Circulating tumor cell physicochemical screen

Abstract

The utility model discloses a circulating tumor cell physicochemical screen which comprises a body, a reaction tank is arranged in the body, one end of the reaction tank is provided with at least two liquid inlets, the other end of the reaction tank is provided with a liquid outlet, and a fluid channel is arranged between the liquid inlets and the liquid outlet. At least two reaction areas are arranged in the fluid channel, and a plurality of micro-columns are arranged in each reaction area; a connecting area is arranged between every two adjacent reaction areas, and no micro-column is arranged in each connecting area. Along the direction from the liquid inlet to the liquid outlet, the distance between the micro-columns in each reaction area is gradually reduced. According to the circulating tumor cell sorting device, circulating tumor cells are sorted in a mode of combining physical blocking and chemical adsorption, blocking pressure is reduced due to the arrangement of the connecting area, fluid can pass through smoothly, and blocking is avoided; the distance between the micro-columns in each reaction area is gradually reduced, so that the separation and screening of the CTC cells are facilitated.

Description

TECHNICAL FIELD

[0001] The utility model belongs to the field of circulating tumor cell analysis, concretely relates to a circulating tumor cell physical and chemical screen. BACKGROUND

[0002] Circulating tumor cell (CTC) is usually called circulating tumor cell which enters the peripheral blood of human body. CTC detection measures the existence of CTC in peripheral blood by capturing, monitors the trend of CTC type and quantity change, so as to monitor tumor dynamics in real time, evaluate treatment effect, and realize real-time individual treatment. However, the number of CTCs in peripheral blood is extremely small, and the number of CTCs in each milliliter of whole blood of tumor metastasis patients is only 1-10, so how to sort and enrich CTCs from millions of white blood cells and tens of billions of red blood cells becomes the main problem of analysis and identification.

[0003] With the deepening influence of microfluidic technology on cell biology and its advantages in integrated sample pretreatment and blood component analysis, it can more gently, quickly and consistently manipulate and sort live cells, which is conducive to more accurate and efficient extraction of information in body fluid samples such as blood, and is very suitable for detection of somatic cells such as blood cells and cancer cells. In recent years, scholars at home and abroad have made a series of achievements in the field of microfluidic sorting of tumor cells. Microfluidic chip technology is gradually becoming the main tool for cell sorting, and application of microfluidic chip is expected to realize high-efficiency and high-purity detection of circulating tumor cells.

[0004] The structure of microfluidic chip directly affects the screening efficiency of circulating tumor cells. There are mainly two methods for detecting circulating tumor cells by using microfluidic chip at present: 1) biological method, based on the different expression of specific proteins on the surface of CTCs and blood cells, affinity recognition and capture are used; 2) physical method, some physical property differences between CTCs and blood cells are used for separation, such as cell size, density, dielectricity and deformability. For example, microporous filtration is used to separate circulating tumor cells and other cells, or the cell size is determined to separate cells according to the cell size. Due to the influence of chip structure design, etc., the current method still has the problems of low screening rate of circulating tumor cells, non-specific adsorption of non-target cells, destruction of circulating tumor cells, poor enrichment effect, poor cell activity and the like, and cannot be cultured and tested in the next step. In addition, in the existing microfluidic chip, the cell clusters formed by cell aggregation will block the front end of the chip earlier, which will affect the dispersion of subsequent materials, interfere with subsequent observation, and it is difficult for technicians to distinguish CTC cells.

[0005] Therefore, the utility model is provided. UTILITY MODEL CONTENT

[0006] The utility model wants to solve the technical problem in at least overcome the deficiency of prior art one aspect, provide a kind of circulating tumor cell physical and chemical sieve.The utility model adopts the way of physical block and chemical adsorption to sort circulating tumor cell, can play the role of dispersing cell and step-by-step screening, can guarantee the smooth flow of blood and reagent simultaneously, avoid to block up and accumulate obscure observation visual field, it is favorable to the screening of CTC cell, also favorable to further observation and discrimination, and the scope of application is extensive.

