Rare cell capturing instrument

Abstract

The invention relates to the technical field of medical instruments, and provides a rare cell capturing instrument. The rare cell capturing instrument comprises a cell capturing instrument main body, at least one micro-fluidic chip and a fluid control unit, the cell capturing instrument main body is provided with a blood sample accommodating cavity, at least one culture medium accommodating cavity, a dyeing cavity, a rare cell collecting cavity and a waste liquid accommodating cavity; the micro-fluidic chip is arranged on the cell capturing instrument main body and is provided with a first port, a second port, a third port and a fourth port; the blood sample accommodating cavity, the culture medium accommodating cavity, the dyeing cavity, the rare cell collecting cavity and the waste liquid accommodating cavity are communicated with the first opening to the fourth opening through the fluid control unit; the fluid control unit is used for controlling liquid in the blood sample accommodating cavity, the dyeing cavity and the at least one culture medium accommodating cavity to flow to the rare cell collecting cavity and the waste liquid accommodating cavity through the micro-fluidic chip. The technical problems that in the prior art, a rare cell capturing instrument is large in operation difficulty and low in operation efficiency are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a rare cell capture device. Background Art

[0002] The rare cell capture instrument is a device used to capture, identify and collect circulating rare cells (CRCs).

[0003] Circulating rare cells can be, for example, circulating tumor cells (CTCs), circulating stem cells (CSCs) and circulating fetal cells (CFCs). Circulating rare cells play an important role in disease diagnosis, condition analysis and confirmation of therapeutic targets, so they are efficiently captured and collected to obtain high-purity and high-activity circulating rare cells for downstream protein characterization.

[0004] However, the existing technology is mainly used in laboratories, and operators are required to be familiar with microfluidic chips. Therefore, the professional requirements for operators are high and the operation is difficult. In addition, if functions such as capture and collection are to be realized, operators are required to spend time manually capturing and collecting respectively, thereby affecting the operator's operating efficiency. Summary of the invention

[0005] The present invention provides a rare cell capture instrument, which is used to solve the technical problems of difficult operation and low operation efficiency of the rare cell capture instrument in the prior art.

[0006] The present invention provides a rare cell capture instrument, comprising a cell capture instrument body, at least one microfluidic chip and a fluid control unit; the cell capture instrument body has at least one blood sample accommodating chamber, at least one culture medium accommodating chamber, a staining chamber, a rare cell collection chamber and a waste liquid accommodating chamber; the microfluidic chip is arranged on the cell capture instrument body, and has a first port, a second port, a third port and a fourth port; the blood sample accommodating chamber, the culture medium accommodating chamber, the staining chamber, the rare cell collection chamber and the waste liquid accommodating chamber are connected from the first port to the fourth port through the fluid control unit, and the fluid control unit is used to control the liquid in the blood sample accommodating chamber, the staining chamber and at least one culture medium accommodating chamber to flow to the microfluidic chip, so as to capture, stain and collect rare cells.

[0007] According to one embodiment of the present invention, there are two culture medium accommodating chambers, namely a first culture medium accommodating chamber and a second culture medium accommodating chamber; the cell capture instrument body includes a supporting unit, at least one blood sample tube, a first culture medium tube, a second culture medium tube, a staining tube, at least one collecting tube and a waste liquid tube; the supporting unit has a blood sample tube interface, a first culture medium tube interface, a second culture medium tube interface, a staining tube interface, a collecting tube interface and a waste liquid tube interface; the blood sample tube is arranged on the blood sample tube interface, and the blood sample accommodating chamber is arranged on the blood sample tube; the first culture medium tube is arranged on the first culture medium tube interface, and the first culture medium accommodating chamber is arranged on the first culture medium tube; the second culture medium tube is arranged on the second culture medium tube interface, and the second culture medium accommodating chamber is arranged on the second culture medium tube; the staining tube is arranged on the staining tube interface, and the staining chamber is arranged on the staining tube; the collecting tube is arranged on the collecting tube interface, and the rare cell collecting chamber is arranged on the collecting tube; the waste liquid tube is arranged on the waste liquid tube interface, and the waste liquid accommodating chamber is arranged on the waste liquid tube.

[0008] According to one embodiment of the present invention, the fluid control unit includes a controller, an air pump and a fluid control mechanism; the controller is connected to the air pump and the fluid control mechanism; the air pump has an inlet and an outlet, and the outlet of the air pump is connected to the fluid control mechanism; there are multiple microfluidic chips, blood sample tubes, and collection tubes, and one microfluidic chip corresponds to one blood sample tube and one collection tube; the blood sample tube, the first culture medium tube, the second culture medium tube, the staining tube, the collection tube and the waste liquid tube are connected to the microfluidic chip through the fluid control mechanism.

[0009] According to one embodiment of the present invention, the fluid control mechanism includes an air circuit control structure and multiple liquid circuit control structures; the air pump is connected to the air inlet of the blood sample tube, the air inlet of the first culture medium tube, the air inlet of the second culture medium tube and the air inlet of the staining tube through the air circuit control structure; one microfluidic chip, one blood sample tube and one collecting tube correspond to one liquid circuit control structure; the liquid outlet of the blood sample tube, the liquid outlet of the first culture medium tube, the liquid outlet of the second culture medium tube, the liquid outlet of the staining tube, the liquid inlet of the collecting tube and the liquid inlet of the waste liquid tube are connected to the microfluidic chip through the liquid circuit control structure.

