each unit of the device is fixedly arranged in the inner space of the housing 31 . The surface of the housing 31 adopts a water-repellent coating to prevent rainwater from affecting the devices in the housing. The side of the housing 31 is provided with a hole for the blood transfusion vessel 30 to penetrate and pass through. The front end of the blood transfusion vessel 30 is connected with an indwelling needle 9, and the indwelling needle 9 is adhered to an adjustable elastic wide waterproof On the strap 8, the strap 8 is convenient for the user to fix the needle and avoid infection, and the material of the strap 8 is a mixed textile material.

The use of this portable design will maximize the freedom of the user's mobility. On the premise that the physical condition permits, the user can study, work normally, and even do mild exercise, which is of great significance to the rehabilitation and recurrence prevention of tumor patients. Positive meaning.

Example 4

A device for capturing, processing and reinfusing circulating tumor cells to stimulate immunity. The device includes a housing 31, a blood transfusion unit, a CTCs capture and processing unit 5 and an energy supply unit 10. The housing 31 is a waterproof Packet container.

The blood transfusion unit includes 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 pass through The blood vessels 30 are connected sequentially; the hemostatic clip 7 is arranged between the indwelling needle 9 and the air bubble detector 6, and is fixed on the blood transfusion vessel 30; the indwelling needle 9 is airtight, and the blood extraction place and the blood reinfusion place are respectively provided with 1; each of the two indwelling needles 9 is attached with a strap 8, and 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 flow channel, and two ends are respectively provided with a blood inlet 13 and a blood outlet 15; the blood inlet 13 and the blood outlet 15 are all communicated with the blood transfusion vessel 30; the capture module is arranged below the operating pool 11, and includes a magnetic bead tank 21, a magnetic bead replenishment device 23 and a return pipe 17; the magnetic bead tank 21 is provided with an immunoassay Selection system; the magnetic bead groove 21 is communicated with the operating pool 11 through the first filter screen 19, and 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 The bead tank 21 is provided with a supplementary port 22; the supplementary port 22 is provided with a check valve; the magnetic bead replenishment device 23 includes a magnetic bead pool and a delivery device; the isotonic suspension of the suspended immune magnetic beads is filled in the magnetic bead pool. solution; the conveying device is a peristaltic pump, and the solution and magnetic beads are input into the magnetic bead tank 21 through the replenishment port 22; the processing module includes a first adsorption magnetic pole 14, a second adsorption magnetic pole 20 and a first thermal vibration magnetic pole 12 , the second thermal vibration pole 16; the thermal vibration pole and the adsorption magnetic pole are electromagnets; the first adsorption magnetic pole 14 is arranged in the operation pool 11U-shaped groove; the second adsorption magnetic pole 20 is located in the magnetic bead groove 21; the first thermal vibration magnetic pole 12 and the second thermal vibration magnetic pole 16 are respectively arranged on the two sides of the U-shaped groove of the operation pool 11; the energy supply unit 10 is connected with the CTCs capture and processing unit 5 and the blood transfusion unit by wires ,, the top of the device is also provided with a monitoring unit 4, the monitoring unit 4 includes a monitoring module and a control module, the monitoring module includes a temperature sensing element, a blood sensor 2, an external interactive system 24, a buzzer element 25 and a data The 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 transfusion vessel 30; the external interaction system 24 and the data analysis system 26 are connected in parallel inside the monitoring unit; the buzzer element 25 is located above the outer surface of the monitoring unit 4, and is connected to the external interactive system 24 with wires. The control module includes a start switch 28 and a stop switch 29. Both the monitoring module and the control module are connected to other units with data lines 27. The blood sensor 2 can analyze, compare and transmit the collected data inside the body, and interact with the user through Bluetooth or WIFI; when the data analysis system 26 of the monitoring unit 4 finds that the information is abnormal, the external interaction system 24 controls the buzzer element 25 to issue a warning, and simultaneously sends a stop command to each unit to ensure the safety of the user.

