Liquid drop collecting device and liquid drop collecting method
By designing a vertical flow channel and an electric field generating component in the droplet collection device, droplets can be suspended in the flow channel and demulsified and merged into larger droplets, solving the problems of droplet residue and loss, and improving collection efficiency and integrity.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-07
- Publication Date
- 2026-03-27
AI Technical Summary
Existing droplet collection devices suffer from droplet residue and loss during the collection process, especially when the droplet volume is small, leading to the failure of screening experiments.
A droplet collection device was designed, including a droplet collection chip and an electric field generating component. By vertically setting the flow channel in the droplet collection chip, the electric field generating component floats the droplets in the flow channel to a high point and suspends them. The droplets are then merged into larger droplets through demulsification and finally enter the droplet collection bottle.
It effectively reduces droplet residue during the collection process, improves the integrity and efficiency of droplet collection, and ensures accurate collection of droplets.
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Abstract
Description
Technical Field
[0001] This application relates to the field of microfluidics, specifically to a droplet collection device and a method for collecting droplets. Background Technology
[0002] Currently, after droplets containing contents are generated, they need to undergo reaction or culturing followed by screening. After obtaining the target droplets, a demulsification operation is required to make the collected droplets easy to handle. Currently, collection after screening still involves directly inserting Teflon tubes or steel needles into the chip, collecting the droplets into centrifuge tubes or well plates through tubing. Chinese patent application 202411277197.3 discloses a microdroplet collection device and method. In this patent, the collection part consists of a dispensing tube, four collection tubes, and four infusion tubes connecting the dispensing tubes and collection tubes. The collection part is a one-piece molded disposable consumable, and is fixed by a fixing part. This patent solves the droplet quality problem caused by changing tubes during droplet collection. The entire collection structure consists of centrifuge tubes and infusion tubes, utilizing gravity to evenly and stably distribute the droplets in the dispensing tube 11 into several collection tubes. However, the device in this patent typically uses fluorinated oil to push the droplets out during droplet collection. Because the droplet density is less than that of fluorinated oil, the droplets float in the fluorinated oil. Furthermore, the flow rate of the fluorinated oil within the pipeline is faster than the droplets, leading to an edge-gathering effect where the droplets tend to adhere to the inner wall of the pipeline. Using only oil for pushing results in a long collection time, and when the droplet volume is small, the droplets will float at higher points in the pipeline instead of flowing with the oil phase. When using gas for pushing, because the droplets accumulate on the inner wall of the pipeline, the gas flow first pushes away the oil phase in the pipeline, while the droplets gradually accumulate at the oil-gas interface, leaving the outermost droplets on the inner wall of the pipeline. This droplet residue on the pipeline causes droplet loss. During the screening stage, when the collected droplet volume is small, droplet loss may lead to the failure of the entire screening experiment. Summary of the Invention
[0003] To solve the above-mentioned technical problems, this application provides a droplet collection device in which no droplets remain in the flow channel within the droplet collection chip during the droplet collection process.
[0004] This application involves the following: This application provides a droplet collection device, which includes a droplet collection component and an electric field generating component. The droplet collection component includes a microfluidic chip, a droplet collection chip, and a droplet collection bottle. The droplet collection chip is connected to the microfluidic chip and the droplet collection bottle, respectively, and the droplet collection chip is arranged perpendicular to the microfluidic chip. The droplet collecting chip has a flow channel that connects the microfluidic chip and the droplet collecting bottle. The flow channel includes a first flow channel that extends from the end near the microfluidic chip into the interior of the droplet collecting chip, and the first flow channel is perpendicular to the microfluidic chip in the longitudinal direction. The electric field generating component is connected to the droplet collecting chip, and is used to fuse the droplets in the droplet collecting chip into large droplets through demulsification.
[0005] Furthermore, the equivalent inner diameter of the first flow channel gradually decreases from the side closer to the microfluidic chip to the side farther away from the microfluidic chip.
[0006] Furthermore, the flow channel also includes a second flow channel, and the first flow channel is connected to the second flow channel. The first flow channel is connected to the microfluidic chip. Preferably, the first flow channel is connected to the microfluidic chip through a guide tube, and at the connection between the guide tube and the first flow channel, the equivalent inner diameter of the guide tube is less than or equal to the equivalent inner diameter of the first flow channel. The second flow channel is connected to the droplet collection bottle. Preferably, the second flow channel is connected to the droplet collection bottle through a third flow channel.
[0007] Furthermore, the second flow channel is connected to the first flow channel at its highest point in the longitudinal direction, and the connection between the first flow channel and the second flow channel is a smooth arc-shaped connection. The highest point in the longitudinal direction of the flow channel is the connection point between the first flow channel and the second flow channel.
