WO2020220684A1 - 一种循环肿瘤细胞在体闭环提取设备 - Google Patents

一种循环肿瘤细胞在体闭环提取设备 Download PDF

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Publication number
WO2020220684A1
WO2020220684A1 PCT/CN2019/124725 CN2019124725W WO2020220684A1 WO 2020220684 A1 WO2020220684 A1 WO 2020220684A1 CN 2019124725 W CN2019124725 W CN 2019124725W WO 2020220684 A1 WO2020220684 A1 WO 2020220684A1
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unit
tumor cells
circulating tumor
blood
separation unit
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PCT/CN2019/124725
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English (en)
French (fr)
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刘忠英
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刘忠英
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Publication of WO2020220684A1 publication Critical patent/WO2020220684A1/zh

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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
    • A61M1/38—Removing constituents from donor blood and storing or returning remainder to body, e.g. for transfusion

Definitions

  • the present invention relates to the field of medical equipment, and more specifically, the present invention relates to a closed-loop extraction device for circulating tumor cells in vivo.
  • Circulating tumor cell (circulating tumor cell) is also referred to as CTC for short.
  • Circulating tumor cells are a general term for all types of tumor cells that exist in peripheral blood. They fall off solid tumor lesions (primary and metastatic) due to spontaneous or diagnosis and treatment operations. Most circulating tumor cells undergo apoptosis or apoptosis after entering the peripheral blood. If swallowed, a few can escape and develop into metastases, increasing the risk of death in patients with malignant tumors. It can be seen that circulating tumor cells are closely related to the recurrence and metastasis of malignant tumor cells.
  • this method of in vitro processing usually only draws a small amount of blood (approximately 10ml), and because the number of circulating tumor cells in the peripheral blood is usually relatively small, it generally requires about hundreds of millions of white blood cells and hundreds of Looking for a smaller number of circulating tumor cells in a billion red blood cells, it is possible to produce a small part of the blood (about 10ml) drawn without circulating tumor cells, which will cause false negatives. Or, the content of circulating tumor cells in a small portion of blood (about 10ml) is extremely low. For example, if there is only one or a few circulating tumor cells, then based on a series of reasons such as detection sensitivity, false negatives may also be caused. Case. It can be seen that the existing in vitro detection of circulating tumor cells is likely to cause inaccurate final results, making it difficult to formulate a suitable treatment plan.
  • An object of the present invention is to provide a new technical solution for an in vivo closed-loop extraction device for circulating tumor cells.
  • a closed-loop extraction device for circulating tumor cells in vivo, including a blood collection unit, a preliminary separation unit, a fine separation unit, a storage unit, a return unit and a control unit;
  • the blood collection unit is connected to the preliminary separation unit through a first blood transfusion tube;
  • the primary separation unit is connected to the fine separation unit or the storage unit through a second blood transfer tube, and the primary separation unit is also connected to the return unit through a third blood transfer tube; the primary separation unit is configured to The blood is separated into components containing circulating tumor cells and components without circulating tumor cells under the action of
  • the fine separation unit is connected to the reinfusion unit through a fourth blood transfusion tube, and the fine separation unit is also connected to the storage unit through a discharge tube; the fine separation unit is configured to treat circulating tumor cells containing The components are separated and extracted from circulating tumor cells;
  • the storage unit is configured to store components containing circulating tumor cells and/or circulating tumor cells;
  • the return unit is configured to return the separated components without circulating tumor cells to the body
  • the control unit is respectively connected with the blood collection unit, the preliminary separation unit, the fine separation unit and the return unit through a communication control line.
  • pressure sensors are provided outside the blood collection unit and the return unit, and the pressure sensors are both connected to the control unit through a communication control line.
  • the in vivo closed-loop extraction equipment for circulating tumor cells further includes a component detection device; the component detection device is connected to the preliminary separation unit through a detection line or a communication control line, and the component detection device also A line or a communication control line is connected to the control unit, and the component detection device is configured to detect the type, purity, and layering state of each component separated by the preliminary separation unit under the control of the control unit.
  • the device for in vivo closed-loop extraction of circulating tumor cells further includes an ultrasonic bubble sensor connected to the return unit, and the ultrasonic bubble sensor is also connected to the control unit through a communication control line connection.
  • the device for in vivo closed-loop extraction of circulating tumor cells further includes a fluid replacement unit connected to the reinfusion unit through a fluid replacement tube; the fluid replacement unit is also connected to the control unit through a communication control line connection.
  • the fine separation unit includes a temporary storage unit, and an injection port and an output port are respectively provided on the temporary storage unit;
  • the injection port is configured to inject immunomagnetic beads for extracting circulating tumor cells into the temporary storage unit
  • the output port is connected to an output pipe, the output pipe is provided with a suction pump, the end of the output pipe is divided into two branches, one branch is connected to the fourth blood transfer tube, and the other branch is connected to the
  • the discharge pipe is connected, a switch is provided at the end of the output pipe, the switch is connected to the control unit through a communication control line, and the switch is configured to control the on or off of the two branches, and
  • the two branches are configured such that at the same time, one branch is turned on and the other branch is turned off;
  • a downwardly concave storage tank is provided on the wall of a section of the output tube, and an electromagnetic unit is provided outside the storage tank, and the electromagnetic unit is connected to the control unit through a communication control line to extract circulating tumors.
  • the outer surface of the immune magnetic beads is wrapped with a coating of circulating tumor cell immune antibodies.
  • the fine separation unit further includes a swing device, and the temporary storage unit is provided on the swing device.
  • the fine separation unit further includes a mesh plate, the mesh plate is made of ferromagnetic material, and the mesh plate is arranged in the output pipe;
  • An electromagnetic coil is wound on the outer wall of the output tube corresponding to the mesh plate, and the electromagnetic coil is connected to the control unit through a communication control line; or, a permanent coil is provided outside the output tube corresponding to the mesh plate. magnet.
  • the multiple mesh plates are arranged in parallel and spaced apart in the output tube.
  • the closed-loop extraction device for circulating tumor cells in the body realizes the closed-loop detection and filtration of circulating tumor cells in the body's blood, which can not only accurately detect, but also directly and continuously filter out the whole body blood
  • the circulating tumor cells contained in it can effectively avoid the recurrence and metastasis of malignant tumors.
  • the whole body blood is used to detect circulating tumor cells, the situation that circulating tumor cells may not be detected or extracted in a small amount of blood is avoided, and false negative test results can be avoided.
  • Fig. 1 is a schematic structural diagram of an in vivo closed-loop extraction device for circulating tumor cells provided by an embodiment of the present invention.
  • Fig. 2 is a schematic structural diagram of another device for in vivo closed-loop extraction of circulating tumor cells provided by an embodiment of the present invention.
  • Fig. 3 is a schematic structural diagram of yet another closed-loop extraction device for circulating tumor cells in vivo provided by an embodiment of the present invention.
  • Fig. 4 is a schematic structural diagram of a preliminary separation unit provided by an embodiment of the present invention.
  • Fig. 5 is a schematic diagram of the first structure of the centrifugal pool in the preliminary separation unit provided by the embodiment of the present invention.
  • Fig. 6 is a schematic diagram of the second structure of the centrifugal pool in the preliminary separation unit provided by the embodiment of the present invention.
  • Fig. 7 is a schematic diagram of a third structure of the centrifugal pool in the preliminary separation unit provided by the embodiment of the present invention.
  • Fig. 8 is a schematic diagram of the fourth structure of the centrifugal pool in the preliminary separation unit provided by the embodiment of the present invention.
  • Fig. 9 is a schematic structural diagram of a fine separation unit provided by an embodiment of the present invention.
  • Fig. 10 is a partial enlarged schematic diagram of the electromagnetic unit part in Fig. 9.
  • Fig. 11 is a schematic structural diagram of another fine separation unit provided by an embodiment of the present invention.
  • Fig. 12 is a schematic diagram of a mesh plate provided by an embodiment of the present invention for adsorbing immunomagnetic beads.
  • Fig. 13 is a schematic diagram of a mesh plate arrangement according to an embodiment of the present invention.
  • Fig. 14 is a schematic structural diagram of another fine separation unit provided by an embodiment of the present invention.
  • 1-blood collection unit 2-preliminary separation unit, 201-centrifugal separation channel, 202-inlet end, 203-outlet end, 204-semi-enclosed blocking groove, 205-connecting pipe, 206-extraction port, 207-feeding port , 208- first discharge port, 209- second discharge port, 210- centrifugal tank, 211- third discharge port, 212- filter screen, 213- feeding pipe, 214- control switch, 215- first Road, 216-second branch, 3-storage unit, 4-fine separation unit, 401-temporary storage unit, 402-injection port, 403-output pipe, 404-storage tank, 405-extraction pump, 406-switch , 407-swing device, 408-mesh plate, 4081-mesh, 409-injection port, 410-immune magnetic beads, 411-electromagnetic coil, 5-return unit, 6-component detection device, 7-anticoagulant Adding device, 8
  • the device for in vivo closed-loop extraction of circulating tumor cells can be used to check and filter out circulating tumor cells in the blood of the patient's body, thereby avoiding the recurrence and metastasis of malignant tumors.
  • the “in-body” refers to being connected with the body to form a whole body.
  • the "closed loop” refers to the formation of a closed system between the entire blood processing system and the body to avoid the intrusion of external bacteria and the like, and to avoid infection and danger.
  • the in vivo closed-loop extraction device for circulating tumor cells provided by the embodiments of the present invention can be applied to humans, animals, etc., which is not limited by the present invention.
  • the device for extracting circulating tumor cells in vivo includes at least: a blood collection unit 1, a preliminary separation unit 2, a storage unit 3, a fine separation unit 4, a return unit 5, and a control unit 11 .
  • the blood collection unit 1 may include a blood collection needle, a blood collection pump, a filter, a blood collection tube and other components well known to those skilled in the art, which will not be described in detail here.
  • the blood collection unit 1 can be connected to the preliminary separation unit 2 through the first blood transfusion tube 14.
  • the blood drawn from the body can be sent to the primary separation unit via the first blood transfusion tube 14. 2 in. That is, the blood collection unit 1 is used to collect blood from the body and send the blood to the preliminary separation unit 2.
  • the blood collection unit 1 in order to realize automatic control (for example, start or stop) of the operation of the blood collection unit 1, the blood collection unit 1 can be connected to the control unit 11 through a communication control line. In this case, the control unit 11 can realize Control the start or stop of the blood collection unit 1.
  • the primary separation unit 2 is connected to the fine separation unit 4 or the storage unit 3 through the second blood transfusion tube 15, and the primary separation unit 2 is also connected to the reinfusion unit through the third blood transfusion tube 16 5Connect.
  • the preliminary separation unit 2 is configured to separate components in the blood into components containing circulating tumor cells and components not containing circulating tumor cells according to specific gravity under the action of centrifugal force. At this time, the components that do not contain circulating tumor cells can be directly sent to the reinfusion unit 5 through the third blood transfusion vessel 16, and the reinfusion unit 5 is returned to the body to realize the circulation process.