In the preparation stage, the monitoring unit 4 commands other units to start self-checking. If there is no abnormality in the returned information, it will enter the standby preparation stage. If there is an abnormality, the monitoring unit 4 will beep to cut off the energy supply path of other components. During the reinfusion process, the blood passes through the blood sensor 2 of the monitoring unit 4 to obtain the user’s blood routine indicators, such as alpha-fetoprotein, carcinoembryonic antigen, etc., are input to the data analysis system 26 through the data line, and the analysis results are passed through the external interactive system 24. Bluetooth or WIFI to send to the specified device. The designated device is the information center of the hospital where the patient sees a doctor.

The particle diameter of the magnetic beads in the magnetic bead tank 21 is 1-4.5 μm, and the magnetic beads are HER2 immune magnetic beads, EGFR immune magnetic beads, EpCAM immune magnetic beads or MUC1 immune magnetic beads; Two adsorption magnetic poles 20, the first thermal vibration magnetic pole 12, and the second thermal vibration magnetic pole 16 are each provided with at least one; the magnetic bead groove 21 is provided with at least one supplementary port 22; the pore size of the first filter screen 19 is not smaller than the particle size of the magnetic beads ; The pore size of the second filter screen 18 is not larger than the particle size of the magnetic beads, and the pore size of the first filter screen 19 is not larger than 6 μm.

The energy supply unit 10 includes two sets of storage batteries, which are connected to the first magnetic pole 14, the second magnetic pole 20, the first thermal vibration pole 12, the second thermal vibration magnetic pole 16 and other electrical components through wires. The energy supply unit 10 is connected with a power line leading to the outside of the device to ensure the efficient operation of the device under various conditions. The housing 31 is a backpack type container, and each unit of the device is fixedly arranged in the inner space of the housing 31 . The surface of the housing 31 adopts a water-repellent coating to prevent rainwater from affecting the devices in the housing. The side of the housing 31 is provided with a hole for the blood transfusion vessel 30 to penetrate and pass through. The front end of the blood transfusion vessel 30 is connected with an indwelling needle 9, and the indwelling needle 9 is adhered to an adjustable elastic wide waterproof On the strap 8, the strap 8 is convenient for the user to fix the needle and avoid infection, and the material of the strap 8 is a mixed textile material.

The use of this portable design will maximize the freedom of the user's mobility. On the premise that the physical condition permits, the user can study, work normally, and even do mild exercise, which is of great significance to the rehabilitation and recurrence prevention of tumor patients. Positive meaning.

The working process of the device is as follows: 1. Preparatory stage: press the start switch 28, the energy supply unit 10 starts to work, the indicator light is on, and will flicker if the battery is low. In the standby preparation stage, the patient has correctly punctured the indwelling needle 9 and fastened the bandage 8 at this time. Press the start switch 28 again, the blood pump 3 starts, the patient's venous blood 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. Processing and reinfusion stage: the blood pump 3 continues to work, the blood flows into the operation pool 11, and the CTCs capture and processing unit 5 starts to work. The magnetic bead replenishing device 23 transports the magnetic bead suspension to the magnetic bead tank 21, the first magnetic adsorption pole 14 starts to be energized, and the immune magnetic beads in the tank pass through the first filter screen 19 and start to diffuse into the operation pool 11 under the action of magnetic force. The second magnetic adsorption pole 20 is supplied with current so that the immunomagnetic beads are not carried away by the blood flow, and CTCs begin to accumulate in the operating pool 11 . After a period of time, the second adsorption magnetic pole 20 is supplied with a strong current, and all the immunomagnetic beads are subjected to magnetic sedimentation, and the immunomagnetic beads adsorbed with CTCs are blocked by the first filter screen 19 at the bottom of the operation pool 11, while the magnetic beads without adsorbed CTCs are It can pass through the first filter screen 19 and enter the magnetic bead tank 21, and be blocked and recovered at the second filter screen 18 to prevent it from entering the user's body. Then the first thermo-vibration pole 12 and the second thermo-vibration pole 16 are supplied with alternating current, and the magnetic beads generate heat effect under the action of the magnetic field until the temperature of the temperature sensing element on the inner wall of the operation pool 11 reaches 70°C, and the thermo-vibration pole is cut off. After 1.5 minutes, the second adsorption magnetic pole 20 was powered off, and the CTCs carrying the immunogenic death were reinfused with the blood flow. After the reinfusion, the CTCs that could not activate the immune response were exposed to the antigen due to immunogenic death, reaching The purpose of strengthening the user's immune effect on tumors. The magnetic bead replenishment device 23 operates again, and a new round of CTCs capture and processing begins.

