Microfluidic micro-droplet sorter

Abstract

The utility model relates to the technical field of microfluidics, and discloses a microfluidics micro-droplet sorter, which comprises an imaging component provided with a detection area for observing a micro-droplet chip; the bearing assembly comprises an objective table used for bearing the micro-droplet chip, and one side of the objective table is provided with a first adjusting structure used for adjusting the displacement of the objective table in the detection area; and the laser assembly comprises a laser emitter, the laser emitter is located between the objective table and the imaging assembly, and one side of the laser emitter is provided with a second adjusting structure used for adjusting the laser emitter to be opposite to the micro-droplet chip in a displacement mode. According to the utility model, the technical effects that the laser transmitter can correctly excite the fluorescent marker, and the use flexibility and convenience can be improved are achieved.

Description

Technical Field

[0001] This utility model belongs to the field of microfluidics technology, specifically relating to a microfluidic microdroplet sorting instrument. Background Technology

[0002] Microdroplet sorting is a high-throughput screening method based on droplet microfluidics. Due to its high throughput, low consumption, and high precision, it has broad application prospects in biomedical research, drug screening, and environmental monitoring. In particular, microdroplet sorting can be applied to cell sorting. It utilizes a water-in-oil droplet preparation method to encapsulate cells to be sorted into numerous independent nanoliter or picoliter microdroplets on a microdroplet chip. These microdroplets act as miniature reactors for the cells, and low-yield and high-yield cells or microorganisms are sorted based on parameters such as fluorescence signals, achieving high-throughput screening.

[0003] During the cell sorting process, the microdroplet chip needs to be used with a microfluidic microdroplet sorter. The microfluidic microdroplet sorter mainly includes a stage for carrying the microdroplet chip. A laser module is set on one side of the stage. The laser module excites the cells containing fluorescent markers in the droplets. The fluorescent markers emit fluorescence of a specific wavelength, which serves as the basis for cell detection and sorting.

[0004] However, the laser module may cause leakage activation of other cells during excitation, making the sorting operation of the microfluidic microdroplet sorter inconvenient. Utility Model Content

[0005] To address the shortcomings of the existing technology, this invention provides a microfluidic microdroplet sorter, in which a first adjustment structure and a second adjustment structure work together, and a laser generator can be adjusted to a position opposite to the microdroplet chip. The laser emitter correctly excites fluorescent markers to reduce the possibility of cell leakage activation.

[0006] The technical effects to be achieved by this utility model are realized through the following technical aspects:

[0007] This invention provides a microfluidic microdroplet sorting instrument, including an imaging component with a detection area for observing microdroplet chips; a support component including a stage for supporting the microdroplet chips, with a first adjustment structure on one side of the stage for displacement adjustment within the detection area; and a laser component including a laser emitter located between the stage and the imaging component, with a second adjustment structure on one side of the laser emitter for displacement adjustment to be opposite to the microdroplet chips.

[0008] In some implementations, the first adjustment structure includes a first adjustment slide, and the stage is disposed on the first adjustment slide. The first adjustment slide allows the stage to be displaced in the X-axis direction and the Y-axis direction, respectively.

[0009] In some implementations, the imaging component includes a microscope and a light source, with the detection area disposed between the microscope and the light source, and the light source providing light to the microscope through the microdroplet chip and the stage.

[0010] In some implementations, the laser emitter is positioned between the microscope and the stage, and the laser emitted by the laser emitter passes through the microdroplet chip and the stage.

[0011] In some implementations, the second adjustment structure includes a second adjustment slide, on which the laser emitter is disposed, and the second adjustment slide allows the laser emitter to be displaced in the X-axis and Y-axis directions, respectively.

[0012] In some implementations, the laser assembly includes a laser receiver, and the stage is located between the laser receiver and the laser emitter.

[0013] In some implementations, the laser receiver includes a laser receiving lens, a support frame is provided on one side of the laser receiving lens, and the adapter plate is provided on the support frame, with the adapter plate detachably connected to the support frame.

[0014] In some implementations, the microscope is an inverted microscope, located at the bottom of the stage.

[0015] In some implementations, the stage has a through hole, the microdroplet chip is suspended in the through hole, and the stage is provided with a clamping member for positioning the microdroplet chip.

