Liquid drop electrofusion chip and liquid drop electrofusion method
By designing a droplet electrofusion chip with adjustable width and height, the problem that existing chips can only fuse droplets of specific sizes has been solved, achieving efficient fusion of droplets of different sizes, improving fusion efficiency and reducing the number of chips.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-22
- Publication Date
- 2026-03-13
AI Technical Summary
Existing droplet electrofusion chips can only fuse droplets of specific sizes, lacking versatility. Multiple chips need to be fabricated to fuse droplets of different sizes.
A droplet electrofusion chip was designed, which includes an adjustment component that can adjust the width or height of the fusion channel to adapt to the fusion of droplets of different sizes. The electrofusion of droplets is achieved by using conductive components.
It enables universal fusion of droplets of different sizes, improving fusion efficiency and flexibility, and reducing the number of chips fabricated and reagent consumption.
Smart Images
Figure CN121648995A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of droplet fusion technology, and in particular to droplet electrofusion chips and droplet electrofusion methods. Background Technology
[0002] Microfluidic droplet electrofusion technology is a cutting-edge technology that combines the precise manipulation of microfluidic droplets with electric field-induced fusion. It has broad and important applications in many fields, including synthetic biology and biomanufacturing, single-cell analysis and biological research, cell therapy and regenerative medicine (especially CAR-T / NK therapy), fertilization and reproductive biology, and materials science and chemical synthesis. Its core advantages are: (1) High throughput. It can generate, manipulate and fuse tens of thousands of droplets per second, meeting the needs of statistical analysis. (2) Precise control. It can achieve programmable precise fusion such as one-to-one and one-to-many, avoiding cross-contamination and waste. (3) High single-cell / single-molecule precision, providing unprecedented resolution for life science research. (4) Extremely low reagent consumption. Reactions are carried out at nanoliter or picoliter levels, greatly saving precious biological samples and expensive reagents. (5) Fast reaction speed. Mixing within the droplet is completed within milliseconds, suitable for studying rapid biochemical reactions. (6) Closed fusion environment. The droplet acts as an independent microreactor, completely isolated from the outside world, avoiding evaporation and contamination.
[0003] However, existing chips for droplet electrofusion are often only designed for specific sizes, meaning one chip corresponds to the fusion of droplets of a specific size, and therefore lack versatility. If multiple droplet sizes need to be fused, multiple chips need to be fabricated accordingly. Summary of the Invention
[0004] The present invention aims to at least solve one of the technical problems existing in the prior art. To this end, the present invention proposes a droplet electrofusion chip and a droplet electrofusion method.
[0005] The solution to the technical problem of this invention is: Firstly, a droplet electrofusion chip is proposed, comprising: The chip body is provided with a first injection channel, a second injection channel, a bus channel, a fusion channel and an exhaust channel. The outlet end of the first injection channel and the outlet end of the second injection channel are respectively connected to the inlet end of the bus channel. The fusion channel extends along a first direction, and the two ends of the fusion channel along the first direction are respectively connected to the outlet end of the bus channel and the inlet end of the exhaust channel. A conductive component includes a first electrode and a second electrode, wherein the first electrode and the second electrode are respectively disposed on both sides of the fusion channel along a second direction or on both sides of the fusion channel along a third direction, and the first direction, the second direction and the third direction are mutually perpendicular. An adjustment component, connected to the sidewall of the fusion channel, is used to adjust the width of the fusion channel along the second direction or the height along the third direction.
[0006] The present invention has at least the following beneficial effects: a first injection channel is used to inject a first droplet into a confluence channel, and a second injection channel is used to inject a second droplet into a confluence channel. After the first and second droplets enter the fusion channel, they undergo electrofusion under the action of a first electrode and a second electrode. Furthermore, due to the inclusion of an adjustment component, the width or height of the fusion channel can be adjusted to accommodate the fusion of droplets of different sizes.
[0007] As a further improvement to the above technical solution, the width of the fusion channel along the second direction is smaller than the width of the outlet end of the confluence channel along the second direction; the height of the fusion channel along the third direction is greater than the height of the outlet end of the confluence channel along the third direction; the adjusting component is driven to one side of the fusion channel to drive the width adjustment of the fusion channel along the second direction.
