Micro-fluidic chip for liquid drop fusion

Abstract

The utility model provides a micro-fluidic chip for liquid drop fusion. The micro-fluidic chip comprises a liquid drop supply area, a liquid drop pairing fusion area and a river protector. Liquid drops with different sizes are generated or introduced in the respective liquid drop supply areas and then converge into the liquid drop pairing fusion area together, and the liquid drop pairing fusion area mainly comprises a fusion channel with a bulge structure and an electrode. By adjusting the flow in the micro-channel in the liquid drop supply area, the liquid drops of different sizes are paired in the fusion channel according to a set proportion and are fused under the action of the four bumps and the external reinforcing electric field, and then the fused liquid drops which are uniform in size and neatly arranged are generated. According to the utility model, the fusion channel bump design and the electric fusion method are adopted, so that the liquid drop fusion efficiency and stability are improved, and commercialization of the liquid drop fusion chip is facilitated.

Description

Technical Field

[0001] The utility model relates to the field of microfluidic control, and more specifically, to a microfluidic chip for droplet fusion. Technical Background

[0002] As a "microreactor", droplet microfluidics has a variety of unique functions, revolutionizing traditional pipettes, beakers, test tubes or flasks in biological and chemical laboratories. Its features include high throughput, low reagent consumption, a closed system, pollution prevention, rapid response, automatic processing, and separation for parallel reactions. In the past decade, with explosive progress, droplet microfluidics has been widely involved in chemical, biological applications, and materials synthesis. Generally, in the application of droplet microfluidics, droplets have the following uses:

[0003] (a) Microreactors for parallel reactions and biological and chemical analysis;

[0004] (b) Templates for preparing functional particles or capsules in materials science.

[0005] Currently, the patent "Chip and Device for Preparing Emulsion Droplets" (Publication No.: CN 112439467 A) and the patent "Microfluidic Chip and Device Containing the Microfluidic Chip, and Application for Preparing Microemulsion Droplets"

[0006] (Authorized Publication No.: CN 110918141 B) each provide a microfluidic chip for preparing emulsion droplets under the action of alternating current. The former only increases the amount of reagent injected into the droplet by changing the width of the main channel in the reagent injection area, but this method is difficult to accurately control the volume ratio of droplet-reagent fusion, and the channel design for droplet fusion is simple and cannot provide better conditions for droplet fusion, thus affecting the droplet fusion efficiency; the latter prepares emulsion droplets by setting a widened microchannel and a flow-limiting part in the channel. Due to the existence of the flow-limiting step (because the flow-limiting structure needs to work at a low flow rate, that is, synchronize two types of droplets), the droplet flow rate is slow, and thus the efficiency of generating droplets is low. Therefore, in view of the above problems, there is an urgent need for a device that can accurately adjust and efficiently generate droplets. Summary of the Utility Model

[0007] In view of the above problems, the present utility model provides a microfluidic chip for droplet fusion. The microfluidic chip includes a droplet supply area, a droplet pairing and fusion area, and a moat. After droplets of different sizes are generated in their respective droplet supply areas, they jointly flow into the droplet pairing and fusion area, which mainly includes a fusion channel with a bulge structure and electrodes. By adjusting the flow rate in the microchannels of the droplet supply area, droplets of different sizes are paired in the fusion channel in a set ratio, and under the action of 4 bulges and an externally applied strong electric field, they fuse, thereby generating fused droplets with uniform size and neat arrangement.

[0008] On the one hand, a microfluidic chip for droplet fusion provided by the present utility model includes a droplet pairing and fusion area for fusing two different droplets into one droplet; the droplet pairing and fusion area includes a fusion channel and electrodes, and the fusion channel is provided with bulges.

[0009] Further, the cross-sectional area of the bulge is larger than that of the fusion channel.

[0010] In the bulge of the fusion channel, due to the widening of the microchannel, the flow rate decreases, the oil film between the paired droplet pairs becomes thinner, and the distance is further reduced; at the same time, the electrodes are closely close to the bulge and a high-voltage electric field is applied thereto. Under the perturbation of the high-voltage electric field, the oil film between the droplets breaks, resulting in the occurrence of droplet fusion, and the fused droplets flow out from the outlet. In short, if the fusion channel does not have this bulge structure, the fusion efficiency of the droplets is very low.