[0007] To solve the above technical problems, the basic idea of the technical scheme of the utility model is:

[0008] The utility model provides a kind of circulating tumor cell physical and chemical sieve, including body, reaction tank is equipped in the body, at least two liquid inlets are equipped in one end of the reaction tank, outlet is equipped in the other end, fluid channel is equipped between the liquid inlet and outlet, at least two reaction zones are equipped in the fluid channel, a plurality of microcolumns are equipped in each reaction zone;Connecting area is arranged between adjacent reaction zones, and the connecting area is not provided with microcolumn.

[0009] Further scheme, along the direction from liquid inlet to outlet, the spacing between microcolumn in each reaction zone gradually decreases.

[0010] Further scheme, along the direction from liquid inlet to outlet, in the two adjacent reaction zones, the microcolumn spacing of the reaction zone located in downstream is 25%-60% of the microcolumn spacing of the upstream reaction zone.

[0011] Further scheme, along the direction from liquid inlet to outlet, the microcolumn spacing of the reaction zone located in downstream is 30%-50% of the microcolumn spacing of the upstream reaction zone.

[0012] Further scheme, the cross section of microcolumn in each reaction zone is circular, or triangular, or hexagonal;

[0013] Preferably, the cross section of microcolumn is circular or triangular.

[0014] Further scheme, the cross section shape and / or height of microcolumn in each reaction zone are same.

[0015] Further scheme, the fluid channel includes reaction part and flow channel part connected, and the flow channel part is located in the upstream and / or downstream of reaction part;The reaction zone and connecting area are arranged in reaction part.

[0016] Further scheme, the width of reaction part is greater than the width of flow channel part.

[0017] Further, the fluid channels include a plurality of fluid channels, one end of each fluid channel is communicated with the liquid inlet, and the other end of each fluid channel is communicated with the liquid outlet; the sample only passes through one fluid channel from the liquid inlet to the liquid outlet; each fluid channel contains a reaction part, and the reaction parts of the fluid channels are arranged in parallel or staggered.

[0018] Further, the reaction parts of two adjacent fluid channels arranged in parallel are provided with one or more flow channel parts of other fluid channels.

[0019] Further, the reaction parts of two adjacent fluid channels share at least part of the flow channel parts upstream and / or downstream.

[0020] Further, the reaction parts of the plurality of fluid channels are arranged in a row in the width direction of the reaction tank, and the center lines are parallel.

[0021] Further, the reaction parts of the plurality of fluid channels are staggered in front and back in the length direction of the reaction tank, and the center lines are parallel but not overlapped.

[0022] Further, the liquid inlet is arranged on the support table, the support table is internally provided with a hollow space, and the hollow space is communicated with the reaction tank; the liquid inlet is communicated with the hollow space of the support table, and the liquid entering through the liquid inlet enters the reaction tank through the hollow space of the support table.

[0023] Preferably, two liquid inlets are arranged on the support table, and the two liquid inlets are communicated with the hollow space of the support table.

[0024] Further, the liquid inlet includes a first liquid inlet and a second liquid inlet, and the center line of the first liquid inlet and the second liquid inlet is parallel to or coincides with the center line in the length direction of the reaction tank.

[0025] Further, the body and the cover plate are integrally formed, the cover plate and the body are hollowly arranged, and the reaction tank is formed; or the body and the cover plate are separately arranged, the cover plate covers the upper surface of the body, and the cover plate and the body are sealingly and fitly connected.

[0026] Further, the liquid outlet is provided with a driving device, and the driving device drives the liquid to move from the liquid inlet to the liquid outlet.

[0027] Further, the driving device is a negative pressure suction device.

[0028] After the above technical scheme is adopted, the present application has the following beneficial effects compared with the prior art.

