Rapid cell sorting device and sorting system

Abstract

The utility model relates to a rapid cell sorting device and a sorting system. The rapid cell sorting device comprises a sorting device body and is characterized in that a cell sample inlet and a large-particle cell recovery opening are sequentially formed in the sorting device body in the flowing direction of cell liquid; the cell sample inlet is communicated with the large-particle cell recovery port through a flowing channel, a plurality of micropore structures which are larger than the flowing channel in diameter and are communicated by the flowing channel are sequentially arranged on the flowing channel, and a small-particle cell separation channel for shunting small-particle cells is arranged on the wall surface of the last micropore structure; the small-granule cell separation channel is communicated with the small-granule cell separation outlet, and the small-granule cell separation outlet is not communicated with the large-granule cell recovery port. Compared with the prior art, the cell sorting device has the advantages that cells with different diameters can be quickly separated, and the cell sorting speed and efficiency are improved.

Description

Technical Field

[0001] The utility model relates to the technical field of cell sorting, in particular to a rapid cell sorting device and a sorting system. Background Art

[0002] Effective screening and separation of cells is a rapidly developing and deepening research demand in the fields of biology, medicine, and biotechnology. As a key link in cell research, the accuracy and efficiency of cell sorting directly affect the reliability of subsequent experiments and the conversion efficiency of scientific research results. Traditional cell sorting methods often have problems such as slow sorting speed, low efficiency, and complex operation, which cannot meet the needs of scientific research and production. Therefore, the development of a device that can quickly and efficiently sort cells is of great significance to improving scientific research efficiency and promoting the development of biotechnology. Considering the expensiveness and scarcity of biological samples, the development of cell separation devices is very necessary.

[0003] Current commonly used cell sorting methods, such as flow cytometry or fluorescence-activated cell sorting, have significant barriers in terms of convenience due to their high cost, bulky instruments, and time-consuming processes. In addition, the fluorescent labeling process may change the intrinsic properties of cells and cause irreversible cell damage. Magnetic-activated cell sorting is another efficient method based on the immune reaction between cells and antibodies on the surface of magnetic beads, but it is very difficult to separate the bound cells from the magnetic beads, which limits their subsequent culture.

[0004] Label-free and non-invasive cell sorting strategies are a research direction that has attracted much attention in the field of modern cell biology and biotechnology. The core of this strategy is to achieve accurate cell sorting while avoiding the use of markers or damage to cells, thereby ensuring the integrity and function of cells. In label-free cell sorting strategies, sorting mainly relies on the physical properties, morphological characteristics or electrical properties of cells. Among them, microfluidics is an important technical means. Through the design of microfluidic chips, precise manipulation and separation of cells can be achieved. The classification and separation of cells can be achieved by utilizing the fluid mechanics effect, inertial effect or acoustic effect in the microfluidic channel. Using mild fluid dynamics effects for cell sorting can largely maintain the integrity and function of cells.

[0005] CN206799584U discloses a microfluidic cell sorting device, the cell sorting principle of which is mainly to obtain target cells by promoting cell migration factors to adhere to the surface of the corresponding channel. However, it still has the technical problems of complex operation and inability to sort cells of different particle sizes.

[0006] Therefore, a cell sorting device for rapid sorting of cells of different particle sizes remains to be developed. Utility Model Content

[0007] The purpose of the utility model is to provide a cell rapid sorting device and a sorting system in order to overcome the defect of the prior art that cells with different particle sizes cannot be quickly sorted.

[0008] The purpose of the utility model can be achieved through the following technical solutions:

[0009] A cell rapid sorting device comprises a sorting device body, wherein a cell sample inlet and a large particle cell recovery port are sequentially provided on the sorting device body along the flow direction of the cell fluid;

[0010] The cell sample inlet and the large particle cell recovery port are connected through a flow channel, and a plurality of microporous structures having a diameter larger than the flow channel and penetrated by the flow channel are sequentially arranged on the flow channel, and a small particle cell separation channel for diverting small particle cells is arranged on the wall of the last microporous structure;

[0011] The small particle cell separation channel is connected to the small particle cell separation outlet, and the small particle cell separation outlet is not connected to the large particle cell recovery port.

[0012] Furthermore, when the main body of the sorting device is placed horizontally, the level of the cell sample inlet is higher than the large particle cell recovery port, so that cells can be separated continuously and efficiently through the naturally formed drop.

[0013] Furthermore, the main body of the sorting device is equipped with a glass cover that can cover the flow channel to reduce contamination during cell separation.