[0008] Furthermore, in the longitudinal direction, the height difference between the lowest point of the second flow channel and the highest point of the first flow channel is greater than or equal to 3 mm.
[0009] Furthermore, a negative pressure elimination component is also provided on the communication path between the first flow channel and the microfluidic chip; The negative pressure elimination assembly includes a connecting pipe and a clamp. The guide pipe passes through the connecting pipe and communicates with the first flow channel. A connecting conduit is also provided between the third flow channel and the droplet collection bottle, and the clamp is detachably mounted on the connecting conduit. The negative pressure elimination component is a connecting pipe fitting with a blocking function. The connecting pipe fitting is provided with a movable blocking unit. The guide pipe passes through the connecting pipe fitting, and the blocking unit can block the flow of liquid in the guide pipe.
[0010] Furthermore, the device also includes a fixed support, on which the droplet collecting chip and the electric field generating component are mounted.
[0011] Furthermore, the device also includes an imaging component, which is used to observe and / or photograph the droplets inside the droplet collection chip when the droplet collection chip is placed on a fixed support.
[0012] Furthermore, the device also includes a pumping assembly that pumps large droplets from the droplet collection chip into the droplet collection bottle.
[0013] Furthermore, the device also includes the transfer observation component, which includes a transfer bracket. The transfer bracket is provided with a first slot, a second slot, and a third slot. The first slot is used to place the droplet collection bottle, the second slot is used to place the droplet collection chip longitudinally, and the third slot is used to place the droplet collection chip horizontally.
[0014] Furthermore, the transfer observation component also includes an imaging component, which is used to observe and / or photograph the droplets inside the droplet collection chip when the droplet collection chip is placed in the third slot.
[0015] This application provides a method for collecting droplets, comprising the following steps: Provide the aforementioned apparatus; The first flow channel within the droplet collection chip is filled with fluorinated oil. The droplets inside the microfluidic chip are delivered to the droplet collection chip. Since the first flow channel is perpendicular to the microfluidic chip, the droplets entering the first flow channel gradually float upwards along the inner wall to the high point of the first flow channel and hover there. The electric field generating component fuses the droplets in the first flow channel into larger droplets through demulsification. The large droplets are transported to the droplet collection bottle.
[0016] The droplet collection device described in this application, because the first flow channel in the droplet collection chip is perpendicular to the microfluidic chip, the droplets entering the first flow channel will gradually float upwards along its inner wall to the high point of the first flow channel and hover there; then the electric field generating component will merge the droplets in the first flow channel into larger droplets through demulsification; finally, the larger droplets will flow into the droplet collection bottle, and there will be very little droplet residue throughout the process. Attached Figure Description
[0017] Figure 1 This is a schematic diagram of the droplet collection device provided in this application.
[0018] Figure 2 This is a partial structural schematic diagram of the droplet collection device provided in this application.
[0019] Figure 3 This is a flowchart illustrating the droplet collection device provided in this application for collecting droplets.
[0020] Figure 4This is a partial structural schematic diagram of the droplet collection device provided in this application.
[0021] Figure 5 This is a partial structural schematic diagram of the droplet collection device provided in this application.
[0022] Explanation of reference numerals in the attached figures 1-Microfluidic chip, 2-Droplet collection chip, 3-Negative pressure elimination component, 3a-Connecting tube, 3b-Connecting tube with blocking function, 4-Droplet collection bottle, 5-First slot, 6-Third slot, 7-Second slot, 8-Transfer bracket, 9-Electrode, 10-Pumping component, 11-Flow channel interface, 12-Electric field control component, 13-Electric field generating component, 13a-Metal spring pin, 13b-Metal needle, 14-First flow channel, 15-Second flow channel, 16-Tube clamp, 17-Fixing bracket, 18-Sample vial, 19-Imaging component. Detailed Implementation
[0023] The present application will now be described in detail with reference to the accompanying drawings, wherein the same numerals in all the drawings denote the same features. While specific embodiments of the present application are shown in the drawings, it should be understood that the present application may be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this application will be thorough and complete, and will fully convey the scope of the present application to those skilled in the art.
[0024] As used throughout the specification and claims, the terms "comprising" or "including" are open-ended and should be interpreted as "comprising but not limited to". The subsequent descriptions in the specification are preferred embodiments for carrying out this application; however, these descriptions are for the purpose of understanding the general principles of the specification and are not intended to limit the scope of this application. The scope of protection of this application shall be determined by the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.