[0029] 1. The utility model discloses a physical block and chemical adsorption combined mode is carried out to circulating tumor cell and is sorted enrichment obtains. On the one hand, the microcolumn spacing is different in each reaction area, and the spacing between the microcolumn in each reaction area gradually reduces along the direction from the liquid inlet to the liquid outlet, so that the macromolecule in the blood can be blocked, thereby effectively screening the CTC cell in different levels, on the other hand, the adsorption matrix attached on the microcolumn and the reaction groove bottom plate of each reaction area specifically combines with the CTC cell, thereby realizing the sorting and enrichment of the CTC cell.

[0030] 2. The utility model discloses a circulating tumor cell physical and chemical screen, including multiple reaction areas in the reaction groove, and the spacing between the microcolumn in each reaction area is gradually reduced, therefore can also play the role of molecular sieve, and the material of different sizes can be blocked in different areas, and the CTC cell wrapped in the cell group or the cell group formed by multiple CTC cells is also easier to disperse, and after dispersion, is blocked and positioned by the microcolumn at different positions. The single CTC cell is easier to distinguish, and therefore the cell screen of the utility model is more conducive to the observation of the next step and the screening and distinguishing of the CTC cell.

[0031] 3. The utility model discloses a circulating tumor cell physical and chemical screen, is provided with the connecting area between the two adjacent reaction areas, the connecting area does not set up the microcolumn, so that the blocking pressure of blood and reagent can be reduced, and the smooth flow of blood and reagent is favorable, and the separation and screening of circulating tumor cell can be realized under the smaller driving pressure, and the blockage is avoided.

[0032] 4. The utility model discloses a circulating tumor cell physical and chemical screen is equipped with multiple fluid channels, and one end of each fluid channel is in communication with the liquid inlet, and the other end is in communication with the liquid outlet, and each fluid channel contains a reaction part, and the reaction area and the connecting area are arranged in the reaction part, and the reaction part of each fluid channel is arranged side by side or staggered. So, on the one hand, multiple fluid channels can be distributed in the width direction of the reaction groove, and blood and reagent can be divided, respectively enter the reaction part of different fluid channels, and the blocking force is small, the smoothness of fluid flow is guaranteed, the blockage is avoided, and the separation, enrichment and screening of circulating tumor cell are favorable.

[0033] 5. In the utility model, the reagent liquid inlet and blood liquid inlet are respectively arranged at one end of the reaction groove, which facilitates the addition of blood and reagent from different liquid inlets. The connecting pipe at the blood liquid inlet does not contact the reagent, reduces the requirement for material corrosion resistance, can adopt low-cost consumables, and the connecting pipe at the reagent liquid inlet is high in cost, but is not contaminated by blood, can be repeatedly used, avoids pollution and reduces material consumption.

[0034] The specific implementation of the utility model will be further described in detail below with reference to the drawings. BRIEF DESCRIPTION OF DRAWINGS

[0035] The accompanying drawings are used to provide further understanding of the present application and serve as a part of the present application. The schematic embodiments of the present application and the descriptions thereof are used to explain the present application, but do not constitute improper limitations on the present application. Obviously, the drawings in the following description are only some embodiments, and other drawings can be obtained by those skilled in the art without creative labor on the basis of these drawings. In the drawings:

[0036] Figure 1 is a top view of the circulating tumor cell physical and chemical sieve of the present application;

[0037] Figure 2 is a side view of the circulating tumor cell physical and chemical sieve of the present application;

[0038] Figure 3 is Figure 2 is a partial structure schematic view of A in FIG. 1;

[0039] Figure 4 is a schematic view of the setting mode of the fluid channel;

[0040] 1-body, 2-reaction tank, 3-first liquid inlet, 4-second liquid inlet, 5-liquid outlet, 6-microcolumn, 7-supporting table, 8-first liquid inlet pipe, 9-second liquid inlet pipe, 10-liquid outlet pipe;

[0041] 100-fluid channel, 101-flow passage part, 102-reaction part, 1021-reaction zone, 1022-connection zone.