[0014] Furthermore, the flow channel includes a dispersion channel, a convergence channel and a plurality of branch flow channels communicating therebetween, and the sorting efficiency is improved by the plurality of branch flow channels.

[0015] Furthermore, the cell sample inlet inputs the cell fluid into each branch flow channel through a gradually widening dispersion channel, and the outlet of the branch flow channel collects the large particle cell fluid into the large particle cell recovery port through a converging convergence channel.

[0016] Furthermore, the microporous structures are arranged at equal intervals on each branch flow channel, and the diameter of the microporous structures is larger than the diameter of the branch flow channel.

[0017] Furthermore, the number of microporous structures on each branch flow channel is equal and no less than 4.

[0018] Furthermore, a small particle cell separation channel is provided in the last microporous structure on each branch flow channel, and the small particle cell separation channels are connected to the corresponding small particle cell separation outlets.

[0019] Furthermore, the small particle cell separation outlets are not connected to the large particle cell recovery outlets.

[0020] Furthermore, the microporous structure is divided into two parts by a flow channel, and the small particle cell separation channels are symmetrically arranged on the two side walls of the microporous structure.

[0021] Furthermore, the ratio of the diameter of the small particle cell separation channel to the diameter of the microporous structure is 1:(15-25), preferably 1:20.

[0022] The utility model also provides a sorting system comprising the above-mentioned rapid cell sorting device. The sorting system also comprises a cell fluid transmission device, and the cell fluid transmission device is connected to the cell sample inlet through a connecting conduit.

[0023] Furthermore, the cell fluid transfer device is preferably a fluid injection controller, which can control the separation speed of the cell fluid in the flow channel by adjusting the flow rate.

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

[0025] (1) The cell rapid sorting device of the utility model can rapidly separate cells of different diameters by setting a flow channel, a microporous structure and a separation channel, thereby improving the speed and efficiency of cell sorting.

[0026] (2) After the cell sample enters the sorting device of the utility model, it will enter the flow channel under the action of fluid dynamics effect. After the cells expand and contract multiple times, large particle cells gather in the middle of the flow channel, and a large number of small particle cells gather on both sides, so that cells of different sizes can be effectively separated.

[0027] (3) The microporous structure of the utility model causes cell particle separation through the inertial force generated by the high flow rate in the microchannel or the elastic force generated by the viscoelasticity of the viscoelastic fluid, and the cell separation ability is enhanced by using a clever expansion and contraction structure. In addition, the cell rapid sorting device of the utility model does not require traditional applied field separation such as electric field, magnetic beads, etc. Through fluid mechanics, the operation is simpler, the cost is low, the separation purity is as high as 85%, and it can be operated continuously.

[0028] (4) The cell rapid sorting device of the utility model has a sophisticated structure and adopts a current-free driving method, which simplifies the operation process; at the same time, it uses the cooperation of the micropore array and the branch channel to achieve rapid cell sorting and efficient capture and collection of target cells.

[0029] (5) The cell rapid sorting device of the utility model is connected to a microfluidic generator capable of controlling the flow rate so as to separate cells of different particle sizes by controlling the feed flow rate. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a schematic diagram of the three-dimensional structure of the rapid cell sorting device of Example 2 of the utility model.

[0031] Figure 2 This is a schematic cross-sectional structure diagram of a rapid cell sorting device according to Example 2 of the utility model.

[0032] Figure 3 This is a schematic diagram of the structure of the rapid cell sorting device of Example 3 of the utility model.

[0033] Figure 4 This is a side view of the rapid cell sorting device of Example 3 of the utility model.

[0034] Figure 5 This is a schematic diagram of the structure of the sorting system of Example 5 of the utility model.

[0035] Description of the markings in the figure:

[0036] 1-sorting device body, 11-glass cover, 2-cell sample inlet, 3-large particle cell recovery port, 4-flow channel, 41-branch flow channel, 42-dispersion channel, 43-convergence channel; 5-microporous structure, 6-small particle cell separation channel, 7-small particle cell separation outlet, 8-cell fluid transfer device. DETAILED DESCRIPTION

[0037] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and a specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0038] In the present utility model, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inside", "outside" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the drawings, and are only for the convenience of describing the present utility model and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific position, be constructed and operated in a specific position, and therefore cannot be understood as a limitation on the present utility model; the terms "first", "second", and "third" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance; in addition, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or an indirect connection through an intermediate medium, or it can be a communication between the two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present utility model can be understood according to specific circumstances.

[0039] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, further definition and explanation thereof is not required in subsequent drawings.