[0008] As a further improvement to the above technical solution, the adjusting component is an airbag. The airbag is located on the outside of the fusion channel and abuts against one side wall of the fusion channel. When the airbag is inflated, the airbag squeezes the side wall of the fusion channel that abuts against it and reduces the width of the fusion channel along the second direction.
[0009] As a further improvement to the above technical solution, the width of the fusion channel along the second direction is greater than the width of the outlet end of the confluence channel along the second direction; the height of the fusion channel along the third direction is less than the height of the outlet end of the confluence channel along the third direction; the adjusting component is driven to one side of the fusion channel to drive the height adjustment of the fusion channel along the third direction.
[0010] As a further improvement to the above technical solution, the adjusting component is a micro-valve, which is provided with a gas valve diaphragm. The gas valve diaphragm abuts against the side wall of the fusion channel. When pressure is applied to the micro-valve, the gas valve diaphragm pushes the side wall of the fusion channel to move and lowers the height of the fusion channel along the third direction.
[0011] As a further improvement to the above technical solution, the first injection channel includes a first flow channel, a second flow channel, and a droplet generation flow channel. The inlet end of the droplet generation flow channel is connected to the outlet ends of the first flow channel and the second flow channel, respectively, and the outlet end of the droplet generation flow channel is connected to the inlet end of the confluence channel.
[0012] As a further improvement to the above technical solution, the droplet electrofusion chip also includes an observation structure, which is disposed on the chip body and located between the inlet end and the outlet end of the discharge channel. The observation structure is used to observe the droplets in the discharge channel.
[0013] As a further improvement to the above technical solution, the first electrode is a liquid metal electrode, and the second electrode is a liquid metal electrode or a brine electrode.
[0014] Secondly, a droplet electrical fusion method is proposed, applied to a droplet electrical fusion chip as described in any of the technical solutions in the first aspect, the droplet electrical fusion method comprising the following steps: The width of the fusion channel along the second direction or the height along the third direction is adjusted by the adjusting component according to the diameter of the droplets to be fused. The droplets to be fused are injected into the confluence channel through the first injection channel and the second injection channel, respectively; When the droplets to be fused flow into the fusion channel, an alternating current is applied to the fusion channel through the first electrode and the second electrode to cause the droplets to fuse.
[0015] As a further improvement to the above technical solution, before performing the step of injecting the droplets to be fused into the confluence channel through the first injection channel and the second injection channel respectively, the injection frequency or generation frequency of the droplets is adjusted.
[0016] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description
[0017] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly explained below. Obviously, the described drawings are only a part of the embodiments of the present invention, and not all of them. Those skilled in the art can obtain other design schemes and drawings based on these drawings without creative effort.
[0018] Figure 1 These are schematic diagrams of the structure of droplet electrofusion chips according to some embodiments of the present invention; Figure 2 yes Figure 1 A magnified view of part A in the middle; Figure 3 This is a schematic diagram of the structure of a droplet electrofusion chip according to other embodiments of the present invention; Figure 4 yes Figure 3A magnified view of part B in the middle section; Figure 5 This is a flowchart of the droplet electrofusion method according to an embodiment of the present invention.
[0019] Reference numerals: 100, First injection channel; 110, First flow channel; 120, Second flow channel; 130, Droplet generation flow channel; 200, Second injection channel; 300, Confluence channel; 400, Fusion channel; 500, Discharge channel; 600, First electrode; 700, Second electrode; 800, Observation structure; 900, Adjustment component; 910, Airbag; 920, Microvalve. Detailed Implementation
[0020] Embodiments of the present invention are described in detail below. Examples of these embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.
[0021] In the description of this invention, the orientation descriptions, such as up, down, front, back, left, right, etc., are 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 limiting this invention.
[0022] In the description of this invention, "several" means one or more, "more than" means two or more, "greater than," "less than," and "exceeding" are understood to exclude the stated number, while "above," "below," and "within" are understood to include the stated number. The use of "first" and "second" in the description is merely for distinguishing technical features and should not be construed as indicating or implying relative importance, or implicitly indicating the number of indicated technical features, or implicitly indicating the order of the indicated technical features.
[0023] In the description of this invention, unless otherwise explicitly defined, terms such as "set up," "install," and "connect" should be interpreted broadly, and those skilled in the art can reasonably determine the specific meaning of the above terms in this invention in conjunction with the specific content of the technical solution.