3. Device cleaning stage: after the whole device is used, press the stop switch 29, the blood pump 3 stops, the hemostatic clip 7 is clamped dead, and after the blood flow is stabilized, the indwelling needle at the blood draw end is removed. The nozzle of the blood pumping port is connected with the blood return saline bottle, and the stop switch 29 is pressed again, then the hemostatic clamp 7 is opened, and the blood pump 3 starts again. After all the backflow of blood in the tube is completed, press the stop switch 29 for the third time, take off the indwelling needle at the blood return end, and flush and seal the tube. Finally, remove the saline bottle and empty the remaining liquid in the tube. For the used device, the pipeline should be disinfected with disinfectant, and finally rinsed with reverse osmosis water for the next use.

It is recommended to perform the starting and ending steps under the supervision of a physician.

As shown in Table 1 and Table 2, taking the specific settings and main functions of the device in Embodiment 4 as an example, the device achieves the following effects after use:

a) Divide early-stage cancer patients with undamaged immune systems and considerable activity into two groups. Patients in the experimental group use the device while being given conventional cancer treatment; patients in the control group are only given conventional cancer treatment;

b) Follow up and compare within 16 months, and do a good job of monitoring and recording the patient's vital signs and blood indicators;

c) During 16 months, the quality of life and mental state of patients in the experimental group were generally better than those in the control group;

d) As shown in Table 1, after 16 months, the survival rate of patients in the experimental group was higher than that in the control group, indicating that the capture and reinfusion of the device can effectively control the transfer of CTCs and stimulate the autoimmune response in patients. played a supporting role in the treatment;

e) As shown in Table 2, after 16 months, the average number of CTCs per unit volume of blood in the experimental group was less than that of the control group, and the tendency of lesion metastasis was smaller than that of the control group;

f) Improve the PFS progression-free survival time and OS overall survival time of most patients in the experimental group within 1-2 years.

Table 1. Survival rate comparison table

Table 2. Comparison table of CTC content per 7.5ml blood

Claims (10)

1. a kind of capture handles and feeds back circulating tumor cell to excite immune device, which is characterized in that described device includes Shell (31), blood transfusion unit, CTCs capture and processing unit (5) and supply unit (10)；

The blood transfusion unit includes remaining needle (9), blood transfusion tube (30), hemostatic clamp (7), gas bubble detection (6), blood pump (3) and liver Element pump (1)；The remaining needle (9), gas bubble detection (6), blood pump (3) and heparin pump (1) are sequentially connected by blood transfusion tube (30)； The hemostatic clamp (7) is set between remaining needle (9) and gas bubble detection (6), is fixed on blood transfusion tube (30)；The remaining needle (9) to be closed, 1 is respectively provided at blood extraction and at blood recovery；2 remaining needles (9) respectively have 1 bandage (8), The bandage (8) is linen-cotton material；