[0010] According to one embodiment of the present invention, the air circuit control structure includes an air circuit assembly and an air circuit control assembly; the air pump connects the air inlet of each blood sample tube, the air inlet of the first culture medium tube, the air inlet of the second culture medium tube and the air inlet of the staining tube through the air circuit assembly; the air circuit control assembly is arranged on the air circuit assembly to control the circulation of gas.

[0011] According to one embodiment of the present invention, the air circuit assembly includes a first air circuit pipeline, a second air circuit pipeline, a third air circuit pipeline, and a fourth air circuit pipeline; the outlet of the air pump is connected to the air inlet of each blood sample tube through the first air circuit pipeline; the outlet of the air pump is connected to the air inlet of the first culture medium tube through the second air circuit pipeline; the outlet of the air pump is connected to the air inlet of the second culture medium tube through the third air circuit pipeline; the outlet of the air pump is connected to the air inlet of the staining tube through the fourth air circuit pipeline; the air circuit control assembly includes a first solenoid valve, a second solenoid valve, a third solenoid valve and a fourth solenoid valve connected to the controller; the first solenoid valve is arranged on the first air circuit pipeline; the second solenoid valve is arranged on the second air circuit pipeline; the third solenoid valve is arranged on the third air circuit pipeline; the fourth solenoid valve is arranged on the fourth air circuit pipeline.

[0012] According to one embodiment of the present invention, the liquid circuit control structure includes a liquid circuit component and a liquid circuit control component; each blood sample tube, the first culture medium tube, the second culture medium tube, the staining tube, each collection tube and the waste liquid tube are connected to the microfluidic chip through the liquid circuit component, and the liquid circuit component is used to transport liquid; the liquid circuit control component is arranged on the liquid circuit component to control the circulation of liquid.

[0013] According to one embodiment of the present invention, the liquid circuit component includes a plurality of first liquid circuit pipelines, a plurality of second liquid circuit pipelines, a plurality of third liquid circuit pipelines, a plurality of fourth liquid circuit pipelines, a plurality of fifth liquid circuit pipelines and a plurality of sixth liquid circuit pipelines; a blood sample tube, a first liquid circuit pipeline; the liquid circuit control component includes a plurality of first one-way valves, a plurality of second one-way valves, a plurality of third one-way valves, a plurality of fourth one-way valves, a plurality of first three-way valves and a plurality of second three-way valves connected to the controller; the liquid outlet of the blood sample tube is connected to the first port through the corresponding first liquid circuit pipeline; the first one-way valve is arranged on the corresponding first liquid circuit pipeline; the liquid outlet of the first culture medium tube is connected to the third port through the corresponding second liquid circuit pipeline; the second one-way valve The valve is arranged on the corresponding second liquid circuit pipeline; the liquid outlet of the second culture medium tube is connected to the upper port of the first three-way valve through the corresponding third liquid circuit pipeline, the lower port of the first three-way valve is connected to the upper port of the corresponding second three-way valve, and the lower port of the second three-way valve is connected to the corresponding second port; the third one-way valve is arranged on the corresponding second culture medium tube; the liquid outlet of the staining tube is connected to the side port of the corresponding first three-way valve through the corresponding fourth liquid circuit pipeline; the liquid inlet of the collection tube is connected to the side port of the corresponding second three-way valve through the corresponding fifth liquid circuit pipeline; the two liquid inlets of the waste liquid tube are respectively connected to the fourth port of each microfluidic chip through the corresponding sixth liquid circuit pipeline; the fourth one-way valve is arranged on the corresponding sixth liquid circuit pipeline.

[0014] According to one embodiment of the present invention, the rare cell capture instrument has a pretreatment state and a capture state; in the pretreatment state, phosphate buffer is contained in the blood sample tube, the first culture medium tube and the second culture medium tube, and the controller can start the air pump, the first solenoid valve to the third solenoid valve, the first one-way valve, the second one-way valve and the third one-way valve, connect the upper port of the first three-way valve and the lower port of the first three-way valve, connect the upper port of the second three-way valve and the lower port of the second three-way valve, and close the fourth solenoid valve and the fourth one-way valve; in the capture state, a blood sample is contained in the blood sample tube, and culture medium is contained in the first culture medium tube and the second culture medium tube, and the controller can start the air pump, the first solenoid valve, the first one-way valve, the second solenoid valve, the second one-way valve, the third solenoid valve, the third one-way valve, the fourth one-way valve, connect the upper port of the first three-way valve and the lower port of the first three-way valve, connect the upper port of the second three-way valve and the lower port of the second three-way valve, and close the fourth solenoid valve.

[0015] According to one embodiment of the present invention, the rare cell capture instrument also has a staining state and a collection state; in the staining state, the staining tube contains a dye, and the controller can start the air pump, the fourth solenoid valve and the fourth one-way valve, connect the lower port of the first three-way valve and the side port of the first three-way valve, connect the upper port of the second three-way valve and the lower port of the second three-way valve, and close the first solenoid valve to the third solenoid valve; in the collection state, the first culture medium tube contains culture medium, and the controller can start the air pump, the second solenoid valve and the second one-way valve, connect the lower port of the second three-way valve and the side port of the second three-way valve, and close the first solenoid valve, the third solenoid valve and the fourth solenoid valve.

