Circulating tumor cell physicochemical screen

Abstract

The utility model discloses a circulating tumor cell physicochemical sieve 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 the reaction areas are arranged along the direction from the liquid inlets to the liquid outlet. And the width of 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 width of each reaction area is gradually reduced, the effect of step-by-step separation and interception can be achieved, the situation that the observation view is blurred due to blockage and accumulation is avoided, screening of the CTC cells is facilitated, and further observation and judgment are also 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 for tumor cell entering peripheral blood of human body. CTC detection measures CTC existing in peripheral blood through capturing, monitors the trend of CTC type and quantity change, so as to monitor tumor dynamics in real time, assess treatment effect, and realize real-time individual treatment. However, the number of CTC in peripheral blood is extremely small, and the number of CTC in each milliliter of whole blood of tumor metastasis patient is only 1 to 10, so how to sort and enrich CTC from several million white blood cells and several billion 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 living 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. At present, there are mainly two methods for detecting circulating tumor cells by using microfluidic chip: 1) biological method, based on the different expression of specific proteins on the surface of CTC and blood cells, affinity recognition and capture are used; 2) physical method, some physical property differences between CTC 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, damage 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 be accumulated at the front end of the chip earlier, which will affect the dispersion of subsequent materials, blur the observation field, interfere with subsequent observation, and it is difficult for the technician to distinguish CTC cells.

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

[0006] The utility model wants to overcome the prior art's insufficient, provide a kind of circulating tumor cell physical and chemical sieve.The utility model adopts the way of physical blocking and chemical adsorption to sort circulating tumor cell, the width of each reaction zone gradually decreases, can play the role of step-by-step separation interception, avoid to accumulate fuzzy observation field of view, it is favorable to the screening of CTC cell, also favorable to further observation and discrimination.

[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, liquid outlet is equipped in the other end, multiple reaction zones are equipped between the liquid inlet and liquid outlet, along the direction from liquid inlet to liquid outlet, the width of each reaction zone gradually decreases.

[0009] Further scheme, along the direction from liquid inlet to liquid outlet, in the two adjacent reaction zones, the width of reaction zone located in downstream is 70%-85% of the width of upstream reaction zone.

[0010] Further scheme, multiple flow channels are equipped in each reaction zone, along the direction from liquid inlet to liquid outlet, the width of flow channel in each reaction zone gradually decreases.

[0011] Further scheme, along the direction from liquid inlet to liquid outlet, in the two adjacent reaction zones, the width of flow channel in reaction zone located in downstream is 65%-75% of the width of flow channel in upstream reaction zone.

[0012] Further scheme, along the direction from liquid inlet to liquid outlet, the number of flow channel in each reaction zone gradually decreases.

[0013] Further scheme, multiple flow channels in each reaction zone are arranged in parallel, and each flow channel includes liquid inlet section, liquid outlet section and intermediate section between the two, the liquid inlet section and liquid outlet section are arranged along horizontal direction, the intermediate section includes at least one inclined section arranged at a certain angle with horizontal direction.

[0014] Further scheme, the intermediate section includes alternatingly connected inclined section and horizontal section, and the inclined section is connected with liquid inlet section and liquid outlet section.

[0015] Further scheme, the angle between the inclined section and horizontal direction is 30°-60°, or 120°-150°.

[0016] Further scheme, the center axis of nth horizontal section and n+1 horizontal section is arranged in parallel, the center axis of nth horizontal section and n+2 horizontal section is coincident.

[0017] Further, a connecting area is arranged between two adjacent reaction areas, and no flow channel is arranged in the connecting area.

[0018] Further, a supporting table is arranged at one end of the reaction tank, a liquid inlet is arranged on the supporting table, a hollow space is arranged in the supporting table, and the hollow space is communicated with the reaction tank; the liquid inlet is communicated with the hollow space of the supporting table, and the liquid entering through the liquid inlet enters the reaction tank through the hollow space of the supporting table.

[0019] Preferably, the two liquid inlets are communicated with the hollow space of the supporting table.

[0020] 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.

[0021] Further, a cover plate is arranged, the cover plate can be integrally formed with the body, and the cover plate and the body are hollowly arranged 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 and connectingly arranged with the body.

[0022] 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.

