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, a plurality of reaction areas are arranged between the liquid inlets and the liquid outlet, and a plurality of micro-columns are arranged in each reaction 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, the distance between the microcolumns in each reaction area is gradually reduced, screening of the CTC cells is facilitated, further observation and judgment are also facilitated, and the circulating tumor cell sorting device is good in compatibility with various coloring agents and wide in application range.

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 overcoming prior art's insufficient, provide a kind of circulating tumor cell physical and chemical screen.The utility model adopts the way of physical blocking and chemical adsorption to sort circulating tumor cell, the spacing between microcolumn in each reaction zone gradually decreases, can play the role of dispersing and step-by-step screening to cell, avoid jamming and stacking and obscure observation field of view, it is favorable to the screening of CTC cell, also favorable to further observation and discrimination, the compatibility of various dyeing agents is good, 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 screen, including body, be equipped with reaction tank in the body, the one end of reaction tank is equipped with at least two liquid inlets, and the other end is equipped with liquid outlet, and it is equipped with multiple reaction zones between liquid inlet and liquid outlet, and it is equipped with multiple microcolumns in each reaction zone;Along the direction from liquid inlet to liquid outlet, the spacing between microcolumn in each reaction zone gradually decreases.

[0009] Further scheme, along the direction from liquid inlet to liquid outlet, in the two reaction zones adjacent to each other, the microcolumn spacing of the reaction zone located in downstream is 66%-80% of the microcolumn spacing of upstream reaction zone.

[0010] Further scheme, the reaction zone includes six, and along the direction from liquid inlet to liquid outlet, the microcolumn spacing in each reaction zone is in turn respectively:

[0011] 30-40 microns, 20-30 microns, 15-20 microns, 10-15 microns, 8-10 microns, 6-8 microns;

[0012] Further scheme, along the direction from liquid inlet to liquid outlet, the microcolumn spacing in each reaction zone is in turn respectively: 30 microns, 20 microns, 15 microns, 10 microns, 8 microns, 6 microns.

[0013] Further scheme, the cross section of microcolumn in each reaction zone is circular, or triangular, or hexagonal;

[0014] Preferably, the cross section of microcolumn is circular or triangular.

[0015] Further scheme, the cross section shape and / or height of microcolumn in each reaction zone is same.

[0016] Further scheme, the bottom of liquid inlet is equipped with support platform, the inside of support platform is equipped with hollow space, and hollow space is communicated with reaction tank;Liquid inlet is communicated with the hollow space of support platform, and the liquid entering through liquid inlet enters reaction tank through the hollow space of support platform;

[0017] Preferably, the supporting table is arranged at the bottom of the two liquid inlets, and the two liquid inlets are communicated with the hollow space of the supporting table.

[0018] Further, 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.

[0019] Further, the utility model discloses a cover plate, which can be integrally formed with the body, and the cover plate is hollowly arranged between the body to form the reaction tank, or the body and the cover plate can be separately arranged, the cover plate covers the upper surface of the body, and is sealingly connected with the body.

[0020] Further, the utility model discloses a driving device arranged at the liquid outlet to drive the liquid to move from the liquid inlet to the liquid outlet.

[0021] Further, the driving device is a negative pressure suction device.

[0022] Further, the body and the cover plate of the utility model are made of transparent rigid materials.

[0023] Compared with the prior art, the utility model has the following beneficial effects.

[0024] 1. The utility model adopts the physical blocking and chemical adsorption combined mode to sort and enrich the circulating tumor cells. On the one hand, the microcolumn spacing in each reaction zone is different, and along the direction from the liquid inlet to the liquid outlet, the spacing between the microcolumns in each reaction zone gradually decreases, so that the macromolecules in the blood can be blocked, thereby effectively screening the CTC cells in different layers; on the other hand, the adsorption matrix attached to the microcolumns in each reaction zone and the bottom plate of the reaction tank specifically combines with the CTC cells, thereby realizing the sorting and enrichment of the CTC cells.

[0025] 2. The utility model discloses a circulating tumor cell physical and chemical screen, and the reaction tank comprises a plurality of reaction zones, and the spacing between the microcolumns in each reaction zone gradually decreases, so that the molecular sieve effect can also be achieved, different sizes of materials can be blocked in different areas, the probability of cell clusters being scattered by the microcolumns is also improved, the CTC cells wrapped in the cell clusters or the cell clusters formed by a plurality of CTC cells are also more easily dispersed, and after dispersion, the cell clusters are blocked and positioned by the microcolumns at different positions. Therefore, the cell screen of the utility model is more conducive to the observation of the next step and the screening and identification of the CTC cells.