[0042] It should be noted that these drawings and textual descriptions are not intended to limit the scope of the concept of the present application in any way, but to illustrate the concept of the present application to those skilled in the art by referring to specific embodiments. DETAILED DESCRIPTION

[0043] In order to make the purpose, technical scheme and advantages of the embodiments of the present application more clear, the technical scheme in the embodiments will be described clearly and completely in conjunction with the drawings of the embodiments of the present application. The following embodiments are used to illustrate the present application, but not to limit the scope of the present application.

[0044] In the description of the present application, it should be noted that the terms "upper", "lower", "front", "rear", "left", "right", "vertical", "inner", "outer" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, therefore, it cannot be understood as a limitation on the present application.

[0045] In the description of the utility model, it needs to explain, unless another explicit provision and limitation, the term "installation", "link", "connection" should do the broad sense understanding, for example, can be fixed connection, also can be detachable connection, or integrally connected;Can be mechanical connection, also can be electrical connection;Can be directly connected, also can be indirectly connected through the intermediate medium.

[0046] As Figures 1 to 4 Indicated in the utility model embodiment provides a kind of circulating tumor cell physical and chemical screen, for sorting enrichment circulating tumor cell (CTC cell).The physical and chemical screen includes body 1 and the cover plate (not marked in drawing) sealed with body 1.

[0047] Body 1 cross section is rectangular, and the shape is same with glass slide. One reaction tank 2 for accommodating reaction solution is arranged in body 1, and the flux of reaction tank 2 requires to accommodate 2-3 milliliter blood. At least two liquid inlets are arranged at one end of reaction tank 2, and liquid outlet 5 is arranged at the other end. Two liquid inlets are respectively connected with liquid inlet pipe, and liquid outlet 5 is connected with liquid outlet pipe 10. At least two reaction zones 1021 are arranged between the liquid inlet and liquid outlet 5, a plurality of microcolumns 6 are arranged in each reaction zone 1021;Connecting zone 1022 is arranged between two adjacent reaction zones, and the connecting zone 1022 is not provided with microcolumn. The microcolumn 6 of each reaction zone and the adsorption matrix attached on the bottom wall of reaction tank 2 can also be attached. The chemical bond of adsorption matrix can be specifically combined with the chemical group on CTC cell, and then the enrichment of CTC cell is realized.

[0048] In use, circulating tumor cell physical and chemical screen is placed horizontally, and blood sample and reagent are moved from liquid inlet to liquid outlet 5 in horizontal direction, so it is horizontal filtration system. The utility model adopts the mode of physical blocking and chemical adsorption to sort and enrich circulating tumor cells. On the one hand, the spacing of microcolumns 6 in each reaction zone is different, and the spacing between microcolumns 6 in each reaction zone gradually decreases along the direction from liquid inlet to liquid outlet 5, so that the macromolecules in blood can be physically intercepted, so that CTC cells are effectively screened in layers;On the other hand, the adsorption matrix attached on the microcolumn 6 of each reaction zone and the bottom plate of reaction tank 2 is specifically combined with CTC cell, and gradually produces the retention effect on cell, and then the sorting and enrichment of CTC cell are realized.

[0049] It should be noted that the adsorption matrix can be any substance that can be combined with CTC cell in the prior art, and can be selected according to the specific type of CTC cell to be enriched.

[0050] The utility model discloses, adjacent two reaction areas 1021 between be provided with connecting area 1022, connecting area 1022 in the micro column not be provided, like this, can reduce the obstruction pressure to blood and reagent, be favorable to blood and reagent smooth flow, can realize the separation screening of circulating tumor cell under smaller driving pressure, avoid producing the blockage.

[0051] And the utility model discloses because including at least two reaction areas, along the direction from inlet to outlet, the spacing between micro column 6 in each reaction area 1021 is gradually reduced, therefore can also play the role of molecular sieve, can block different size materials in different areas, therefore the cell screen of the utility model is more favorable to the observation of next step, is more favorable to the screening and discrimination of CTC cell.