[0023] Preferably, the driving device is a negative pressure suction device.

[0024] Compared with the prior art, the utility model has the following beneficial effects.

[0025] 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 widths of the reaction areas are different, and the widths of the reaction areas gradually decrease along the direction from the liquid inlet to the liquid outlet, so that the macromolecules in the blood can be physically blocked in stages, and the CTC cells can be effectively dispersed and screened; on the other hand, the adsorption matrix attached in the flow channels of the reaction areas and on the bottom plate of the reaction tank specifically combines with the CTC cells, and then the sorting and enrichment of the CTC cells are realized.

[0026] 2. The circulating tumor cell physical and chemical screen of the utility model comprises a plurality of flow channels in each reaction area, and the widths of the flow channels in each reaction area also gradually decrease, and the number gradually decreases, so that the cells can be dispersed, the process of moving in the flow channels is the cell screening process and the process of uniformly distributing the CTC cells, and the cells are uniformly distributed in each reaction area, so that the subsequent microscopic observation is facilitated.

[0027] 3、The flow channel in each reaction zone is also improved and arranged, the horizontal section and the inclined section are alternately connected, so that the speed of the reagent and the blood advancing is slowed down, the CTC cells are beneficial to being captured while being dispersed, and the enrichment effect of the CTC cells is improved.

[0028] 4、In the utility model, the reagent inlet and the blood inlet are arranged at one end of the reaction tank respectively, blood and reagent are added from different inlets, the connecting pipe at the blood inlet does not contact the reagent, the requirement for material corrosion resistance is reduced, low-cost consumables can be used, the connecting pipe at the reagent inlet is high in cost, but is not polluted by blood, can be reused, pollution is avoided, and material consumption is reduced.

[0029] The specific embodiments of the utility model will be further described in detail below with reference to the drawings. BRIEF DESCRIPTION OF DRAWINGS

[0030] The drawings are part of the utility model, which is used to provide further understanding of the utility model, the schematic embodiments of the utility model and the description thereof are used to explain the utility model, but do not constitute improper limitation on the utility model. Obviously, the drawings in the following description are only some embodiments, and other drawings can be obtained according to the drawings without creative labor for ordinary skilled in the art. In the drawings:

[0031] Figure 1 It is the top view of the circulating tumor cell physical and chemical screen of the utility model;

[0032] Figure 2 It is the schematic diagram of the reaction zone and the connecting zone;

[0033] Figure 3 It is the schematic diagram of a flow channel arrangement;

[0034] Figure 4 It is the side view of the circulating tumor cell physical and chemical screen of the utility model.

[0035] 1-body, 2-reaction tank, 3-first inlet, 4-second inlet, 5-outlet, 6-supporting table, 7-reaction zone, 8-connecting zone, 9-first inlet pipe, 10-second inlet pipe, 11-outlet pipe;

[0036] 100-flow channel, 101-inlet section, 102-outlet section, 200-intermediate section;

[0037] 201-first inclined section, 202-first horizontal section, 203-second inclined flow section, 204-second horizontal section, 205-third inclined section.

[0038] It should be noted that the drawings and the written description are not intended to limit the scope of the present application in any way, but are merely to illustrate the concept of the present application to those skilled in the art by referring to specific embodiments. DETAILED DESCRIPTION

[0039] 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 below with reference to the drawings in 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.

[0040] In the description of the present application, it should be noted that the terms "upper", "lower", "front", "back", "left", "right", "vertical", "inner", "outer" and the like indicate the orientation or positional relationship shown in the drawings, and are merely 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, and therefore cannot be understood as a limitation on the present application.