  • the primary separation unit 2 can be connected to the control unit 11 through a communication control line, that is, the control unit 11 can realize the operation or stop of the primary separation unit 2 control.
  • the fine separation unit 4 is configured to extract circulating tumor cells from components containing circulating tumor cells. Specifically, after the preliminary separation unit 2, the blood is separated into components containing circulating tumor cells and components not containing circulating tumor cells. In fact, this separation did not completely extract circulating tumor cells. What was separated was Containing components of circulating tumor cells, that is, circulating tumor cells are also mixed with other monocyte components. Therefore, in this embodiment, it is designed to add a fine separation unit 4 after the initial separation unit 2.
  • the fine separation unit 4 extracts circulating tumor cells by the immunomagnetic bead method, and the extracted circulating tumor cells can be passed through the discharge pipe 9.
  • the components are sent to the storage unit 3 for storage, and the remaining components without circulating tumor cells are sent to the return unit 5, which is controlled by the return unit 5 to be returned to the body to realize the closed loop circulation process in the body.
  • This can achieve precise extraction of circulating tumor cells in the blood. Because of the two separation and extraction processes, circulating tumor cells can be accurately extracted from the blood, and the circulating tumor cells can be effectively filtered out.
  • the storage unit 3 may be, for example, a storage bag or a storage pool and other devices with storage functions, which are not limited in the present invention.
  • the storage unit 3 adopts a storage bag, which has a simple structure, low manufacturing cost, and is convenient to use.
  • the reinfusion unit 5 may include blood transfusion needles, blood transfusion pumps, filters, blood transfusion tracts, and other components well known to those skilled in the art, which will not be described in detail here.
  • the reinfusion unit 5 can be connected to the fine separation unit 4 through the fourth blood transfusion tube 17, thereby realizing the communication between the reinfusion unit 5 and the fine separation unit 4.
  • the reinfusion unit 5 can also be connected to the preliminary separation unit 2 through the third blood transfer vessel 16 to realize the communication between the reinfusion unit 5 and the preliminary separation unit 2.
  • the reinfusion unit 5 is configured to: under the action of the reinfusion pump, the components separated by the fine separation unit 4 without circulating tumor cells can be directly returned to the body, or the components separated by the primary separation unit 2 without circulating tumor The components of the cells are returned to the body.
  • the combination of the reinfusion unit 5 and the blood sampling unit 1 can realize a closed loop circulation process in vivo.
  • the feedback unit 5 in order to realize automatic control (for example, start or stop) of the operation of the feedback unit 5, the feedback unit 5 can be connected to the control unit 11 through a communication control line, and the control unit 11 realizes the Unit 5 start or stop control.
  • control unit 11 can be used to separately control the operations of the blood collection unit 1, the preliminary separation unit 2, the fine separation unit 4, and the return unit 5.
  • the control unit 11 may have a display unit, and the user can control and observe the working status of each component by operating the display unit.
  • the display unit may be, for example, a display device known to those skilled in the art such as a touch screen, which is not limited in the present invention.
  • the device for extracting circulating tumor cells in vivo can detect and filter circulating tumor cells in the blood of the whole body.
  • the circulating tumor cell in vivo closed-loop extraction equipment uses the primary separation unit 2 (primary separation and extraction) and the fine separation unit 4 (secondary separation and extraction) to repeatedly detect and filter circulating tumor cells in the blood, which can completely remove the blood contained
  • the circulating tumor cells effectively overcome the drawbacks in the prior art.
  • the circulating tumor cell in vivo closed-loop extraction device has the characteristics of accurate detection results and high safety, which can avoid false negative detection results, and can improve the detection level of circulating tumor cells.
  • the circulating tumor cell in vivo closed-loop extraction equipment has a high degree of automation, saves time and effort, and is convenient to operate.
  • the in vivo closed loop extraction device for circulating tumor cells can also adopt a single needle mode, that is, the blood sampling unit 1 and the reinfusion unit 5 are combined.
  • the control unit 11 may be used to control blood sampling and reinfusion alternately.
  • a needle can be used, which can serve as a blood sampling needle or a blood transfusion needle. The needle is connected to the pipeline, and when blood is collected from the body, blood will not be returned to the body for transfusion, that is, blood collection and transfusion work in a time-sharing manner, and there will be no mutual interference.
  • the control unit 11 controls the blood sampling pump to operate, and at the same time controls the return pump to stop working (or small flow).
  • the blood sampling pump is controlled to stop by the control unit 11 (the flow rate is 0 when stopped, which is equivalent to closing the pipeline and the operation of the return pump is controlled at the same time).
  • the flow rate of the blood sampling pump is greater than the flow rate of the infusion pump, blood flows outward from the needle, and vice versa.
  • the first blood transfusion tube 14, the second blood transfusion tube 15, the third blood transfusion tube 16, the fourth blood transfusion tube 17, and the discharge tube 9 are all tubes that are well-known to those skilled in the art to facilitate blood delivery. .
  • the size of the above-mentioned pipes can be flexibly adjusted according to needs, which is not limited by the present invention.
  • the device for in vivo closed-loop extraction of circulating tumor cells may also include an anticoagulant addition device 7.
  • the anticoagulant adding device 7 is configured to add an anticoagulant to the blood sampling unit 1. Specifically, when the blood sampling unit 1 draws blood into the first blood transfusion tube 14 and starts to circulate, the anticoagulant can be added to prevent the blood being processed from clotting, thereby ensuring the smooth progress of the entire blood circulation process. It should be noted that the addition amount of the anticoagulant can be flexibly controlled as required, and the present invention does not limit this.
  • the anticoagulant adding device 7 can be directly combined with the blood sampling unit 1.
  • the anticoagulant adding device 7 can also be connected to the blood sampling unit 1 through a pipeline. Both of these two methods can realize the addition of anticoagulant, which can be flexibly selected according to the actual situation in specific applications.
  • the anticoagulant adding device 7 can also be connected to the control unit 11 through a communication control line.
  • This design can realize the control of the anticoagulant adding device 7 by the control unit 11, that is, it can control the anticoagulant adding device 7 to add an anticoagulant to the blood, or stop adding an anticoagulant to the blood. That is to say, the automatic control of the addition of anticoagulant can be realized by the control unit 11, which is more convenient to operate and easy to control the addition amount.
  • the anticoagulant adding device 7 may not be connected to the control unit 11. In this case, the addition and the amount of the anticoagulant can be manually controlled. In specific applications, it can be flexibly selected according to needs, which is not limited in the present invention.
  • the device for in vivo closed-loop extraction of circulating tumor cells provided by the embodiment of the present invention further includes a pressure sensor 8.
  • pressure sensors 8 are provided outside the blood collection unit 1 and the reinfusion unit 5, respectively.
  • the pressure sensors 8 are all connected to the control unit 11 through communication control lines. In order to achieve accurate pressure detection, the pressure sensor 8 should be located close to the corresponding blood vessel.
  • the pressure sensor 8 provided outside the blood collection unit 1 is used to detect the blood collection end, such as the pressure of the blood collection tube in the blood collection unit, and the pressure in the first blood transfusion tube 14 connected to the blood collection unit 1.
  • the pressure sensor 8 arranged outside the reinfusion unit 5 is used to detect the reinfusion end, for example, the pressure in the blood transfusion channel in the reinfusion unit 5, and the third blood transfusion blood vessel 16 and the fourth blood transfusion vessel 16 connected to the reinfusion unit 5 The pressure in the blood vessel 17.
  • the pressure detection can determine whether the needle (for example, blood sampling needle, blood transfusion needle) and the corresponding pipeline are blocked. Once blockage occurs, it is easy to cause abnormal pressure in the pipe and cause danger.
  • the pressure sensor 8 is arranged on the first blood transfer tube 14 and the second blood transfer tube 15 respectively.
  • the pressure sensor 8 is provided in the first blood transfer tube 14 and the second blood transfer tube 15 respectively. It can be flexibly adjusted according to the actual situation, and the present invention does not limit this. In addition, the present invention does not specifically limit the number of pressure sensors 8 installed, and an appropriate number can be flexibly selected according to needs.
  • each pressure sensor 8 can be connected to the control unit 11 through a communication control line.
  • This design can realize the control of the pressure sensor 8 by the control unit 11, that is, the pressure sensor 8 can be controlled to start pressure detection at an appropriate time, and of course, the pressure sensor 8 can also be controlled not to perform pressure detection.
  • the device for in vivo closed-loop extraction of circulating tumor cells may further include a component detection device 6.
  • the component detection device 6 can be connected to the initial separation unit 2 through a detection line or a communication control line, and the component detection device 6 is also connected to the control unit 11 through a detection line or a communication control line.
  • the component detection device 6 is configured to detect the components and purity of each part separated by the primary separation unit 2 under the control of the control unit 11, and the component detection device 6 can also perform the component separation process of the primary separation unit 2 Control so that different components can form a good layered state, which is conducive to separate extraction of different components. That is, when the separation unit 2 originally divided blood into different components, the component detection device 6 can detect the stratification state, type and purity of each component, for example, it can be determined whether it contains circulating tumor cells or the like.
  • the component detection device 6 can also be connected to the fine separation unit 4 through a communication control line, which is not limited in the present invention.
  • the component detection device 6 can use detection equipment well known to those skilled in the art, which will not be described in detail here.
  • the component detection device 6 can be selected to be set or not set according to needs, which is not limited in the present invention.
  • the device for in vivo closed-loop extraction of circulating tumor cells provided by the embodiment of the present invention further includes an ultrasonic bubble sensor 12 located at one end of the reinfusion unit 5.
  • the ultrasonic bubble sensor 12 is connected to the return unit 5. Specifically, the ultrasonic bubble sensor 12 uses ultrasound to detect whether the returned blood contains bubbles. Once it detects that the blood contains bubbles, immediately stop the infusion of blood into the body and give an alarm, otherwise the blood entering the body will be dangerous.
  • the ultrasonic bubble sensor 12 is also connected to the control unit 11 through a communication control line.
  • This design can realize the control of the ultrasonic bubble sensor 12 by the control unit 11, that is, the ultrasonic bubble sensor 12 can be controlled to start the detection at an appropriate time, and of course, the ultrasonic bubble sensor 12 can also be controlled not to perform detection. That is to say, the automatic control of the ultrasonic bubble sensor 12 can be realized by the control unit 11.
  • the device for in vivo closed-loop extraction of circulating tumor cells may further include a fluid replacement unit 13.
  • the fluid replacement unit 13 is configured to replenish fluid into the blood when returning blood, for example, can replenish nutrient solution in the body.
  • the liquid supplement unit 13 may be connected to the return unit 5 through a liquid supplement tube.
  • the fluid replacement unit 13 can also be combined with the return unit 5. Both of the above-mentioned methods can realize the addition of nutrient solution or medical solution to the returned blood.
  • the fluid replacement unit 13 may be connected to the control unit 11 through a communication control line. This design can realize the control of the replenishment unit 13 by the control unit 11 to realize the automation of replenishment.
  • the condensing agent adding device 7 and the replenishing unit 13 in the present invention can be dedicated pumps, and their operation or stopping can be controlled by the control unit 11.