[0011] Further, the different droplets are two kinds, including large droplets and small droplets.

[0012] Further, the cross-sectional area of the fusion channel is smaller than that of the large droplet but larger than that of the small droplet.

[0013] Due to the difference between the cross-sectional areas of different droplets and the microchannel, during the flow of the large droplet in the microchannel, the resistance it receives is greater than that of the small droplet, enabling the small droplet to catch up with the large droplet, pair with it, and always follow the large droplet into the fusion channel.

[0014] Further, the electrodes are arranged on both sides of the fusion channel, and the position of the electrodes lags behind the position of the bulge.

[0015] Further, the number of the bulges is not less than 4.

[0016] During use, by adjusting the high voltage applied to the electrodes, it can ensure the stable fusion of the paired large and small droplets; by integrating multiple bulges in the fusion channel, the probability of successful fusion can be increased.

[0017] Further, the number of the electrodes is not less than 4.

[0018] The optimal number of bulges is 4. When the number of bulges is less than 4, the fusion efficiency is low. When the number is greater than 4, the chip manufacturing difficulty and cost increase, and the fusion efficiency does not increase significantly.

[0019] Furthermore, the material of the electrode includes low-temperature metal, and the low-temperature metal includes any one or more of gallium, indium, and tin.

[0020] Compared with brine and ordinary metals, when using electrodes made of low-temperature metal, the droplet fusion rate of the chip is generally higher. In addition, due to problems such as easy water evaporation and flow of brine, a stable sealing process is required, so it is not convenient to make products; although conductive materials such as gold and platinum can also be used as electrode materials for fusion chips, due to the need for semiconductor deposition processes, their cost is high and it is difficult to control the cost. Considering comprehensively, low-temperature metal (gallium-indium-tin) is preferably selected as the electrode material.

[0021] Furthermore, the voltage generated by the electrode is a variable voltage of 500V to 1500V. Preferably, the optimal voltage is a variable voltage of 1,000V.

[0022] Furthermore, the distance between the electrode and the fusion channel is 10μm to 2mm.

[0023] Preferably, the optimal distance between the electrode and the bulge is 40μm. When the distance between the electrode and the bulge is too small, the electric field strength is too large, and the droplet is easily torn; when the distance between the electrode and the bulge is too large, the electric field strength weakens, affecting the success rate of fusion. Furthermore, the ratio of the cross-sectional area of the bulge to the cross-sectional area of the fusion channel is (1.5 to 4):1.

[0024] Preferably, taking droplets with particle sizes of 47μm and 29μm as the research objects, the effects of the cross-sectional areas of the fusion channel (without bulges) and the bulge on the droplet fusion efficiency were explored respectively. The closer the width of the fusion channel is to the diameter of the large droplet, the higher the success rate of droplet fusion, that is, the cross-sectional area is 40*50μm 2 The droplet fusion efficiency of the fusion channel is the highest; when the height of the bulge <50μm, the effect of reducing the droplet flow rate is not obvious, and the oil film is thicker, affecting the success rate of fusion; when the height of the bulge >100μm, the droplet enters the bulge and is prone to deviate from the center and flow laterally, also resulting in a low success rate of fusion. The optimal length of the bulge is 100μm, and the width is 67μm; in summary, the optimal ratio of the cross-sectional area of the bulge to the cross-sectional area of the fusion channel is 3.35:1.

[0025] Furthermore, the bulges are uniformly arranged on the fusion channel, and the distance between two adjacent bulges is 0.02 to 1mm.

[0026] Preferably, when the interval between the bulges > 70 μm, the fusion efficiency of the droplets is as high as 95%. When the distance between the bulges is too small, the matching adjustment of the droplets in the channels between the bulges is limited, so the improvement of the fusion success rate is limited; correspondingly, when the distance between the bulges is sufficient, the large and small droplets continue to match in the channels, thus effectively improving the fusion success rate; however, when the distance is too large, it will increase the area of the chip and raise the cost, so the optimal distance between two adjacent bulges is 70 μm.

[0027] Furthermore, the aspect ratio of the bulge is (1 - 10):1. Preferably, the optimal aspect ratio is 100:67.