[0041] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or integrally connected; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0042] As shown in Figures 1 to 4 The present application provides a physical and chemical screen for circulating tumor cells, which is used for sorting and enriching circulating tumor cells (CTC cells). The physical and chemical screen comprises a body 1 and a cover plate (not marked in the figure) in sealing cooperation with the body 1. The body 1 is rectangular in cross section and has the same shape as a glass slide. A reaction tank 2 for accommodating a reaction solution is arranged in the body 1, and the flux of the reaction tank 2 is required to be able to accommodate 2-3 milliliters of blood. In the present application, the cover plate can be integrally formed with the body, and a hollow is arranged between the cover plate and the body to form the reaction tank. Alternatively, the body and the cover plate can be arranged separately, the cover plate covers the upper surface of the body, and the cover plate and the body are connected in sealing cooperation. One end of the reaction tank 2 is provided with at least two liquid inlet ports, and the other end is provided with a liquid outlet port 5. Two liquid inlet ports are respectively connected with liquid inlet pipes, and the liquid outlet port 5 is connected with a liquid outlet pipe 11. A plurality of reaction zones 7 are arranged between the liquid inlet ports and the liquid outlet port 5, and a plurality of flow channels are further arranged in each reaction zone 7. The width of each reaction zone 7 gradually decreases along the direction from the liquid inlet port to the liquid outlet port 5.

[0043] In use, the circulating tumor cell physical and chemical screen is horizontally placed, 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. On one hand, the widths of the reaction zones 7 are different, and the widths of the reaction zones 7 gradually decrease along the direction from the liquid inlet to the liquid outlet, so the macromolecules in the blood can be physically blocked step by step, and the CTC cells can be effectively dispersed and screened; on the other hand, the surface of the flow channel 100 of each reaction zone 7 and the adsorption matrix attached to the bottom plate of the reaction tank 2 are specifically combined with the CTC cells, so the sorting and enrichment of the CTC cells are realized.

[0044] 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, a large number of biotin is attached to the surface of the flow channel 100 of each reaction zone 7 and the bottom plate of the reaction tank 2, and the antibodies in the biotin can be specifically combined with the antigens on the CTC cells, which is equivalent to a number of "tentacles" that continuously capture the moving CTC cells until the CTC cells stop moving forward, and then the enrichment of the CTC cells is realized.

[0045] The existing microfluidic chip for screening circulating tumor cells has only one reaction zone 7, or the widths of the multiple reaction zones 7 are the same, and some cell groups are formed into cell groups with large sizes, so the cell groups are accumulated at the front end of the chip early, and the dispersion of the subsequent materials is affected; if the CTC cells are wrapped in the cell groups, or multiple CTC cells are aggregated, the next step of observation is also disturbed, and it is difficult to distinguish.

[0046] In the utility model, since multiple reaction zones 7 are included and the widths of the reaction zones 7 gradually decrease, the molecular sieve function can also be realized, the materials can be blocked step by step, so the cell screen of the utility model is more conducive to the next step of observation and the screening and distinguishing of the CTC cells.

[0047] It should be noted that, in the utility model, the direction from the liquid inlet to the liquid outlet is the length direction of the circulating tumor cell physical and chemical screen, and the direction perpendicular to the length direction in the same plane is the width direction.

[0048] As an alternative embodiment, in the cell screen of the utility model, along the direction from the liquid inlet to the liquid outlet 5, the width of the reaction zone 7 located at the downstream in the two adjacent reaction zones 7 is 70%-85% of the width of the upstream reaction zone 7. In this way, the width reduction of the two reaction zones 7 is appropriate, which is conducive to the dispersion of the cells and the blocking of the materials at different levels.

[0049] The number of the reaction zones 7 is not limited, and can be two, three, four, five, six, and the like, and the specific number can be set according to actual needs.

[0050] As a specific scheme, as shown in the figure, Figure 2 The reaction zone 7 includes five zones, A zone, B zone, C zone, D zone and E zone along the direction from the liquid inlet to the liquid outlet 5, and the widths of the five reaction zones 7 are different, and are 20mm, 17mm, 14mm, 11mm and 8mm respectively.

[0051] The circulation tumor cell physical and chemical sieve has a plurality of flow channels 100 arranged in each reaction zone 7, and the plurality of flow channels 100 are arranged in parallel. The width of the flow channel 100 gradually decreases along the direction from the liquid inlet to the liquid outlet, and the width of the flow channel 100 in each reaction zone 7 gradually decreases.

[0052] As an alternative embodiment, the width of the flow channel 100 in the downstream reaction zone 7 is 65%-75% of the width of the flow channel 100 in the upstream reaction zone 7 along the direction from the liquid inlet to the liquid outlet.