[0024] Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention. The various technical features of the present invention can be combined interactively without contradicting each other.
[0025] Reference Figures 1 to 4Firstly, the present invention provides a droplet electrofusion chip that is applicable to droplet fusion of different sizes and has versatility.
[0026] The droplet electrofusion chip includes a chip body, conductive components, and an adjustment component 900. The chip body is provided with a first injection channel 100, a second injection channel 200, a confluence channel 300, a fusion channel 400, and an outlet channel 500. The outlet ends of the first injection channel 100 and the second injection channel 200 are respectively connected to the inlet end of the confluence channel 300. The fusion channel 400 extends along a first direction, and its two ends along the first direction are respectively connected to the outlet end of the confluence channel 300 and the inlet end of the outlet channel 500. The conductive components include a first electrode 600 and a second electrode 700, which are respectively disposed on both sides of the fusion channel 400 along the second direction or on both sides of the fusion channel 400 along a third direction. When the first electrode 600 and the second electrode 700 are energized, they enable two or more close-proximity droplets located within the fusion channel 400 to fuse. The adjusting component 900 is connected to the side wall of the fusion channel 400, and the adjusting component 900 is used to adjust the width of the fusion channel 400 along the second direction or the height along the third direction.
[0027] It is understandable that the first direction, the second direction, and the third direction are perpendicular to each other. For ease of description, the left and right direction will be used as the first direction, the front and back direction as the second direction, and the up and down direction as the third direction.
[0028] In some embodiments, the first electrode 600 is disposed on the rear side of the fusion channel 400, while the second electrode 700 is disposed on the front side of the fusion channel 400.
[0029] In this embodiment, the first injection channel 100 is used to inject a first droplet into the confluence channel 300, and the second injection channel 200 is used to inject a second droplet into the confluence channel 300. After the first and second droplets enter the fusion channel 400, they undergo electrofusion under the action of the first electrode 600 and the second electrode 700. Because an adjustment component 900 is provided, the width or height of the fusion channel 400 can be adjusted to accommodate the fusion of droplets of different sizes.
[0030] In some embodiments, refer to Figure 1 and Figure 2 The width of the fusion channel 400 in the front-to-back direction is smaller than the width of the outlet end of the confluence channel 300 in the front-to-back direction, while the height of the fusion channel 400 in the vertical direction is greater than the height of the outlet end of the confluence channel 300 in the vertical direction. The adjusting component 900 is driven to the front or rear side of the fusion channel 400, and under the action of the adjusting component 900, the width of the fusion channel 400 in the front-to-back direction can be increased or decreased.
[0031] To achieve high-throughput electrofusion, in some embodiments, the width of the fusion channel 400 in the front-to-back direction is smaller than the diameter of the larger droplet to be fused, while its height in the vertical direction is greater than the diameter of the larger droplet to be fused. For example, in some embodiments, the diameter of the first droplet is larger than the diameter of the second droplet, the width of the fusion channel 400 in the front-to-back direction is smaller than the diameter of the first droplet, and the height of the fusion channel 400 in the vertical direction is greater than the diameter of the first droplet. When the first droplet and the second droplet are electrofused using a droplet electrofusion chip, the first droplet flows into the fusion channel 400. The front and rear sides of the first droplet are clamped by the sidewalls of the fusion channel 400, reducing the velocity of the first droplet. The gaps between the upper and lower sides of the first droplet and the sidewalls of the fusion channel 400 prevent complete blockage of the fusion channel 400. The second droplet can flow at its original velocity or a faster velocity. The second droplet approaches the first droplet and, under the action of the first electrode 600 and the second electrode 700, achieves high-throughput fusion.
[0032] It is understood that, based on the above embodiments, the width of the fusion channel 400 in the front-to-back direction is greater than the diameter of the second droplet. The fusion channel 400 will not reduce the flow velocity of the second droplet, so as to ensure that the generation velocity of the second droplet matches the fusion velocity and achieve high-throughput fusion.
[0033] In some embodiments, refer to Figure 1 and Figure 2 The adjusting component 900 is an airbag 910, which is located on the rear side of the fusion channel 400 and abuts against the rear side of the fusion channel 400. When the airbag 910 is inflated, the airbag 910 squeezes the rear wall of the fusion channel 400 and reduces the width of the fusion channel 400 in the front-back direction, thereby enabling the clamping of the smaller first droplet.