[0016] The characteristics and advantages of the rare cell capture device of the present invention are: The blood sample holding chamber can hold a blood sample, so as to facilitate the subsequent capture of the blood sample from the blood sample by a microfluidic chip. The culture medium holding chamber can hold a culture medium. The staining chamber can hold a stain (such as an antibody). The rare cell collection chamber can collect rare cells. The waste liquid holding chamber can collect waste liquid (such as blood without rare cells). Rare cells can be captured by means of a microfluidic chip. The fluid control unit is used to control the liquid in the blood sample holding chamber, the culture medium holding chamber and the staining chamber to flow through the microfluidic chip. When the blood sample enters the microfluidic chip, the microfluidic chip can capture the rare cells. If the rare cells in the microfluidic chip flow into the rare cell collection chamber, the collection of the rare cells is realized. If the staining chamber The agent enters the microfluidic chip, and the rare cells in the microfluidic chip can be stained; in summary, the present invention can achieve the capture, staining and collection of rare cells; because the present invention relies on the cell capture instrument body, at least one microfluidic chip and a fluid control unit to achieve the capture, staining and collection of rare cells, in specific applications, it can be achieved by controlling the fluid control unit, and the operator does not need to be familiar with the internal working principles of the microfluidic chip and the fluid control unit. Therefore, compared with the prior art, the professional requirements for the operator are lower, the operation difficulty is less, and it can be completed automatically by relying on the rare cell capture instrument, and the operator does not need to spend time manually capturing and collecting separately, so the operation efficiency can be improved. Solve the technical problems of the rare cell capture instrument in the prior art that the operation is difficult and the operation efficiency is low. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0018] Figure 1 It is a three-dimensional schematic diagram of the rare cell capture device of the present invention.

[0019] Figure 2 is a schematic diagram of an embodiment of a fluid control unit of the present invention, Figure 2 In the figure, the microfluidic chip is one.

[0020] Figure 3 is a schematic diagram of another embodiment of the fluid control unit of the present invention, Figure 3 In the method, there are multiple microfluidic chips.

[0021] Figure 4 It is a control principle diagram of the controller of the present invention.

[0022] Reference numerals: 100, cell capture instrument body; 110, support unit; 120, blood sample tube; 130, first culture medium tube; 140, second culture medium tube; 150, staining tube; 160, collection tube; 170, waste liquid tube; 200, microfluidic chip; 300, fluid control unit; 310, controller; 320, air pump; 330, fluid control mechanism; 331, air path control structure; 3310, air path assembly; 3311, first air path pipeline; 3312, second air path pipeline; 3313, third air path pipeline; 3314, fourth air path pipeline; 3301, air path control assembly; H1, first solenoid valve; H2, second solenoid valve; H3, third solenoid valve; H4, fourth solenoid valve; P1, The first air pressure sensor; P2, the second air pressure sensor; P3, the third air pressure sensor; P4, the fourth air pressure sensor; R1, the first gas pressure regulating valve; R2, the second gas pressure regulating valve; R3, the third gas pressure regulating valve; R4, the fourth gas pressure regulating valve; 332, the liquid circuit control structure; 3320, the liquid circuit assembly; 3321, the first liquid circuit pipeline; 3322, the second liquid circuit pipeline; 3323, the third liquid circuit pipeline; 3324, the fourth liquid circuit pipeline; 3325, the fifth liquid circuit pipeline; 3326, the sixth liquid circuit pipeline; 3302, the liquid circuit control assembly; S1, the first single-way valve; S2, the second single-way valve; S3, the third single-way valve; S4, the fourth single-way valve; T1, the first three-way valve; T2, the second three-way valve. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be clearly and completely described below in conjunction with the drawings of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] In the description of the present embodiment, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present embodiment and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present embodiment.

[0025] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of this embodiment, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0026] In this embodiment, unless otherwise clearly specified and limited, the terms "set", "install", "connect", "connect", "fix" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection or a connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in this embodiment can be understood according to specific circumstances.

[0027] In the embodiments of the present invention, unless otherwise clearly specified and limited, the first feature being "above" or "below" the second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature being "above", "above" and "above" the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. The first feature being "below", "below" and "below" the second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0028] Figures 1 to 4 The rare cell capture instrument provided by the present invention is shown. As can be seen from the figure, the present invention provides a rare cell capture instrument, including a cell capture instrument body 100, at least one microfluidic chip 200 and a fluid control unit 300; the cell capture instrument body 100 has at least one blood sample accommodating chamber, at least one culture medium accommodating chamber, a staining chamber, a rare cell collection chamber and a waste liquid accommodating chamber; the microfluidic chip 200 is arranged on the cell capture instrument body 100, and has a first port, a second port, a third port and a fourth port, and the order of the first port, the second port, the third port and the fourth port can be arranged in sequence from right to left along the microfluidic chip 200 in the figure; the blood sample accommodating chamber, the culture medium accommodating chamber, the staining chamber, the rare cell collection chamber and the waste liquid accommodating chamber are connected from the first port to the fourth port through the fluid control unit 300, and the fluid control unit 300 is used to control the liquid in the blood sample accommodating chamber, the staining chamber and at least one culture medium accommodating chamber to flow to the microfluidic chip 200 to capture, stain and collect rare cells.