[0053] As a specific scheme, the width of the flow channel 100 in the A zone is 30 microns, the width of the flow channel 100 in the B zone is 20 microns, the width of the flow channel 100 in the C zone is 15 microns, the width of the flow channel 100 in the D zone is 10 microns, and the width of the flow channel 100 in the E zone is 7.5 microns.

[0054] The diameter of the CTC cell is generally 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, different sizes of materials are dispersed and blocked layer by layer in the process of flowing from the liquid inlet to the liquid outlet 5, and the flow channel 100 surface and the adsorption matrix on the reaction tank 2 bottom plate adsorb the CTC cell.

[0055] The circulation tumor cell physical and chemical sieve has a plurality of flow channels 100 arranged in each reaction zone 7, and the plurality of flow channels 100 are arranged in parallel.

[0056] As an alternative implementation, the depth of the flow channels 100 in each reaction zone 7 and the spacing between adjacent flow channels 100 can be set as needed. For example, as a specific embodiment, the depth of the flow channels 100 in each reaction zone 7 is 20 micrometers, and the spacing between adjacent flow channels 100 is 3 micrometers.

[0057] In this invention, the flow channel 100 can be formed in any form in the prior art. For example, the flow channel 100 can be a recessed groove on the bottom wall of the reaction tank 2; or, a pair of upwardly protruding baffles can be provided on the bottom wall of the reaction tank 2, with the flow channel 100 between the baffles for liquid to pass through.

[0058] In addition, such as Figure 2 As shown, due to the different widths of adjacent reaction zones 7, a connecting zone 8 is provided between two adjacent reaction zones 7 to connect them. The cross-section of the connecting zone 8 is trapezoidal. No flow channels 100 are provided within the connecting zone 8, and the bottom surface of the connecting zone 8 is the same as the bottom surface of the main body 1. After the cover plate is sealed to the main body 1, the upper part of the connecting zone 8 is also sealed, with only its two ends communicating with the two adjacent reaction zones 7. In this way, the solutions in each flow channel 100 of the upstream reaction zone 7 converge in the connecting zone 8 and then enter each flow channel 100 of the downstream reaction zone 7 for further separation, while also preventing liquid from overflowing from the reaction tank 2.

[0059] As an alternative implementation, the length of the connecting region 8 can be set as needed. For example, as a specific solution, the length of the connecting region 8 can be 1000 micrometers, that is, the distance between the flow channels 100 of two adjacent reaction regions 7 is 1000 micrometers.

[0060] Furthermore, multiple flow channels 100 in each reaction zone 7 are arranged in parallel, and each flow channel 100 includes an inlet section 101, an outlet section 102, and an intermediate section 200 located between the two. The inlet section 101 and the outlet section 102 are arranged in the horizontal direction, and the intermediate section 200 includes at least one inclined section that is set at a certain angle to the horizontal direction.

[0061] In this invention, the circulating tumor cell physicochemical sieve is designed such that the flow channels 100 in each reaction zone 7 are not all horizontally arranged, but are divided into multiple segments. To facilitate the entry and exit of liquid into the flow channels 100, the inlet segment 101 and the outlet segment 102 are both horizontally arranged, and there is at least one inclined segment connecting the two. In this way, each flow channel 100 is formed by alternating horizontal and inclined segments, which slows down the forward speed of reagents and blood, which is beneficial for CTC cells to be captured while being dispersed, thereby improving the enrichment effect of CTC cells.

[0062] As an alternative embodiment, the intermediate section 200 comprises alternating inclined sections and horizontal sections, and the inclined sections connected with the liquid inlet section 101 and the liquid outlet section 102. The angle between the inclined section and the horizontal direction is 30°-60°, or 120°-150°.

[0063] The arrangement of the intermediate section 200 can be set according to actual needs, which can include only one inclined section, or multiple inclined sections and horizontal sections, as long as the overall flow channel 100 is connected by alternating inclined sections and horizontal sections. The angle between the inclined section and the horizontal direction is preferably 45°, so that the resistance is appropriate when the liquid flow changes direction, and it will not be too large to cause accumulation, nor too small to slow down the speed, thereby facilitating the CTC cell to stay and be captured.