[0034] The droplet electrofusion chip can fuse droplets with diameters ranging from 10 μm to 300 μm. Taking microbial culture sorting as an example, using a first droplet with a diameter of 67 μm and a second droplet with a diameter of 30 μm, a fusion channel width of 55 μm is suitable for fusing 67 μm and 30 μm droplets. If a first droplet with a diameter of 55 μm is used, a fusion channel width of 55 μm is too large. In this case, by inflating the air bladder 910, the width of the fusion channel 400 is further compressed and narrowed to 50 μm to accommodate the 55 μm diameter first droplet.
[0035] In some embodiments, two first electrodes 600 are provided, and an airbag 910 is located between the two first electrodes 600.
[0036] The width of the fusion channel 400 in the front-to-back direction is greater than or equal to 0.3 times the diameter of the first droplet and less than or equal to 0.99 times the diameter of the first droplet. The height of the fusion channel 400 in the vertical direction is greater than or equal to 1.01 times the diameter of the first droplet and less than or equal to 10 times the diameter of the first droplet. It is understood that the height of the fusion channel 400 in the vertical direction also needs to take into account the size of the second droplet to ensure that the second droplet does not flow through the gap between the fusion channel 400 and the first droplet. Preferably, the height of the fusion channel 400 in the vertical direction is greater than the diameter of the first droplet and less than the sum of the diameters of the two droplets.
[0037] Understandably, within this size range, the fusion channel 400 can effectively clamp the front and rear sides of the incoming first droplet, reducing the speed of the first droplet while ensuring that the first droplet can still move along the extension direction of the fusion channel 400. It also prevents the fusion channel 400 from being blocked by the first droplet, thus slowing down the second droplet, allowing the first and second droplets to approach and merge within the fusion channel 400.
[0038] In other embodiments, reference is made to Figure 3 and Figure 4 The width of the fusion channel 400 in the front-to-back direction is greater than the width of the outlet end of the confluence channel 300 in the front-to-back direction, and the height of the fusion channel 400 in the vertical direction is less than the height of the outlet end of the confluence channel 300 in the vertical direction. The adjustment component 900 is driven to the upper or lower side of the fusion channel 400. Under the driving action of the adjustment component 900, the height of the fusion channel 400 can be adjusted.
[0039] To achieve high-throughput electrofusion, in some embodiments, the height of the fusion channel 400 in the vertical direction is smaller than the diameter of the larger droplet to be fused, while the width in the front-back direction is larger than the diameter of the larger droplet to be fused. For example, in some embodiments, the diameter of the first droplet is larger than the diameter of the second droplet, the height of the fusion channel 400 in the vertical direction is smaller than the diameter of the first droplet, and the width of the fusion channel 400 in the front-back direction is larger than the diameter of the first droplet. When the droplet electrofusion chip of this embodiment is used to electrofuse the first droplet and the second droplet, the first droplet flows into the fusion channel 400, and its upper and lower sides are clamped by the sidewalls of the fusion channel 400, reducing its velocity. Since there are gaps between the front and back sides of the first droplet and the sidewalls of the fusion channel 400, the fusion channel 400 is not completely blocked. The second droplet can flow at its original velocity or a faster velocity, and the second droplet approaches the first droplet, achieving high-throughput fusion under the action of the first electrode 600 and the second electrode 700.
[0040] It is understood that, based on the above embodiments, the height of the fusion channel 400 in the vertical direction is greater than the diameter of the second droplet. The fusion channel 400 will not reduce the flow velocity of the second droplet, so as to ensure that the generation rate of the second droplet matches the fusion rate and achieve high-throughput fusion.
[0041] In some embodiments, refer to Figure 3 and Figure 4 The regulating component 900 is a micro valve 920. The micro valve 920 is equipped with a gas valve diaphragm. The gas valve diaphragm abuts against the lower wall of the fusion channel 400. When the operator applies pressure to the micro valve 920, the gas valve diaphragm can push the lower wall of the fusion channel 400 to move upward, thereby reducing the height of the fusion channel 400 and enabling it to hold the smaller first droplet.