[0026] 3、The utility model discloses a circulating tumor cell physical and chemical screen, the body and the cover plate are made of transparent rigid material, can have certain rigid support performance, avoid producing wrinkle and producing bubble, still have excellent light transmittance, be suitable for silver dyeing, fluorescence dyeing etc. Variety of observation detection method.

[0027] The utility model discloses a circulating tumor cell physical and chemical screen, the body and the cover plate are made of transparent rigid material, can have certain rigid support performance, avoid producing wrinkle and producing bubble, still have excellent light transmittance, be suitable for silver dyeing, fluorescence dyeing etc. Variety of observation detection method. ACCOMPA

[0028] The accompanying drawings are part of the utility model and serve to provide further understanding of the utility model, and the illustrative embodiments of the utility model and the description thereof serve to explain the utility model but do not constitute undue limitation on the utility model. 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. In the drawings:

[0029] Figure 1 is the top view of the utility model discloses a circulating tumor cell physical and chemical screen;

[0030] Figure 2 is the side view of the utility model discloses a circulating tumor cell physical and chemical screen;

[0031] Figure 3 is Figure 2 the local structure schematic view of A in;

[0032] Figure 4 is the structure schematic view of reaction tank;

[0033] Figure 5 is the schematic diagram of microcolumn spacing in each reaction zone.

[0034] 1-body, 2-reaction tank, 3-first liquid inlet, 4-second liquid inlet, 5-liquid outlet, 6-microcolumn, 7-supporting platform, 8 first liquid pipe, 9 second liquid pipe, 10 liquid outlet pipe.

[0035] It should be noted that these drawings and textual descriptions are not intended to limit the scope of the concept of the utility model in any way, but to illustrate the concept of the utility model to those skilled in the art by referring to specific embodiments. DETAILED DESCRIPTION

[0036] To make the purpose, technical scheme and advantages of the embodiments of the utility model more clear, the technical scheme in the embodiments will be described clearly and completely in conjunction with the drawings in the embodiments of the utility model below, and the following embodiments are used to illustrate the utility model but not to limit the scope of the utility model.

[0037] In the description of the utility model, it needs to explain, the term "upper", "lower", "front", "back", "left", "right", "vertical", "internal", "external" and so on indicate the orientation or position relation is based on the orientation or position relation shown in the drawing, only for the convenience of describing the utility model and simplifying the description, and not indicate or imply that the device or element must have a particular orientation, with a particular orientation structure and operation, therefore cannot be understood as the limitation of the utility model.

[0038] In the description of the utility model, it needs to explain, unless otherwise explicitly provided and limited, the term "installation", "connection", "connect" should be broad sense, for example, can be fixed connection, can be detachable connection, or integrally connected, can be mechanical connection, can be electrical connection, can be directly connected, can be indirectly connected through the intermediate medium. For ordinary skilled in the art, the above-mentioned terms can be understood in the specific meaning of the utility model according to the specific circumstances.

[0039] As Figures 1 to 5 Indicated in the utility model embodiment, a kind of circulating tumor cell physical and chemical screen is provided 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.

[0040] Body 1 cross section is rectangular, and the shape is same with glass slide. One end of body 1 is provided with at least two liquid inlet, the other end is provided with liquid outlet 5. Two liquid inlet are connected with liquid inlet pipe respectively, and liquid outlet 5 is connected with liquid outlet pipe 10. Multiple reaction zones are arranged between liquid inlet and liquid outlet 5, and multiple micro columns 6 are arranged in each reaction zone. Along the direction from liquid inlet to liquid outlet 5, the spacing between micro columns 6 in each reaction zone gradually decreases. In addition, micro columns 6 in each reaction zone and the bottom wall of reaction groove 2 can also be attached with adsorption matrix, and the chemical bond of adsorption matrix can be specifically combined with the chemical group on CTC cell, to realize the enrichment of CTC cell.

[0041] In use, the circulating tumor cell physical and chemical screening level is placed horizontally, and blood sample and reagent are moved from the liquid inlet to the liquid outlet 5 in the horizontal direction, so it is a horizontal filtering system. The circulating tumor cells are sorted and enriched by the physical blocking and chemical adsorption combination. On the one hand, the micro columns 6 in each reaction zone have different spacings, and the spacing between the micro columns 6 in each reaction zone gradually decreases along the direction from the liquid inlet to the liquid outlet 5, so that the macromolecules in the blood can be physically intercepted, and the CTC cells can be effectively screened in layers; on the other hand, the micro columns 6 in each reaction zone and the adsorption matrix attached to the bottom plate of the reaction tank 2 are specifically combined with the CTC cells, and the cells are gradually retained, so that the CTC cells are sorted and enriched.