[0029] In a specific implementation, the blood sample holding chamber can hold a blood sample, so as to facilitate the subsequent capture of the blood sample from the blood sample through the microfluidic chip 200, the culture medium holding chamber can hold the culture medium, the staining chamber can hold the stain (such as an antibody), the rare cell collection chamber can collect rare cells, and the waste liquid holding chamber can collect waste liquid (such as blood without rare cells). The rare cells can be captured by the microfluidic chip 200, and the fluid control unit 300 is used to control the liquid in the blood sample holding chamber, the culture medium holding chamber and the staining chamber to flow through the microfluidic chip 200, wherein when the blood sample enters the microfluidic chip 200, the microfluidic chip 200 can capture the rare cells; if the rare cells in the microfluidic chip 200 flow into the rare cell collection chamber, the collection of the rare cells is realized; if The dye enters the microfluidic chip 200, and the rare cells in the microfluidic chip 200 can be stained. In summary, the present invention can achieve the capture, staining and collection of rare cells. Since the present invention relies on the cell capture instrument body 100, at least one microfluidic chip 200 and the fluid control unit 300 to achieve the capture, staining and collection of rare cells, in specific applications, the fluid control unit 300 can be controlled, and the operator does not need to be familiar with the internal working principle of the microfluidic chip 200 and the fluid control unit 300. Therefore, compared with the prior art, the professional requirements for the operator are lower, the operation difficulty is less, and it can be automatically completed by relying on the rare cell capture instrument, and the operator does not need to spend time manually capturing and collecting separately, so the operation efficiency can be improved. Solve the technical problems of the rare cell capture instrument in the prior art that the operation is difficult and the operation efficiency is low.

[0030] In this embodiment, according to one embodiment of the present invention, there are two culture medium accommodating chambers, namely a first culture medium accommodating chamber and a second culture medium accommodating chamber; the cell capture instrument body 100 includes a support unit, at least one blood sample tube 120, a first culture medium tube 130, a second culture medium tube 140, a dyeing tube 150, at least one collection tube 160 and a waste liquid tube 170; the support unit has a blood sample tube interface, a first culture medium tube interface, a second culture medium tube interface, a dyeing tube interface, a collection tube interface and a waste liquid tube interface; the blood sample tube 120 is arranged on the blood sample tube interface, and the blood sample The sample accommodating chamber is arranged on the blood sample tube 120; the first culture medium tube 130 is arranged on the first culture medium tube interface, and the first culture medium accommodating chamber is arranged on the first culture medium tube 130; the second culture medium tube 140 is arranged on the second culture medium tube interface, and the second culture medium accommodating chamber is arranged on the second culture medium tube 140; the staining tube 150 is arranged on the staining tube interface, and the staining chamber is arranged on the staining tube 150; the collecting tube 160 is arranged on the collecting tube interface, and the rare cell collecting chamber is arranged on the collecting tube 160; the waste liquid tube 170 is arranged on the waste liquid tube interface, and the waste liquid accommodating chamber is arranged on the waste liquid tube 170.

[0031] According to one embodiment of the present invention, the fluid control unit 300 includes a controller 310, an air pump 320 and a fluid control mechanism 330; the controller 310 is connected to the air pump 320 and the fluid control mechanism 330; the air pump 320 has an inlet and an outlet, and the outlet of the air pump 320 is connected to the fluid control mechanism 330; there are multiple microfluidic chips 200, blood sample tubes 120, and collection tubes 160, and one microfluidic chip 200 corresponds to one blood sample tube 120 and one collection tube 160; the blood sample tube 120, the first culture medium tube 130, the second culture medium tube 140, the staining tube 150, the collection tube 160 and the waste liquid tube 170 are connected to the microfluidic chip 200 through the fluid control mechanism 330.

[0032] In this embodiment, the fluid control mechanism 330 includes an air circuit control structure 331 and multiple liquid circuit control structures 332; the air pump 320 is connected to the air inlet of the blood sample tube 120, the air inlet of the first culture medium tube 130, the air inlet of the second culture medium tube 140 and the air inlet of the staining tube 150 through the air circuit control structure 331; one microfluidic chip 200, one blood sample tube 120 and one collection tube 160 correspond to one liquid circuit control structure 332; the liquid outlet of the blood sample tube 120, the liquid outlet of the first culture medium tube 130, the liquid outlet of the second culture medium tube 140, the liquid outlet of the staining tube 150, the liquid inlet of the collection tube 160 and the liquid inlet of the waste liquid tube 170 are connected to the microfluidic chip 200 through the liquid circuit control structure 332.

[0033] According to one embodiment of the present invention, there may be multiple microfluidic chips, thereby enabling multiple operations to be performed simultaneously, thereby improving throughput and efficiency.

[0034] According to one embodiment of the present invention, the air circuit control structure 331 includes an air circuit component 3310 and an air circuit control component 3311; the air pump 320 is connected to the air inlet of each blood sample tube 120, the air inlet of the first culture medium tube 130, the air inlet of the second culture medium tube 140 and the air inlet of the staining tube 150 through the air circuit component 3310; the air circuit control component 3311 is arranged on the air circuit component 3310 to control the circulation of gas.

[0035] According to one embodiment of the present invention, the air circuit control component 3311 may also include a first air pressure sensor P1, a second air pressure sensor P2, a third air pressure sensor P3 and a fourth air pressure sensor P4 connected to the controller 310; the first air pressure sensor P1 is arranged on the first air circuit pipeline 3311, the second air pressure sensor P2 is arranged on the second air circuit pipeline 3312, the third air pressure sensor P3 is arranged on the third air circuit pipeline 3313, and the fourth air pressure sensor P4 is arranged on the fourth air circuit pipeline 3314.