[0042] The droplet electrofusion chip can fuse droplets with diameters ranging from 10 μm to 300 μm. Taking microbial culture sorting as an example, using a first droplet with a diameter of 67 μm and a second droplet with a diameter of 30 μm, a height of 55 μm for the fusion channel 400 is suitable for fusing 67 μm and 30 μm droplets. If a first droplet with a diameter of 55 μm is used, a height of 55 μm for the fusion channel 400 is too high. In this case, by pressurizing the microvalve 920, the valve diaphragm bulges upwards, thereby reducing the height of the fusion channel 400 to 50 μm to accommodate the 55 μm diameter first droplet.
[0043] The height of the fusion channel 400 in the vertical direction is greater than or equal to 0.3 times the diameter of the first droplet and less than or equal to 0.99 times the diameter of the first droplet. The width of the fusion channel 400 in the front-back direction is greater than or equal to 1.01 times the diameter of the first droplet and less than or equal to 10 times the diameter of the first droplet. It is understood that the width of the fusion channel 400 in the front-back direction also needs to take into account the size of the second droplet to ensure that the second droplet does not flow through the gap between the fusion channel 400 and the first droplet. Preferably, the width of the fusion channel in the front-back direction is greater than the diameter of the first droplet and less than the sum of the diameters of the two droplets.
[0044] Understandably, within this size range, the fusion channel 400 can effectively clamp the upper and lower sides of the incoming first droplet, reducing the speed of the first droplet while ensuring that the first droplet can still move along the extension direction of the fusion channel 400. It also prevents the fusion channel 400 from being blocked by the first droplet, thus slowing down the second droplet, allowing the first and second droplets to approach and merge within the fusion channel 400.
[0045] In some embodiments, the manifold 300 extends in the left-right direction, and its width in the front-back direction gradually increases from its inlet end to its outlet end, or its height in the vertical direction gradually increases from its inlet end to its outlet end. The manifold 300 forms a gradually expanding structure, which allows the distance between the first droplet and the second droplet to shorten within the manifold 300, bringing them closer together to facilitate fusion when they subsequently enter the fusion channel 400.
[0046] In some embodiments, the length of the manifold 300 is greater than or equal to 0.01 cm and less than or equal to 5 cm, and the width of the outlet end of the manifold 300 in the front-to-back direction or the height in the up-down direction is extended to no more than 1.4 times the diameter of the first droplet according to the droplet flow phenomenon.
[0047] Understandably, the length of the manifold 300 should not be too long. The specific length is set according to the size of the droplets to be fused, so as to avoid multiple droplets overlapping within the manifold 300. For example, for the fusion of droplets with a diameter of 70 micrometers and a diameter of 25 micrometers, the length of the manifold 300 is greater than or equal to 1 cm and less than or equal to 3 cm.
[0048] In some embodiments, the first injection channel 100 includes a first flow channel 110, a second flow channel 120, and a droplet generation flow channel 130. The inlet end of the droplet generation flow channel 130 is connected to the outlet ends of the first flow channel 110 and the second flow channel 120, respectively, and the outlet end of the droplet generation flow channel 130 is connected to the inlet end of the confluence channel 300.
[0049] It is understood that the first droplet can be injected directly through the first flow channel 110 after generation, or it can be generated directly through the first flow channel 110 and the second flow channel 120. In some embodiments, the inlet end of the first flow channel 110 is the aqueous phase port and the inlet end of the second flow channel 120 is the oil phase port. The aqueous phase fluid enters from the first flow channel 110 and the oil phase fluid enters from the second flow channel 120. By utilizing the interaction between the two immiscible fluid phases, one of the fluid phases is dispersed into independent microdroplets in the droplet generation flow channel 130, which are then used as the first droplet for electrofusion.
[0050] It is understandable that after the second droplet is prepared, it is injected from the inlet end of the second injection channel 200, and the generation frequency of the first droplet is adjusted to match the injection frequency of the second droplet, so as to achieve a 1:1 or more:1 pairing between the two.
[0051] In some embodiments, the width of the outlet end of the second injection channel 200 for injecting the second droplet is equal to the diameter of the first droplet.
[0052] In some embodiments, the droplet electrofusion chip further includes an observation structure 800, which is disposed on the chip body and located between the inlet end and the outlet end of the discharge channel 500. The observation structure 800 is used to observe the droplets in the discharge channel 500.