[0028] Furthermore, it further includes a droplet supply area, and the droplet supply area includes a generation area and / or a droplet introduction area. The droplet introduction area further includes a filter column array for filtering the oil phase.

[0029] Furthermore, the number of the droplet supply areas is 2 or greater than 2.

[0030] The droplet supply area is divided into two structures: external introduction type and on-chip generation type. The former directly introduces the generated droplets into the chip, and the latter generates droplets in the chip by adding an aqueous phase and an oil phase. Liquids such as the droplets, the oil phase, and the aqueous phase can adopt injection pumps, pressure pumps, and other sample injection methods. These two droplet supply areas can be flexibly selected and combined according to requirements. In addition, multiple droplet supply areas can be included on the droplet fusion chip, so this chip can fuse two or more kinds of micro-droplets.

[0031] Furthermore, the chip further includes a moat, and the moat is used to isolate the influence generated by the electrodes.

[0032] Furthermore, the moat surrounds the chip in a circle, enclosing each area of the chip, and the areas include a droplet supply area, an electrode area, a droplet pairing and fusion area, and an outlet area.

[0033] Furthermore, the flow rate of the droplets in the microfluidic chip is 0.01 mL / h - 1 mL / h, and the particle size of the droplets is 20 μm - 90 μm.

[0034] Preferably, the particle size of the large droplets is 47 μm - 51 μm, and the flow rate is 0.2 - 4 mL / h; the particle size of the small droplets is 25 μm - 35 μm, and the flow rate is 0.05 - 0.5 mL / h, and the pairing number ratio of the large and small droplets is 1:1.

[0035] The beneficial effects of the present utility model include:

[0036] 1. The fusion channel provided by the present utility model is ingeniously designed, introducing the design of the bulges, and using physical means to pair and fuse large and small droplets with low cost but high efficiency.

[0037] 2. The electrodes are made of low-temperature metal; the chip is fabricated by injection molding process, and the electrode adapter (PCB) is fixed on the chip for convenient docking.

[0038] 3. The active fusion chip design and electrofusion method adopted by the present utility model improve the fusion efficiency and stability, and are beneficial to the commercialization of the droplet fusion chip. Description of the Drawings

[0039] In order to more clearly illustrate the technical solutions in the embodiments of the present utility model or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present utility model. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0040] Figure 1 : Schematic structural diagram of the droplet fusion microfluidic chip

[0041] Figure 2 : Three-dimensional view of the droplet fusion microfluidic chip

[0042] Figure 3 : Schematic structural diagram of the externally introduced droplet supply area

[0043] Figure 4 : Schematic structural diagram of the on-chip generated droplet supply area

[0044] Figure 5 : Schematic structural diagram of the droplet pairing and fusion area

[0045] Figure 6 : Schematic structural diagram of the fusion channel

[0046] Figure 7 : Influence of the number of electrodes on the droplet fusion efficiency; the number of electrodes in Figure A is 1, Figure B is 2, Figure C is 3, and Figure D is 4

[0047] Figure 8 : Comparison diagram of large and small droplets with particle sizes of 47μm and 29μm before and after fusion in Example 10; Figure A is before fusion and Figure B is after fusion

[0048] Figure 9 : Comparison diagram of large and small droplets with particle sizes of 49μm and 29μm before and after fusion in Example 10; Figure A is before fusion and Figure B is after fusion

[0049] Figure 10 : Comparison diagram of large and small droplets with particle sizes of 51μm and 29μm before and after fusion in Example 10; Figure A is before fusion and Figure B is after fusion Detailed Embodiments

[0050] The present utility model will be further elaborated in detail below in conjunction with the accompanying drawings of the specification and specific embodiments. The embodiments are only used to explain the present utility model and are not used to limit the scope of the present utility model. The test methods used in the following embodiments are all conventional methods unless otherwise specified; the materials, reagents, etc. used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0051] Embodiment 1: The droplet fusion microfluidic chip provided by the present utility model

[0052] The droplet fusion microfluidic chip provided by the present utility model includes a droplet supply area 1-2, a droplet pairing and fusion area 3, an electrode 4, a moat 5, and an outlet 6. It should be noted that the structure and number of the droplet supply area can be flexibly selected and matched according to requirements. The structural types of the droplet supply area are divided into an externally introduced type ( Figure 3 ) and an on-chip generation type ( Figure 4 ); since the droplet fusion chip can include multiple droplet supply areas, it can be used for the fusion of two or more micro-droplets. In addition, instruments such as injection pumps and pressure pumps are used for sample injection, and the samples include an oil phase, a reagent phase, a droplet emulsion, etc.; the electrode 4 and the moat 5 can be made of metal materials, brine, and other conductive materials, and these materials can be made by means such as metal deposition, perfusion, and screen printing.