[0036] In this embodiment, the gas circuit control component 3311 may also include a first gas pressure regulating valve R1, a second gas pressure regulating valve R2, a third gas pressure regulating valve R3 and a fourth gas pressure regulating valve R4 connected to the controller 310. The first gas pressure regulating valve R1 is arranged on the first liquid circuit pipeline 3321, the second gas pressure regulating valve R2 is arranged on the second liquid circuit pipeline 3322, the third gas pressure regulating valve R3 is arranged on the third liquid circuit pipeline 3323, and the fourth gas pressure regulating valve R4 is arranged on the fourth liquid circuit pipeline 3324. The first gas pressure regulating valve R1 can be opened at the same time as the first solenoid valve H1, the second gas pressure regulating valve R2 can be opened at the same time as the second solenoid valve H2, the third gas pressure regulating valve R3 can be opened at the same time as the third solenoid valve H3, and the fourth gas pressure regulating valve R4 can be opened at the same time as the fourth solenoid valve H4.

[0037] It can be understood that the air pressure (gas) can be delivered to the corresponding solenoid valve only after the pressures of the first gas pressure regulating valve R1 to the fourth gas pressure regulating valve R4 are set and opened, that is, the first gas pressure regulating valve R1 corresponds to the first solenoid valve H1, and the first air pressure sensor P1 is used to detect whether the air pressure on the first gas pipeline 3311 meets the pressure set by the first gas pressure regulating valve R1; the second gas pressure regulating valve R2 corresponds to the second solenoid valve H2, and the second air pressure sensor P2 is used to detect whether the air pressure on the second gas pipeline 3312 meets the pressure set by the second gas pressure regulating valve R2; the third gas pressure regulating valve R3 corresponds to the third solenoid valve H3, and the third air pressure sensor P3 is used to detect whether the air pressure on the third gas pipeline 3313 meets the pressure set by the third gas pressure regulating valve R3; the fourth gas pressure regulating valve R4 corresponds to the fourth solenoid valve H4, and the fourth air pressure sensor P4 is used to detect whether the air pressure on the fourth gas pipeline 3314 meets the pressure set by the fourth gas pressure regulating valve R4.

[0038] According to one embodiment of the present invention, the gas circuit assembly 3310 includes a first gas circuit pipeline 3311, a second gas circuit pipeline 3312, a third gas circuit pipeline 3313, and a fourth gas circuit pipeline 3314; the outlet of the air pump 320 is connected to the gas inlet of each blood sample tube 120 through the first gas circuit pipeline 3311; the outlet of the air pump 320 is connected to the gas inlet of the first culture medium tube 130 through the second gas circuit pipeline 3312; the outlet of the air pump 320 is connected to the gas inlet of the second culture medium tube 140 through the third gas circuit pipeline 3313 ; The outlet of the air pump 320 is connected to the air inlet of the dyeing tube 150 through the fourth air circuit pipeline 3314; the air circuit control component 3311 includes a first solenoid valve H1, a second solenoid valve H2, a third solenoid valve H3 and a fourth solenoid valve H4 connected to the controller 310; the first solenoid valve H1 is arranged on the first air circuit pipeline 3311; the second solenoid valve H2 is arranged on the second air circuit pipeline 3312; the third solenoid valve H3 is arranged on the third air circuit pipeline 3313; the fourth solenoid valve H4 is arranged on the fourth air circuit pipeline 3314.

[0039] According to one embodiment of the present invention, the liquid circuit control structure 332 includes a liquid circuit component 3320 and a liquid circuit control component 3321; each blood sample tube 120, the first culture medium tube 130, the second culture medium tube 140, the staining tube 150, each collection tube 160 and the waste liquid tube 170 are connected to the microfluidic chip 200 through the liquid circuit component 3320, and the liquid circuit component 3320 is used to transport liquid; the liquid circuit control component 3321 is arranged on the liquid circuit component 3320 to control the circulation of liquid.

[0040] In this embodiment, the liquid circuit component 3320 includes multiple first liquid circuit pipelines 3321, multiple second liquid circuit pipelines 3322, multiple third liquid circuit pipelines 3323, multiple fourth liquid circuit pipelines 3324, multiple fifth liquid circuit pipelines 3325 and multiple sixth liquid circuit pipelines 3326; a blood sample tube 120, a first liquid circuit pipeline 3321; the liquid circuit control component 3321 includes multiple first single-way valves S1, multiple second single-way valves S2, multiple third single-way valves S3, multiple fourth single-way valves S4, multiple first three-way valves T1 and multiple second three-way valves T2 connected to the controller 310; the liquid outlet of the blood sample tube 120 is connected to the first port through the corresponding first liquid circuit pipeline 3321; the first single-way valve S1 is set on the corresponding first liquid circuit pipeline 3321; the liquid outlet of the first culture medium tube 130 is connected to the third port through the corresponding second liquid circuit pipeline 3322 ; The second one-way valve S2 is arranged on the corresponding second liquid circuit pipeline 3322; the liquid outlet of the second culture medium tube 140 is connected to the upper port of the first three-way valve T1 through the corresponding third liquid circuit pipeline 3323, the lower port of the first three-way valve T1 is connected to the upper port of the corresponding second three-way valve T2, and the lower port of the second three-way valve T2 is connected to the corresponding second port; the third one-way valve S3 is arranged on the corresponding second culture medium tube 140; the liquid outlet of the staining tube 150 is connected to the side port of the corresponding first three-way valve T1 through the corresponding fourth liquid circuit pipeline 3324; the liquid inlet of the collection tube 160 is connected to the side port of the corresponding second three-way valve T2 through the corresponding fifth liquid circuit pipeline 3325; the two liquid inlets of the waste liquid tube 170 are respectively connected to the fourth port of each microfluidic chip 200 through the corresponding sixth liquid circuit pipeline 3326; the fourth one-way valve S4 is arranged on the corresponding sixth liquid circuit pipeline 3326.