[0052] As an alternative embodiment, the cell screen of the utility model embodiment, along the direction from inlet to outlet 5, in the adjacent two reaction areas, the spacing of micro column 6 in the downstream reaction area is 25%-60% of the spacing of micro column 6 in the upstream reaction area. For example, along the direction from inlet to outlet 5, it includes A reaction area, connecting area, B reaction area in proper order, the spacing between micro column 6 in B reaction area is 25%-60% of the spacing between micro column 6 in A reaction area, the connecting area is blank area, does not set up micro column, and is same with the bottom plate of reaction tank, like this, ensure that the spacing difference of two reaction areas is appropriate, the spacing of micro column in the upstream reaction area is larger, prevent its adsorption CTC cell from affecting the spacing of subsequent cells that can pass through, avoid blockage, ensure that fluid passes smoothly, so that cells can disperse in the whole reaction area, and the spacing of micro column in the reaction area close to the outlet is small, which can avoid the desorption of adsorbed cells.

[0053] The number of reaction areas in the utility model is not limited, and can be two, three, four, etc. The specific number can be set according to actual needs. The blank connecting area is arranged between the adjacent two reaction areas. The following specific examples of the utility model do not limit the protection scope of the utility model.

[0054] As a specific embodiment, as shown in Figure 4 The reaction area includes two, along the direction from inlet to outlet 5, A area 1021, blank connecting area 1022, B area 1021 respectively, and the spacing between micro column 6 in A area to B area gradually reduces, the spacing of micro column in A area is 20-30 (not including) microns, and the spacing of micro column in B area is 8-10 (not including) microns.

[0055] CTC cells typically have a diameter of approximately 10-20 μm, which is relatively large compared to blood cells, such as blood cells which are generally 7-12 μm in diameter. In reaction tank 2, as the blood flows from the inlet to the outlet 5, materials of different sizes are dispersed and blocked layer by layer; at the same time, the adsorption matrix on the microcolumn 6 and the bottom plate of reaction tank 2 adsorbs CTC cells, while ensuring smooth fluid flow and avoiding blockage.

[0056] In this invention, the cross-section of the micropillars 6 in each reaction zone can be a conventional setting in the prior art, such as a circle, a triangle, or a hexagon.

[0057] In a preferred embodiment, the cross-section of the micropillar 6 is circular or triangular. A triangular cross-section of the micropillar 6 is most conducive to liquid flow.

[0058] It should be noted that the spacing between the micropillars 6 in this utility model refers to the shortest distance between the outer walls of two micropillars 6.

[0059] In one specific implementation, when the cross-section of the micropillar 6 is circular, all micropillars 6 have the same diameter, and the spacing between micropillars 6 refers to the distance between the centers of two micropillars 6 minus the diameter of the micropillar 6 (i.e., two radii). When the cross-section of the micropillar 6 is triangular, the spacing between micropillars 6 refers to the shortest distance between the nearest adjacent surfaces, or between points, or between a point and a surface.

[0060] In the embodiments of this utility model, the cross-sectional shape and height of the micropillars 6 in each reaction zone are the same.

[0061] As a specific setup, the height of the micropillar 6 is set to 10-30 micrometers.

[0062] like Figure 4 As shown, in this invention, the fluid channel 100 includes a connected reaction section 102 and a flow channel section 101, with the flow channel section 101 located upstream and / or downstream of the reaction section 102; the reaction zone 1021 and the connecting zone 1022 are disposed in the reaction section 102. The width of the reaction section 102 is greater than the width of the flow channel section 101.

[0063] As an alternative implementation, the fluid channel 100 includes multiple channels, one end of each fluid channel 100 is connected to the inlet 3,4, and the other end is connected to the outlet 5; the sample passes through only one fluid channel 100 from the inlet 3,4 to the outlet 5; each fluid channel 100 contains a reaction section 102, and the reaction sections 102 of each fluid channel 100 are arranged side by side or staggered.