[0040] Embodiment 1:

[0041] A rapid cell sorting device comprises a sorting device body 1, on which a cell sample inlet 2 and a large particle cell recovery port 3 are sequentially provided along the flow direction of the cell fluid. The cell sample inlet 2 and the large particle cell recovery port 3 are connected through a flow channel 4, and a plurality of microporous structures 5 having a diameter larger than that of the flow channel 4 and penetrated by the flow channel 4 are sequentially provided on the flow channel 4. Since the cells expand and contract multiple times when passing through the microporous structure 5, large particle cells gather in the middle of the flow channel 4, and a large number of small particle cells gather on both sides, a small particle cell separation channel 6 for diverting small particle cells is provided on the wall surface of the last microporous structure 5. The small particle cell separation channel 6 is connected to the small particle cell separation outlet 7, and the small particle cell separation outlet 7 is not connected to the large particle cell recovery port 3.

[0042] Embodiment 2:

[0043] A rapid cell sorting device, such as Figure 1-2 As shown, it includes a sorting device body 1, which is different from Example 1 in that when the sorting device body 1 of this embodiment is placed horizontally, the horizontal height of the cell sample inlet 2 is higher than the large particle cell recovery port 3.

[0044] In addition, a glass cover plate 11 capable of covering the flow channel 4 is installed on the sorting device body 1 of this embodiment to reduce cell contamination during the cell sorting process as much as possible.

[0045] Embodiment 3:

[0046] A rapid cell sorting device, such as Figure 3-4 As shown, it includes a sorting device body 1, which is different from Example 1 in that this embodiment can divert and separate cell fluid through multiple channels. Specifically, the flow channel 4 includes a dispersion channel 42, a convergence channel 43 and multiple branch flow channels 41 connected therebetween. The cell sample inlet 2 inputs the cell fluid into each branch flow channel 41 through the gradually widening dispersion channel 42, and the outlet of the branch flow channel 41 converges the large particle cell fluid into the large particle cell recovery port 3 through the convergent convergence channel 43, thereby realizing the separation and convergence of cells in multiple channels.

[0047] In this embodiment, the microporous structures 5 are arranged at equal intervals on each branch flow channel 41, and the diameter of the microporous structures 5 is larger than the diameter of the branch flow channel 41. The number of microporous structures 5 on each branch flow channel 41 is equal, and is not less than 4. A small particle cell separation channel 6 is provided in the last microporous structure 5 on each branch flow channel 41, and the small particle cell separation channel 6 is connected to the corresponding small particle cell separation outlet 7, and the small particle cell separation outlet 7 is not connected to the large particle cell recovery port 3.

[0048] Embodiment 4:

[0049] A cell rapid sorting device includes a sorting device body 1, which is different from Example 1 in that a small particle cell separation channel 6 of this embodiment is symmetrically arranged on both side walls of a microporous structure 5. The ratio of the diameter of the small particle cell separation channel 6 to the diameter of the microporous structure 5 is 1:20, so as to effectively separate large particles and small particles.

[0050] Embodiment 5:

[0051] This embodiment provides a cell sorting system, such as Figure 5 As shown, it includes the cell rapid sorting device described in Example 1, and also includes a cell fluid transmission device 8, which is connected to the cell sample inlet 2 through a connecting conduit. The cell fluid transmission device 8 of this embodiment is preferably a microflow generator, which can adjust the flow rate according to cells of different particle sizes to control the transmission speed of the cell fluid from the feed port 2 to the flow channel 4, so as to control the separation speed and separation efficiency.

[0052] Embodiment 6:

[0053] This embodiment provides a rapid cell sorting device, the main body of which is made of polydimethylsiloxane. The sorting device of this embodiment can be divided into a feeding module, a flow channel, a sorting module and a collection module.

[0054] The feeding module includes a cell sample inlet 2. After simple pretreatment, the cell culture fluid or serum sample is mixed with a buffer solution and then connected to the cell sample inlet 2 through a microflow generator. Cells can be separated according to the flow rate of the feed to obtain the desired cells. The cell sample enters the flow channel 4 through the cell sample inlet 2.

[0055] The flow channel 4 includes 5 branch flow channels 41, each of which is provided with 5 fluid power units (i.e., microporous structures 5). The cell samples to be separated enter the 5 branch flow channels 41 respectively after entering from the cell sample inlet 2, and then experience 5 fluid expansion and contraction, and enter the sorting module after reaching the 5th fluid power unit. The inertial force generated by the high flow rate in the microchannel or the elastic force generated by the viscoelasticity of the viscoelastic fluid will cause particle separation. Driven by the fluid force, the cells are moved to the center line of the microchannel according to their size and gathered, and the larger particles finally reach the center line, and the small particles are separated to both sides of the pipeline.