[0025] This application provides a droplet collection device, including a droplet collection component and an electric field generating component 13. The droplet collection component includes a microfluidic chip 1, a droplet collection chip 2 and a droplet collection bottle 4. The droplet collection chip 2 is connected to the microfluidic chip 1 and the droplet collection bottle 4 respectively, and the droplet collection chip 2 is arranged perpendicular to the microfluidic chip 1. The droplet collecting chip 2 has a flow channel connecting the microfluidic chip 1 and the droplet collecting bottle 4. The flow channel includes a first flow channel 14 extending from near the microfluidic chip 1 into the droplet collecting chip 2, and the first flow channel 14 is perpendicular to the microfluidic chip 1 in the longitudinal direction. The droplet collecting chip 2 maintains a vertical position, thus ensuring that the first flow channel 14 within the droplet collecting chip 2 has a high point. This allows droplets to float and remain at the high point of the first flow channel. When the droplets float at the highest point of the first flow channel, the collected target droplets after demulsification can all form a complete large droplet, thereby being pushed into the droplet collecting bottle, reducing droplet loss during collection. If droplets overflow the first flow channel, as the amount of target droplets increases, small droplets may be directly pushed into the droplet collecting bottle without demulsification. Subsequently, the droplet collecting bottle will contain both large droplets after demulsification and small droplets that entered directly without demulsification, requiring further demulsification work, which contradicts the original design intent.
[0026] The electric field generating component 13 is connected to the droplet collecting chip 2, and is used to fuse the droplets in the droplet collecting chip 2 into larger droplets through demulsification. In the electric field generated by the electric field generating component, the droplets in the droplet collecting chip 2 lose stability, and the unstable small droplets will collide and aggregate with each other, eventually fusing into larger droplets.
[0027] The droplet collection device described in this application, since the first flow channel 14 in the droplet collection chip 2 is perpendicular to the microfluidic chip 1, the droplets entering the first flow channel 14 will gradually float upward along its inner wall to the high point of the first flow channel 14 and hover there; then the electric field generating component 13 will merge the droplets in the first flow channel 14 into large droplets through demulsification; finally, the large droplets flow into the droplet collection bottle 4, and droplet residue remains throughout the process.
[0028] In this paper, the microfluidic chip 1 and the droplet collection bottle 4 are conventional products in the prior art, and their specific structures are not described in this paper.
[0029] In this application, the equivalent inner diameter of the first flow channel gradually decreases from the side closer to the microfluidic chip to the side farther away from the microfluidic chip. The gradually decreasing channel allows air bubbles to be expelled during the process of droplet propagation within the first flow channel.
[0030] The equivalent inner diameters of the second and third flow channels can be constant or gradually change.
[0031] In this application, the flow channel further includes a second flow channel 15, and the first flow channel 14 is connected to the second flow channel 15. The first flow channel 14 is connected to the microfluidic chip 1. Preferably, the first flow channel 14 is connected to the microfluidic chip 1 through a guide tube, and at the connection between the guide tube and the first flow channel 14, the equivalent inner diameter of the guide tube is less than or equal to the equivalent inner diameter of the first flow channel 14. With this design, the droplets flow from the small channel into the large flow channel (from the guide tube into the droplet collection chip 2), ensuring that there are no dead corners where droplets get stuck at the pipe junction.
[0032] The second flow channel 15 is connected to the droplet collection bottle 4. Preferably, the flow channel further includes a third flow channel, and the second flow channel 15 is connected to the droplet collection bottle 4 through the third flow channel.
[0033] In this application, the second flow channel 15 is connected to the first flow channel 14 at its highest point along the longitudinal direction of the first flow channel 14, and the connection between the first flow channel 14 and the second flow channel 15 is a smooth arc-shaped connection; the second flow channel 15 is connected to the third flow channel at its lowest point along the longitudinal direction of the second flow channel, and the connection between the second flow channel 15 and the third flow channel is also a smooth arc-shaped connection. Using an arc-shaped connection reduces dead angles within the flow channels, preventing small droplets from accumulating in these dead angles, thereby reducing the loss of target droplets during the collection process.
[0034] The highest point of the flow channel in the longitudinal direction is the connection between the first flow channel 14 and the second flow channel 15; the lowest point in the longitudinal direction is the connection between the second flow channel 15 and the third flow channel. The first flow channel 14 is perpendicular to the third flow channel. Droplets undergo demulsification in the first flow channel 14, and merge into larger droplets in the first flow channel 14 and the second flow channel 15. The larger droplets then enter the third flow channel and subsequently enter the droplet collection bottle.