  • the pressure sensor 8, the ultrasonic bubble sensor 12, and the component detection device 6 in the present invention are also controlled by the control unit 11, which realizes the automation of operation.
  • the primary separation unit 2 is mainly based on the centrifugal separation principle to separate blood to separate the blood into different components, for example, components that do not contain circulating tumor cells And components containing circulating tumor cells.
  • the preliminary separation unit 2 may have a structure including a centrifugal separation channel 201, and the centrifugal separation channel 201 has an inlet end 202 and an outlet end 203, respectively.
  • the inlet end 202 is configured to input blood into the centrifugal separation channel 201 to wait for separation of raw materials.
  • the centrifugal separation channel 201 is configured to rotate around its center at a predetermined speed, and generate centrifugal force through the rotation, so as to separate components of different specific gravities in the blood under the action of centrifugal force to form different component layers.
  • Extraction ports 206 are provided on the outlet end 203 corresponding to the positions of each component layer (for example, the number of the extraction ports 206 can be flexibly set according to needs, and the present invention is not limited here), and each extraction port 206 is used to output the current components.
  • Floor The size of a section of the centrifugal separation channel 201 close to the outlet end 203 gradually becomes wider, and the wall surface of this section forms an involute structure, which is beneficial to improve the separation accuracy.
  • the centrifugal separation channel 201 can be a single-loop structure, a double-loop structure, or a multi-loop structure, which can be flexibly selected according to actual conditions.
  • the double-loop structure does not refer to a completely closed two-loop structure, and only needs to exceed one loop, such as a one-and-a-half loop structure.
  • the multi-loop structure which does not refer to a completely closed multi-loop structure.
  • a semi-enclosed blocking groove 204 is formed at the extraction port 206 as shown in FIG. 4.
  • the semi-enclosed blocking groove 204 is configured to enable the components to gather together before taking out the current component layer from the extraction port 206 and to prevent the mixing of components of other component layers.
  • This design is very suitable for the extraction of rare components, such as the extraction of circulating tumor cells in the blood.
  • the above-mentioned preliminary separation unit 2 may further include a centrifugal tank 210 having a feed end and a discharge end, respectively.
  • a filter screen 212 can be provided in the centrifuge tank 210, and the filter screen 212 extends from the feed end to the discharge end.
  • a feeding port 207 is provided on the feeding end, and at least one discharging port is provided on the discharging end (for example, the first discharging port 208 and the second discharging port 209 in FIG. 4, or the The first discharge port 208, the second discharge port 209, and the third discharge port 211).
  • the feed port 207 of the centrifugal tank 210 and a certain extraction port 206 of the centrifugal separation channel 201 can be connected by a connecting pipe 205.
  • the centrifugal pool 210 is configured such that when the centrifugal separation channel 201 rotates, the centrifugal pool 210 can rotate together with the centrifugal separation channel 201, and is used for re-centrifugation and centrifugal separation of the components taken out from the extraction port 206, for example, further from blood Separate and extract circulating tumor cells, and try to avoid mixing other components into circulating tumor cells.
  • one or more filter screens 212 may be provided in the centrifuge tank 210.
  • the mesh size of the filter screens 212 may be the same or different.
  • the size of the feed opening 207 can be flexibly adjusted as required.
  • the number and size of the discharge ports can also be adjusted flexibly according to needs. The present invention does not limit this.
  • the primary separation unit 2 of the present invention adopts a centrifugal separation channel 201 and a centrifugal pool 210 to cooperate, of course, the present invention is not limited to this structure.
  • the blood is first centrifuged through the centrifugal separation channel 201.
  • the components containing circulating tumor cells can be separated and gathered in a semi-enclosed type.
  • the blocking groove 204 it can then be output through the corresponding extraction port 206, and then the components containing circulating tumor cells can be introduced into the centrifuge tank 210 through the connecting pipe 205 connected to the extraction port 206.
  • two filter screens 212 are provided in the centrifuge tank 210.
  • the two filter screens 212 can be arranged oppositely. The pore sizes of the two filter screens 212 can be designed to be different.
  • the two filter screens 212 can connect the centrifuge tank 210 The inner space is divided into three areas, and the feed inlet 207 can be located in the area enclosed by the two filter screens 212. At this time, the components containing circulating tumor cells separated by the centrifugal separation channel 201 are directly sent into the area surrounded by two filters 212. Under the action of centrifugal force, one filter 212 can supply light and small plasma and The platelets pass through and are extracted from the first discharge port 208. The other filter 212 can allow the heavier and smaller red blood cells to pass through and is extracted from the second discharge port 209, while the larger circulating tumor cells and White blood cells and the like can remain in the area enclosed by the two filters 212, and can be extracted through the third discharge port 211 provided in the area. At this time, the separated components containing circulating tumor cells can be sent out through the third discharge port 211 and transported by the feed pipe 213 connected to the third discharge port 211.
  • the feeding pipe 213 provided by the embodiment of the present invention can be divided into two branches at its end (for example, it is divided into a first branch 215 and a second branch 216), and a control switch 214 is provided at the position of the end branch.
  • the first branch 215 can be connected to the reinfusion unit 5 (if there is no circulating tumor cell, the reinfusion unit 5 can be connected).
  • the second branch 216 can be connected to the storage unit 3 or the fine separation unit 4.
  • the above-mentioned control switch 214 can be connected to the control unit 11 through a communication control line, that is, under the control of the control unit 11, the feeding pipe 213 can be connected to Any branch is turned on.
  • the control switch 214 controls the feeding tube 213 and the first branch 215 to achieve conduction, it is possible that the circulating tumor cells have not been extracted (if there are no circulating tumor cells in the blood) or do not need to be extracted.
  • the corresponding components are sent into the fourth blood transfusion tube 17 and returned to the body by the reinfusion unit 5.
  • the control switch 214 controls the feeding tube 213 to be connected to the second branch 216, the separated components containing circulating tumor cells are sent to the storage unit 3 for storage, or the components containing circulating tumor cells pass through the second branch.
  • the blood vessel 15 is sent to the fine separation unit 4 for further extraction of circulating tumor cells.
  • the preliminary separation unit 2 of the present invention may further include a washing mechanism 19.
  • the flushing mechanism 19 includes a flushing head 1901, the flushing head 1901 is connected to a flushing pipe 1902, and the flushing pipe 1902 is provided with a circulating pump 1903.
  • the flushing mechanism 19 can be used to flush the filter screen 212 in the centrifuge tank 210. Specifically, when there are many attachments on the filter screen 212, which block the mesh on the filter screen 212, the flushing head 1901 can be used to flush the filter screen 212; and the filter screen 212 can also be flushed at the end of the circulating tumor cell extraction. 212 is flushed to prevent circulating tumor cells from remaining on the filter 212.
  • the flushing head 1901 can be provided on one side of the filter screen 212, or can be provided on both sides of the filter screen 212. At this time, the flushing heads 1901 can be distributed around the filter screen 212 to achieve Flush the filter 212 without dead corners. It should be noted that when flushing is performed, the flushing pipe 1902 can supply water or cleaning liquid, which will not be described in detail here.
  • the centrifugal tank 210 provided by the embodiment of the present invention may not be provided with a filter 212 inside.
  • the width of the discharge end can be increased, that is, the centrifuge tank 210 is from the feed end to the discharge end.
  • the width of the material end gradually becomes larger (refer to Figure 7 for the discharge end).
  • the component detection device 6 can be used for detection. Specifically:
  • One of the discharge ports (shown in FIG. 7 is the first discharge port 208) is connected to the discharge pipe 18, and the component detection device 6 can be arranged on the outside of the discharge pipe 18 for opposite discharge
  • the components conveyed in the material pipeline 18 are tested to determine the type and purity of the components conveyed in the discharge pipeline 18.
  • the end of the discharge pipeline 18 can also be divided into two branches (denoted as the first branch and the second branch), and a first control is provided at the position of the end branch of the discharge pipeline 18
  • the switch 1801 and the first control switch 1801 are connected to the control unit 11 through a communication control line, that is, the control unit 11 can control the first control switch 1801. Through the first control switch 1801, the first branch or the second branch can be turned on.
  • the first branch may be connected to the storage unit 3 or the fine separation unit 4, and the second branch may be connected to the return unit 5. That is, when the component detection device 6 detects that the component in the discharge pipeline 18 contains circulating tumor cells, it can be sent to the storage unit 3 or the fine separation unit 4 through the first branch (to continue to analyze the circulating tumor cells). selected). When the component detection device 6 detects that the component in the discharge pipeline 18 does not contain circulating tumor cells, it can be delivered to the return unit 5 through the second branch, and finally returned to the body.
  • the component detection device 6 can use the spectral absorption characteristics of circulating tumor cells for detection or the spectral absorption characteristics of monocytes for detection, which will not be described in detail here.
  • the component detection device 6 may be a reflection sensor or a transmission sensor.
  • the above-mentioned washing mechanism 19 may be connected to another discharge port to facilitate washing of the centrifugal tank 210.
  • the discharge port connected to the washing mechanism 19 generally does not output circulating tumor cells or components containing circulating tumor cells.
  • the flushing head 1901 of the flushing mechanism 19 is connected to the discharge port, the flushing head 1901 is connected to a flushing pipe 1902, and a circulating pump 1903 is provided on the flushing pipe 1902.
  • the end of the flushing pipe 1902 is divided into two branches.
  • a second control switch 1904 is provided at the position of the end branch of the flushing pipe 1902.
  • the second control switch 1904 is connected to the control unit 11 through a communication control line, that is, The second control switch 1904 is controlled by the control unit 11.
  • the two branches can be turned on or off (but at the same time, one branch is turned on and the other branch is turned off), that is, one branch can be connected to the feedback unit 5, and In order to return the components without circulating tumor cells to the body, the other branch is shut off at this time.
  • the other branch is turned on, and water and/or cleaning fluid for washing can be injected into the washing pipe 1902, which can be used to wash the centrifuge tank 210 at this time .
  • the two branches do not affect each other.
  • the flushing mechanism 19 can be selected to be installed or not installed according to needs, and the installation position can also be flexibly adjusted, which is not limited in the present invention.
  • the primary separation unit provided in the embodiments of the present invention has various forms, and is not limited to the above-mentioned forms.
  • the centrifugal separation before the centrifugal pool 210 may use centrifugal equipment known to those skilled in the art such as centrifugal cups, centrifugal bags, and centrifugal discs, which are not limited in the present invention.
  • the fine separation unit 4 is used as the lower separation and screening unit of the primary separation unit 2, and is used to continue the precise separation of circulating tumor cell-containing components separated from the blood, so as to realize the circulation
  • the tumor cells are purified, and the remaining components that do not contain circulating tumor cells are transported back to the body through the infusion unit 5.
  • the fine separation unit 4 of the present invention may include a temporary storage unit 401, and an injection port 402 and an output port are respectively provided on the temporary storage unit 401.
  • the components containing circulating tumor cells can be transported to the temporary storage unit 401 in the fine separation unit 4 via the second blood transfer vessel 15 for temporary storage, and then the circulating tumor cells can be extracted Wait for subsequent processing to achieve separation and extraction of circulating tumor cells.