[0064] The utility model discloses a plurality of fluid channels 100 can be distributed in the width direction of the reaction tank 2, and the fluid composed of blood and reagent can be divided into streams and enter the reaction part 102 of different fluid channels 100 respectively, so that the blocking force is small, the fluency of fluid flow can be guaranteed, and the separation, enrichment and screening of circulating tumor cells are facilitated.

[0065] As an alternative embodiment, one or more flow channel parts 101 of other fluid channels 100 are arranged between the reaction parts 102 of the two adjacent fluid channels 100 arranged side by side.

[0066] As an alternative embodiment, the reaction parts 102 of the two adjacent fluid channels 100 share at least part of the upstream and / or downstream flow channel part 101.

[0067] As a specific embodiment, the reaction parts 102 of the plurality of fluid channels 100 are arranged in a row in the width direction of the reaction tank 2, and the center lines are parallel.

[0068] In the length direction of the reaction tank 2, the reaction parts 102 of the plurality of fluid channels 100 are staggered in front and back, and the center lines are parallel but not overlapped.

[0069] The above scheme can fully utilize the space of the reaction tank, reasonably distribute the plurality of fluid channels 100, and also guarantee that all fluids only pass through one reaction part, ensure the fluency of fluid flow, avoid blockage, and facilitate the separation, enrichment and screening of circulating tumor cells.

[0070] The liquid inlet of the utility model discloses first liquid inlet 3 and second liquid inlet 4, and the first liquid inlet 3 is reagent liquid inlet, and the second liquid inlet 4 is blood liquid inlet. The structure of two liquid inlets is same, and is adjacent. Blood is inputted into the reaction tank 2 through the blood liquid inlet, and all reagents except blood are inputted through the reagent liquid inlet. The first liquid inlet is connected with the first liquid inlet pipe 8, and the second liquid inlet pipe is connected with the second liquid inlet pipe 9.

[0071] It should be pointed out that "first" and "second" described herein are only for convenient description, and are not used to limit the position or function of the liquid inlet / liquid inlet pipe.

[0072] Because contact with blood leads to contamination, the contaminated parts must be discarded after each use, and the connecting tubes require high-quality materials, resulting in high costs. If both blood and reagents are fed through the same inlet, the connecting tubes become contaminated and corroded, requiring frequent replacement. To reduce material consumption, reagent and blood inlets are located at opposite ends of reaction tank 2, allowing for separate inputs. The connecting tube at the blood inlet, not in contact with the reagents, has lower requirements for corrosion resistance, allowing the use of lower-cost consumables. While the connecting tube at the reagent inlet is more expensive, it is not contaminated by blood and can be reused, thus avoiding contamination and reducing material consumption.

[0073] In a preferred embodiment, the line connecting the centers of the first inlet 3 and the second inlet 4 is parallel to or coincides with the centerline along the length of the reaction tank 2. This facilitates a faster and more uniform flow of blood and reagents into the reaction tank 2, which is beneficial for the screening of CTC cells.

[0074] In this invention, the cover plate can be integrally formed with the body, with a hollow space between the cover plate and the body to form a reaction tank. Alternatively, the body and the cover plate can be separate parts, with the cover plate covering the upper surface of the body and sealingly connected to it.

[0075] An inlet pipe is provided at the liquid inlet, and an outlet pipe is provided at the liquid outlet. The arrangement of the inlet and outlet pipes can be configured as needed; they can be fixedly mounted on the main body or fixedly mounted on the cover plate.

[0076] As one implementation method, such as Figure 2 As shown in the embodiment of this utility model, the liquid inlet is disposed on the support platform 7, and the liquid inlet pipe is fixedly disposed on the support platform. The support platform 7 has a hollow space inside, and the hollow space is connected to the reaction tank 2. The liquid inlet is connected to the hollow space of the support platform 7, and the liquid entering through the liquid inlet enters the reaction tank 2 through the hollow space of the support platform 7. Both liquid inlets are disposed on the support platform 7, and both liquid inlet pipes are disposed on the support platform. The first liquid inlet 3 and the second liquid inlet 4 are both connected to the hollow space of the support platform 7.