[0016] In some implementations, a sorting electrode for sorting cells at the microdroplet chip is provided on one side of the stage.

[0017] In summary, this utility model has at least the following advantages:

[0018] The microfluidic microdroplet sorting instrument provided by this invention, during cell sorting experiments, places a microdroplet chip on a stage. A first adjustment structure adjusts the position of the stage within the detection area, ensuring the stage and imaging component maintain a relative position. The imaging component observes, identifies, and records the dynamic behavior and characteristics of cells within the microdroplet chip. A second adjustment structure repositions the laser generator, adjusting it to a position relative to the microdroplet line on the stage. This ensures the laser generator correctly excites fluorescent markers within the droplets, improving the excitation accuracy of the laser component and its flexibility. This also helps to mitigate the problem of missed activation of other cells within the microdroplet chip. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the structure of a microfluidic microdroplet sorting instrument according to Embodiment 1 of this utility model.

[0020] Figure 2 This is a schematic diagram of the overall structure of a microfluidic microdroplet sorting instrument according to a specific embodiment of the present invention.

[0021] Figure 3 This is a schematic diagram of the first and second adjustment structures according to a specific embodiment of the present invention.

[0022] Figure 4 This is a schematic diagram of the structure of the first adjustment structure hidden behind the lifting platform in a specific embodiment of this utility model.

[0023] Figure 5 for Figure 2 A structural diagram from another angle.

[0024] Figure 6 This is a schematic diagram of the structure of the laser component in a specific embodiment of the present invention.

[0025] Marked in the image:

[0026] 1. Imaging assembly; 11. Microscope; 12. Light source; 13. Microscope camera; 14. Detection area; 2. Support assembly; 21. Stage; 211. Through hole; 212. Clamping component; 22. First adjustment structure; 221. First adjustment slide; 2211. Z-axis adjustment seat; 2212. Lifting platform; 2213. Top block; 2214. Z-axis micrometer; 2215. Locking component; 3. Laser assembly; 31. Laser emitter; 32. Second adjustment structure; 321. Second adjustment slide; 33. Laser receiver; 331. Laser receiving lens; 332. PMT detection device; 34. Support frame; 35. Adapter plate; 4. Sorting electrode; 5. Data processing system; 6. First liquid phase drive component; 61. Second liquid phase drive component. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. The described embodiments are only some embodiments of this utility model, not all embodiments.

[0028] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0029] Example 1:

[0030] Please see the appendix Figure 1 and Figure 2 The microfluidic microdroplet sorting instrument of this invention includes an imaging component 1, a carrier component 2 and a laser component 3, which can realize high-throughput screening processes such as cell sorting and is easy to use.

[0031] The imaging component 1 of this invention has a detection area 14 for observing microdroplet chips. A support component 2 is provided on one side of the imaging component 1. The support component 2 includes a stage 21 for supporting the microdroplet chips. The stage 21 is located within the detection area 14. When the microdroplet chips are fixed on the stage 21, the imaging component 1 performs imaging and recording of the microdroplet chips in the detection area 14. A first adjustment structure 22 is provided on one side of the stage 21. The first adjustment structure 22 adjusts the displacement of the stage 21 within the detection area 14, so that the stage 21 is positioned opposite to the imaging component 1. The imaging component 1 can accurately and clearly capture and record the cells in the microdroplet chips.

[0032] A laser assembly 3 is provided on one side of the stage 21. The laser assembly 3 includes a laser emitter 31, which is located between the stage 21 and the imaging assembly 1. A second adjustment structure 32 is provided on one side of the laser emitter 31 for displacement adjustment so that the laser emitter 31 is opposite to the microdroplet chip. The second adjustment structure 32 adjusts the position of the laser emitter 31 so that the laser emitter 31 is opposite to the microdroplet chip. The laser emitted by the laser emitter 31 can accurately activate the cells to be sorted, improve the accuracy of the use of the laser assembly 3, and reduce the occurrence of missed activation of other cells.

