Single cell sorting device and use method thereof

Abstract

The embodiment of the invention provides a single cell sorting device. The single cell sorting device comprises a distributor, a mixer and an on-demand titrator, the distributor comprises a sample container and a leading-out device, a containing cavity is formed in the sample container, at least part of the cavity wall of the containing cavity is arranged to be a deformable part, the leading-out device is arranged below the sample container and connected to a bottom outlet of the containing cavity, the mixer is arranged relative to the sample container, and the on-demand titrator is arranged relative to the leading-out device; the use method of the single cell sorting device comprises the following steps: S1, adding a cell solution sample into the accommodating cavity from the input port of the accommodating cavity; and S2, starting the mixer and the on-demand titrator, applying an external force to the deformable part by the mixer so as to uniformly mix the cell solution in the accommodating cavity, enabling the uniformly mixed cell solution to enter the exporting device, and applying an external force to the exporting device by the on-demand titrator so as to export the cell solution from the exporting device in a liquid drop form. According to the embodiment of the invention, the technical effects of relatively high automation degree and prevention of pollution caused by manual intervention are achieved.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and more specifically, to a single-cell sorting device and its method of use. Background Technology

[0002] Currently, conventional cell mixing involves manually aspirating liquid from the container using a pipette, but this method is too reliant on manual labor and cannot meet the needs of automated equipment.

[0003] Therefore, existing mixing methods are relatively inefficient due to their low level of automation, which cannot meet the needs of large-scale experiments or production, and excessive manual intervention can easily lead to contamination. Summary of the Invention

[0004] In view of the shortcomings of existing methods, this invention proposes a single-cell sorting device and its usage method to solve the technical problems of low efficiency due to low automation and easy contamination during manual operation in existing technologies.

[0005] In a first aspect, embodiments of the present invention provide a single-cell sorting device, comprising: a dispenser, a mixer, and an on-demand titrator; The dispenser includes a sample container and an outlet. The sample container has a receiving cavity, and at least a portion of the cavity wall is configured as a deformable part. The outlet is located below the sample container and connected to the bottom outlet of the receiving cavity. The mixer is positioned relative to the sample container, and the on-demand titrator is positioned relative to the outlet.

[0006] Optionally, the dispenser further includes a body; The main body is provided with a first mounting position and a second mounting position arranged vertically. The sample container is disposed in the first mounting position and the exporter is disposed in the second mounting position.

[0007] Optionally, each of the first and second mounting positions has an open opening on one side to allow for the insertion or removal of the sample container and the exporter.

[0008] Optionally, the main body is provided with a plurality of limiting posts, which are arranged to form the first mounting position.

[0009] Optionally, the cavity wall is provided with a rigid part, which is disposed close to the inner wall of the first mounting position, and the deformable part is disposed facing the opening of the first mounting position.

[0010] Optionally, the body further includes a support block; The support block is provided with a fluid channel, the bottom outlet of the receiving cavity is connected to one end of the fluid channel, and the outlet is connected to the other end of the fluid channel to communicate with the bottom outlet of the receiving cavity.

[0011] Optionally, it also includes a positioning block, which is disposed at the bottom of the sample container, and the top of the support block is provided with a positioning groove for positioning the positioning block; The sample container is positioned at the first mounting position, and the locking block is engaged in the positioning groove.

[0012] Optionally, the mixer includes a reciprocating propeller and an actuating rod disposed on the reciprocating propeller; The reciprocating propeller reciprocates to drive the actuator to reciprocate against the deformable portion. Optionally, the number of the actuating rods may be multiple.

[0013] Optionally, the on-demand titrator is located on one side of the body to serve as a tapping device for selectively outputting droplets containing a preset number of cells from the cell solution within the device at preset intervals.

[0014] A method of using a single-cell sorting device, characterized in that it includes: S1. Add the cell solution sample into the receiving cavity through the inlet of the receiving cavity; S2. Start the mixer and the on-demand titrator. The mixer applies an external force to the deformable part, which deforms to disturb the cell solution in the receiving cavity and mix the cell solution. The mixed cell solution enters the outlet. The on-demand titrator applies an external force to the outlet. The cell solution in the outlet can selectively output droplets containing a preset number of cells at preset times.

[0015] The beneficial technical effects brought about by the technical solutions provided in the embodiments of the present invention include: The cell solution entering the dispenser is automatically mixed using a mixer, thereby improving mixing efficiency and enabling batch mixing production, thus meeting the needs of large-scale experiments or production. Furthermore, the reduced human intervention can more effectively prevent operational contamination problems, avoiding product waste and increased time costs.