  • the temporary storage unit 401 may be a storage bag or a storage pool and other devices with storage functions, which are not limited in the present invention. Moreover, the present invention does not limit the storage capacity of the storage unit 401, and can be adjusted according to actual conditions.
  • the injection port 402 is configured to: after the components containing circulating tumor cells output by the primary separation unit 2 enter the temporary storage unit 401, especially when a predetermined amount is reached, the injection port 402 can be injected into the temporary storage unit 402 Immunomagnetic beads 410 for extracting circulating tumor cells. The purpose of this is to make the immunomagnetic beads fully contact with components containing circulating tumor cells.
  • the immunomagnetic beads 410 are superparamagnetic beads, and the immunomagnetic beads 410 are coated with immune antibodies corresponding to circulating tumor cells (for example, coating, that is, the antibody is coated on the surface of the immunomagnetic beads).
  • the circulating tumor cells encounter the immunomagnetic beads 410, they will be attracted and captured, and the immunomagnetic beads 410 can exhibit good magnetic properties in a magnetic field.
  • the injection volume of the immunomagnetic beads 410 can be flexibly adjusted according to the actual situation, which is not limited in the present invention.
  • an output pipe 403 is connected to the output port of the temporary storage unit 401, and an extraction pump 405 is provided on the output pipe 403.
  • the end of the output tube 403 is divided into two branches, one of which is connected to the fourth blood transfer tube 17 for communication with the reinfusion unit 5, and the other branch is connected to the discharge tube 9 for communication with Connection of storage unit 3.
  • a switch 406 is also provided at the position of the end branch of the output tube 403, and the switch 406 is connected to the control unit 11 through a communication control line.
  • the switch 406 is configured to control the on or off of the two branches, where the two branches are configured to: one branch is turned on at the same time, and the other branch is turned off, that is, at the same time, When the control output tube 403 is connected to one branch, the other branch is turned off, and vice versa.
  • a storage tank 404 that is recessed downward is provided on the wall of a section of the output tube 403.
  • the longitudinal cross-sectional shape of the storage tank 404 may be, for example, a rectangular shape or a semi-circular arc shape, which is not limited in the present invention.
  • the storage tank 404 of the present invention is used to retain the immunomagnetic beads 410 from which circulating tumor cells are extracted.
  • An electromagnetic unit 10 is provided outside the storage tank 404.
  • the electromagnetic unit 10 is connected to the control unit 11 through a communication control line, that is, the electromagnetic unit 10 can be controlled by the control unit 11.
  • the electromagnetic unit 10 can generate an electromagnetic field.
  • the immune magnetic beads 410 that capture circulating tumor cells are attracted to the storage tank 404 to achieve immunity
  • the magnetic bead method extracts circulating tumor cells to prevent magnetic beads from being infused into the body.
  • the immunomagnetic beads 410 can be used to adsorb circulating tumor cells.
  • the fluid in the temporary storage unit 401 will continue to flow into the output tube 403.
  • the immune magnetic beads 410 After the electromagnetic unit 10 is activated, when the immunomagnetic beads When 410 enters the electromagnetic field generated by the electromagnetic unit 10, the immune magnetic beads 410 will be attracted and then remain in the storage tank 404. Since the immunomagnetic beads 410 have been combined with the circulating tumor cells before, the circulating tumor cells are also retained in the storage tank 404. At this time, the components not extracted by the immunomagnetic beads 410 can be returned to the unit through the switch 406. 5. When the fluid in the temporary storage unit 401 is completely drawn, another branch can be turned on through the switch 406 and the electromagnetic unit 10 can be closed, so that the immunomagnetic beads 410 in the storage tank 404 can be under the action of the extraction pump 405 Transported to the storage unit 3. The immunomagnetic beads in the storage unit 3 can be removed for further testing.
  • the blood can be directly sent to the return unit 5 through the output tube 403 via the branch by adjusting the switch 406 , Inject back into the body.
  • a permanent magnet in addition to the electromagnetic unit 10, a permanent magnet can also be provided outside the storage tank 404, but when a permanent magnet is used, it is necessary to manually place the permanent magnet or It is troublesome to remove the permanent magnet.
  • the electromagnetic unit 10 is adopted in the present invention, and the automatic control of the electromagnetic unit 10 can be realized through the connection with the control unit 11.
  • the immunomagnetic beads 410 injected into the temporary storage unit 401 can capture circulating tumor cells to achieve the extraction of circulating tumor cells, and the immunomagnetic beads 410 can exhibit good magnetic properties in a magnetic field. Move to the electromagnetic unit 10 along the lines of magnetic force, and be absorbed and fixed by the electromagnetic unit 10, while other components will not be captured by the immunomagnetic beads 410 because they do not have corresponding antibodies. They can flow and transport away normally under the action of the extraction pump 405. Enter the return unit 5 and return to the body.
  • the fine separation unit 4 provided by the implementation of the present invention may further include a swing device 407.
  • the temporary storage unit 401 may be provided on the swing device 407. After the swinging device 407 is activated, the swinging device 407 can drive the temporary storage unit 401 to swing back and forth, which can promote the sufficient combination of the internal immunomagnetic beads 410 with the circulating tumor cells.
  • the swing device 407 is mainly used to realize the back and forth swing of the temporary storage unit 401, and a device well known to those skilled in the art, such as a swing frame, can be used, which will not be described in detail here.
  • the fine separation unit 4 provided by the embodiment of the present invention further includes a mesh plate 408.
  • the mesh plate 408 is provided in the output tube 403.
  • the mesh 4081 on the mesh plate 408 can be round or square.
  • the mesh plate 408 is made of a magnetic material, such as a ferromagnetic material.
  • an electromagnetic coil 411 is wound on the outer wall of the output tube 403 corresponding to the mesh plate 408.
  • the electromagnetic coil 411 When the electromagnetic coil 411 is energized, a magnetic field can be formed.
  • the electromagnetic coil 411 may be connected to the control unit 11 through a communication control line. Based on the superparamagnetism of the immunomagnetic bead 410, it can exhibit good magnetic properties in a magnetic field.
  • the immunomagnetic beads 410 carrying circulating tumor cells hits the mesh plate 408, the immunomagnetic beads 410 will be adsorbed on the mesh plate 408.
  • the immunomagnetic beads 410 have adsorbed circulating tumor cells before, the circulating tumor cells can also be adsorbed on the mesh plate 408, and other components can pass through the mesh plate 408 and be delivered to the return unit through the output tube 403 5. Finally return to the body. Referring to FIG. 12, when the immunomagnetic beads 410 are adsorbed on the mesh plate 408, the immunomagnetic beads 410 are usually fixed beside the mesh 4081.
  • permanent magnets may also be used outside the output tube 403 corresponding to the mesh plate 408.
  • the permanent magnet can also generate a magnetic field.
  • the immunomagnetic beads 410 pass by, the immunomagnetic beads 410 can also be adsorbed on the mesh plate 408.
  • one mesh plate 408 can be provided, of course, multiple mesh plates can also be provided.
  • different mesh plates 408 can be arranged in parallel with each other, and there is a space between two adjacent mesh plates 408.
  • the mesh plate 408 may be provided in two, and the two mesh plates 408 are arranged parallel to each other in the output tube 403 with a space between them.
  • the aperture sizes of different mesh plates 408 can be the same or different, and can be flexibly adjusted according to actual application conditions.
  • the mesh plate 408 should be arranged along the cross section of the output pipe 403 to avoid a gap between the mesh plate 408 and the inner wall of the output pipe 403. There should be an appropriate distance between the mesh plate 408 and the storage tank 404.
  • At least one injection port 409 is provided on the output pipe 403 near the mesh plate 408.
  • the injection port 409 can be used to inject the immunomagnetic beads 410 or corresponding drugs. Since the injection port 409 is closer to the mesh plate 408, once the immunomagnetic beads 410 enter the output tube 403, the mesh plate 408 can easily adsorb the immunomagnetic beads 410. When the raw materials to be separated in the temporary storage unit 401 pass through the mesh When the plate 408 is set, the immunomagnetic beads 410 adsorbed on the mesh plate 408 can further capture circulating tumor cells. When the oscillating device 407 is not activated, the method of injecting the immunomagnetic beads 410 from the injection port 409 can be used to fully extract the circulating tumor cells.
  • the fine separation unit 4 of the present invention may also include the aforementioned washing mechanism 19.
  • the flushing mechanism 19 can be used to flush the attachments on the mesh plate 408.
  • the mesh plate 408 needs to be washed; of course, when the circulating tumor cell extraction is completed, the mesh plate 408 can also be washed to prevent circulating tumor cells from remaining On the mesh plate 408.
  • flushing head 1901 may be only arranged on either side of the mesh plate 408.
  • flushing heads 1901 can also be provided on both sides of the mesh plate 408, so that the flushing heads 1901 can be evenly distributed around the mesh plate 408. This design is beneficial to achieve sufficient flushing of the mesh plate 408.
  • control unit 11 is used to control the entire circulating tumor cells in the body closed-loop extraction device for various components, such as various pumps, various switches, etc., to realize the automation of the entire device.
  • various components such as various pumps, various switches, etc.
  • FIGS. 1 to 14 the positions of the pumps, switches, and branch pipelines can be changed and moved.
  • the pump can drive fluid movement regardless of the front or back, and the present invention does not limit this.