[0064] As an alternative embodiment, the center axis of the nth horizontal section is parallel to the center axis of the n+1th horizontal section, and the center axis of the nth horizontal section is coincident with the center axis of the n+2th horizontal section. In this way, the two inclined sections at both ends of the same horizontal section will be inclined in different directions, and the sum of the angles between the two inclined sections and the horizontal direction is preferably 180°, which can better utilize the limited space and avoid excessive width of the reaction zone 7.

[0065] As an alternative embodiment, the sum of the angles between the nth inclined section and the n+1th inclined section and the horizontal direction is 180°; the angles between the nth inclined section and the n+2th inclined section and the horizontal direction are the same, i.e., the nth inclined section and the n+2th inclined section are parallel.

[0066] As a specific scheme, as shown in Figure 3 the flow channel 100 comprises, in sequence, a liquid inlet section 101, a first inclined section 201, a first horizontal section 202, a second inclined section 203, a second horizontal section 204, a third inclined section 205, and a liquid outlet section 102. The liquid inlet section 101 and the liquid outlet section 102 are both horizontally arranged. The first horizontal section 202 and the second horizontal section 204 both extend along the horizontal direction, the center axis of the liquid inlet section 101 is parallel to but not coincident with the center axis of the first horizontal section 202, and the center axis of the second horizontal section 204 is coincident with the center axis of the liquid inlet section 101. The angle between the first inclined section 201 and the horizontal direction is 45 degrees, the angle between the second inclined section 203 and the horizontal direction is 135 degrees, and the angle between the third inclined section 205 and the horizontal direction is 45 degrees.

[0067] The above scheme is an example of the arrangement of the flow channel 100, and the number of inclined sections and horizontal sections can be set according to the length of the reaction zone 7 and other specific needs.

[0068] As shown in Figure 1 and Figure 4As shown, the liquid inlet of the utility model includes first liquid inlet 3 and second liquid inlet 4, first liquid inlet 3 is reagent liquid inlet, and second liquid inlet 4 is blood liquid inlet. The structure of two liquid inlets is same, and is adjacent. Blood is inputted into reaction tank 2 through blood liquid inlet, and all reagents except blood are inputted through reagent liquid inlet. First liquid inlet 3 is connected with first liquid inlet pipe 9, and second liquid inlet 4 is connected with second liquid inlet pipe 10.

[0069] 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 liquid inlet / liquid inlet pipe.

[0070] Due to contact with blood, the contaminated part needs to be discarded each time after use, and the material quality of the connecting pipe is required to be high, and the cost is high. If blood and reagent are inputted through the same inlet, the replacement frequency of the connecting pipe is high after being contaminated and corroded. In order to reduce the consumption of materials, therefore, reagent liquid inlet and blood liquid inlet are respectively arranged at one end of reaction tank 2, so as to facilitate blood and reagent to be added from different liquid inlets. The connecting pipe at the blood liquid inlet does not contact the reagent, reduces the requirement for material corrosion resistance, and can use low-cost consumables. The connecting pipe at the reagent liquid inlet is high in cost, but is not contaminated by blood and can be repeatedly used, so as to avoid contamination and reduce material consumption.

[0071] As a preferred embodiment, the center line of first liquid inlet 3 and second liquid inlet 4 is parallel to or coincides with the center line of the length direction of reaction tank 2. In this way, blood and reagent can flow to reaction tank 2 more quickly and uniformly, which is beneficial to the screening of CTC cells.

[0072] The liquid inlet is provided with a liquid inlet pipe, and the liquid outlet is provided with a liquid outlet pipe. The setting mode of the liquid inlet pipe and the liquid outlet pipe can be set as required, which can be fixedly arranged on the body or the cover plate.

[0073] As an embodiment, as shown in Figure 1 and Figure 4 As shown in the embodiment of the utility model, one end of reaction tank 2 is provided with a support table 7, first liquid inlet 3 and second liquid inlet 4 are arranged on the support table, and first liquid inlet pipe 9 and second liquid inlet pipe 10 are connected respectively. The inside of support table 6 is provided with a hollow space, and the hollow space is communicated with reaction tank 2; the liquid inlet is communicated with the hollow space of support table 6, and the liquid entering through the liquid inlet enters reaction tank 2 through the hollow space of support table 6. First liquid inlet 3 and second liquid inlet 4 are both communicated with the hollow space of support table 6.