[0056] The sorting module includes a small particle cell separation channel 6. After the cell sample has been expanded and contracted by the fluid power unit 5 times, a large number of small particle cells are gathered on both sides of the fifth fluid power unit, and large particle cells are gathered in the middle of the flow channel. The small particle cells are diverted from the small particle cell separation channel 6 to the small particle cell separation outlet 7, while the large particle cells continue to enter the large particle cell recovery outlet 3 along the fluid channel 4 and are collected.

[0057] The collection module includes a large particle cell recovery port 3 and a small particle cell separation port 7. After the sample is separated by the device, the large particle cells enter the large particle cell recovery port 3, and the smaller particle cells enter the small particle cell separation port 7. The required cells are recovered according to their needs. In addition, cells of different particle sizes can be separated by controlling the flow rate of the feed.

[0058] In specific implementation, parameters such as the size of the flow channel 4, the arrangement of the microporous structure 5, and the number of small particle cell separation channels 6 can be adjusted according to actual needs to adapt to different cell types and sorting requirements.

[0059] In summary, the rapid cell sorting device of the utility model realizes rapid sorting and efficient collection of cells by optimizing the physical structure design, thereby improving scientific research efficiency and the level of biotechnology development.

[0060] The above description of the embodiments is to facilitate the understanding and use of the utility model by those skilled in the art. It is obvious that those familiar with the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the utility model is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the utility model without departing from the scope of the utility model should be within the scope of protection of the utility model.

Claims

1. A rapid cell sorting device, comprising a sorting device body (1), characterized in that: The separation device body (1) is provided with a cell sample inlet (2) and a large particle cell recovery port (3) in sequence along the flow direction of the cell fluid; The cell sample inlet (2) and the large particle cell recovery port (3) are connected via a flow channel (4), and a plurality of microporous structures (5) having a diameter larger than the flow channel (4) and penetrated by the flow channel (4) are sequentially arranged on the flow channel (4), and a small particle cell separation channel (6) for diverting small particle cells is arranged on the wall surface of the last microporous structure (5); The small particle cell separation channel (6) is connected to the small particle cell separation outlet (7), and the small particle cell separation outlet (7) is not connected to the large particle cell recovery port (3).

2. A rapid cell sorting device according to claim 1, characterized in that: When the separation device body (1) is placed horizontally, the cell sample inlet (2) is at a higher level than the large particle cell recovery port (3).

3. A rapid cell sorting device according to claim 1, characterized in that: The sorting device body (1) is provided with a glass cover plate (11) capable of covering the flow channel (4).

4. A rapid cell sorting device according to claim 1, characterized in that: The flow channel (4) comprises a dispersion channel (42), a convergence channel (43) and a plurality of branch flow channels (41) communicating therebetween; The cell sample inlet (2) inputs the cell fluid into each branch flow channel (41) through a gradually widening dispersion channel (42), and the outlet of the branch flow channel (41) collects the large particle cell fluid into the large particle cell recovery port (3) through a converging convergence channel (43).

5. A rapid cell sorting device according to claim 4, characterized in that: The microporous structures (5) are arranged at equal intervals on each branch flow channel (41), and the diameter of the microporous structures (5) is greater than the diameter of the branch flow channel (41).

6. A rapid cell sorting device according to claim 5, characterized in that: The number of microporous structures (5) on each branch flow channel (41) is equal and no less than 4.

7. A rapid cell sorting device according to claim 4, characterized in that: A small particle cell separation channel (6) is provided in the last microporous structure (5) on each branch flow channel (41), and the small particle cell separation channel (6) is connected to a corresponding small particle cell separation outlet (7); The small particle cell separation outlets (7) are not connected to the large particle cell recovery outlets (3).

8. A rapid cell sorting device according to claim 1, characterized in that: The small particle cell separation channels (6) are symmetrically arranged on the two side walls of the microporous structure (5).

9. A rapid cell sorting device according to claim 1, characterized in that: The ratio of the diameter of the small particle cell separation channel (6) to the diameter of the microporous structure (5) is 1:(15-25).

10. A sorting system comprising the rapid cell sorting device according to any one of claims 1 to 9, characterized in that: It also comprises a cell fluid transmission device (8), wherein the cell fluid transmission device (8) is connected to the cell sample inlet (2) via a connecting conduit.

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