[0077] The support platform 7 of this invention can be formed in any way. For example, it can be integrally formed with the main body 1, or it can be set separately and then fixedly connected to the main body 1. The support platform 7 is hollow and has an opening on the side facing the reaction zone, which communicates with the reaction tank 2, so that the liquid entering through the liquid inlet can enter the reaction tank 2 through the hollow space for reaction and screening.

[0078] In addition, further, the bottom of the liquid outlet 5 can also be provided with a support table 7, the liquid outlet pipe 8, 9 is fixedly arranged on the support table, the support table 7 is also hollowly arranged, the upper end of the support table 7 is communicated with the liquid outlet 5, and the side facing the reaction tank 2 has an opening. In this way, the liquid in the reaction tank 2 can enter the hollow space of the support table 7 and be discharged from the liquid outlet 5 and the liquid outlet pipe 10.

[0079] The cover plate is provided with a through hole, when the cover plate covers the body, the liquid inlet pipe 8, 9 and the liquid outlet pipe 10 respectively pass through the corresponding through hole; the liquid inlet pipe 8, 9 and the liquid outlet pipe 10 are all sealed and fixed with the cover plate.

[0080] As another embodiment, the liquid inlet pipe and the liquid outlet pipe can be fixedly arranged on the cover plate, the lower end of the liquid inlet pipe is opened to form a liquid inlet, and the lower end of the liquid outlet pipe forms a liquid outlet, the liquid inlet and the liquid outlet are respectively communicated with the reaction tank. In order to enable the blood and reagent added into the reaction tank 2 to be quickly moved in the direction of the liquid outlet 5, the liquid outlet 5 is provided with a driving device to drive the liquid to be moved in the direction of the liquid outlet 5 from the liquid inlet;

[0081] Preferably, the driving device is a negative pressure suction device.

[0082] Embodiment 1

[0083] The circulating tumor cell screening device of the embodiment comprises a body 1 and a cover plate in sealing cooperation with the body 1. The body 1 and the cover plate are both made of transparent rigid material. The body 1 is rectangular in cross section and has the same shape as a glass slide. The body 1 is provided with a reaction groove 2. The reaction groove 2 is provided with a blood inlet port and a reagent inlet port at one end and an outlet port 5 at the other end. The blood inlet port and the reagent inlet port are respectively connected with inlet tubes, and the outlet port 5 is connected with an outlet tube 10. The cover plate is provided with through holes. When the cover plate covers the body 1, the inlet tubes and the outlet tube 10 respectively pass through the corresponding through holes. The inlet tubes and the outlet tube 10 are in sealing cooperation with the cover plate. The periphery of the cover plate is sealingly fixed to the inner wall of the body 1. A support table 7 is arranged at the bottom of the two inlet ports. A first inlet tube 8 and a second inlet tube 9 are fixedly arranged on the support table. The first inlet port 3 and the second inlet port 4 are both in communication with the hollow space of the support table 7. The support table 7 is hollow inside and has an opening on the side facing the reaction area, which is in communication with the reaction groove 2. The blood and the reagent entering through the inlet ports pass through the hollow space and enter the reaction groove 2 to react and be screened. A plurality of fluid channels 100 are arranged between the inlet ports and the outlet port 5. One end of each fluid channel 100 is in communication with the inlet ports 3 and 4, and the other end is in communication with the outlet port 5. The sample passes through only one fluid channel from the inlet port to the outlet port. Each fluid channel 100 contains a reaction part 102. The reaction part 102 and the upstream and downstream are both provided with flow channel parts 101. The reaction parts of the fluid channels are arranged in parallel or staggered. One or two flow channel parts of other fluid channels are arranged between the reaction parts of two adjacent fluid channels arranged in parallel. Two reaction areas 1021, A area and B area, are arranged in each reaction part of each fluid channel. A plurality of micro columns 6 are arranged in the reaction area 1021. A connecting area 1022 is arranged between the two reaction areas. The connecting area 1022 is not provided with micro columns 6. The micro column spacing of the A area at the upstream is 20 um, and the micro column spacing of the B area at the downstream is 9 um. The bottom plate of the reaction groove 2 and the surface of the micro columns 6 of each reaction area are attached with antibodies. In each reaction area, the cross section of the micro column 6 is circular, and the height of the micro column 6 is set to 30 microns.