[0053] Taking a droplet fusion microfluidic chip with two different types of droplet supply areas as an example in this embodiment, the technical principle of the droplet fusion chip provided by the present utility model is introduced. The schematic diagram of the droplet fusion microfluidic chip provided in this embodiment is as shown in Figure 1 and Figure 2 . This droplet fusion chip is provided with two droplet supply areas (1 and 2), a droplet pairing and fusion area 3, an electrode 4, a moat 5, and an outlet 6. The droplet supply area is used for externally introducing droplets or for on-chip generation of droplets; the droplet pairing and fusion area is the place where droplets from different droplet supply areas converge and pair, and provides a material basis for the fusion of liquids (fusion channels 11 and bulges 12); the electrode 4 can apply a high-voltage electric field near the bulge in the droplet fusion area to cause the droplets to merge under high-voltage conditions; the conductive substance in the moat plays a role of electrostatic shielding, confining the high-voltage electricity near the bulge area and avoiding the damage of the high-voltage electricity to the upstream droplets (such as causing a large amount of fusion and tearing of the droplets in the droplet introduction and generation areas); the outlet 6 is used for the outflow of the fused droplets.

[0054] As shown in Figure 1 and 3As shown, the structural type of the droplet supply area is the externally introduced type, and this structure includes: an oil phase inlet 7, a droplet inlet 8, a filter column array 9, and an outlet 61. The oil phase inlet 7 is used to add the oil phase, which is used to adjust the interval between droplets; the droplet inlet 8 is used to introduce externally synthesized droplets; the filter column array 9 can separate the oil component in the droplet emulsion, and the oil phase here is consistent with the component in the oil phase inlet 7; the outlet 61 can introduce the prepared droplets with uniform size into the droplet pairing and fusion area 3.

[0055] After the droplet emulsion is introduced from the droplet inlet 8, the loose droplets are filtered by the filter column array, and the oil phase is controllably filtered out, so that the interval between droplets can be effectively adjusted, thus achieving the effect of close-pack of droplets; finally, these droplets flow out of the outlet in sequence and regularly under the adjustment of the oil phase (added from the oil phase inlet). During use, the frequency of the droplets flowing out of the outlet and the interval between droplets are controlled by adjusting the flow rates at the droplet inlet 8 or the oil phase inlet 7 respectively.

[0056] As Figure 1 and Figure 4 shown, the on-chip generated droplet supply area structure includes an oil phase inlet 71, a water phase inlet 10, an intersection 13, and an outlet 62. The reagent phase is introduced from the water phase inlet 10, and the oil phase is introduced from the oil phase inlet 71; at the intersection 13, the reagent phase and the oil phase intersect, and under the action of the oil phase shear force, the reagent phase is sheared and broken into micro-droplets; finally, these droplets flow out of the outlet in sequence and regularly. During the use process, the frequency, size, and interval of the droplets flowing out of the outlet can be controlled by adjusting the flow rates at the water phase inlet 10 and the oil phase inlet 71.

[0057] As Figure 5 and Figure 6 shown, the droplet pairing and fusion area includes: an inlet 14, a fusion channel 11 containing a bulge 12, an electrode 41, moats 51 - 53, and an outlet 63. The bulge 12 is located on the fusion channel, and its cross-sectional area is higher than that of the fusion channel, and different types and sizes of droplets are fused here; the electrode 41 is in the shape of a needle-like protrusion and is integrated around the bulge 12 in the fusion area, and the number of the needle-like protrusions matches the bulge; the moats 51 - 53 surround the chip in a circle and enclose each area on the chip (the droplet supply areas 1 - 2, the electrode 4 and 41 areas, the droplet pairing and fusion area 3, and the outlet 6 area) to achieve the effect of electrostatic shielding.