[0033] During cell sorting, the microdroplet chip is fixed on the stage 21. The first adjustment structure 22 adjusts the stage 21 to a suitable position within the detection area 14. The imaging component 1 accurately observes and records the cells in the microdroplet chip and can monitor the dynamic behavior of the cells. The second adjustment structure 32 adjusts the laser emitter 31. The laser emitter 31 irradiates the droplets in the microdroplet chip with a laser to excite the fluorescent markers within the droplets. By identifying and distinguishing different fluorescent signals, cell detection and sorting are achieved. The laser emitter 31 is precisely aligned with the microdroplet chip, thereby reducing cell activation loss. The first adjustment structure 22 and the second adjustment structure 32 work together to improve the ease of use and flexibility.

[0034] Example 2:

[0035] The difference between this embodiment and Embodiment 1 is that this embodiment further optimizes the structure of the first adjusting structure 22 and the second adjusting structure 32 of this utility model. Please refer to [link / reference]. Figure 3 and Figure 4 .

[0036] The first adjustment structure 22 in this embodiment includes a first adjustment slide 221, and a stage 21 is disposed on the first adjustment slide 221. The first adjustment slide 221 allows the stage 21 to be displaced in the X-axis direction and the Y-axis direction, respectively.

[0037] As shown in some specific embodiments, the first adjusting slide 221 includes an X-axis adjusting plate group and a Y-axis adjusting plate group. The stage 21 is tractably connected to the X-axis adjusting plate group. The X-axis adjusting plate group drives the stage 21 to move along the X-axis direction for displacement adjustment. The Y-axis adjusting plate group drives both the stage 21 and the X-axis adjusting plate group to move together along the Y-axis direction for displacement adjustment. Further, both the X-axis and Y-axis adjusting plate groups include a sliding plate and a fixed plate, which are slidably connected. A micrometer is mounted on the sliding plate, and rotation of the micrometer drives the sliding plate to adjust its displacement relative to the fixed plate. The method by which the first adjusting slide 221 drives the stage 21 to adjust its displacement is known to those skilled in the art and is achievable; therefore, it will not be described in detail in this embodiment.

[0038] In some other specific embodiments, the first adjusting slide 221 further includes a Z-axis adjusting seat 2211, which can be disposed on the X-axis adjusting plate assembly of the first adjusting slide 221. A top block 2213 is rotatably disposed inside the Z-axis adjusting seat 2211, and a Z-axis micrometer 2214 is disposed on the top block 2213. The Z-axis micrometer 2214 extends into or retracts from the Z-axis adjusting seat 2211 during rotation, thereby pushing the top block 2213 to rotate within the Z-axis adjusting seat 2211 or move away from the top block 2213. A lifting seat is provided on the top of the Z-axis adjusting seat 2211, and the platform 21 is mounted on the lifting seat. The top block 2213 includes a protrusion. When the Z-axis micrometer 2214 rotates into the Z-axis adjusting seat 2211, it can push the top block 2213 to rotate. The top block 2213 lifts the lifting seat at the protrusion, causing the lifting seat to rise. When the Z-axis micrometer 2214 is rotated in the opposite direction, the lifting seat descends. The first adjusting slide 221 can drive the platform 21 to adjust its displacement along the Z-axis direction. A locking member 2215 is provided between the lifting seat and the Z-axis adjusting seat 2211. The locking member 2215 can be a bolt, which secures the lifting seat.

[0039] The first adjustment slide 221 adjusts the displacement of the stage 21, which helps the microdroplet chip on the stage 21 to maintain a relative setting with the imaging component 1, thereby achieving precise imaging. The stage 21 can also correspond to the laser emitter 31.

[0040] The second adjustment structure 32 includes a second adjustment slide 321. Similarly, the second adjustment slide 321 may also include an X-axis adjustment plate group and a Y-axis adjustment plate group. That is, the structure of the second adjustment slide 321 can be the same as that of the first adjustment slide 221. The laser emitter 31 is mounted on the second adjustment slide 321. The second adjustment slide 321 enables the laser emitter 31 to be displaced in the X-axis direction and the Y-axis direction, respectively.

[0041] Example 3:

[0042] The difference between this embodiment and the above embodiments is that, please refer to [link / reference needed]. Figure 5 and Figure 6 The imaging component 1 in this embodiment includes a microscope 11 and a light source 12. A detection area 14 is disposed between the microscope 11 and the light source 12. When the microdroplet chip is placed on the stage 21, the light source 12 provides light to the microscope 11 through the microdroplet chip and the stage 21. At this time, the stage 21 is displaced by the first adjusting slide 221, which allows the light source of the light source 12 to smoothly and accurately illuminate the microdroplet chip.