[0053] Understandably, operators can observe and measure the fused droplets through observation structure 800.
[0054] In some embodiments, the observation structure 800 is a transparent structure, which is disposed on the surface of the chip body and above the discharge channel 500. The observation structure 800 is positioned at a height higher than the top of the fused droplet, so as to avoid the observation structure 800 interfering with the discharge of the droplet.
[0055] In other embodiments, the observation structure 800 is transparent and has a through hole. The discharge channel 500 passes through the through hole of the observation structure 800. The diameter of the through hole of the observation structure 800 is larger than the diameter of the fused droplet, so as to avoid the observation structure 800 from interfering with the flow of the droplet.
[0056] In some embodiments, the first electrode 600 is a liquid metal electrode, and the second electrode 700 is a liquid metal electrode or a brine electrode.
[0057] The first electrode 600 and the second electrode 700 are perfused with liquid metal to apply force to the droplets in three-dimensional space. Compared with the nano-thickness metal-coated electrode, the liquid metal electrode has a stronger force, which means that droplet fusion can be achieved with a lower voltage in a shorter experimental time, avoiding electrostatic damage to cell droplets and ensuring cell viability.
[0058] In some embodiments, during use, an AC voltage greater than 50Hz and greater than 50V is applied to the first electrode 600 and the second electrode 700.
[0059] In some embodiments, the chip body can be fabricated by photolithography or two-photon methods.
[0060] The chip body can be made of materials such as PDMS, COP, and COC.
[0061] Secondly, embodiments of the present invention propose a droplet electrofusion method, which is applied to the droplet electrofusion chip proposed in any of the embodiments of the first aspect and is applicable to the fusion of droplets of different sizes. The droplet electrofusion method includes steps S101, S102, and S103, as described below. Figure 5 .
[0062] In step S101, the width of the fusion channel 400 along the second direction or the height along the third direction is adjusted by the adjusting component 900 according to the diameter of the droplets to be fused. By adjusting the width or height of the fusion channel 400, it can accommodate the electrofusion of droplets of different sizes.
[0063] In some embodiments, by narrowing the width of the fusion channel 400, the first droplet slows down upon entering the fusion channel 400, and the height of the fusion channel 400 is greater than the diameter of the first droplet, which is the largest size applicable to the droplet electrofusion chip, ensuring that the first droplet does not completely block the fusion channel 400. In some embodiments, the width of the fusion channel 400 is adjusted by an airbag 910. Depending on the actual diameter of the first droplet, the airbag 910 is inflated or deflated to drive the movement of the front or rear wall of the fusion channel 400, thereby increasing or decreasing the width of the fusion channel 400.
[0064] In other embodiments, by reducing the height of the fusion channel 400, the first droplet slows down upon entering the fusion channel 400, and the width of the fusion channel 400 is greater than the diameter of the first droplet, which is the largest size applicable to the droplet electrofusion chip, ensuring that the first droplet does not completely block the fusion channel 400. In some embodiments, the height of the fusion channel 400 is adjusted by a microvalve 920. Depending on the actual diameter of the first droplet, pressure is applied or depressurized to the microvalve 920, causing the valve diaphragm to move upwards or downwards, thereby driving the lower wall of the fusion channel 400 to move, thus increasing or decreasing the height of the fusion channel 400.
[0065] In step S102, the droplets to be fused are injected into the confluence channel 300 through the first injection channel 100 and the second injection channel 200, respectively. It can be understood that the first droplet can be injected directly after generation, or it can be generated within the first injection channel 100.
[0066] In some embodiments, before performing step S102, it is necessary to adjust the generation frequency of the first droplet so that the generation frequency of the first droplet matches the injection frequency of the second droplet in order to meet the subsequent fusion ratio of the first droplet and the second droplet.
[0067] In step S103, when the droplets to be fused flow into the fusion channel 400, alternating current is applied to the fusion channel 400 through the first electrode 600 and the second electrode 700 to fuse the droplets. Since the width or height of the fusion channel 400 is smaller than the diameter of the first droplet, the fusion channel 400 can clamp the larger first droplet, causing it to flow at a reduced speed within the fusion channel 400. Because the fusion channel 400 is not completely blocked by the first droplet, the second droplet can maintain its original speed or accelerate its flow, causing the first and second droplets to approach each other and fuse under the action of the first electrode 600 and the second electrode 700, ultimately being discharged through the discharge channel 500.