[0058] Regularly arranged large and small droplets from different droplet supply areas flow into the droplet pairing and fusion area 3 from the inlet 14. Since the cross-sectional area of the microchannel (the non-bulging area of the fusion channel 11) is smaller than that of the large droplet but larger than that of the small droplet, when the large droplet flows in the microchannel, the resistance it encounters is greater than that of the small droplet, enabling the small droplet to catch up with the large droplet, thus pairing, and trailing the large droplet into the fusion channel 11 all the time; in the bulge 12 of the fusion channel, due to the widening of the microchannel and the decrease in flow velocity, the distance between the paired droplets further decreases, and the oil film between the two becomes thinner; meanwhile, under the perturbation of the high-voltage electric field generated by the electrode 41, the oil film between the droplets breaks, resulting in the occurrence of droplet fusion; finally, the fused droplets flow out from the outlet 63. During the process of droplet fusion, the flow rate matching of the large and small droplets can be achieved by adjusting the flow rate of the oil phase in the droplet supply areas 1 - 2, and then the large and small droplets can enter the fusion channel 11 at a certain quantitative ratio interval.

[0059] The optimal operating conditions of the microfluidic chip for droplet fusion provided by the present utility model are as follows: the particle size of the large droplet is 47μm - 51μm, that of the small droplet is (unspecified range in the original, seems incorrect, should be something like 25μm - 35μm), the pairing quantity ratio of the large and small droplets is 1:1; the number of bulges in the chip is 4, the interval between the bulges is 70μm, the length of the bulge is 100μm, the height is 67μm or the aspect ratio of the bulge is 10:6.7; the cross-sectional area of the microchannel without bulges is 40 * 50μm 2 ; the electrode material is a low-temperature gallium-indium-tin alloy, the number of electrodes is 4, the voltage is a variable voltage of 1,000V, and the distance between the electrode and the bulge is 40μm. Under these operating conditions, the droplet fusion efficiency is as high as 95%.

[0060] Example 2: Influence of the number of bulges on the droplet fusion efficiency

[0061] Theoretically, using multiple bulges can improve the stability of fusion. In some cases, if the large and small droplets do not fuse when passing through the first bulge, passing through other bulges successively will promote their fusion, thereby increasing the success rate of fusion. Therefore, in this example, the droplet fusion chip and the number of bulges provided in Example 1 are used to explore the influence of the number of bulges on the droplet fusion efficiency. Among them, in this example, the particle sizes of the large and small droplets are 47μm and 29μm respectively, and the quantity ratio is 1:1. The results are shown in Table 1.

[0062] Table 1 Influence of the number of bulges on the droplet fusion efficiency

[0063] Number of bulges / piece Fusion success rate 0 <5％ 1 <10％ 2 30％ 3 50％ 4 95％ 5 96％

[0064] It should be noted that there seems to be an error in the description of the small droplet size range in item . It is recommended to check and correct it for a more accurate translation.As can be seen from Table 1, when there are no bulges, droplets can hardly fuse; as the number of bulges increases, the success rate of droplet fusion also increases; when there are 4 bulges in the fusion channel, the fusion success rate reaches a relatively large value (95%), indicating that at least 4 bulges are required for stable droplet fusion; when the number of bulges > 4, the increase in fusion efficiency is limited, but the more the number of bulges, the higher the chip manufacturing difficulty and cost. Therefore, the optimal number of bulges is 4.

[0065] Example 3: Influence of the interval between bulges on the droplet fusion efficiency

[0066] Large and small droplets are paired in the channels between the bulges, providing a basis for subsequent fusion. Within a certain range, the larger the interval between the bulges, the better the matching effect. However, when the interval exceeds a certain value, it will cause the channels of the chip to become longer, resulting in an increase in the flow resistance of the chip channels and an increase in the area occupied by the chip. Therefore, this example explores the influence of the interval between the bulges on the droplet fusion efficiency. Among them, in this example, the particle sizes of the large and small droplets are 47μm and 29μm respectively, the quantity ratio is 1:1, and the number of bulges is 4; the experimental results are shown in Table 2.