[0035] In this application, the height difference between the lowest point of the second flow channel 15 and the highest point of the first flow channel 14 in the vertical direction is greater than or equal to 3 mm, preferably 3-10 mm, for example, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, etc. This design ensures that the target droplets gather at a higher point and do not flow into the second flow channel.
[0036] In this application, a negative pressure elimination component 3 is also provided on the communication path between the first flow channel 14 and the microfluidic chip 1.
[0037] like Figure 4A. The negative pressure elimination component 3 includes a connecting pipe 3a and a pipe clamp 16. The guide pipe passes through the connecting pipe 3a and communicates with the first flow channel 14. A connecting conduit is also provided between the third flow channel and the droplet collection bottle 4, and the pipe clamp 16 is detachably mounted on the connecting conduit.
[0038] Furthermore, the material of the connecting conduit is a non-rigid material, preferably a soft material, such as a silicone tube.
[0039] like Figure 4 B, the negative pressure elimination component 3 is a connecting pipe 3b with a blocking function. The connecting pipe is provided with a movable blocking unit. The guide pipe passes through the connecting pipe, and the blocking unit can block the flow of liquid in the guide pipe.
[0040] Furthermore, the guide tube includes a first guide tube and a second guide tube. One end of the first guide tube is inserted into the microfluidic chip 1, and the other end is inserted into the connecting tube. One end of the second guide tube is inserted into the droplet collecting chip 2, and the other end is inserted into the connecting tube. The first guide tube and the second guide tube are connected within the connecting tube. The blocking unit blocks the connection between the first guide tube and the second guide tube by extending into the connecting tube. At the same time, the blocking unit can also make the first guide tube and the second guide tube connected by moving in the opposite direction.
[0041] Specifically, such as Figure 4 The negative pressure elimination component 3 in B can be a connecting valve, which can block the flow of liquid in the guide tube.
[0042] During droplet collection, the pressure inside microfluidic chip 1 and droplet collection chip 2 is the same. When droplet collection chip 2 is removed, the negative pressure causes the droplets at the higher position of droplet collection chip 2 to flow back, which may result in droplet loss. The negative pressure problem when droplet collection chip 2 is removed is solved by designing a negative pressure elimination component 3. For example... Figure 4 In structure A, by forming a sleeve through which the guide tube passes through the connecting pipe, the bottom end of the droplet collecting chip 2 is gradually exposed to atmospheric pressure when it is pulled out. Before the tube is pulled out, the connecting pipe is clamped by the pipe clamp 16, maintaining the same pressure in the flow channel within the droplet collecting chip 2, thus preventing the droplets from flowing back due to a momentary pressure difference. Figure 4 In structure B, the tube at the bottom of the droplet collecting chip 2 is sealed off by the blocking unit, isolating it from the microfluidic chip 1. At this time, the flow channels of the microfluidic chip 1 and the droplet collecting chip 2 are two pressure systems. Thus, when the droplet collecting chip 2 is pulled out, the droplets in its flow channel will not flow back, and the pressure in the flow channel of the droplet collecting chip 2 is stable, so the droplets in the flow channel will not flow out of the droplet collecting chip 2.
[0043] In this application, as Figure 1 As shown, the device also includes a fixed bracket 17, on which the droplet collecting chip 2 and the electric field generating component 13 are both mounted.
[0044] like Figure 2 As shown, the device also includes an imaging component 19. When the droplet collection chip 2 is placed on the fixed support 17, the imaging component 19 is used to observe and / or photograph the droplets inside the droplet collection chip 2. This design allows for real-time observation of the target droplet collection during microdroplet sorting, ensuring visualization of the sorting process.
[0045] In this application, the electric field generating component 13 can be a metal spring pin or a metal needle.
[0046] In this application, the droplet collection chip 2 is provided with electrodes, which are electrically connected to the electric field generating component 13. The number of electrodes is at least two, and for example, there can be two, three, four, five, six, seven, or more. The electrodes are used to form an electric field that covers the first flow channel and the second flow channel, thereby ensuring that the collected target droplets can be completely demulsified.
[0047] like Figure 5 As shown in Figure A, 2A and 2B are two different droplet collection chips.
[0048] like Figure 5 As shown in 2A of A, the droplet collecting chip has two electrodes, which are respectively disposed on both sides of the third flow channel. One electrode is close to the second flow channel and the other electrode is close to the first flow channel, so that the electric field formed therein can cover the first and second flow channels.
[0049] like Figure 5 As shown in 2B of A, the droplet collecting chip has two electrodes, one of which is located near the first flow channel and the other is located near the second flow channel, so that the electric field formed by them can cover the first and second flow channels.