[0016] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and will become apparent from the description or may be learned by practice of the invention. Attached Figure Description

[0017] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments taken in conjunction with the accompanying drawings, wherein: Figure 1 This is an exploded view of a single-cell sorting device product provided in an embodiment of the present invention; Figure 2 This is an assembly diagram of a single-cell sorting device product provided in an embodiment of the present invention; Figure 3 This is an assembly diagram of a sample container for a cell sorting device product provided in an embodiment of the present invention; Figure 4 This is an exploded view of a sample container of a cell sorting device product provided in an embodiment of the present invention; Figure 5 This is a schematic diagram of a reciprocating propulsion component of a cell sorting device product provided in an embodiment of the present invention.

[0018] The meanings of the reference numerals in the attached figures are as follows: 10. Dispenser; 11. Sample container; 12. Exporter; 13. Body; 131. Limiting post; 132. Support block; 1321. Fluid channel; 1322. Positioning groove; 1301. First mounting position; 1302. Second mounting position; 20. Mixer; 21. Reciprocating propeller; 22. Actuating rod; 30. On-demand titrator; 31. Propeller; 32. Propeller rod; 33. Printing bead; 50. Locking block. Detailed Implementation

[0019] The present invention will now be described in detail. Examples of embodiments of the invention are illustrated in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar parts or parts having the same or similar functions throughout. Furthermore, detailed descriptions of known technologies that are unnecessary for the features of the illustrated invention are omitted. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the invention, and should not be construed as limiting the invention.

[0020] It will be understood by those skilled in the art that, unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. It should also be understood that terms such as those defined in general dictionaries should be understood to have the same meaning as in the context of the prior art, and should not be interpreted in an idealized or overly formal sense unless specifically defined as herein.

[0021] Those skilled in the art will understand that, unless specifically stated otherwise, the singular forms “a,” “an,” “the,” and “the” used herein may also include the plural forms. It should be further understood that the term “comprising” as used in this specification means the presence of the stated features, integers, steps, operations, elements, and / or components, but does not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. It should be understood that when we say an element is “connected” or “coupled” to another element, it can be directly connected or coupled to the other element, or there may be intermediate elements. Furthermore, “connected” or “coupled” as used herein can include wireless connections or wireless coupling. The term “and / or” as used herein includes all or any units and all combinations of one or more associated listed items.

[0022] The present invention provides a single-cell sorting device, which aims to solve the above-mentioned technical problems of the prior art.

[0023] The technical solution of the present invention and how the technical solution of the present invention solves the above-mentioned technical problems are described in detail below with specific embodiments.

[0024] This invention provides a single-cell sorting device, the structural schematic of which is shown below. Figures 1 to 3 As shown, it includes: a dispenser 10, a mixer 20, and an on-demand titrator 30; the dispenser 10 includes a sample container 11 and an outlet 12, the sample container 11 is provided with a receiving cavity, at least a portion of the cavity wall is configured as a deformable part, the outlet 12 is disposed below the sample container 11 and connected to the bottom outlet of the receiving cavity, the mixer 20 is disposed relative to the sample container 11, and the on-demand titrator 30 is disposed relative to the outlet 12; the cell solution sample enters the receiving cavity from the inlet of the receiving cavity, the mixer 20 is used to apply external force to the deformable part, the deformable part deforms to disturb the cell solution in the receiving cavity, and the on-demand titrator 30 is used to apply external force to the outlet 12 so that the cell solution in the outlet 12 can selectively output droplets containing a preset number of cells at preset times.

[0025] In this embodiment, the cell solution is injected into the receiving cavity of the sample container 11. The deformable part deforms under the force of the mixer (which can be direct contact, indirect contact, or non-contact action), thereby changing the volume of the receiving cavity and thus creating a mixing effect on the cell solution within the receiving cavity, resulting in a uniform distribution of cells within the receiving cavity. It is understood that the exporter 12 is configured to communicate with the bottom outlet of the receiving cavity to export the cell solution from the receiving cavity. Then, the on-demand titrator 30 is activated to act on the exporter 12 (which can be direct contact, indirect contact, or non-contact action), and the exporter 12 selectively outputs droplets containing a preset number of cells at a preset time.

[0026] It should be noted that the deformable part is made of an elastic material, and its main deformation mode is elastic deformation. The mixer 20 acts on the deformable part to cause it to deform, and the deformable part returns to its original shape after the action is removed. The deformable part on the sample container 11 can be part or all of it; this is not limited here. It is known that the more deformable parts there are, the greater the degree of deformation under stress. Furthermore, the exporter 12 in this embodiment is preferably a microfluidic chip.