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Abstract

一种循环肿瘤细胞在体闭环提取设备，包括采血单元（1），采血单元（1）通过第一输血管（14）与初分离单元（2）连接；初分离单元（2）通过第二输血管（15）与精分离单元（4）或者存储单元（3）连接，初分离单元（2）还通过第三输血管（16）与回输单元（5）连接；初分离单元（2）用于使血液分离成含循环肿瘤细胞的成分和不含循环肿瘤细胞的成分；精分离单元（4）通过第四输血管（17）与回输单元（5）连接，精分离单元（4）还通过排放管（9）与存储单元（3）连接；精分离单元（4）用于对含循环肿瘤细胞的成分进行循环肿瘤细胞的提取；存储单元（3）用于存储含循环肿瘤细胞的成分和/或循环肿瘤细胞；控制单元（11）分别与采血单元（1）、初分离单元（2）、精分离单元（4）、回输单元（5）连接。该设备能对全身血液中的循环肿瘤细胞进行滤除。

Description

一种循环肿瘤细胞在体闭环提取设备 技术领域
本发明涉及医疗器械领域，更具体地，本发明涉及一种循环肿瘤细胞在体闭环提取设备。
背景技术
循环肿瘤细胞(circulating tumor cell)，又被简称为CTC。循环肿瘤细胞是存在于外周血中的各类肿瘤细胞的统称，因自发或诊疗操作从实体肿瘤病灶(原发灶、转移灶)脱落，大部分循环肿瘤细胞在进入外周血后发生凋亡或被吞噬，少数能够逃逸并发展成为转移灶，增加恶性肿瘤患者死亡风险。可见，循环肿瘤细胞与恶性肿瘤细胞的复发和转移有着较为密切的关系。
如今，医学技术在不断的发展和革新，为了进一步实现对循环肿瘤细胞的深入研究，避免恶性肿瘤细胞的产生，出现了一些与循环肿瘤细胞检测、提取等相关的仪器或设备。但是，这些仪器或设备都是用于对循环肿瘤细胞进行体外处理，即需要先抽取一定量的血液，之后在体外对血液中是否含有循环肿瘤细胞进行检测，以及制定相应的治疗方案等。实际上，这种体外处理的方法通常只能抽取少量的血液(大约为10ml)，而由于循环肿瘤细胞在外周血中的数量通常是比较少的，一般需要在约上亿个白细胞和几百亿个红细胞中寻找较少量的循环肿瘤细胞，就有可能会产生所抽取的一小部分血液(大约为10ml)中没有循环肿瘤细胞，从而造成假阴性。又或者是，抽取的一小部分血液(大约为10ml)中循环肿瘤细胞的含量极低，比如：只有一个或几个循环肿瘤细胞，那么基于检测灵敏度等一系列的原因，也可能造成假阴性的情况。由此可见，现有的体外检测循环肿瘤细胞很有可能造成最终结果不准确，导致难以制定合适的治疗方案。
发明内容
本发明的一个目的在于提供一种循环肿瘤细胞在体闭环提取设备的新技术方案。
根据本发明的一个方面，提供了一种循环肿瘤细胞在体闭环提取设备，包括采血单元、初分离单元、精分离单元、存储单元、回输单元和控制单元；
所述采血单元通过第一输血管与所述初分离单元连接；
所述初分离单元通过第二输血管与所述精分离单元或者存储单元连接，所述初分离单元还通过第三输血管与所述回输单元连接；所述初分离单元被配置为在离心力的作用下使血液分离成含循环肿瘤细胞的成分和不含循环肿瘤细胞的成分；
所述精分离单元通过第四输血管与所述回输单元连接，所述精分离单元还通过排放管与所述存储单元连接；所述精分离单元被配置为用于对含循环肿瘤细胞的成分进行循环肿瘤细胞的分离提取；
所述存储单元被配置为用于存储含循环肿瘤细胞的成分和/或循环肿瘤细胞；
所述回输单元被配置为用于将分离出的不含循环肿瘤细胞的成分输回身体；
所述控制单元分别通过通讯控制线与所述采血单元、初分离单元、精分离单元、回输单元连接。
可选地，所述采血单元和回输单元的外部分别设置有压力传感器，且所述压力传感器均通过通讯控制线与所述控制单元连接。
可选地，所述的循环肿瘤细胞在体闭环提取设备，还包括成分检测装置；所述成分检测装置通过检测线或者通讯控制线与所述初分离单元连接，所述成分检测装置还通过检测线或者通讯控制线与所述控制单元连接，所述成分检测装置被配置为：在控制单元的控制下检测经初分离单元分离出的各成分的种类，纯度，以及分层状态。
可选地，所述的循环肿瘤细胞在体闭环提取设备，还包括超声气泡传感器，所述超声气泡传感器与所述回输单元连接，所述超声气泡传感器还通过通讯控制线与所述控制单元连接。
可选地，所述的循环肿瘤细胞在体闭环提取设备，还包括补液单元，所述补液单元通过补液管与所述回输单元连接；所述补液单元还通过通讯控制线与所述控制单元连接。
可选地，所述精分离单元包括暂存单元，所述暂存单元上分别设置有注射口、输出口；
所述注射口被配置为用于向暂存单元内注入提取循环肿瘤细胞用的免疫磁珠；
所述输出口连接输出管，所述输出管上设置有抽取泵，所述输出管的末端分为两个支路，一个支路与所述第四输血管连接，另一个支路与所述排放管连接，在所述输出管的末端设置有开关，所述开关通过通讯控制线与所述控制单元连接，所述开关被配置为用于控制两个支路的导通或关断，且所述两个支路被配置为：在同一时间一个支路导通，另一个支路关断；
所述输出管的一段的管壁上设置有向下凹的储留槽，在所述储留槽外部设置有电磁单元，所述电磁单元通过通讯控制线与所述控制单元连接，提取循环肿瘤细胞后的免疫磁珠当流过储留槽时，在电磁单元的磁力作用下将免疫磁珠吸引并留存到储留槽中。
可选地，所述免疫磁珠外表面包裹有循环肿瘤细胞免疫抗体涂层。
可选地，所述精分离单元还包括摆动装置，所述暂存单元设置在摆动装置上。
可选地，所述精分离单元还包括网孔板，所述网孔板采用铁磁性材料制成，所述网孔板设置在所述输出管内；
在所述网孔板对应的输出管外壁上绕制有电磁线圈，所述电磁线圈通过通讯控制线与所述控制单元连接；或者是，在所述网孔板对应的输出管外设置有永久磁铁。
可选地，所述网孔板设置为一个或者多个；当设置多个网孔板时，多个网孔板在所述输出管内呈相互平行且间隔设置。
本发明实施例提供的循环肿瘤细胞在体闭环提取设备，实现了闭环地对体内全身血液进行循环肿瘤细胞的检查、滤除，不仅可以准确的检测，还可以直接、连续的滤除掉全身血液中所含有的循环肿瘤细胞，从而可以 有效地避免恶性肿瘤的复发和转移现象。而且，由于采用的是全身血液检测循环肿瘤细胞的方式，避免了少量血液中有可能检测或提取不到循环肿瘤细胞的情况，即可以避免造成检测结果的假阴性。
通过以下参照附图对本发明的示例性实施例的详细描述，本发明的其它特征及其优点将会变得清楚。
附图说明
被结合在说明书中并构成说明书的一部分的附图示出了本发明的实施例，并且连同其说明一起用于解释本发明的原理。
图1是本发明实施例提供的一种循环肿瘤细胞在体闭环提取设备的结构示意图。
图2是本发明实施例提供的另一种循环肿瘤细胞在体闭环提取设备的结构示意图。
图3是本发明实施例提供的又一种循环肿瘤细胞在体闭环提取设备的结构示意图。
图4是本发明实施例提供的初分离单元的结构示意图。
图5本发明实施例提供的初分离单元内离心池的第一种结构示意图。
图6本发明实施例提供的初分离单元内离心池的第二种结构示意图。
图7本发明实施例提供的初分离单元内离心池的第三种结构示意图。
图8本发明实施例提供的初分离单元内离心池的第四种结构示意图。
图9是本发明实施例提供的一种精分离单元的结构示意图。
图10是图9中电磁单元部分的局部放大示意图。
图11是本发明实施例提供的另一种精分离单元的结构示意图。
图12是本发明实施例提供的网孔板吸附免疫磁珠的示意图。
图13是本发明实施例提供一种网孔板设置方式示意图。
图14是本发明实施例提供的又一种精分离单元的结构示意图。
附图标记说明：
1-采血单元，2-初分离单元，201-离心分离通道，202-入口端，203-出口端，204-半包围式挡槽，205-连接管，206-提取口，207-进料口，208- 第一出料口，209-第二出料口，210-离心池，211-第三出料口，212-滤网，213-送料管，214-控制开关，215-第一支路，216-第二支路，3-存储单元，4-精分离单元，401-暂存单元，402-注射口，403-输出管，404-储留槽，405-抽取泵，406-开关，407-摇摆装置，408-网孔板，4081-网孔，409-注入口，410-免疫磁珠，411-电磁线圈，5-回输单元，6-成分检测装置，7-抗凝剂添加装置，8-压力传感器，9-排放管，10-电磁单元，11-控制单元，12-超声气泡传感器，13-补液单元，14-第一输血管，15-第二输血管，16-第三输血管，17-第四输血管，18-出料管路，1801-第一控制开关，19-冲洗机构，1901-冲洗头，1902-冲洗管，1903-循环泵，1904-第二控制开关。
具体实施方式
现在将参照附图来详细描述本发明的各种示例性实施例。应注意到：除非另外具体说明，否则在这些实施例中阐述的部件和步骤的相对布置、数字表达式和数值不限制本发明的范围。
以下对至少一个示例性实施例的描述实际上仅仅是说明性的，决不作为对本发明及其应用或使用的任何限制。
对于相关领域普通技术人员已知的技术、方法和设备可能不作详细讨论，但在适当情况下，所述技术、方法和设备应当被视为说明书的一部分。
在这里示出和讨论的所有例子中，任何具体值应被解释为仅仅是示例性的，而不是作为限制。因此，示例性实施例的其它例子可以具有不同的值。
应注意到：相似的标号和字母在下面的附图中表示类似项，因此，一旦某一项在一个附图中被定义，则在随后的附图中不需要对其进行进一步讨论。
本发明实施例提供的循环肿瘤细胞在体闭环提取设备，可用于对患者全身的血液进行循环肿瘤细胞的检查、滤除，从而可以避免恶性肿瘤的复发和转移。需要说明的是，在本发明中，所述“在体”是指与身体连接在一起形成一体。所述“闭环”是指整个血液处理系统与身体形成一个封闭 系统，以避免外部细菌等侵入，避免感染而造成危险。另外，本发明实施例提供的循环肿瘤细胞在体闭环提取设备可应用于人体、动物体等，本发明对此不作限制。
参考图1所示，本发明实施例提供的循环肿瘤细胞在体闭环提取设备，至少包括：采血单元1、初分离单元2、存储单元3、精分离单元4、回输单元5以及控制单元11。
其中，采血单元1可以包括采血针、采血泵、过滤器以及采血管等本领域技术人员熟知的部件，在此不再具体说明。具体来说，采血单元1可以通过第一输血管14与初分离单元2连接，此时，在采血泵的作用下，从身体抽取出的血液可以经第一输血管14送入到初分离单元2中。也就是说，采血单元1用于从身体抽取血液并将血液送入初分离单元2。并且，本实施例中，为了实现对采血单元1运行的自动化控制(例如启动或者停止)，可以将采血单元1通过通讯控制线与控制单元11连接在一起，此时，可以由控制单元11实现对采血单元1启动或者停止的控制。