[0084] The above is only a preferred embodiment of the present application, and does not limit the present application in any form. Although the present application has been disclosed as above with a preferred embodiment, it is not intended to limit the present application. Any skilled person in the art can make some changes or modifications to the above-mentioned technical content without departing from the technical solution range of the present application to obtain equivalent embodiments with equivalent changes. Any simple modification, equivalent change and modification of the above embodiments based on the technical essence of the present application are still within the scope of the present application.

Claims

1. A physicochemical sieve for circulating tumor cells, characterized in that, The device comprises a body, a reaction tank is arranged in the body, at least two liquid inlets are arranged at one end of the reaction tank, a liquid outlet is arranged at the other end of the reaction tank, a fluid channel is arranged between the liquid inlets and the liquid outlet, at least two reaction zones are arranged in the fluid channel, a plurality of micro columns are arranged in each reaction zone, a connecting zone is arranged between two adjacent reaction zones, and no micro column is arranged in the connecting zone.

2. The circulating tumor cell physico-chemical screen of claim 1, wherein, The spacing between the micro columns in each reaction zone gradually decreases along the direction from the liquid inlet to the liquid outlet.

3. The physical-chemical screening of circulating tumor cells according to claim 2, characterized in that, The spacing between the micro columns in the reaction zone located at the downstream is 25%-60% of the spacing between the micro columns in the reaction zone located at the upstream along the direction from the liquid inlet to the liquid outlet.

4. The physical-chemical circulating tumor cell screening according to any one of claims 1-3, wherein, The fluid channel comprises a reaction part and a flow channel part which are connected, the flow channel part is arranged upstream and / or downstream of the reaction part, and the reaction zone and the connecting zone are arranged in the reaction part.

5. The physical-chemical circulating tumor cell screen of claim 4, wherein, The width of the reaction part is greater than the width of the flow channel part.

6. The physical-chemical screening of circulating tumor cells according to claim 4, characterized in that, The fluid channel comprises a plurality of fluid channels, one end of each fluid channel is connected with the liquid inlet, and the other end of each fluid channel is connected with the liquid outlet; the sample only passes through one fluid channel from the liquid inlet to the liquid outlet; each fluid channel comprises a reaction part, and the reaction parts of the fluid channels are arranged in parallel or staggered.

7. The physical-chemical circulating tumor cell screen of claim 6, wherein, One or more flow channel parts of other fluid channels are arranged between the reaction parts of two adjacent fluid channels arranged in parallel.

8. The physical-chemical circulating tumor cell screen of claim 6, wherein, The reaction parts of two adjacent fluid channels share at least part of the flow channel parts upstream and / or downstream thereof.

9. The circulating tumor cell physico-chemical sieve of claim 6, wherein, In the width direction of the reaction tank, the reaction parts of the plurality of fluid channels are arranged in a row, and the center lines are parallel. In the length direction of the reaction tank, the reaction parts of the plurality of fluid channels are staggered in front and back, and the center lines are parallel but not overlapped.

10. The physical-chemical circulating tumor cell screening according to any one of claims 1-3, wherein, The liquid inlet comprises a first liquid inlet and a second liquid inlet, and the center line of the first liquid inlet and the second liquid inlet is parallel to or coincides with the center line of the length direction of the reaction tank.

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