[0050] Furthermore, the electric field generating component 13a connects to the electrodes 9 on the droplet collecting chips 2A / 2B, forming an electric field within the droplet collecting chips 2A / 2B, thereby causing the droplets within the droplet collecting chips 2A / 2B to fuse. The arrangement of the metal spring pins 13a depends on the position of the electrodes 9 of the droplet collecting chips 2A / 2B used.
[0051] like Figure 5As shown in Figure B, the droplet collection chip 2C does not have an electrode 9. The electric field generating component 13 used with it is a metal needle 13b that can generate electricity through corona discharge. There can be one or more metal needles 13b, for example, three. The three metal needles 13b are located near the connection between the first flow channel and the second flow channel. For example, one is located outside the highest point of the first flow channel, another is located outside the second flow channel near the highest point of the first flow channel, and the last is located outside the first flow channel near the highest point of the first flow channel.
[0052] Furthermore, the device of this application also includes an electric field control component 12, which is electrically connected to the electric field generating component 13, and the electric field control component 12 is used to supply power to the electric field generating component.
[0053] In this application, the device further includes a sample introduction component, which is connected to the microfluidic chip 1.
[0054] In this application, as Figure 1 as well as Figure 3 As shown, the device also includes a pumping assembly 10, which pumps large droplets from the droplet collection chip 2 to the droplet collection bottle 4.
[0055] The pumping device can be a peristaltic pump or an air pump.
[0056] Figure 3 A flowchart for droplet collection, including... Figure 3 A, Figure 3 B Figure 3 C1 and Figure 3 C2, where Figure 3 A represents the process of droplet transfer to droplet collection chip 2. Figure 3 B represents the process of the droplet being transferred to the droplet collection chip 2 and then observed. Figure 3 C1 and Figure 3 C2 represents the process of droplet demulsification and fusion. Figure 3 C1 is Figure 3 Side view of C2.
[0057] In this application, as Figure 3 As shown, the device also includes the transfer observation component, which includes a transfer bracket 8. The transfer bracket 8 is provided with a first slot 5, a second slot 7 and a third slot 6. The first slot 5 is used to place the droplet collection bottle 4, the second slot 7 is used to place the droplet collection chip 2 longitudinally, and the third slot 6 is used to place the droplet collection chip 2 horizontally.
[0058] Furthermore, the transfer observation component also includes a photographing component 19, which is used to observe and / or photograph the droplets inside the droplet collection chip 2 when the droplet collection chip 2 is placed in the third slot 6.
[0059] This application also includes a method for collecting droplets, comprising the following steps: Step 1: Provide the aforementioned device; Step 2: Fill the first flow channel 14 within the droplet collection chip 2 with fluorinated oil. Step 3: The droplets in the microfluidic chip 1 are transported to the droplet collection chip 2. Since the first flow channel 14 is perpendicular to the microfluidic chip 1, the droplets entering the first flow channel 14 gradually float upward along the inner wall to the high point of the first flow channel 14 and hover there. Step 4: The electric field generating component 13 fuses the droplets in the first flow channel 14 into larger droplets through demulsification; Step 5: Transport the large droplet to the droplet collection bottle 4.
[0060] Example This application provides a general and / or specific description of the materials and test methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. Reagents or instruments used, unless otherwise specified, are all commercially available conventional reagent products.
[0061] Example 1 like Figure 1 As shown, the device in this embodiment includes a droplet collection component, a pumping component 10, a sample injection component, a fixing bracket 17, an electric field generating component 13, an electric field control component 12, and an imaging component 19.