其中，参考图1以及图2所示，初分离单元2通过第二输血管15与精分离单元4或者存储单元3连接，并且，该初分离单元2还通过第三输血管16与回输单元5连接。该初分离单元2被配置为：可以在离心力的作用下使血液中的各成分按照比重分离为含循环肿瘤细胞的成分和不含循环肿瘤细胞的成分。此时，不含循环肿瘤细胞的成分可以通过第三输血管16被直接送到回输单元5中，由回输单元5回输到体内，实现循环过程。而对于从血液中分离出来的含循环肿瘤细胞的成分则有两种处理方式：其中一种是直接送入到存储单元3中存储；还有一种是送入精分离单元4中，由精分离单元4对含循环肿瘤细胞的成分进行进一步的分离提取处理，以提取出循环肿瘤细胞。并且，为了实现对初分离单元2运行的自动化控制，在本实施例中，可以将初分离单元2通过通讯控制线与控制单元11连接，即由控制单元11实现对初分离单元2运行或者停止的控制。
其中，精分离单元4被配置为用于从含循环肿瘤细胞的成分中提取出循环肿瘤细胞。具体来说，经初分离单元2后，血液被分离成含循环肿瘤细胞的成分和不含循环肿瘤细胞的成分，实际上，这次分离并没有完全将 循环肿瘤细胞提取出来，分离出的是含循环肿瘤细胞的成分，即循环肿瘤细胞中还混有其它的单核细胞成分。因此，本实施例中设计了在初分离单元2之后加设一个精分离单元4，由精分离单元4通过免疫磁珠法提取出循环肿瘤细胞，所提取出的循环肿瘤细胞可以经排放管9送入到存储单元3中进行存储，而剩余的不含循环肿瘤细胞的成分则被送到回输单元5中，由回输单元5控制回输到体内，实现在体闭环循环过程。这样可以实现对血液中的循环肿瘤细胞的精确提取。由于经过了两次分离提取过程，可以精确的将循环肿瘤细胞从血液中提取出来，就实现了对循环肿瘤细胞的有效滤除。
其中，存储单元3例如可以是存储袋或者存储池等具有存储功能的装置，本发明对此不作限制。在本实施例中，存储单元3采用的是存储袋，结构简单、制作成本低，使用起来方便。
其中，回输单元5可以包括输血针、输血泵、过滤器以及输血管道等本领域技术人员熟知的部件，在此不再具体说明。回输单元5可以通过第四输血管17与精分离单元4连接，从而实现了回输单元5与精分离单元4的连通。当然，当无需使用精分离单元4时，也可以将回输单元5通过第三输血管16与初分离单元2连接，以实现回输单元5与初分离单元2的连通。回输单元5被配置为：可以在回输泵的作用下，使精分离单元4分离出的不含循环肿瘤细胞的成分直接送回体内，或者将初分离单元2分离出的不含循环肿瘤细胞的成分送回体内。回输单元5与采血单元1相配合可以实现在体闭环循环过程。并且，在本实施例中，为了实现对回输单元5运行的自动化控制(例如启动或者停止)，可以将回输单元5通过通讯控制线与控制单元11连接，由控制单元11实现对回输单元5启动或者停止的控制。
本实施例中，可以通过控制单元11实现对采血单元1、初分离单元2、精分离单元4、以及回输单元5工作的分别控制。通过该设计可以使循环肿瘤细胞在体闭环提取设备具有自动化控制的特点。可选的是，控制单元11可以具有显示单元，用户可以通过操作显示单元来控制和观察各部件的工作状态等。其中，显示单元例如可以是触摸式显示屏等本领域技术人员 熟知的显示装置，本发明对此不作限制。
本发明实施例提供的循环肿瘤细胞在体闭环提取设备，可以对全身血液中的循环肿瘤细胞进行检测以及滤除。该循环肿瘤细胞在体闭环提取设备采用初分离单元2(一次分离提取)和精分离单元4(二次分离提取)对血液中的循环肿瘤细胞进行反复检测和滤除，可以彻底去除血液中含有的循环肿瘤细胞，有效克服了现有技术中存在的弊端。该循环肿瘤细胞在体闭环提取设备具有检测结果准确和安全性高的特点，可以避免造成检测结果假阴性的情况，可以提高检测循环肿瘤细胞的水平。而且，该循环肿瘤细胞在体闭环提取设备自动化程度高，省时省力，操作方便。
另外，参考图3所示，本发明实施例提供的循环肿瘤细胞在体闭环提取设备，还可以采用单针模式，即将采血单元1与回输单元5合并在一起。此时，可以通过控制单元11控制采血与回输交替进行。具体来说：可以采用一个针，该针可以充当采血针，也可以充当输血针。将该针连接管路，当从体内采血的时候不会向体内回输血，即采血与输血是分时进行工作的，不会产生相互之间的干扰现象。在进行采血时，由控制单元11控制采血泵进行运转，同时控制回输泵停止工作(或小流量)。在回输血液时，由控制单元11控制采血泵停转(停止时流量为0，相当于管路关闭，同时控制回输泵运转)。其中，采血泵的流量大于回输泵流量时，血液自针向外流，反之向体内流。需要说明的是，对于上述的单针模式，其内部可以仅设置初分离单元2，也可以将初分离单元2与精分离单元4配合起来使用(如图3所示)，本发明对此不作限制。
本实施例中，第一输血管14、第二输血管15、第三输血管16、第四输血管17以及排放管9等管道均采用本领域技术人员熟知的软管，以便于血液的输送。并且，上述这些管道的尺寸可以根据需要灵活调整，本发明对此不作限制。
参考图1-图3所示，本发明实施例提供的循环肿瘤细胞在体闭环提取设备，还可以包括抗凝剂添加装置7。其中，该抗凝剂添加装置7被配置为：可以向采血单元1中添加抗凝剂。具体来说，当采血单元1将血液抽取出来送入第一输血管14内并开始进行循环时，通过添加抗凝剂可以防止 正在处理的血液凝固，从而能保证整个血液循环过程的顺利进行。需要说明的是，抗凝剂的添加量可以根据需要灵活控制，本发明对此不作限制。
其中，抗凝剂添加装置7可以与采血单元1直接结合在一起。当然，抗凝剂添加装置7也可以通过管道与采血单元1连接。这两种方式均可以实现抗凝剂的添加，在具体的应用中，可以根据实际情况灵活选择。
并且，抗凝剂添加装置7还可以通过通讯控制线与控制单元11连接。该设计可以实现控制单元11对抗凝剂添加装置7的控制，即可以控制抗凝剂添加装置7向血液中添加抗凝剂，或者停止向血液中添加抗凝剂。也就是说，可以通过控制单元11实现对抗凝剂添加的自动控制，这种方式操作起来比较方便，也容易控制添加量。当然，抗凝剂添加装置7也可以不与控制单元11连接，此时，可以采用手动控制抗凝剂的添加以及添加量。在具体应用中可以根据需要灵活选择，本发明对此不作限制。
参考图1-图3所示，本发明实施例提供的循环肿瘤细胞在体闭环提取设备，还包括压力传感器8。具体来说，在采血单元1和回输单元5的外部分别设置有压力传感器8。压力传感器8均通过通讯控制线与控制单元11连接。而为了实现准确的压力检测，压力传感器8在设置时均要靠近相应的输血管。
其中，设置在采血单元1外部的压力传感器8用于检测采血端，例如采血单元内采血管的压力情况，以及与采血单元1连接的第一输血管14内的压力情况。同样地，设置在回输单元5外部的压力传感器8用于检测回输端，例如回输单元5内输血管道内的压力情况，以及与回输单元5连接的第三输血管16和第四输血管17内的压力情况。通过压力检测可以判断针(例如采血针、输血针)和相应的管路是否产生堵塞。一旦出现堵塞，很容易造成管内压力异常，引发危险。
需要说明的是，压力传感器8的设置位置有多种，并不限于上述实施例中的方式。例如：将压力传感器8分别设置在第一输血管14上和第二输血管15上。或者是，将压力传感器8分别设置在第一输血管14内和第二输血管15内。可以根据实际情况灵活调整，本发明对此不作限制。另外，对于压力传感器8的设置数量本发明也不作具体限定，可以根据需要灵活 选择合适的数量。
并且，每个压力传感器8均可以通过通信控制线与控制单元11连接。该设计可以实现控制单元11对压力传感器8的控制，即可以控制压力传感8在合适的时机启动压力检测，当然也可以控制压力传感器8不进行压力检测。
参考图1-图3所示，本发明实施例提供的循环肿瘤细胞在体闭环提取设备，还可以包括成分检测装置6。成分检测装置6可以通过检测线或者通讯控制线与初分离单元2连接，该成分检测装置6还通过检测线或者通讯控制线与控制单元11连接。成分检测装置6被配置为：在控制单元11的控制下检测经初分离单元2分离出的各部分的成分和纯度，并且，该成分检测装置6还可以对初分离单元2的成分分离过程进行控制，以使不同的成分能形成良好的分层状态，有利于对不同的成分进行分别提取。也就是说，当初分离单元2将血液分成不同的成分时，通过成分检测装置6可以检测出各成分的分层状态、种类和纯度，例如可以确定是否含有循环肿瘤细胞等。
需要说明的是，成分检测装置6也可以通过通讯控制线与精分离单元4连接，本发明对此不作限制。并且，成分检测装置6可以采用本领域技术人员熟知的检测设备，在此不再具体说明。另外，成分检测装置6可以根据需要选择设置或者不设置，本发明对此不作限制。
参考图1-图3所示，本发明实施例提供的循环肿瘤细胞在体闭环提取设备，还包括超声气泡传感器12，该超声气泡传感器12位于回输单元5所在的一端。该超声气泡传感器12与回输单元5连接。具体来说，超声气泡传感器12是采用超声检测回输的血液中是否含有气泡，一旦检测到血液中含有气泡就要立即停止向体内回输血液并报警，否则血液进入身体中会发生危险。
并且，超声气泡传感器12还通过通讯控制线与控制单元11连接。该设计可以实现控制单元11对超声气泡传感器12的控制，即可以控制超声气泡传感器12在合适的时机启动检测，当然也可以控制超声气泡传感器12不进行检测。也就是说，通过控制单元11可以实现对超声气泡传感器 12的自动化控制。
参考图1-图3所示，本发明实施例提供的循环肿瘤细胞在体闭环提取设备，还可以包括补液单元13。该补液单元13被配置为：在回输血液时，向血液中内进行补液，例如可以向体内补充营养液等。其中，补液单元13可以通过补液管与回输单元5连接。当然，补液单元13也可以与回输单元5结合在一起。所述的两种方式均可以实现向回输的血液中添加营养液或药液。
并且，补液单元13可以通过通讯控制线与控制单元11连接。该设计可以实现控制单元11对补液单元13的控制，以实现补液的自动化。
需要说明的是，本发明中的凝剂添加装置7和补液单元13可以采用专用的泵，其运行或者停止可以由控制单元11进行控制。本发明中的压力传感器8、超声气泡传感器12、成分检测装置6也由控制单元11进行控制，实现了操作的自动化。
本发明实施例提供的循环肿瘤细胞在体闭环提取设备，其中的初分离单元2主要是基于离心分离原理对血液进行分离处理，以将血液分离成不同的成分，例如不含有循环肿瘤细胞的成分和含有循环肿瘤细胞的成分等。
参考图4所示，本发明实施例提供的初分离单元2，其结构可以为：包括离心分离通道201，该离心分离通道201分别具有入口端202、出口端203。其中，入口端202被配置为：用于向离心分离通道201内输入血液等待分离原料。离心分离通道201被配置为：能围绕其中心进行预定速度的旋转，并通过旋转产生离心力，用于使血液中不同比重的成分在离心力的作用下产生分离，以形成不同的成分层。在出口端203上对应于各个成分层的位置均设置有提取口206(例如提取口206的数量可以根据需要灵活设置，本发明在此不作限制)，各个提取口206分别用于输出当前的成分层。离心分离通道201接近出口端203的一段的尺寸是逐渐变宽的，且该段的壁面形成渐开线结构，该设计有利于提高分离精度。