[0041] According to one embodiment of the present invention, the rare cell capture instrument has a pre-treatment state, a capture state, a staining state and a collection state. In the pre-treatment state, the capture state, the staining state and the collection state, the pressure of the corresponding pressure regulating valve (the first gas pressure regulating valve R1 to the fourth gas pressure regulating valve R4) can be set; for example, in the pre-treatment state, the first gas pressure regulating valve R1, the second gas pressure regulating valve R2, and the third gas pressure regulating valve R3 are all set to 1500 mbar; in the capture state, the gas pressure of the first gas pressure regulating valve R1 can be set to 1000 mbar; in the staining state, the gas pressure of the fourth pressure regulating valve R4 can be set to 1000 mbar; in the collection state, the gas pressure of the second gas pressure regulating valve R2 can be set to 2000 mbar.

[0042] In the following embodiments, the air pump 320 and the first to fourth gas pressure regulating valves R1 to R4 can be kept open all the time, and the pressures of the first to fourth gas pressure regulating valves R1 to R4 can be automatically set and switched according to different processes.

[0043] In the pretreatment state, phosphate buffer is contained in the blood sample tube 120, the first culture medium tube 130 and the second culture medium tube 140, and the controller 310 can open the first solenoid valve H1 to the third solenoid valve H3, the first one-way valve S1, the second one-way valve S2 and the third one-way valve S3, connect the upper port of the first three-way valve T1 and the lower port of the first three-way valve T1, connect the upper port of the second three-way valve T2 and the lower port of the second three-way valve T2, and close the fourth solenoid valve H4 and the fourth one-way valve S4.

[0044] Among them, the phosphate buffer can prevent rare cells from absorbing water and bursting, or prevent rare cells from losing water and shrinking; during pretreatment, the blood sample tube 120, the first culture medium tube 130 and the second culture medium tube 140 are all filled with phosphate buffer. Under the action of the air pump 320, the phosphate buffer in the blood sample tube 120, the first culture medium tube 130 and the second culture medium tube 140 will flow into the microfluidic chip 200. Since the microfluidic chip 200 is air permeable, the phosphate buffer can discharge the gas in the microfluidic chip 200 and fill the microfluidic chip 200 with phosphate buffer, thereby completing the pretreatment.

[0045] In the capture state, the blood sample tube 120 contains a blood sample, the first culture medium tube 130 and the second culture medium tube 140 contain culture medium, and the controller 310 can open the first solenoid valve H1, the first one-way valve S1, the second solenoid valve H2, the second one-way valve S2, the third solenoid valve H3, the third one-way valve S3, the fourth one-way valve S4, the upper port of the first three-way valve T1 and the lower port of the first three-way valve T1, the upper port of the second three-way valve T2 and the lower port of the second three-way valve T2, and close the fourth solenoid valve H4.

[0046] Among them, the blood sample in the blood sample tube 120 flows into the microfluidic chip 200, and the rare cells will be captured by the microfluidic chip 200 after flowing in, and the waste liquid will flow into the waste liquid tube 170; at the same time, the culture medium contained in the first culture medium tube 130 and the second culture medium tube 140 will flow to the microfluidic chip 200, and the culture medium will flush out the blood cells in the microfluidic chip 200 to prevent the blood cells in the microfluidic chip 200 from interfering with the rare cells, and the waste liquid will flow into the waste liquid tube 170.

[0047] In the dyeing state, the dyeing tube 150 contains dye, and the controller 310 can open the fourth solenoid valve H4 and the fourth one-way valve S4, connect the lower port of the first three-way valve T1 and the side port of the first three-way valve T1, connect the upper port of the second three-way valve T2 and the lower port of the second three-way valve T2, and close the first solenoid valve H1 to the third solenoid valve H3.

[0048] The dye will flow into the microfluidic chip 200 to dye the rare cells captured in the microfluidic chip 200 , and the waste liquid will flow into the waste liquid pipe 170 .

[0049] In the collection state, the first culture medium tube 130 contains culture medium, and the controller 310 can open the second solenoid valve H2 and the second one-way valve S2, connect the lower port of the second three-way valve T2 and the side port of the second three-way valve T2, and close the first solenoid valve H1, the third solenoid valve H3 and the fourth solenoid valve H4.

[0050] The culture medium in the reagent tube will flush the rare cells on the microfluidic chip 200 into the collection tube 160 for collection, which can achieve high-throughput collection compared to the prior art.

[0051] In specific implementation, through the above-mentioned structural setting, the present invention can achieve pretreatment, capture, staining and collection.

[0052] In some embodiments, the rare cell capture instrument also has a cleaning state. In the cleaning state, the blood sample tube 120 contains cleaning fluid, that is, the cleaning fluid can be replaced in the blood sample tube 120, and the controller 310 can open the first solenoid valve H1, the first one-way valve S1 and the fourth one-way valve S4, connect the upper port and the lower port of the first three-way valve T1, connect the upper port and the lower port of the second three-way valve T2, close the second solenoid valve H2 to the fourth solenoid valve H4, the second one-way valve S2 and the third one-way valve S3, so that the cleaning fluid can clean the pipeline, and the chip can be removed to flow out after cleaning.