[0027] This embodiment achieves automatic mixing of the cell solution, improving work efficiency. However, if additional mixing is performed before transferring the solution to the exporter 12 via another transfer container, there is a risk of contamination between the transfer container and the exporter 12.

[0028] Optionally, the dispenser 10 also includes a body 13; the body 13 is provided with a first mounting position 1301 and a second mounting position 1302 arranged vertically, the sample container 11 is disposed in the first mounting position 1301, and the dispenser 12 is disposed in the second mounting position 1302.

[0029] It is understood that the body 13 is used for the installation and placement of the sample container 11 and the exporter 12, so that the sample container 11 and the exporter 12 are easy to fix and the fixation effect is good, thereby ensuring a convenient and tight connection between the sample container 11 and the exporter 12 and preventing leakage of cell solution.

[0030] Optionally, each side of the first mounting position 1301 and the second mounting position 1302 is designed with an open opening to allow the sample container 11 and the exporter 12 to be loaded or unloaded.

[0031] In this embodiment, the sample container 11 and the exporter 12 are arranged vertically, and the side openings facilitate the insertion or removal of the sample container 11 and the exporter 12 from their respective openings. Furthermore, the bottom of the second mounting position 1302 can also be an open structure.

[0032] Optionally, the main body 13 is provided with a plurality of limiting posts 131, which are arranged to form a first mounting position 1301.

[0033] In this embodiment, taking the aforementioned sample container 11 as an example of a rectangular structure, there are four limiting posts 131. The four limiting posts 131 form a barrier around the sample container 11 at the four corners. Since there is a hollow space between two limiting posts 131 on the same side, the sample container 11 can be gripped on both sides for installation or removal. Preferably, the limiting posts 131 are four-sided posts.

[0034] Optionally, the cavity wall is provided with a rigid part, which is disposed in close contact with the inner wall of the first mounting position 1301, and the deformable part is disposed facing the opening of the first mounting position 1301.

[0035] For example, at least one sidewall of the receiving cavity is a rigid portion for maintaining the posture of the sample container 11 so that the sample container 11 is held in place in the first mounting position 1301. Preferably, when the sample container 11 is installed, the rigid portion faces the inner wall of the first mounting position 1301, and the deformable portion faces away from the inner wall (i.e., towards the opening).

[0036] Preferably, taking only one mixer 20 as an example, in this embodiment only the sidewall facing the mixer 20 is deformable, because the deformation range of the outward deformable part is greater, which is conducive to greater stress deformation and mixing, while the rigid wall surface forcibly guides and constrains the fluid (cell solution), making the flow concentrated, reflected, and intensified mixing.

[0037] In other embodiments, based on the fact that the inner and outer sides of the sample container 11 are respectively a rigid part and a deformable part, the peripheral sidewall of the sample container 11 can be selected as a deformable part or a rigid part. Alternatively, the peripheral sidewall can be partly deformable and partly rigid. There is no specific limitation here. For example, the half of the peripheral sidewall near the opening is deformable and the other half is rigid. This makes the overall rigidity of the sample container 11 relatively higher, and its installation in the first mounting position 1301 more stable. Or, the half of the peripheral sidewall near the opening is rigid and the other half is deformable. This also makes the overall rigidity of the sample container 11 relatively higher. The end near the opening is not easy to fall, but the other end can cooperate with the side near the opening to deform under stress.

[0038] Optionally, the body 13 also includes a support block 132; the support block 132 is provided with a fluid channel 1321 from top to bottom, the bottom outlet of the receiving cavity is connected to one end of the fluid channel 1321, and the outlet 12 is connected to the other end of the fluid channel 1321 to communicate with the bottom outlet of the receiving cavity.

[0039] In this embodiment, the support block 132 supports the sample container 11 at the top; in addition, the sample container 11 and the outlet 12 can be connected to the fluid channel 1321 respectively, so that the installation and disassembly of the two are more convenient.

[0040] As can be seen from the above, the cell solution mixed in the containment cavity flows to the outlet 12 through the fluid channel 1321, and is output from the bottom of the outlet 12 in the form of droplets after the outlet 12 is acted upon by the on-demand titrator 30.

[0041] Optionally, it also includes a positioning block 50, which is disposed at the bottom of the sample container 11, and the top of the support block 132 is provided with a positioning groove 1322 for positioning the positioning block 50; the sample container 11 is disposed at the first mounting position 1301, and the positioning block 50 is engaged in the positioning groove 1322.