[0062] The droplet collection assembly includes a microfluidic chip 1, a droplet collection chip 2, and a droplet collection bottle 4. The droplet collection chip 2 is connected to both the microfluidic chip 1 and the droplet collection bottle 4. The droplet collection chip 2 is mounted on the fixed support 17 and is perpendicular to the microfluidic chip 1. The droplet collection chip 2 has a flow channel connecting the microfluidic chip 1 and the droplet collection bottle 4. The flow channel includes a first flow channel 14, a second flow channel 15, and a third flow channel connected in sequence. The first flow channel 14 extends from the end near the microfluidic chip 1 into the interior of the droplet collection chip 2, and its inner diameter gradually decreases (the inner diameter at the minimum inner diameter of the first flow channel is 300 μm, and the inner diameter at the maximum inner diameter of the first flow channel is 710 μm). The third flow channel is connected to the droplet collection bottle 4, and the first flow channel 14 is perpendicular to the microfluidic chip 1 in the longitudinal direction. The second flow channel 15 is connected to the first flow channel 14 at its highest point along the longitudinal direction of the first flow channel 14, and the connection between the first flow channel 14 and the second flow channel 15 is a smooth arc-shaped connection. The height difference between the lowest point of the second flow channel 15 and the highest point of the first flow channel 14 along the longitudinal direction is 6 mm. The second flow channel 15 is connected to the third flow channel at its lowest point along the longitudinal direction of the second flow channel, and the connection between the second flow channel 15 and the third flow channel is a smooth arc-shaped connection. The first flow channel 14 is perpendicular to the third flow channel. Both the second flow channel 15 and the third flow channel have equal diameters, and the inner diameter of the second flow channel is 300 μm. The inner diameter of the third flow channel is also 300 μm. The first flow channel 14 is connected to the microfluidic chip 1 through a guide tube (the guide tube is a pipe with a uniform inner diameter; the outer diameter of the guide tube is 1.31 ± 0.1 mm, and the inner diameter is 0.66 ± 0.1 mm), and the connection point between the guide tube and the first flow channel 14 is [not specified]. The droplet collecting chip 2 is provided with two electrodes 9, which are respectively located on both sides of the third flow channel, with one electrode closer to the second flow channel and the other closer to the first flow channel (e.g., ...). Figure 5 (As shown in ②A in A).
[0063] The sample introduction component is connected to the pumping component 10 and the microfluidic chip 1. The sample introduction component is a sample bottle 18.
[0064] The electric field control component 12 is electrically connected to the electric field generating component 13. The electric field generating component 13 is disposed on the fixed bracket 17 and connected to the electrode 9 on the droplet collecting chip 2. The electric field generating component 13 is a metal spring pin 13a, and the electric field it generates can cover the first flow channel and the second flow channel.
[0065] The camera component 19 is positioned directly in front of the droplet collection chip 2.
[0066] In use, the device of this embodiment pumps the liquid sample from the sample introduction component into the microfluidic chip 1 via the pumping component 10. The liquid sample forms droplets within the microfluidic chip 1, and these droplets then enter the droplet collection chip 2 through a guide tube. Since the first flow channel 14 is perpendicular to the microfluidic chip 1, the droplets entering the first flow channel 14 gradually float upwards along its inner wall to the highest point of the first flow channel 14, where they hover. Then, the electric field generating component 13 demulsifies the droplets in the first flow channel 14 and the second flow channel 15, fusing them into larger droplets. Finally, the pumping component 10 pumps these larger droplets through the third flow channel into the droplet collection bottle 4. No droplets remain throughout the process. Before the larger droplets enter the droplet collection bottle 4, the droplets in the first flow channel 14 and the second flow channel 15 can be observed and photographed using the imaging component 19.
[0067] Example 2 like Figure 3 As shown, the device in this embodiment includes a droplet collection component, a first pumping component and a second pumping component, a sample injection component, a negative pressure elimination component 3, a transfer observation component, an electric field generating component 13, an electric field control component 12, and an imaging component 19.
[0068] The droplet collection assembly includes a microfluidic chip 1, a droplet collection chip 2, a longitudinal fixing groove, and a droplet collection bottle 4. The droplet collection chip 2 is connected to both the microfluidic chip 1 and the droplet collection bottle 4. The droplet collection chip 2 is disposed on the longitudinal fixing groove and is perpendicular to the top of the microfluidic chip 1. The droplet collection chip 2 has a flow channel connecting the microfluidic chip 1 and the droplet collection bottle 4. The flow channel includes a first flow channel 14, a second flow channel 15, and a third flow channel connected in sequence. The first flow channel 14 extends from the end near the microfluidic chip 1 into the interior of the droplet collection chip 2, and its inner diameter gradually decreases (the inner diameter at the minimum inner diameter of the first flow channel is 300 μm, and the inner diameter at the maximum inner diameter of the first flow channel is 710 μm). The third flow channel is connected to the droplet collection bottle 4, and the first flow channel 14 is perpendicular to the microfluidic chip 1 in the longitudinal direction. The second flow channel 15 is connected to the first flow channel 14 at its highest point along the longitudinal direction of the first flow channel 14, and the connection between the first flow channel 14 and the second flow channel 15 is a smooth arc-shaped connection. In the longitudinal direction, the height difference between the lowest point of the second flow channel 15 and the highest point of the first flow channel 14 is 6 mm. The second flow channel 15 is connected to the third flow channel at its lowest point along the longitudinal direction of the second flow channel, and the connection between the second flow channel 15 and the third flow channel is a smooth arc-shaped connection. The first flow channel 14 is perpendicular to the third flow channel. Both the second flow channel 15 and the third flow channel have equal diameter structures, with the inner diameter of the second flow channel being 300 μm and the inner diameter of the third flow channel being 300 μm. The first flow channel 14 is connected to the microfluidic chip 1 via a guide tube (the outer diameter of the guide tube is 1.31±0.1mm, and its inner diameter is 0.66±0.1mm, and the guide tube is located at the connection point between the guide tube and the first flow channel 14). The droplet collection chip 2 is equipped with three electrodes 9: one electrode 9 is located outside the highest point of the first flow channel, another electrode 9 is located outside the second flow channel near the highest point of the first flow channel, and the last electrode 9 is located outside the first flow channel near the highest point of the first flow channel (e.g., ...). Figure 5 As shown in B).