[0053] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "mode", "specific mode", or "some modes" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or mode are included in at least one embodiment or mode of the embodiment of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or mode. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or modes in a suitable manner.

[0054] In addition, in the absence of contradiction, those skilled in the art may combine and combine the different embodiments or methods and the features of different embodiments or methods described in this specification. Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention is described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some of the technical features therein by equivalents; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A rare cell capture device, characterized in that: It comprises a cell capture instrument body (100), at least one microfluidic chip (200) and a fluid control unit (300); The cell capture instrument body (100) has at least one blood sample accommodating chamber, at least one culture medium accommodating chamber, a staining chamber, a rare cell collection chamber and a waste liquid accommodating chamber; The microfluidic chip (200) is arranged on the cell capture instrument body (100), and has a first port, a second port, a third port and a fourth port; The blood sample holding chamber, the culture medium holding chamber, the staining chamber, the rare cell collection chamber and the waste liquid holding chamber are connected from the first port to the fourth port via the fluid control unit (300). The fluid control unit (300) is used to control the liquid in the blood sample holding chamber, the staining chamber and at least one of the culture medium holding chambers to flow toward the microfluidic chip (200) so as to capture, stain and collect rare cells.

2. The rare cell capture instrument according to claim 1, characterized in that: There are two culture medium accommodating chambers, namely a first culture medium accommodating chamber and a second culture medium accommodating chamber; The cell capture instrument body (100) comprises a support unit (110), at least one blood sample tube (120), a first culture medium tube (130), a second culture medium tube (140), a staining tube (150), at least one collection tube (160) and a waste liquid tube (170); The support unit (110) has a blood sample tube interface, a first culture medium tube interface, a second culture medium tube interface, a dyeing tube interface, a collection tube interface and a waste liquid tube interface; The blood sample tube (120) is arranged on the blood sample tube interface, and the blood sample accommodating cavity is arranged on the blood sample tube (120); The first culture medium tube (130) is arranged on the first culture medium tube interface, and the first culture medium accommodating cavity is arranged on the first culture medium tube (130); The second culture medium tube (140) is arranged on the second culture medium tube interface, and the second culture medium accommodating cavity is arranged on the second culture medium tube (140); The dyeing tube (150) is arranged on the dyeing tube interface, and the dyeing cavity is arranged on the dyeing tube (150); The collection tube (160) is arranged on the collection tube interface, and the rare cell collection chamber is arranged on the collection tube (160); The waste liquid pipe (170) is arranged on the waste liquid pipe interface, and the waste liquid accommodating chamber is arranged on the waste liquid pipe (170).

3. The rare cell capture device according to claim 2, characterized in that: The fluid control unit (300) comprises a controller (310), an air pump (320) and a fluid control mechanism (330); The controller (310) is connected to the air pump (320) and the fluid control mechanism (330); The air pump (320) has an inlet and an outlet, and the outlet of the air pump (320) is connected to the fluid control mechanism (330); There are a plurality of the microfluidic chip (200), the blood sample tube (120), and the collection tube (160), and one microfluidic chip (200) corresponds to one blood sample tube (120) and one collection tube (160); The blood sample tube (120), the first culture medium tube (130), the second culture medium tube (140), the staining tube (150), the collection tube (160) and the waste liquid tube (170) are connected to the microfluidic chip (200) via the fluid control mechanism (330).

4. The rare cell capture instrument according to claim 3, characterized in that: The fluid control mechanism (330) comprises a gas path control structure (331) and a plurality of liquid path control structures (332); The air pump (320) is connected to the air inlet of the blood sample tube (120), the air inlet of the first culture medium tube (130), the air inlet of the second culture medium tube (140) and the air inlet of the staining tube (150) through the air path control structure (331); One of the microfluidic chip (200), one of the blood sample tube (120), and one of the collection tubes (160) corresponds to one of the liquid path control structures (332); The liquid outlet of the blood sample tube (120), the liquid outlet of the first culture medium tube (130), the liquid outlet of the second culture medium tube (140), the liquid outlet of the staining tube (150), the liquid inlet of the collection tube (160) and the liquid inlet of the waste liquid tube (170) are connected to the microfluidic chip (200) through the liquid path control structure (332).

5. The rare cell capture device according to claim 4, characterized in that: The gas circuit control structure (331) comprises a gas circuit component (3310) and a gas circuit control component (3301); The air pump (320) is connected to the air inlet of each of the blood sample tubes (120), the air inlet of the first culture medium tube (130), the air inlet of the second culture medium tube (140), and the air inlet of the staining tube (150) through the air path assembly (3310); The gas circuit control component (3301) is arranged on the gas circuit component (3310) and is used to control the flow of gas.

6. The rare cell capture device according to claim 5, characterized in that: The gas circuit assembly (3310) comprises a first gas circuit pipeline (3311), a second gas circuit pipeline (3312), a third gas circuit pipeline (3313), and a fourth gas circuit pipeline (3314); The outlet of the air pump (320) is connected to the air inlet of each of the blood sample tubes (120) through the first air pipeline (3311); The outlet of the air pump (320) is connected to the air inlet of the first culture medium tube (130) through the second air pipeline (3312); The outlet of the air pump (320) is connected to the air inlet of the second culture medium tube (140) through the third air pipeline (3313); The outlet of the air pump (320) is connected to the air inlet of the dyeing tube (150) via the fourth air pipeline (3314); The gas circuit control component (3301) comprises a first solenoid valve (H1), a second solenoid valve (H2), a third solenoid valve (H3) and a fourth solenoid valve (H4) connected to the controller (310); The first solenoid valve (H1) is arranged on the first gas pipeline (3311); The second solenoid valve (H2) is arranged on the second gas pipeline (3312); The third solenoid valve (H3) is arranged on the third gas pipeline (3313); The fourth solenoid valve (H4) is arranged on the fourth gas pipeline (3314).