[0043] In a preferred embodiment, the microscope 11 is an inverted microscope, located at the bottom of the stage 21. The inverted microscope design reduces interference with the light source, and because cells tend to sink, it facilitates the observation of cultured live cells and tissues. Specifically, the inverted microscope is equipped with a phase-contrast objective lens, enabling clear differentiation of samples with high transparency and indistinct structural contrast, and allowing researchers to observe samples from below, providing greater operational space. A microscope camera 13 may be mounted on the microscope 11 to image the microdroplet chip.

[0044] In a preferred embodiment, the laser emitter 31 is located between the microscope 11 and the stage 21. The laser emitted by the laser emitter 31 passes through the microdroplet chip and the stage 21, forming a reasonable optical path system with the laser assembly 3 and the imaging assembly 1. In some specific embodiments, the laser assembly 3 includes a laser receiver 33, with the stage 21 located between the laser receiver 33 and the laser emitter 31. The laser emitter 31 emits a laser to excite a fluorescent marker in the droplet, which emits a fluorescent signal. The laser receiver 33 receives and converts the fluorescent signal. Specifically, the laser receiver 33 includes a laser receiving lens 331 and a PMT detection device 332. The laser receiving lens 331 is located above the stage 21 to capture the fluorescent signal, and the PMT detection device 332 converts the fluorescent signal into an electrical signal.

[0045] In some specific embodiments, a support frame 34 is provided on one side of the laser receiving lens 331, and an adapter plate 35 is provided on the support frame 34. The adapter plate 35 is detachably connected to the support frame 34. The laser receiving lens 331 is mounted on the adapter plate 35, and the angle of the laser receiving lens 331 can be adjusted through the adapter plate 35. Specifically, the adapter plate 35 and the support frame 34 can be assembled using bolts and nuts. The support frame 34 and the adapter plate 35 position the laser receiving lens 331 to facilitate laser reception.

[0046] In some specific embodiments, the laser receiver 33 is connected to the data processing system 5. The laser receiver 33 receives fluorescence signals and converts them into electrical signals. The electrical signals are input to the data processing system 5, which determines whether the droplet is the desired one. The data processing system 5 is connected to a sorting electrode 4 for sorting cells at the microdroplet chip. The data processing system 5 controls the sorting electrode 4 to perform cell sorting. Specifically, the microfluidic microdroplet sorter of this invention also includes a first liquid phase drive 6 and a second liquid phase drive 61. Both the first liquid phase drive 6 and the second liquid phase drive 61 can be micropumps, which apply pressure to drive the liquid to flow in the microdroplet chip.

[0047] In a preferred embodiment, a through hole 211 is provided on the stage 21, and the microdroplet chip is suspended in the through hole 211. A clamping member 212 for positioning the microdroplet chip is provided on the stage 21. Specifically, the clamping member 212 can be a spring clip. The clamping member 212 clamps and fixes the microdroplet chip. The light source of the light source 12 illuminates the microdroplet chip, and the light passes through the through hole 211 to illuminate the microscope 11. The laser emitted by the laser emitter 31 also illuminates the microdroplet chip through the through hole 211 and is received by the laser receiving lens 331 after passing through the chip.

[0048] Example 4:

[0049] The difference between this embodiment and the above embodiment is that the stage 21 has been further structurally optimized in this embodiment.

[0050] The stage 21 in this embodiment includes a positioning plate with a slot. Specifically, the length direction of the slot is aligned with the X-axis direction, and a support plate passes through the slot. A through hole 211 is formed in the support plate, and a spring is provided on the inner wall of the slot. When the support plate is inserted into the slot, the spring is compressed and abuts against the support plate, and the elastic force acts on the support plate to fix it. The support plate can be displaced and adjusted along the X-axis direction within the slot, which is beneficial for further fine-tuning the position of the microdroplet chip. The stage 21 accurately positions the microdroplet chip onto the optical path formed by the laser component 3 and the imaging component 1.