[0067] Table 2 Influence of the interval between bulges on the droplet fusion efficiency

[0068] Interval between bulges / μm Fusion success rate 30 50％ 50 70％ 70 95％ 100 95％ 120 95％ 150 94％

[0069] As can be obtained from Table 2, when the interval between the bulges is 70μm, the fusion efficiency of the droplets is the highest. During the droplet fusion process, (due to the insufficient matching degree of the large and small droplets and the relatively thick oil film between the droplets), the situation where the first (or the previous) bulge fails to fuse the droplets may occur. In this case, when the interval between the bulges is too small, the matching adjustment of the droplets in the channels between the bulges is limited, so the increase in the fusion success rate is limited. Correspondingly, when the interval between the bulges is sufficient, the large and small droplets continue to match in the channels, thus effectively improving the fusion success rate.

[0070] Example 4: Influence of the cross-sectional area of the microchannel (excluding bulges) on the droplet fusion efficiency

[0071] Since the resistances received by the large and small droplets in the microchannel are inconsistent, that is, the larger the mass, the greater the resistance, the distance between the two becomes closer and closer, and preliminary pairing is completed. This step plays an important role in droplet fusion. Therefore, this example takes 47μm large droplets and 29μm small droplets (the quantity ratio of the two is 1:1) as the research object to explore the influence of the cross-sectional area of the microchannel (excluding bulges) on the droplet fusion efficiency. The specific results are shown in Table 3.

[0072] Table 3 Influence of the cross-sectional area of the fusion channel (excluding bulges) on the droplet fusion efficiency

[0073]

[0074] As can be seen from Table 3, to a certain extent (the height of 50 μm remains unchanged, and the width is 20 - 100 μm), the closer the width of the fusion channel (excluding the bulge) is to the diameter of the large droplet, the higher the success rate of droplet fusion, that is, the cross-sectional area is 40 * 50 μm 2 The droplet fusion efficiency of the fusion channel (excluding the bulge) is the highest. This is because when the width of the fusion channel is much smaller than the size of the large droplet, both the large droplet and the small droplet are subject to a large resistance, and they flow at almost the same speed. When the width of the fusion channel is much larger than the size of the large droplet, neither the large droplet nor the small droplet is subject to resistance, and they also flow at almost the same speed. In both cases, the distance between the large and small droplets is not effectively reduced, so the matching and fusion success rate is low. Only when the width of the fusion channel (excluding the bulge) is closer to the diameter of the large droplet, at this time the large droplet is subject to a large resistance and the small droplet is hardly subject to resistance, so the effect of the small droplet catching up with the large droplet will occur, and the matching and fusion success rate is effectively improved.

[0075] Example 5: Influence of the cross-sectional area of the bulge on the droplet fusion efficiency

[0076] The bulge provides a place for droplet fusion, and its size will also affect the droplet fusion efficiency. Therefore, this example explores the influence of this factor on the droplet fusion efficiency. Among them, in this example, the particle sizes of the large and small droplets are 47 μm and 29 μm respectively, the quantity ratio is 1:1, the number of bulges is 4, and the interval between the bulges is 70 μm; the cross-sectional area of the microchannel is 40 * 50 μm 2 , and the results are shown in Table 4.

[0077] Table 4 Influence of the cross-sectional area of the bulge on the droplet fusion efficiency

[0078]

[0079]

[0080] As can be seen from Table 4, when the bulge length is 100 μm, the height is 67 μm, or the bulge length-to-height ratio is 1:0.67, the fusion efficiency is the highest. In the fusion channel, the purpose of using the bulge is to widen the microchannel, reduce the flow rate, thin the oil film between the paired droplet pairs, further reduce the spacing, and then cause fusion under the action of the electric field. When the height of the bulge is relatively low (50 μm), the effect of reducing the droplet flow rate is not obvious, and the oil film is relatively thick, which affects the success rate of fusion. When the height of the bulge is relatively high (100 μm), the droplets enter the bulge and are prone to deviate from the center and flow laterally, which also results in a low success rate of fusion. At the same time, the above table also shows that when the length of the bulge channel exceeds 100 μm, this size has almost no effect on the success rate of fusion. Therefore, from the perspective of reducing the channel length and reducing the chip flow resistance, a 100-μm-long bulge is preferably selected.