7. The rare cell capture device according to claim 6, characterized in that: The fluid circuit control structure (332) includes a fluid circuit component (3320) and a fluid circuit control component (3302); Each of the blood sample tubes (120), the first culture medium tube (130), the second culture medium tube (140), the staining tube (150), each of the collection tubes (160) and the waste liquid tube (170) is connected to the microfluidic chip (200) via the liquid path component (3320), and the liquid path component (3320) is used to transport liquid; The liquid circuit control component (3302) is arranged on the liquid circuit component (3320) and is used to control the circulation of the liquid.

8. The rare cell capture device according to claim 7, characterized in that: The liquid circuit assembly (3320) comprises a plurality of first liquid circuit pipelines (3321), a plurality of second liquid circuit pipelines (3322), a plurality of third liquid circuit pipelines (3323), a plurality of fourth liquid circuit pipelines (3324), a plurality of fifth liquid circuit pipelines (3325) and a plurality of sixth liquid circuit pipelines (3326); A blood sample tube (120), and a first liquid pipeline (3321); The fluid circuit control component (3302) comprises a plurality of first one-way valves (S1), a plurality of second one-way valves (S2), a plurality of third one-way valves (S3), a plurality of fourth one-way valves (S4), a plurality of first three-way valves (T1) and a plurality of second three-way valves (T2) connected to the controller (310); The liquid outlet of the blood sample tube (120) is connected to the first port through the corresponding first liquid pipeline (3321); the first one-way valve (S1) is arranged on the corresponding first liquid pipeline (3321); The liquid outlet of the first culture medium tube (130) is connected to the third port through the corresponding second liquid pipeline (3322); the second one-way valve (S2) is arranged on the corresponding second liquid pipeline (3322); The liquid outlet of the second culture medium tube (140) is connected to the upper port of the first three-way valve (T1) through the corresponding third liquid pipeline (3323), the lower port of the first three-way valve (T1) is connected to the corresponding upper port of the second three-way valve (T2), and the lower port of the second three-way valve (T2) is connected to the corresponding second port; the third one-way valve (S3) is arranged on the corresponding second culture medium tube (140); The liquid outlet of the dyeing tube (150) is connected to the corresponding side port of the first three-way valve (T1) through the corresponding fourth liquid pipeline (3324); The liquid inlet of the collecting tube (160) is connected to the corresponding side port of the second three-way valve (T2) through the corresponding fifth liquid pipeline (3325); The two liquid inlets of the waste liquid pipe (170) are respectively connected to the fourth port of each microfluidic chip (200) through the corresponding sixth liquid circuit pipeline (3326); the fourth one-way valve (S4) is arranged on the corresponding sixth liquid circuit pipeline (3326).

9. The rare cell capture device according to claim 8, characterized in that: The rare cell capture instrument has a pre-treatment state and a capture state; In the pretreatment state, phosphate buffer is contained in the blood sample tube (120), the first culture medium tube (130) and the second culture medium tube (140), and the controller (310) can open the air pump (320), the first solenoid valve (H1) to the third solenoid valve (H3), the first one-way valve (S1), the second one-way valve (S2) and the third one-way valve (S3), connect the upper port of the first three-way valve (T1) and the lower port of the first three-way valve (T1), connect the upper port of the second three-way valve (T2) and the lower port of the second three-way valve (T2), and close the fourth solenoid valve (H4) and the fourth one-way valve (S4); In the capture state, the blood sample tube (120) contains a blood sample, the first culture medium tube (130) and the second culture medium tube (140) contain culture medium, and the controller (310) can open the air pump (320), the first solenoid valve (H1), the first one-way valve (S1), the second solenoid valve (H2), the second one-way valve (S2), the third solenoid valve (H3), the third one-way valve (S3), the fourth one-way valve (S4), connect the upper port of the first three-way valve (T1) and the lower port of the first three-way valve (T1), connect the upper port of the second three-way valve (T2) and the lower port of the second three-way valve (T2), and close the fourth solenoid valve (H4).

10. The rare cell capture device according to claim 9, characterized in that: The rare cell capture instrument also has a staining state and a collection state; In the dyeing state, the dyeing tube (150) contains dye, and the controller (310) can open the air pump (320), the fourth solenoid valve (H4) and the fourth one-way valve (S4), connect the lower port of the first three-way valve (T1) and the side port of the first three-way valve (T1), connect the upper port of the second three-way valve (T2) and the lower port of the second three-way valve (T2), and close the first solenoid valve (H1) to the third solenoid valve (H3); In the collection state, the first culture medium tube (130) contains culture medium, and the controller (310) can open the air pump (320), the second solenoid valve (H2) and the second one-way valve (S2), connect the lower port of the second three-way valve (T2) and the side port of the second three-way valve (T2), and close the first solenoid valve (H1), the third solenoid valve (H3) and the fourth solenoid valve (H4).

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