[0042] The fitting block 50 and the positioning groove 1322 are installed at the bottom of the sample container 11 to play a positioning and limiting role, which makes it easier to install and fix the sample container 11.

[0043] Preferably, one side of the aforementioned first mounting position 1301 is open, so that the sample container 11 is installed in the first mounting position 1301 from the side opening. Similarly, the side of the positioning groove 1322 near the opening is also open.

[0044] Alternatively, the aforementioned fluid channel 1321 may or may not pass through the locking block 50; in this embodiment, the former is preferred.

[0045] Optionally, combined Figure 5 The mixer 20 includes a reciprocating pusher 21 and an actuating rod 22 disposed on the reciprocating pusher 21; the reciprocating pusher 21 reciprocates to drive the actuating rod 22 to reciprocate to act on the deformable part.

[0046] For example, the reciprocating propeller 21 can be a linear motor, which pushes the actuating rod 22 to reciprocate on the deformable part (in this embodiment, the mixer acts directly on the sample container 11). It should be noted that the deformable part here can be a deformable part at any position. More preferably, multiple reciprocating propellers 21 can be set to apply pressure to the deformable part in different directions.

[0047] In addition, as explained above, the combination of the mixer 20 and the sample container 11 allows the sample container 11 to be squeezed and mixed by the mixer 20, and the entire mixing process does not come into contact with the cell solution, thus avoiding cell solution contamination.

[0048] Optionally, there may be multiple actuating rods 22. Preferably, the multiple actuating rods 22 are arranged along the height or width direction of the deformable portion.

[0049] When there are multiple actuators 22, the reciprocating propeller 21 can control the overall movement of the actuators 22, increasing the contact area and ensuring thorough mixing; alternatively, it can drive multiple actuators 22 individually, controlling them to move sequentially like waves, performing a "squeeze-release" operation upwards / downwards (or from left to right), generating directional flow in the liquid and forming a unidirectional circulation, which is beneficial for better and more uniform mixing. Furthermore, the array of actuators 22 can be controlled to sequentially squeeze the flexible wall from the center to both ends, or from both ends to the center, causing the liquid to converge in the central region and tumble upwards / downwards, forming convection.

[0050] Therefore, the design of these multiple action rods 22 enables the cell solution to be mixed more evenly, and the mixing intensity, time and mode can be precisely controlled, ensuring a high degree of consistency in the mixing results each time.

[0051] In addition, the multiple action rods 22 can be arranged in S-shape, ring shape, X-shape, etc., which will not be listed one by one here.

[0052] Optionally, the on-demand titrator 30 is located on one side of the body 13 to serve as a tapping extractor 12, and allows the cell solution in the extractor 12 to selectively output droplets containing a preset number of cells at preset times.

[0053] Specifically, the on-demand titrator 30 is located on one side of the outlet 12, and the outlet 12 is tapped to create a shock to the outlet 12.

[0054] For example, the on-demand titrator 30 is located on the side away from the open end of the second mounting position 1302, so that the on-demand titrator 30 strikes the outlet 12 to create a shock (in this embodiment, the on-demand titrator 30 and the outlet 12 interact directly). Alternatively, non-contact impacts, including shock waves such as sound waves, are also acceptable.

[0055] For example, the on-demand titrator 30 includes a printed bead 33 disposed near the outlet 12. The printed bead 33 of the on-demand titrator 30 delivers a micron-level linear tap to the outlet 12. In this embodiment, the printed bead 33 has a smooth contact point, enabling precise tapping without damaging the outlet 12.

[0056] Furthermore, it also includes a pusher 31 and a push rod 32 disposed on the pusher 31, the pusher 31 being preferably a linear motor. The pusher 31 drives the push rod 32 to move the on-demand titrator 30 (the on-demand titrator 30 is movably disposed on the base) to a working position where it makes zero-pressure contact with the exporter 12, and then the printing beads 33 of the on-demand titrator 30 perform micron-level linear tapping on the exporter 12, causing the exporter 12 to selectively output droplets containing a preset number of cells at a preset time.

[0057] In summary, the method of using the single-cell sorting device is described here, which includes: S1. Add the cell solution sample into the container through the inlet of the container.

[0058] S2. Start the mixer 20 and the on-demand titrator 30. The mixer 20 applies external force to the deformable part, and the deformable part deforms to disturb the cell solution in the receiving cavity and mix the cell solution. The mixed cell solution enters the outlet 12. The on-demand titrator 30 applies external force to the outlet 12. The cell solution in the outlet 12 can selectively output droplets containing a preset number of cells at preset times.