其中，离心分离通道201可以为单环道结构，也可以为双环道结构，还可以为多环道结构，具体可以根据实际情况灵活选择。需要说明的是，所述的双环道结构并非是指完全闭合的两圈结构，只需要超过一圈即可， 例如一圈半的结构。当然，所述的多环道结构也如此，并非是指完全闭合的多圈结构。
可选的是，参考图4所示在提取口206处形成有半包围式挡槽204。该半包围式挡槽204被配置为：在从提取口206取出当前的成分层之前，用于使成分能够先汇聚在一起，以及防止其它成分层的成分混入。该设计非常适合对于含量稀少成分的提取，例如提取血液中的循环肿瘤细胞。
参考图4以及图5，上述的初分离单元2，还可以包括离心池210，该离心池210分别具有进料端以及出料端。在该离心池210内可以设置有滤网212，且滤网212自进料端延伸至出料端。在进料端上设置有进料口207，出料端上设置有至少一个出料口(例如图4中的第一出料口208和第二出料口209，或者是，图5中的第一出料口208、第二出料口209和第三出料口211)。其中，离心池210的进料口207与离心分离通道201的某一个提取口206之间可以通过连接管205连接。其中，离心池210被配置为：当离心分离通道201进行旋转时，离心池210能随离心分离通道201一起转动，用于对从提取口206取出的成分再次、离心分离，例如进一步从血液中分离提取出循环肿瘤细胞，并尽量避免其它成分混入循环肿瘤细胞中。
其中，在离心池210中滤网212可以设置一个或者多个。当在离心池210中设置多个滤网212时，滤网212的网孔尺寸可以相同，也可以不同。进料口207的尺寸可以根据需要灵活调整。出料口的数量和尺寸等也可以根据需要灵活调整。本发明对此均不作限制。
实际上，由于循环肿瘤细胞通常含量是比较低的(在血液中属于稀有细胞)，在进行离心分离后，在离心分层中的位置同其它单核细胞相接近，在提取时非常容易混入其它的单核细胞。为了能良好的分离提取出血液中的循环肿瘤细胞，本发明的初分离单元2采用了离心分离通道201与离心池210配合的方式，当然本发明中也不限于该结构。
在本发明的一个具体实施方式中，参考图5所示，首先通过离心分离通道201对血液进行离心分离，在离心力的作用下含有循环肿瘤细胞的成分可以被分离出来，并汇聚在半包围式挡槽204内，之后可以通过对应的提取口206输出，再通过与该提取口206相连的连接管205将含有循环肿 瘤细胞的成分引入到离心池210内。其中，在离心池210内设置有两个滤网212，这两个滤网212可以呈相对设置，这两个滤网212的孔径尺寸可以设计为不同，两个滤网212可以将离心池210内的空间分隔成三个区域，进料口207可以位于两个滤网212围成的区域内。此时，经离心分离通道201分离出的含循环肿瘤细胞的成分被直接送入两个滤网212围成的区域内，在离心力的作用下，一个滤网212可以供轻而小的血浆和血小板通过，并由第一出料口208抽取走，另一个滤网212可以供比较重而体积小的红细胞通过，并由第二出料口209抽取走，而体积较大的循环肿瘤细胞以及白细胞等可以留存在两个滤网212围成的区域内，可以通过设置在该区域内的第三出料口211将其抽取出来。此时，分离出的含循环肿瘤细胞的成分可以经第三出料口211送出，并由与第三出料口211连接的送料管213进行输送。
本发明实施例提供的送料管213，其末端可以分为两个支路(例如分为记为第一支路215、第二支路216)，且在末端分支路的位置设置有控制开关214。其中，第一支路215可以与回输单元5连通(若不含循环肿瘤细胞则可以接通回输单元5)。而第二支路216可以与存储单元3或者精分离单元4连通，上述的控制开关214可以通过通讯控制线与控制单元11连接，即在控制单元11的控制下，送料管213可以与其中的任一个支路导通。具体来说：当控制开关214控制输料管213与第一支路215实现导通时，有可能是没有提取到循肿瘤细胞(如果血液中没有循环肿瘤细胞)或不用提取，此时可以直接将相应的成分送入第四输血管17，并由回输单元5送回体内。当控制开关214控制输料管213与第二支路216导通时，分离出的含循环肿瘤细胞的成分送入到存储单元3中进行存储，或者是，含循环肿瘤细胞的成分通过第二输血管15被送入精分离单元4中，以进行进一步的循环肿瘤细胞的提取。
参考图6所示，在本发明的初分离单元2还可以包括冲洗机构19。该该冲洗机构19包括冲洗头1901，冲洗头1901连接冲洗管1902，且在冲洗管1902上设置有循环泵1903。冲洗机构19可用于冲洗离心池210内的滤网212。具体来说，当过滤网212上附着物较多，阻塞滤网212上的网孔 时，可采用冲洗头1901对滤网212进行冲洗；并且，在循环肿瘤细胞提取结束时也可以对滤网212进行冲洗，以防止滤网212上残留循环肿瘤细胞。
可选的是，冲洗头1901可以设置在滤网212的一侧，也可以在滤网212的两侧均设置冲洗头1901，此时可以使滤网212的四周均分布冲洗头1901，以实现对滤网212的无死角冲洗。需要说明的是，在进行冲洗时，冲洗管1902可以供应水，也可以供应清洗液，在此不再具体说明。
参考图7所示，本发明实施例提供的离心池210，在其内部也可以不设置滤网212，在该结构下可以加大出料端的宽度尺寸，即离心池210从进料端到出料端，其宽度是逐渐变大的(参考图7示出了出料端)。当血液经离心分离通道201离心分离后，含循环肿瘤细胞的部分被分离出来(实际上，此时分离出的成分中不仅含有循环肿瘤细胞，还含有循环肿瘤细胞以外的很多种细胞)，并被引入到离心池210中进行再次离心分离。在离心池210内经离心后，比重大的细胞会向外侧聚集，并可以通过第二出料口209提取走，而比重轻的细胞会向内侧聚集，并可以通过第一出料口208提取走。为了确定从各个出料口提取出的细胞成分和纯度，可以采用成分检测装置6进行检测。具体来说：
在其中一个出料口处(图7中示出的是在第一出料口208)连接出料管路18，成分检测装置6可以设置在该出料管路18的外侧，用于对出料管路18内输送的成分进行检测，以确定出料管路18内输送的成分中了种类、纯度等。该出料管路18的末端也可以分为两个支路(分为记为第一支路、第二支路)，且在出料管路18的末端分支路的位置设置有第一控制开关1801，第一控制开关1801通过通讯控制线与控制单元11连接，即可以由控制单元11对该第一控制开关1801进行控制。通过第一控制开关1801，可以实现第一支路或第二支路的导通。其中，第一支路可以与存储单元3或者精分离单元4连通，第二支路可以与回输单元5连通。即，当成分检测装置6检测到出料管路18中的成分含有循环肿瘤细胞时，可以通过第一支路其送入到存储单元3或者精分离单元4(以对循环肿瘤细胞进行继续分选)。当成分检测装置6检测到出料管路18中的成分不含循环肿瘤细胞时，可以通过第二支路将输送至回输单元5，最终回输体内。
需要说明的是，成分检测装置6可以利用循环肿瘤细胞的光谱吸收特性进行检测或者利用单核细胞的光谱吸收特性进行检测，在此不再具体说明。成分检测装置6可以反射传感器或者透射传感器。
参考图8所示，在图7示出离心池210的基础上，可以在另一个出料口处连接上述的冲洗机构19，以便于对离心池210进行冲洗。
需要说明的是，在连接冲洗机构19的出料口一般不会输出循环肿瘤细胞或者含循环肿瘤细胞的成分。具体来说：该冲洗机构19的冲洗头1901与该出料口相接，冲洗头1901连接冲洗管1902，在冲洗管1902上设置循环泵1903。并且，在冲洗管1902的末端分为两个支路，在冲洗管1902的末端分支路的位置设置有第二控制开关1904，第二控制开关1904通过通讯控制线与控制单元11连接，即可以由控制单元11对该第二控制开关1904进行控制。通过第二控制开关1904可以实现两个支路的导通或者关断(但是在同一时间一个支路导通，另一个支路关断)，即一个支路可以与回输单元5连通，用于将不含循环肿瘤细胞的成分输回体内，此时另一个支路是关断的。当将不含循环肿瘤细胞的成分回输完后，另一个支路被导通，可以向冲洗管1902内注入冲洗用的水和/或清洗液，此时可用于对离心池210进行冲洗处理。在同一时间，两个支路不互相影响。
其中，对于初分离单元2而言，冲洗机构19可以根据需要选择设置或者不设置，设置位置也可以灵活调整，本发明对此不作限制。
另外，需要说明的是，本发明实施例提供的初分离单元具有多种形式，并不限于上述的形式。例如在离心池210之前的离心分离可以采用离心杯、离心袋和离心盘等本领域技术人员熟知的离心设备，本发明对此不作限制。
参考图9所示，本发明中，将精分离单元4作为初分离单元2的下级分离筛选单元，用于从血液中分离出的含循环肿瘤细胞的成分继续进行精准分离，以便于实现对循环肿瘤细胞的提纯处理，而将不含循环肿瘤细胞的其余成分通过回输单元5输送回体内。
参考图9所示，本发明的精分离单元4，可以包括暂存单元401，在该暂存单元401上分别设置有注射口402、输出口。经初分离单元2对血液进行离心分离后，含循环肿瘤细胞的成分可以经第二输血管15输送到精 分离单元4内的暂存单元401内进行暂时存储，之后再进行循环肿瘤细胞的提取等后续处理，以实现对循环肿瘤细胞的分离提取。
其中，暂存单元401可以采用存储袋或者存储池等具有存储功能的装置，本发明对此不作限制。并且，对于存储单元401的存储量，本发明也不作限制，可以根据实际情况进行调整。
其中，注射口402被配置为：经初分离单元2输出的含循环肿瘤细胞的成分进入暂存单元401后，特别是当达到预定量后，通过该注射口402可以向暂存单元402内注入提取循环肿瘤细胞用的免疫磁珠410。这样的目的是为了使免疫磁珠能充分的与含循环肿瘤细胞的成分接触。
其中，免疫磁珠410属于超顺磁珠，免疫磁珠410上被相应循环肿瘤细胞的免疫抗体包被(例如涂层，即将抗体包被于免疫磁珠的表面)。当循环肿瘤细胞遇到免疫磁珠410时就会被吸引捕获，免疫磁珠410可以在磁场中表现出良好磁性。其中，免疫磁珠410的注入量可以根据实际情况灵活调整，本发明对此不作限制。
并且，参考图9所示，在暂存单元401的输出口上连接有输出管403，在输出管403上设置有抽取泵405。且输出管403的末端分为两个支路，其中一个支路与第四输血管17连接，用于实现与回输单元5的连通，另一个支路与排放管9连接，用于实现与存储单元3的连接。而且，在输出管403的末端分支路的位置还设置有开关406，该开关406通过通讯控制线与控制单元11连接。开关406被配置为用于控制两个支路的导通或关断，其中，两个支路被配置为：在同一时间一个支路导通，另一个支路关断，即在同一时间，当控制输出管403与一个支路连通时，另一个支路是关断的，反之亦然。