[0042] It should be noted that the adsorption matrix can be any substance that can be combined with the CTC cells in the prior art, and can be selected according to the specific type of the CTC cells to be enriched. As a specific embodiment, the adsorption matrix can be a colloidal gold labeled specific binding substance.

[0043] The existing microfluidic chip has only one reaction zone or the spacings between the micro columns 6 in multiple reaction zones are all the same. If the size of the cell group formed by the aggregation of some cells is greater than the spacing of the micro columns 6, the chip front end will be blocked earlier, and the dispersion of the subsequent materials will be affected; if the CTC cells are wrapped in the cell group or multiple CTC cells are aggregated, the next step of observation will be disturbed, and it is difficult to distinguish.

[0044] In the utility model, since multiple reaction zones are included and the spacings between the micro columns 6 in each reaction zone gradually decrease, the molecular sieve effect can also be achieved, different sizes of materials can be blocked in different areas, so that the cell screen of the utility model is more conducive to the next step of observation and more conducive to the screening and identification of CTC cells.

[0045] As an alternative embodiment, in the cell screen of the utility model embodiment, along the direction from the liquid inlet to the liquid outlet 5, the spacing of the micro columns 6 in the downstream reaction zone in the two adjacent reaction zones is 66%-80% of the spacing of the micro columns 6 in the upstream reaction zone. For example, along the direction from the liquid inlet to the liquid outlet 5, the A reaction zone and the B reaction zone are included in sequence, and the spacing between the micro columns 6 in the B reaction zone is 66%-80% of the spacing between the micro columns 6 in the A reaction zone. In this way, the spacing difference of the two reaction zones is appropriate, which is conducive to dispersing the cell group, blocking different sizes of materials in layers, and also conducive to the passage of single small molecules.

[0046] The number of the reaction zones is not limited, and can be two, three, four, five, six, or the like, and the specific number can be set according to actual needs.

[0047] As a specific embodiment, as shown in Figure 4 and Figure 5 The reaction zone includes six zones, namely, A zone, B zone, C zone, D zone, E zone and F zone along the direction from the liquid inlet to the liquid outlet 5, the spacing between the micro columns 6 in the A zone to the F zone gradually decreases, the spacing in the A zone is 30-40 microns, the spacing in the B zone is 20-30 (not including) microns, the spacing in the C zone is 15-20 (not including) microns, the spacing in the D zone is 10-15 (not including) microns, the spacing in the E zone is 8-10 (not including) microns, and the spacing in the F zone is 6-8 (not including) microns.

[0048] The diameter of the CTC cell is usually about 10-20 microns, and compared with blood cells, the diameter of the CTC is relatively large, for example, the diameter of the blood cell is generally 7-12 microns. In the reaction tank 2, the blood flows from the liquid inlet to the liquid outlet 5, and different sizes of materials are dispersed and blocked layer by layer, and the micro column 6 and the adsorption matrix on the bottom plate of the reaction tank 2 adsorb the CTC cell. Generally, the captured CTC cell appears in the C zone-E zone, which is convenient for subsequent microscopic observation and identification.

[0049] As a preferred specific embodiment, the spacing between the micro columns 6 in each reaction zone is respectively: the spacing in the A zone is 30 microns, the spacing in the B zone is 20 microns, the spacing in the C zone is 15 microns, the spacing in the D zone is 10 microns, the spacing in the E zone is 8 microns, and the spacing in the F zone is 6 microns. When the spacing between the micro columns 6 in each reaction zone is the above scheme, the effect of sorting out the CTC cell is more favorable.

[0050] The cross section of the micro column 6 in each reaction zone in the utility model can be a conventional setting in the prior art, for example, can be circular, or triangular, or hexagonal.

[0051] As a preferred embodiment, the cross section of the micro column 6 is circular or triangular. When the cross section of the micro column 6 is triangular, it is most favorable for liquid flow.

[0052] It should be noted that the spacing between the micro columns 6 in the utility model refers to the shortest distance between the outer walls of two micro columns 6.

[0053] As a specific embodiment, when the cross section of the micro column 6 is circular, the diameters of the micro columns 6 are the same, and the distance between the micro columns 6 refers to the distance between the centers of two micro columns 6 minus the diameter of the micro column 6 (i.e. two radii). When the cross section of the micro column 6 is triangular, the distance between the micro columns 6 refers to the shortest distance between the adjacent nearest surfaces, or between the points and the points, or between the points and the surfaces.

[0054] In the embodiment of the utility model, the cross section shape and the height of the micro column 6 in each reaction zone are the same.