[0081] Example 6: Influence of Electrode Material on Droplet Fusion Efficiency

[0082] The material of the electrode will affect the conductivity of the electrode and the generated voltage, and thus affect the efficiency of droplet fusion. In this example, metal materials and brine are respectively used to make the electrodes to explore the influence of electrode materials on droplet fusion efficiency; in addition, in this example, the particle sizes of the large and small droplets are 47 μm and 29 μm respectively, and the quantity ratio is 1:1; the number of bulges is 4, the interval between the bulges is 70 μm, and the cross-sectional area of the microchannel is 40*50 μm 2 , and the bulge length and height are 100 μm and 67 μm respectively; the specific experimental results are shown in Table 5.

[0083] Table 5 Influence of Electrode Material on Droplet Fusion Efficiency

[0084]

[0085] As can be seen from Table 5, compared with brine and ordinary metals, the droplet fusion rate of the electrodes made of low-temperature metals is generally higher. In addition, due to problems such as easy water evaporation and flow of brine, a stable sealing process is required, so it is not convenient to make products; although conductive materials such as gold and platinum can also be used as electrode materials for fusion chips, due to the need to rely on semiconductor deposition processes, the cost is relatively high and the cost is difficult to control. Considering comprehensively, low-temperature metals (gallium indium tin) are preferably selected as electrode materials.

[0086] Example 7: Influence of the Number of Electrodes on Droplet Fusion Efficiency

[0087] Example 2 proves that when the number of bulges is 4, the droplet fusion efficiency is the highest. Since the electrodes are arranged opposite to the bulges, the number of electrodes will affect the electric field strength received by the droplets in the bulges, and thus affect the droplet fusion efficiency. Therefore, this example explores this factor. In this example, the particle sizes of the large and small droplets are 47 μm and 29 μm respectively, and the quantity ratio is 1:1; the number of bulges is 4, the interval between the bulges is 70 μm, and the cross-sectional area of the microchannel is 40*50 μm 2 , the length and height of the bulge are 100 μm and 67 μm respectively; the material for making the electrodes is a low-temperature metal. The specific experimental results are shown in Figure 7 and Table 6.

[0088] Table 6 Influence of the number of electrodes on the droplet fusion efficiency

[0089] Number of electrodes / piece Fusion success rate 1 70%, there are more remaining after small droplet fusion 2 80%, the probability of small droplet leakage fusion is relatively high 3 85%, the proportion of small droplet leakage fusion > 5% 4 95%, remaining amount of small droplets < 5%

[0090] From Figure 7 and Table 6, it can be seen that the sizes of the fused droplets are uniform, and there are very few droplets with too large a volume, indicating that the number of electrodes will not cause excessive droplet fusion; when the number of electrodes increases, the remaining amount of small droplets decreases, and the fusion efficiency is higher; when the number of electrodes reaches 4, the remaining amount of small droplets < 5%, and the fusion success rate reaches 98%. In summary, the optimal number of electrodes is 4.

[0091] Example 8: Influence of the voltage generated by the electrodes on the droplet fusion efficiency

[0092] The strength of the electric field will affect the fusion of droplets. Therefore, this example explores the influence of voltage on the droplet fusion efficiency. In this example. In this example, the particle sizes of the large and small droplets are 47 μm and 29 μm respectively, and the quantity ratio is 1:1; the number of bulges is 4, the interval between the bulges is 70 μm, and the cross-sectional area of the microchannel is 40*50 μm 2 , the length and height of the bulge are 100 μm and 67 μm respectively; the material for making the electrodes is a low-temperature metal, and the number of electrodes is 4. The specific experimental results are shown in Table 7.

[0093] Table 7 Influence of voltage on the droplet fusion efficiency

[0094] Voltage type Voltage / V Fusion success rate Constant voltage 500 Droplets are fragile and abnormal Constant voltage 1,000 Droplets are fragile and abnormal Variable voltage 500 75％ Variable voltage 1,000 95％

[0095] From Table 7, it can be seen that variable voltage is more suitable for application in droplet fusion, and when the voltage is 1,000 V, the fusion efficiency is the highest, that is, when the variable voltage is 1,000 V, the effect of using this droplet fusion chip is the best.