并且，参考图9所示，在输出管403的一段的管壁上设置有向下凹的储留槽404。该储留槽404的纵截面形态例如可以为矩形或者半圆弧形等，本发明对此不作限制。本发明的储留槽404用于留存提取了循环肿瘤细胞的免疫磁珠410。
在储留槽404的外部设置有电磁单元10。电磁单元10通过通讯控制线与控制单元11连接，即可以由控制单元11对电磁单元10进行控制。流 入输出管403内的流体在流经储留槽404时，电磁单元10可以产生电磁场，在电磁场的作用下将捕获循环肿瘤细胞的免疫磁珠410吸引到储留槽404中，以实现通过免疫磁珠法对循环肿瘤细胞进行提取，避免磁珠被输回体内。也就是说，免疫磁珠410可用于吸附循环肿瘤细胞，在抽取泵405的作用下暂存单元401内的流体会持续的流入到输出管403内，在电磁单元10启动后，当免疫磁珠410进入电磁单元10产生的电磁场中，免疫磁珠410就会被吸引住，然后留存在储留槽404。由于之前免疫磁珠410已经和循环肿瘤细胞相结合，这样循环肿瘤细胞也就被留在了储留槽404内，此时通过开关406，可以使未被免疫磁珠410提取的成分回输单元5。而当暂存单元401内的流体被抽取完时，可以通过开关406导通另一条支路，并关闭电磁单元10，可以使储留槽404内的免疫磁珠410在抽取泵405的作用下输送至存储单元3中。存储单元3内的免疫磁珠可以被取出后进一步的进行检测。
需要说明的是，若血液中不含循环肿瘤细胞，则血液经初分离单元2进入精分离单元4内后，通过调整开关406，血液可以由输出管403经支路直接送入回输单元5，回输体内。
其中，为了实现对免疫磁珠410的吸引，除了采用电磁单元10外，还可以在储留槽404外部设置永久磁铁，但是当采用永久磁铁时，需要手动在储留槽404外放置永久磁铁或者移走永久磁铁，较为麻烦。本发明中采用了电磁单元10，通过与控制单元11的连接，可以实现对电磁单元10的自动控制。
实际上，参考图10所示，注入暂存单元401内的免疫磁珠410可以捕获循环肿瘤细胞，以实现对循环肿瘤细胞的提取，而免疫磁珠410在磁场中可以表现出良好磁性，会沿磁力线向电磁单元10移动，被电磁单元10吸住、固定住，而其它成分由于没有相应抗体，不会被免疫磁珠410所捕获，在抽取泵405的作用下可以正常流动传输走，能进入回输单元5，并回输体内。
参考图11所示，本发明实施提供的精分离单元4，还可以包括摆动装置407。暂存单元401可以设置在摆动装置407上。启动摆动装置407后，摆动装置407可以带动暂存单元401来回晃动，这样可以促进内部的免疫 磁珠410与循环肿瘤细胞的充分结合。其中，摆动装置407主要用于实现暂存单元401的来回晃动，可以采用本领域技术人员熟知的设备，例如摆动架，在此不再具体说明。
参考图11所示，本发明实施例提供的精分离单元4，还包括网孔板408。网孔板408被设置在输出管403内。该网孔板408上的网孔4081可以为圆形或方形等形状。
其中，网孔板408采用磁性材料制成，例如铁磁材料。并且，在网孔板408对应的输出管403的外壁上绕制有电磁线圈411。当电磁线圈411通电后就可以形成磁场。具体地，电磁线圈411可以通过通讯控制线与控制单元11连接。基于免疫磁珠410的超顺磁性，可以在磁场中表现出良好的磁性。当携带着循环肿瘤细胞的免疫磁珠410碰到网孔板408时，免疫磁珠410会被吸附到网孔板408上。由于免疫磁珠410之前已经吸附了循环肿瘤细胞，则循环肿瘤细胞也可以被吸附在网孔板408上，而其它的成分可以穿过网孔板408，并经输出管403输送至回输单元5，最终回输到体内。参考图12所示，免疫磁珠410被吸附在了网孔板408时，免疫磁珠410通常是被固定在网孔4081的旁边。
另外，在网孔板408对应的输出管403的外部也可以采用永久磁铁。永久磁铁也可以产生磁场，当免疫磁珠410经过时，也可以使免疫磁珠410吸附在网孔板408上。
其中，网孔板408可以设置一个，当然也可以设置多个。当在输出管403内设置多个网孔板408时，不同的网孔板408之间可以采用相互平行的方式排布，且相邻的两个网孔板408之间具有间隔。例如，参考图13所示，网孔板408可以设置为两个，这两个网孔板408在输出管403内呈相互平行布置且二者之间具有间隔。需要说明的是，当在输出管403内设置多个网孔板408时，不同的网孔板408其孔径尺寸可以相同，也可以不同，可以根据实际应用情况灵活调整。并且，网孔板408应当沿输出管403的横截面设置，以避免网孔板408与输出管403内壁之间形成空隙。网孔板408应当与储留槽404之间具有适当的距离。
另外，参考图14所示，在输出管403上靠近网孔板408处还设置有 至少一个注入口409。该注入口409可用于注入免疫磁珠410或者相应的药物。由于注入口409距离网孔板408更近，一旦免疫磁珠410进入输出管403，网孔板408可以很容易的吸附住免疫磁珠410，当暂存单元401中的待分离原料通过网孔板408时，网孔板408上吸附的免疫磁珠410可以进一步的捕获循环肿瘤细胞。当不启动摆动装置407时，可以采用从注入口409也注入免疫磁珠410的方式，以便于充分提取循环肿瘤细胞。
参考图14所示，本发明的精分离单元4，也可以包括前述的冲洗机构19。此处，冲洗机构19可用于对网孔板408上的附着物进行冲洗。例如：当网孔板408上附着物多堵塞网孔时，需要对网孔板408进行冲洗；当然，当循环肿瘤细胞提取结束时，也可以对网孔板408进行冲洗，防止循环肿瘤细胞残留在网孔板408上。
其中，冲洗头1901可以仅设置在网孔板408的任意一侧。当然，也可以在网孔板408的两侧均设置冲洗头1901，以使冲洗头1901能均匀分布在网孔板408的四周，该设计有利于实现对网孔板408的充分冲洗。
需要说明的是，本发明中采用控制单元11对整个循环肿瘤细胞在体闭环提取设备内的各个部件进行控制，例如各种泵、各种开关等，以实现整个设备的自动化。另外，图1-图14中，各个泵、开关、以及分支管路的位置是可以变化、移动的，例如：泵无论在前或者在后都可以驱动流体运动，本发明对此均不作限制。
虽然已经通过例子对本发明的一些特定实施例进行了详细说明，但是本领域的技术人员应该理解，以上例子仅是为了进行说明，而不是为了限制本发明的范围。本领域的技术人员应该理解，可在不脱离本发明的范围和精神的情况下，对以上实施例进行修改。本发明的范围由所附权利要求来限定。

Claims (10)

  1. 一种循环肿瘤细胞在体闭环提取设备，其特征在于，包括采血单元、初分离单元、精分离单元、存储单元、回输单元和控制单元；
    所述采血单元通过第一输血管与所述初分离单元连接；
    所述初分离单元通过第二输血管与所述精分离单元或者存储单元连接，所述初分离单元还通过第三输血管与所述回输单元连接；所述初分离单元被配置为在离心力的作用下使血液分离成含循环肿瘤细胞的成分和不含循环肿瘤细胞的成分；
    所述精分离单元通过第四输血管与所述回输单元连接，所述精分离单元还通过排放管与所述存储单元连接；所述精分离单元被配置为用于对含循环肿瘤细胞的成分进行循环肿瘤细胞的分离提取；
    所述存储单元被配置为用于存储含循环肿瘤细胞的成分和/或循环肿瘤细胞；
    所述回输单元被配置为用于将分离出的不含循环肿瘤细胞的成分输回身体；
    所述控制单元分别通过通讯控制线与所述采血单元、初分离单元、精分离单元、回输单元连接。
  2. 根据权利要求1所述的循环肿瘤细胞在体闭环提取设备，其特征在于，所述采血单元和回输单元的外部分别设置有压力传感器，且所述压力传感器均通过通讯控制线与所述控制单元连接。
  3. 根据权利要求1所述的循环肿瘤细胞在体闭环提取设备，其特征在于，还包括成分检测装置；
    所述成分检测装置通过检测线或者通讯控制线与所述初分离单元连接，所述成分检测装置还通过检测线或者通讯控制线与所述控制单元连接，所述成分检测装置被配置为：在控制单元的控制下检测经初分离单元分离出的各成分的种类，纯度，以及分层状态。
  4. 根据权利要求1所述的循环肿瘤细胞在体闭环提取设备，其特征在于，还包括超声气泡传感器，所述超声气泡传感器与所述回输单元连接， 所述超声气泡传感器还通过通讯控制线与所述控制单元连接。
  5. 根据权利要求1所述的循环肿瘤细胞在体闭环提取设备，其特征在于，还包括补液单元，所述补液单元通过补液管与所述回输单元连接；所述补液单元还通过通讯控制线与所述控制单元连接。
  6. 根据权利要求1所述的循环肿瘤细胞在体闭环提取设备，其特征在于，所述精分离单元包括暂存单元，所述暂存单元上分别设置有注射口、输出口；
    所述注射口被配置为用于向暂存单元内注入提取循环肿瘤细胞用的免疫磁珠；
    所述输出口连接输出管，所述输出管上设置有抽取泵，所述输出管的末端分为两个支路，一个支路与所述第四输血管连接，另一个支路与所述排放管连接，在所述输出管的末端设置有开关，所述开关通过通讯控制线与所述控制单元连接，所述开关被配置为用于控制两个支路的导通或关断，且所述两个支路被配置为：在同一时间一个支路导通，另一个支路关断；
    所述输出管的一段的管壁上设置有向下凹的储留槽，在所述储留槽外部设置有电磁单元，所述电磁单元通过通讯控制线与所述控制单元连接，提取循环肿瘤细胞后的免疫磁珠当流过储留槽时，在电磁单元的磁力作用下将免疫磁珠吸引并留存到储留槽中。
  7. 根据权利要求6所述的循环肿瘤细胞在体闭环提取设备，其特征在于，所述免疫磁珠外表面包裹有循环肿瘤细胞免疫抗体涂层。
  8. 根据权利要求6所述的循环肿瘤细胞在体闭环提取设备，其特征在于，所述精分离单元还包括摆动装置，所述暂存单元设置在摆动装置上。
  9. 根据权利要求6所述的循环肿瘤细胞在体闭环提取设备，其特征在于，所述精分离单元还包括网孔板，所述网孔板采用铁磁性材料制成，所述网孔板设置在所述输出管内；
    在所述网孔板对应的输出管外壁上绕制有电磁线圈，所述电磁线圈通过通讯控制线与所述控制单元连接；或者是，
    在所述网孔板对应的输出管外设置有永久磁铁。
  10. 根据权利要求9所述的循环肿瘤细胞在体闭环提取设备，其特征在 于，所述网孔板设置为一个或者多个；当设置多个网孔板时，多个网孔板在所述输出管内呈相互平行且间隔设置。
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