[0059] Those skilled in the art will understand that the steps, measures, and schemes in the various operations, methods, and processes discussed in this invention can be alternated, modified, combined, or deleted. Furthermore, other steps, measures, and schemes in the various operations, methods, and processes discussed in this invention can also be alternated, modified, rearranged, decomposed, combined, or deleted. Furthermore, steps, measures, and schemes in the prior art that are similar to those disclosed in this invention can also be alternated, modified, rearranged, decomposed, combined, or deleted.

[0060] In the description of this invention, it should be understood that the terms "center", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

[0061] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0062] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0063] In the description of this specification, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0064] It should be understood that although the steps in the flowcharts of the accompanying figures are shown sequentially as indicated by the arrows, these steps are not necessarily executed in the order indicated by the arrows. Unless explicitly stated herein, there is no strict order restriction on the execution of these steps, and they can be executed in other orders. Moreover, at least some steps in the flowcharts of the accompanying figures may include multiple sub-steps or multiple stages. These sub-steps or stages are not necessarily completed at the same time, but can be executed at different times, and their execution order is not necessarily sequential, but can be performed alternately or in turn with other steps or at least some of the sub-steps or stages of other steps.

[0065] The above description is only a partial embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A single-cell sorting device, characterized in that, Includes a dispenser (10), a mixer (20), and an on-demand titrator (30); The dispenser (10) includes a sample container (11) and an outlet (12). The sample container (11) has a receiving cavity, and at least a portion of the cavity wall is configured as a deformable part. The outlet (12) is located below the sample container (11) and connected to the bottom outlet of the receiving cavity. The mixer (20) is located relative to the sample container (11), and the on-demand titrator (30) is located relative to the outlet (12).

2. The single-cell sorting device according to claim 1, characterized in that, The dispenser (10) also includes a body (13); The main body (13) is provided with a first mounting position (1301) and a second mounting position (1302) arranged vertically. The sample container (11) is located in the first mounting position (1301), and the exporter (12) is located in the second mounting position (1302).

3. The single-cell sorting device according to claim 2, characterized in that, The first mounting position (1301) and the second mounting position (1302) are each designed with an open opening on one side to allow the sample container (11) and the exporter (12) to be inserted or removed.

4. The single-cell sorting device according to claim 3, characterized in that, The main body (13) is provided with a plurality of limiting posts (131), and the plurality of limiting posts (131) are arranged to form the first mounting position (1301).

5. The single-cell sorting device according to claim 3 or 4, characterized in that, The cavity wall is provided with a rigid part, which is disposed close to the inner wall of the first mounting position (1301), and the deformable part is disposed facing the opening of the first mounting position (1301).

6. The single-cell sorting device according to any one of claims 2-4, characterized in that, The main body (13) also includes a support block (132); The support block (132) is provided with a fluid channel (1321), the bottom outlet of the receiving cavity is connected to one end of the fluid channel (1321), and the outlet (12) is connected to the other end of the fluid channel (1321) to communicate with the bottom outlet of the receiving cavity.

7. The single-cell sorting device according to claim 6, characterized in that, It also includes a positioning block (50), which is located at the bottom of the sample container (11), and the top of the support block (132) is provided with a positioning groove (1322) for positioning the positioning block (50). The sample container (11) is set in the first mounting position (1301), and the locking block (50) is engaged in the positioning groove (1322).

8. The single-cell sorting device according to claim 2, 3 or 7, characterized in that, The mixer (20) includes a reciprocating propulsion member (21) and an actuating rod (22) disposed on the reciprocating propulsion member (21). The reciprocating propulsion member (21) reciprocates to drive the actuating rod (22) to reciprocate on the deformable part.

9. The single-cell sorting device according to claim 1, characterized in that, The on-demand titrator (30) is located on one side of the body (13) to be used as a tapper (12) to selectively output droplets containing a preset number of cells from the cell solution in the extractor (12) at preset times.

10. The method of using the single-cell sorting device as described in claims 1-9, characterized in that, include: S1. Add the cell solution sample into the receiving cavity through the inlet of the receiving cavity; S2. Start the mixer (20) and the on-demand titrator (30). The mixer (20) applies external force to the deformable part. The deformable part deforms to disturb the cell solution in the receiving cavity and mix the cell solution. The mixed cell solution enters the outlet (12). The on-demand titrator (30) applies external force to the outlet (12). The cell solution in the outlet (12) can selectively output droplets containing a preset number of cells at preset times.

Images