[0055] As a specific setting mode, the height of the micro column 6 is set to 10-30 microns. In the reaction tank 2, the fluid channel length between the liquid inlet and the liquid outlet is 20 microns.

[0056] The liquid inlet of the utility model includes first liquid inlet 3 and second liquid inlet 4, and the first liquid inlet 3 is a reagent liquid inlet, and the second liquid inlet 4 is a blood liquid inlet. The structure of the two liquid inlets is the same, and is adjacently arranged. The blood is input into the reaction tank 2 through the blood liquid inlet, and all reagents except the blood are input 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.

[0057] It should be pointed out that "first" and "second" described herein are only for convenience of description, and are not used to limit the position or function of the liquid inlet / liquid inlet pipe.

[0058] Due to the contact with the blood, i.e. pollution, the polluted part needs to be discarded each time after use, so as to reduce the consumption of materials, and therefore the reagent liquid inlet and the blood liquid inlet are arranged at one end of the reaction tank 2 respectively, so as to facilitate the blood and the reagent to be added from different liquid inlets, avoid pollution, and reduce the consumption of materials.

[0059] As a preferred embodiment, the center line of the first liquid inlet 3 and the second liquid inlet 4 is parallel to or coincides with the center line of the length direction of the reaction tank 2. In this way, the blood and the reagent can flow to the reaction tank 2 more quickly and uniformly, which is beneficial to the screening of CTC cells.

[0060] In the utility model, the cover plate can be integrally formed with the body, and the cover plate and the body are hollowly arranged, forming a reaction tank. Alternatively, the body and the cover plate can be arranged in a split mode, the cover plate covers the upper surface of the body, and is sealingly connected with the body.

[0061] The liquid inlet pipe is arranged at the liquid inlet, and the liquid outlet pipe is arranged at the liquid outlet. The arrangement mode of the liquid inlet pipe and the liquid outlet pipe can be arranged as required, which can be fixedly arranged on the body or the cover plate.

[0062] As an embodiment, as shown in Figure 2As shown in the embodiment of the utility model, the bottom of the liquid inlet is provided with a support table 7, the liquid inlet pipe is fixedly arranged on the support table, the inside of the support table 7 is provided with a hollow space, and the hollow space is communicated with the reaction tank 2; the liquid inlet is communicated with the hollow space of the support table 7, and the liquid entering through the liquid inlet enters the reaction tank 2 through the hollow space of the support table 7. The support table 7 is arranged at the bottom of the two liquid inlets, the two liquid inlet pipes are arranged on the support table, and the first liquid inlet 3 and the second liquid inlet 4 are communicated with the hollow space of the support table 7.

[0063] The support table 7 of the utility model can be formed in any way, for example, can be integrally formed with the body 1, or can be separately arranged and then fixedly connected with the body 1. The support table 7 is hollow, and the side thereof facing the reaction area has an opening and is communicated 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.

[0064] 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 hollow, the upper end of the support table 7 is communicated with the liquid outlet 5, and the side thereof facing the reaction tank 2 has an opening, so that 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.

[0065] The cover plate is provided with through holes, 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 holes; the liquid inlet pipe 8, 9 and the liquid outlet pipe 10 are all sealed and fixed with the cover plate.

[0066] As another embodiment, the liquid inlet pipe and the liquid outlet pipe can be fixedly arranged on the cover plate, the lower end opening of the liquid inlet pipe forms a liquid inlet, the lower end of the liquid outlet pipe forms a liquid outlet, and the liquid inlet and the liquid outlet are both communicated with the reaction tank. In order to enable the blood and the reagent added into the reaction tank 2 to be directionally and quickly moved to the liquid outlet 5, a driving device is arranged at the liquid outlet 5 to directionally move the liquid from the liquid inlet to the liquid outlet 5.

[0067] Preferably, the driving device is a negative pressure suction device.

[0068] Further, the body 1 and the cover plate of the utility model are both made of transparent rigid material, which not only has certain rigid support performance and avoids wrinkles and bubbles, but also has excellent light transmittance and is suitable for silver staining, fluorescence staining and other observation and detection methods.

[0069] In the existing microfluidic chip for sorting circulating tumor cells, some microfluidic chips are flexible membranes, which are prone to wrinkle when being fixed on the filter. In the experiment, the flexible membrane is prone to bubble, which affects the subsequent microscopic observation. Some chips use rigid membranes, such as stainless steel, which can solve the problem of wrinkle and bubble of the flexible chip, but the rigid membrane has poor light transmittance, which can be used when the membrane is opaque, but it is difficult to observe under the microscope when silver staining is performed.