[0068] It is understandable that, since the droplet electrofusion method is applied to the droplet electrofusion chip in the first aspect, the droplet electrofusion method also has all the beneficial effects brought by the droplet electrofusion chip mentioned above, which will not be elaborated here.
[0069] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.
Claims
1. A droplet electrofusion chip, characterized in that, include: The chip body is provided with a first injection channel, a second injection channel, a bus channel, a fusion channel and an exhaust channel. The outlet end of the first injection channel and the outlet end of the second injection channel are respectively connected to the inlet end of the bus channel. The fusion channel extends along a first direction, and the two ends of the fusion channel along the first direction are respectively connected to the outlet end of the bus channel and the inlet end of the exhaust channel. A conductive component includes a first electrode and a second electrode, wherein the first electrode and the second electrode are respectively disposed on both sides of the fusion channel along a second direction or on both sides of the fusion channel along a third direction, and the first direction, the second direction and the third direction are mutually perpendicular. An adjustment component, connected to the sidewall of the fusion channel, is used to adjust the width of the fusion channel along the second direction or the height along the third direction.
2. The droplet electrofusion chip according to claim 1, characterized in that, The width of the fusion channel along the second direction is less than the width of the outlet end of the confluence channel along the second direction; the height of the fusion channel along the third direction is greater than the height of the outlet end of the confluence channel along the third direction; the adjusting component is driven to one side of the fusion channel to drive the width adjustment of the fusion channel along the second direction.
3. The droplet electrofusion chip according to claim 2, characterized in that, The adjusting component is an airbag, which is located on the outside of the fusion channel and abuts against one side wall of the fusion channel. When the airbag is inflated, it squeezes the side wall of the fusion channel that abuts against it and reduces the width of the fusion channel along the second direction.
4. The droplet electrofusion chip according to claim 1, characterized in that, The width of the fusion channel along the second direction is greater than the width of the outlet end of the confluence channel along the second direction; the height of the fusion channel along the third direction is less than the height of the outlet end of the confluence channel along the third direction; the adjusting component is driven to one side of the fusion channel to drive the height adjustment of the fusion channel along the third direction.
5. The droplet electrofusion chip according to claim 4, characterized in that, The regulating component is a micro-valve, which is equipped with a gas valve diaphragm. The gas valve diaphragm abuts against the side wall of the fusion channel. When pressure is applied to the micro-valve, the gas valve diaphragm pushes the side wall of the fusion channel to move and lowers the height of the fusion channel along the third direction.
6. The droplet electrofusion chip according to claim 1, characterized in that, The first injection channel includes a first flow channel, a second flow channel, and a droplet generation flow channel. The inlet end of the droplet generation flow channel is connected to the outlet ends of the first flow channel and the second flow channel, respectively, and the outlet end of the droplet generation flow channel is connected to the inlet end of the confluence channel.
7. The droplet electrofusion chip according to claim 1, characterized in that, The droplet electrofusion chip also includes an observation structure disposed on the chip body and located between the inlet end and the outlet end of the discharge channel. The observation structure is used to observe the droplets in the discharge channel.
8. The droplet electrofusion chip according to claim 1, characterized in that, The first electrode is a liquid metal electrode, and the second electrode is a liquid metal electrode or a brine electrode.
9. A method for droplet electrofusion, characterized in that, Applied to the droplet electrofusion chip as described in any one of claims 1 to 8, the droplet electrofusion method includes the following steps: The width of the fusion channel along the second direction or the height along the third direction is adjusted by the adjusting component according to the diameter of the droplets to be fused. The droplets to be fused are injected into the confluence channel through the first injection channel and the second injection channel, respectively; When the droplets to be fused flow into the fusion channel, an alternating current is applied to the fusion channel through the first electrode and the second electrode to cause the droplets to fuse.
10. The droplet electrofusion method according to claim 9, characterized in that, Before performing the step of injecting the droplets to be fused into the confluence channel through the first injection channel and the second injection channel respectively, the injection frequency or generation frequency of the droplets is adjusted.