[0051] In this utility model, unless otherwise explicitly specified and limited, the terms "installation," "connection," "joining," and "fixing," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. Those skilled in the art can understand the specific meaning of the above terms in this utility model according to the specific circumstances.

[0052] In the description of this utility model, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product of this utility model is in use. They are only for the convenience of describing this utility model 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 utility model. In addition, the terms "first," "second," and "third," etc., are only used to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0053] Furthermore, terms such as "horizontal," "vertical," and "sag" do not imply that components must be absolutely horizontal or suspended, but rather that they can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal relative to "vertical," and does not mean that the structure must be completely horizontal, but can be slightly tilted.

[0054] In this invention, unless otherwise expressly specified and limited, "above or below" the first feature may include direct contact between the first and second features, or contact between the first and second features through another feature between them. Furthermore, "above," "over," and "on" the first feature includes the first feature directly above or diagonally above the second feature, or simply indicates that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the first feature includes the first feature directly below or diagonally below the second feature, or simply indicates that the first feature is at a lower horizontal level than the second feature.

[0055] Although the description of this utility model has been given in conjunction with the specific embodiments described above, it is obvious to those skilled in the art that many substitutions, modifications, and variations can be made based on the above description. Therefore, all such substitutions, modifications, and variations are included within the spirit and scope of the appended claims.

Claims

1. A microfluidic microdroplet sorter, characterized in that, The imaging assembly (1) is formed with a detection area (14) for observing a microdroplet chip; The carrying assembly (2) comprises a stage (21) for carrying the microdroplet chip, one side of the stage (21) is provided with a first adjusting structure (22) for adjusting the stage (21) to displace within the detection area (14); and The laser assembly (3) comprises a laser emitter (31), the laser emitter (31) is located between the stage (21) and the imaging assembly (1), one side of the laser emitter (31) is provided with a second adjusting structure (32) for adjusting the laser emitter (31) to displace opposite to the microdroplet chip. The first adjusting structure (22) comprises a first adjusting sliding table (221), the stage (21) is arranged on the first adjusting sliding table (221), and the first adjusting sliding table (221) adjusts the stage (21) to displace in the X-axis direction and the Y-axis direction, respectively.

2. The microfluidic microdroplet sorter of claim 1, wherein, The imaging assembly (1) comprises a microscope (11) and a light source member (12), the detection area (14) is arranged between the microscope (11) and the light source member (12), and the light source member (12) provides light source for the microscope (11) through the microdroplet chip and the stage (21).

3. The microfluidic microdroplet sorter of claim 1, wherein, The laser emitter (31) is arranged between the microscope (11) and the stage (21), and the laser emitted by the laser emitter (31) passes through the microdroplet chip and the stage (21).

4. The microfluidic microdroplet sorter of claim 3, wherein, The second adjusting structure (32) comprises a second adjusting sliding table (321), the laser emitter (31) is arranged on the second adjusting sliding table (321), and the second adjusting sliding table (321) adjusts the laser emitter (31) to displace in the X-axis direction and the Y-axis direction, respectively.

5. The microfluidic microdroplet sorter of claim 1 or 4, wherein, The laser assembly (3) comprises a laser receiver (33), and the stage (21) is located between the laser receiver (33) and the laser emitter (31).

6. The microfluidic microdroplet sorter of claim 4, wherein, The laser receiver (33) comprises a laser receiving lens (331), one side of the laser receiving lens (331) is provided with a support frame (34), the support frame (34) is provided with an adapter plate (35), and the adapter plate (35) is detachably connected with the support frame (34).

7. The microfluidic microdroplet sorter of claim 6, wherein, The microscope (11) is an inverted microscope, and the microscope (11) is located at the bottom of the stage (21).

8. The microfluidic microdroplet sorter of claim 4, wherein, A through hole (211) is formed in the stage (21), the microdroplet chip is placed in the through hole (211) in a suspended manner, and a clamping piece (212) for positioning the microdroplet chip is arranged on the stage (21).

9. The microfluidic microdroplet sorter of claim 1, wherein, One side of the stage (21) is provided with a sorting electrode (4) for sorting cells at the microdroplet chip.

10. The microfluidic microdroplet sorter of claim 1, wherein, ​

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