[0070] The circulating tumor cell physical and chemical screen of the utility model has certain rigidity, can avoid wrinkle and bubble, has good light transmittance, can reduce the experimental cost, has good compatibility to various staining agents, is more widely applicable and used.

[0071] Embodiment 1

[0072] The circulating tumor cell screen of the embodiment comprises a body 1 and a cover plate in sealed cooperation with the body 1. The body 1 and the cover plate are 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 tank 2, one end of the reaction tank 2 is provided with a blood inlet and a reagent inlet, and the other end is provided with an outlet 5. The blood inlet and the reagent inlet are respectively connected with inlet pipes, and the outlet 5 is connected with an outlet pipe 10. The cover plate is provided with through holes, and when the cover plate covers the body 1, the inlet pipes and the outlet pipe 10 respectively pass through the corresponding through holes. The inlet pipes and the outlet pipe 10 are in sealed connection with the cover plate. The periphery of the cover plate is in sealed and fixed connection with the inner wall of the body 1. A support table 7 is arranged at the bottom of the two inlets, a first inlet pipe 8 and a second inlet pipe 9 are fixedly arranged on the support table, and a first inlet 3 and a second inlet 4 are in communication with the hollow space of the support table 7. The support table 7 is hollow, and the side thereof facing the reaction area has an opening and is in communication with the reaction tank 2. The blood and the reagent entering through the inlets pass through the hollow space and enter the reaction tank 2 for reaction and screening. Six reaction areas are arranged between the inlets and the outlet 5, and the interval of the micropillars 6 in each reaction area is 30 microns in A area, 20 microns in B area, 15 microns in C area, 10 microns in D area, 8 microns in E area, and 6 microns in F area. The bottom plate of the reaction tank 2 and the surface of the micropillars 6 of each reaction area are attached with specific binding substances marked with colloidal gold. In each reaction area, the cross section of the micropillar 6 is circular, and the height of the micropillar 6 is 30 microns. The length of the fluid channel between the inlets and the outlet 5 is 20 mm.

[0073] The above merely describes preferred embodiments of the present application and is not intended to limit the present application in any form. Although the present application has been disclosed with preferred embodiments, 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 of the present application, and equivalent embodiments with equivalent changes can be obtained. 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 application relates to a reaction device, which comprises a body, a reaction groove arranged in the body, at least two liquid inlets arranged at one end of the reaction groove, a liquid outlet arranged at the other end of the reaction groove, a plurality of reaction zones arranged between the liquid inlets and the liquid outlet, and a plurality of micro columns arranged in each reaction zone; the spacing between the micro columns in each reaction zone gradually decreases along the direction from the liquid inlets to the liquid outlet.

2. The circulating tumor cell physico-chemical screen of claim 1, wherein, The spacing between the micro columns in the downstream reaction zone is 66%-80% of the spacing between the micro columns in the upstream reaction zone in the two adjacent reaction zones along the direction from the liquid inlets to the liquid outlet.

3. The physical-chemical screening of circulating tumor cells according to claim 2, characterized in that, The reaction zones comprise six reaction zones, and the spacing between the micro columns in each reaction zone along the direction from the liquid inlets to the liquid outlet is 30-40 microns, 20-30 microns, 15-20 microns, 10-15 microns, 8-10 microns and 6-8 microns respectively.

4. The physical-chemical circulating tumor cell screen of claim 3, wherein, The spacing between the micro columns in each reaction zone along the direction from the liquid inlets to the liquid outlet is 30 microns, 20 microns, 15 microns, 10 microns, 8 microns and 6 microns respectively.

5. The physical-chemical circulating tumor cell screening according to any one of claims 1-4, wherein, The cross section of the micro column in each reaction zone is circular, triangular or hexagonal.

6. The physical-chemical circulating tumor cell screening according to any one of claims 1-4, wherein, The cross section shape and / or height of the micro column in each reaction zone are the same.

7. The physical-chemical circulating tumor cell screening according to any one of claims 1-4, wherein, The bottom of the liquid inlet is provided with a support platform, the inside of the support platform is provided with a hollow space, and the hollow space is communicated with the reaction groove; the liquid inlet is communicated with the hollow space of the support platform, and the liquid entering through the liquid inlet enters the reaction groove through the hollow space of the support platform.

8. The physical-chemical circulating tumor cell screening according to any one of claims 1-4, 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 groove.

9. The physical-chemical circulating tumor cell screening according to any one of claims 1-4, wherein, The liquid outlet is provided with a driving device for driving the liquid to move from the liquid inlet to the liquid outlet.

10. The circulating tumor cell physico-chemical screen of claim 9, wherein, The driving device is a negative pressure suction device.

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