[0069] The negative pressure elimination component 3 includes a connecting pipe and a pipe clamp 16. The guide pipe passes through the connecting pipe and communicates with the first flow channel 14. A connecting conduit is also provided between the second flow channel 15 and the droplet collection bottle 4, and the pipe clamp 16 is detachably mounted on the connecting conduit.
[0070] The sample introduction component is connected to the first pumping component and the microfluidic chip 1.
[0071] The second pumping component is connected to the flow channel interface 11 of the droplet collection chip 2.
[0072] The transfer observation assembly includes a transfer bracket 8, which is provided with a first slot 5, a second slot 7 and a third slot 6. The first slot 5 is used to place the droplet collection bottle 4, the second slot 7 is used to place the droplet collection chip 2 longitudinally, and the third slot 6 is used to place the droplet collection chip 2 horizontally.
[0073] The electric field control component 12 is electrically connected to the electric field generating component 13. The electric field generating component 13 is connected to the electrode 9 on the droplet collecting chip 2. The electric field generating component 13 is a metal spring pin 13a, and the electric field it generates can cover the first flow channel and the second flow channel.
[0074] The camera component 19 is positioned directly in front of the droplet collection chip 2.
[0075] In use, the device of this embodiment pumps the liquid sample from the sample introduction component into the microfluidic chip 1 via the first pumping component. The liquid sample forms droplets within the microfluidic chip 1, and then the droplets enter the droplet collection chip 2 through the guide tube. Since the first flow channel 14 is perpendicular to the microfluidic chip 1, the droplets entering the first flow channel 14 gradually float upwards along its inner wall to the highest point of the first flow channel 14 and hover there. Then, the connection between the droplet collection chip 2 and the microfluidic chip 1 is disconnected. When the droplet collection chip 2 is pulled out, the bottom end of the droplet collection chip 2 is gradually exposed to atmospheric pressure. Before pulling out the tube, the connecting tube is clamped by the tube clamp 16 to maintain the same pressure in the flow channel within the droplet collection chip 2, thereby preventing the droplets in the flow channel from flowing back due to a momentary pressure difference. Then, the droplet collecting chip 2 is transferred to the second slot 7 or the third slot 6, while the droplet collecting bottle 4 is transferred to the first slot 5. The droplets in the droplet collecting chip 2 are observed and photographed by the imaging component 19. After the photographing is completed, the droplets in the first flow channel 14 are fused into larger droplets in the first flow channel 14 and the second flow channel 15 by the electric field generating component 13 through demulsification. Finally, the larger droplets are pumped into the droplet collecting bottle 4 through the third flow channel by the second pumping component, and no droplets remain throughout the process.
[0076] The droplet collection device in Example 3 differs from that in Example 1 in that the height difference between the lowest point of the second flow channel and the highest point of the first flow channel is 1 mm, while all other parameters are the same.
[0077] The droplet collection device in Example 4 differs from that in Example 1 in that the outer diameter of the guide tube is 1.41±0.1 mm and the inner diameter is 0.81±0.1 mm, while all other parameters are the same. The parameters of the device in this application are shown in Table 1.
[0078] The droplet collecting device in Example 5 differs from that in Example 1 in that the position of the electrode on the droplet collecting chip is different. In this example, the electrode is set on the droplet collecting chip 2 with one electrode 9. The electrode 9 is located outside the second flow channel, but the electric field formed by the electrode cannot completely cover the first and second flow channels. All other parameters are the same.
[0079] The droplet collection device of Comparative Example 1 includes a microfluidic chip and a droplet collection bottle, which are connected by a conduit. The parameters of the device in Comparative Example 1 are shown in Table 1.