[0074] The support table 6 can be formed by any mode, for example, can be integrally formed with the body 1, or can be separately arranged and then fixedly connected with the body 1.

[0075] In addition, further, the other end of the reaction tank liquid can also be provided with the support table 6, the support table 6 is provided with the liquid outlet 5, the liquid outlet pipe is fixedly arranged on the support table, the support table 6 is hollowly arranged, and the side towards 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 6 and be discharged from the liquid outlet 5 and the liquid outlet pipe 11.

[0076] The cover plate is provided with a through hole, when the cover plate covers the body, the liquid inlet pipe and the liquid outlet pipe 11 pass through the corresponding through holes respectively; the liquid inlet pipe and the liquid outlet pipe 11 are both sealingly fixed with the cover plate.

[0077] 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 forms the liquid inlet, the lower end of the liquid outlet pipe forms the liquid outlet, and the liquid inlet and the liquid outlet are both communicated with the reaction tank respectively.

[0078] In addition, in order to enable the blood and reagent added into the reaction tank 2 to be directionally and quickly moved to the liquid outlet 5, the liquid outlet 5 is provided with a driving device for driving the liquid to be directionally moved from the liquid inlet to the liquid outlet 5; the driving device is a negative pressure suction device.

[0079] The above is only a preferred embodiment of the utility model, and does not limit the utility model in any form, although the utility model has been disclosed as above, however, it is not used to limit the utility model, any skilled person in the art can make some changes or modifications to the above-mentioned technical content without departing from the technical scheme of the utility model, and equivalent embodiments with equivalent changes are obtained, but as long as the content of the utility model is not deviated, any simple modification, equivalent change and modification of the above-mentioned embodiments according to the technical essence of the utility model are still within the scope of the utility model.

Claims

1. A physicochemical sieve for circulating tumor cells, characterized in that, The device includes a main body, which contains a reaction tank. One end of the reaction tank has at least two liquid inlets, and the other end has a liquid outlet. Multiple reaction zones are provided between the liquid inlets and the liquid outlet, and the width of each reaction zone gradually decreases along the direction from the liquid inlet to the liquid outlet.

2. The circulating tumor cell physicochemical sieve according to claim 1, characterized in that, Along the direction from the inlet to the outlet, in two adjacent reaction zones, the width of the downstream reaction zone is 70%-85% of the width of the upstream reaction zone.

3. The circulating tumor cell physicochemical sieve according to claim 1, characterized in that, Each reaction zone has multiple flow channels, and the width of the flow channels in each reaction zone gradually decreases along the direction from the inlet to the outlet.

4. The circulating tumor cell physicochemical sieve according to claim 3, characterized in that, Along the direction from the inlet to the outlet, in two adjacent reaction zones, the width of the flow channel in the downstream reaction zone is 65%-75% of the width of the flow channel in the upstream reaction zone.

5. The circulating tumor cell physicochemical sieve according to claim 3, characterized in that, Along the direction from the inlet to the outlet, the number of flow channels in each reaction zone gradually decreases.

6. The circulating tumor cell physicochemical sieve according to any one of claims 3-5, characterized in that, Multiple flow channels in each reaction zone are arranged in parallel, and each flow channel includes an inlet section, an outlet section, and an intermediate section located between the two. The inlet section and the outlet section are arranged in a horizontal direction, and the intermediate section includes at least one inclined section that is set at a certain angle to the horizontal direction.

7. The circulating tumor cell physicochemical sieve according to claim 6, characterized in that, The intermediate section includes alternating inclined and horizontal sections, and the sections connected to the inlet and outlet sections are all inclined sections.

8. The circulating tumor cell physicochemical sieve according to claim 6, characterized in that, The angle between the inclined segment and the horizontal direction is 30°-60° or 120°-150°.

9. The circulating tumor cell physicochemical sieve according to claim 7, characterized in that, The central axes of the nth horizontal segment and the (n+1)th horizontal segment are set parallel to each other, and the central axes of the nth horizontal segment and the (n+2)th horizontal segment coincide.

10. The circulating tumor cell physicochemical sieve according to claim 1, characterized in that, A connecting region is provided between two adjacent reaction zones, and no flow channel is provided in the connecting region.

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