The CTCs capture and processing unit (5) include operation pond (11), trapping module and processing module；The operation pond (11) For the blood circulation pipeline of U-shaped structure, both ends are respectively equipped with blood entry port (13) and blood outlet (15)；The blood entry port (13) it is connected to blood transfusion tube (30) with blood outlet (15)；The trapping module is set to below operation pond (11), including magnetic bead Slot (21), magnetic bead supplementary device (23) and return pipe (17)；Immune sorting system is equipped in the magnetic bead slot (21)；The magnetic bead slot (21) it is connected to by the first strainer (19) with operation pond (11), and is connected to by the second strainer (18) with the return pipe (17)； The return pipe (17) is connected to blood outlet (15)；The magnetic bead slot (21) is equipped with supply port (22)；The supply port (22) it is equipped with non-return valve；The magnetic bead supplementary device (23) includes magnetic bead pond and conveying device；Filled with suspension in the magnetic bead pond The isotonic solution of immunomagnetic beads；The conveying device is peristaltic pump, and solution and magnetic bead are input to magnetic bead by supply port (22) In slot (21)；The processing module include first absorption magnetic pole (14), second absorption magnetic pole (20) and first heat shake magnetic pole (12), Second heat vibration magnetic pole (16)；The heat vibration magnetic pole and absorption magnetic pole are electromagnet；First absorption magnetic pole (14) is set to behaviour Make in pond (11) U-shaped groove；Second absorption magnetic pole (20) is set to the lower section of magnetic bead slot (21)；The first heat vibration magnetic pole (12) and the second heat vibration magnetic pole (16) is respectively arranged on the two sides for operating pond (11) U-type groove；

The supply unit (10) is captured with conducting wire with CTCs to be connected with processing unit (5) and blood transfusion unit.

2. a kind of capture according to claim 1 handles and feeds back CTCs to excite immune device, it is characterised in that: It is additionally provided with above described device monitoring unit (4), the monitoring unit (4) includes monitoring modular and control module, the prison Surveying module includes temperature-sensing element, blood sensor (2), external interactive system (24), buzzing element (25) and data analysis system (26)；The temperature-sensing element is set to operation pond (11) inner wall；The blood sensor (2) is set to blood transfusion tube (30) inner wall；It is described External interactive system (24) and data analysis system (26) are parallel to inside monitoring unit；The buzzing element (25) is set to monitoring Above unit (4) lateral surface, and it is connected with external interactive system (24) with conducting wire, the control module includes starting switch (28) With shutdown switch (29), the monitoring modular and control module are connected with data line (27) with other units.

3. a kind of capture according to claim 1 handles and feeds back CTCs to excite immune device, it is characterised in that: Magnetic bead partial size in the magnetic bead slot (21) is 1-4.5 μm, and the magnetic bead is HER2 immunomagnetic beads, EGFR immunomagnetic beads, EpCAM Immunomagnetic beads or MUC1 immunomagnetic beads.

4. a kind of capture according to claim 1 handles and feeds back CTCs to excite immune device, it is characterised in that: First absorption magnetic pole (14), the second absorption magnetic pole (20) and the first heat vibration magnetic pole (12), the second heat vibration magnetic pole (16) are respectively set At least one.

5. a kind of capture according to claim 1 handles and feeds back CTCs to excite immune device, it is characterised in that: The magnetic bead slot (21) is equipped at least one supply port (22).

6. a kind of capture according to claim 3 handles and feeds back CTCs to excite immune device, it is characterised in that: First strainer (19) aperture is not less than the magnetic bead partial size；Second strainer (18) aperture is not more than the magnetic bead grain Diameter.

7. a kind of capture according to claim 1 handles and feeds back CTCs to excite immune device, it is characterised in that: First strainer (19) aperture is not more than 6 μm.

8. a kind of capture according to claim 1 handles and feeds back CTCs to excite immune device, it is characterised in that: The shell (31) is a kind of packet mode container of waterproof.

9. a kind of capture according to claim 1 handles and feeds back CTCs to excite immune device, it is characterised in that: The supply unit (10) contains energy-storage travelling wave tube, and the energy-storage travelling wave tube is battery, solar battery or energy mix battery；Institute It states energy-storage travelling wave tube and is connected with energy indicator light.

10. a kind of capture, processing described in -9 any claims and feeding back CTCs according to claim 1 to excite immune dress Set the application in terms for the treatment of or adjuvant therapy of tumors.