[0080] Experimental Example Take 15µl of green fluorescent microspheres (470 / 515nm, particle size 5µm, Aladdin), dilute with 500µl PBS + 470µl PVP as aqueous phase reagent, and generate droplets with a diameter of approximately 30µm using droplet generation oil (provided by Luoyang Huaqing Tianmu Biotechnology Co., Ltd.) and droplet generation chip (provided by Luoyang Huaqing Tianmu Biotechnology Co., Ltd.).
[0081] The droplets were pumped to the droplet collection devices of Examples 1-5 and Comparative Example 1 of this application for collection, and the results are shown in Table 1.
[0082] Table 1 shows the parameters for each embodiment and comparative example.
[0083] Summary: As shown in the table above, when using the device of this application for cell collection, there are fewer residual droplets in the droplet collection chip, and the droplet collection rate in both the droplet collection chip and the droplet collection bottle is relatively high.
[0084] The description in this disclosure is provided for illustrative and descriptive purposes only and is not intended to be exhaustive or to limit the disclosure to its forms. Many modifications and variations will be apparent to those skilled in the art. The embodiments were chosen and described in order to better illustrate the principles and practical application of this disclosure and to enable those skilled in the art to understand this disclosure and to design various embodiments with various modifications suitable for a particular purpose.
Claims
1. A droplet collecting device, wherein, The device includes a droplet collection component and an electric field generating component. The droplet collection component includes a microfluidic chip, a droplet collection chip, and a droplet collection bottle. The droplet collection chip is connected to the microfluidic chip and the droplet collection bottle, respectively, and the droplet collection chip is arranged perpendicular to the microfluidic chip. The droplet collecting chip has a flow channel that connects the microfluidic chip and the droplet collecting bottle. The flow channel includes a first flow channel that extends from the end near the microfluidic chip into the interior of the droplet collecting chip, and the first flow channel is perpendicular to the microfluidic chip in the longitudinal direction. The electric field generating component is connected to the droplet collecting chip, and is used to fuse the droplets in the droplet collecting chip into large droplets through demulsification.
2. The apparatus according to claim 1, wherein, The equivalent inner diameter of the first flow channel gradually decreases from the side closer to the microfluidic chip to the side farther away from the microfluidic chip.
3. The apparatus according to claim 1, wherein, The flow channel further includes a second flow channel, and the first flow channel is connected to the second flow channel. The first flow channel is connected to the microfluidic chip. Preferably, the first flow channel is connected to the microfluidic chip through a guide tube, and at the connection between the guide tube and the first flow channel, the equivalent inner diameter of the guide tube is less than or equal to the equivalent inner diameter of the first flow channel. The second flow channel is connected to the droplet collection bottle. Preferably, the second flow channel is connected to the droplet collection bottle through a third flow channel.
4. The apparatus according to claim 3, wherein, The second flow channel is connected to the first flow channel at its highest point in the longitudinal direction, and the connection between the first flow channel and the second flow channel is a smooth arc-shaped connection; The highest point in the longitudinal direction of the flow channel is the connection point between the first flow channel and the second flow channel.
5. The apparatus according to claim 4, wherein, In the longitudinal direction, the height difference between the lowest point of the second flow channel and the highest point of the first flow channel is greater than or equal to 3 mm.
6. The apparatus according to claim 3, wherein, A negative pressure elimination component is also provided on the connection path between the first flow channel and the microfluidic chip; The negative pressure elimination assembly includes a connecting pipe and a clamp. The guide pipe passes through the connecting pipe and communicates with the first flow channel. A connecting conduit is also provided between the third flow channel and the droplet collection bottle, and the clamp is detachably mounted on the connecting conduit. The negative pressure elimination component is a connecting pipe fitting with a blocking function. The connecting pipe fitting is provided with a movable blocking unit. The guide pipe passes through the connecting pipe fitting, and the blocking unit can block the flow of liquid in the guide pipe.
7. The apparatus according to claim 1, wherein, The device also includes a fixed bracket, on which the droplet collecting chip and the electric field generating component are mounted.
8. The apparatus according to claim 7, wherein, The device also includes an imaging component, which is used to observe and / or photograph the droplets inside the droplet collection chip when the droplet collection chip is placed on a fixed support.
9. The apparatus according to claim 1, wherein, The device also includes a pumping assembly that pumps large droplets from the droplet collection chip into the droplet collection bottle.
10. The apparatus according to claim 1, wherein, The device further includes the transfer observation component, which includes a transfer bracket. The transfer bracket is provided with a first slot, a second slot, and a third slot. The first slot is used to place the droplet collection bottle, the second slot is used to place the droplet collection chip longitudinally, and the third slot is used to place the droplet collection chip horizontally.
Citation Information
Patent Citations
Micro-droplet collecting device and collecting method
CN119114175A