[0096] Example 9: Influence of the distance between the electrodes and the bulges on the droplet fusion efficiency

[0097] The distance between the electrode and the bulge affects the electric field force on the droplet, thereby affecting the droplet fusion efficiency. Therefore, in this embodiment, the influence of the distance between the electrode and the bulge on the droplet fusion efficiency was explored. In this embodiment. In this embodiment, the particle sizes of the large and small droplets are 47 μm and 29 μm respectively, and the quantity ratio is 1:1; the number of bulges is 4, the interval between the bulges is 70 μm, and the cross-sectional area of the microchannel is 40*50 μm 2 , the length and height of the bulge are 100 μm and 70 μm respectively; the material for making the electrode is a low-temperature metal, the number of electrodes is 4, and the voltage is a variable voltage of 1,000 V. The specific experimental results are shown in Table 8.

[0098] Table 8 Influence of the distance between the electrode and the bulge on the droplet fusion efficiency

[0099]

[0100] As can be seen from Table 8, the optimal distance between the electrode and the bulge is 40 μm. When the distance between the electrode and the bulge is too small, the electric field strength is too large, and the droplet is easily torn; when the distance between the electrode and the bulge is too large, the electric field strength weakens, affecting the success rate of fusion.

[0101] Example 10: Influence of droplet particle size on droplet fusion efficiency

[0102] In this embodiment, the droplet fusion chip provided in Example 1 and droplets of different sizes were used to explore the influence of droplet particle size on droplet fusion efficiency. In this embodiment. In this embodiment, the particle sizes of the large droplets are 47 μm, 49 μm, and 51 μm respectively, the particle size of the small droplet is 29 μm, and the quantity ratio is 1:1; the number of bulges is 4, the interval between the bulges is 70 μm, and the cross-sectional area of the microchannel is 40*50 μm 2 , the length and height of the bulge are 100 μm and 70 μm respectively; the material for making the electrode is a low-temperature metal, the number of electrodes is 4, and the voltage is a variable voltage of 1,000 V; the distance between the electrode and the bulge is 40 μm. The specific experimental results are shown in Figures 8 - 10 and Table 9.

[0103] Table 9 Influence of droplet particle size on droplet fusion efficiency

[0104]

[0105]

[0106] From Figures 8 - 10 and Table 9, it can be seen that the large droplet after fusion will be 3-5 μm larger than that before fusion; when the particle size of the large droplet is 47-51 μm and the particle size of the small droplet is 29 μm, the droplet fusion efficiency is as high as 95%.

[0107] The above-described embodiments have elaborated on the technical solutions of the present utility model. It should be understood that the above is only the specific embodiments of the present utility model and is not used to limit the present utility model. Any modifications, supplements, or substitutions in a similar manner within the principle scope of the present utility model shall be included within the protection scope of the present utility model.

Claims

1. A microfluidic chip for droplet fusion, characterized in that, It includes a droplet pairing and fusion region for fusing two different droplets into one droplet; the droplet pairing and fusion region includes a fusion channel and electrodes, and there are bulges on the fusion channel.

2. The microfluidic chip according to claim 1, characterized in that, The cross-sectional area of the bulge is larger than that of the fusion channel.

3. The microfluidic chip according to claim 1, wherein The different droplets are two types, including large droplets and small droplets.

4. The microfluidic chip according to claim 3, wherein, The cross-sectional area of the fusion channel is smaller than that of the large droplets but larger than that of the small droplets.

5. The microfluidic chip according to claim 1, characterized in that, The electrodes are arranged on both sides of the fusion channel, and the positions of the electrodes lag behind the positions of the bulges.

6. The microfluidic chip according to claim 1, characterized in that, The number of the bulges is not less than 4.

7. The microfluidic chip according to claim 1, wherein The number of the electrodes is not less than 4.

8. The microfluidic chip according to claim 1, characterized in that, The material of the electrodes includes low-temperature metals, and the low-temperature metals include any one or more of gallium, indium, and tin.

9. The microfluidic chip according to claim 1, characterized in that, The voltage generated by the electrodes is a variable voltage of 500V to 1500V.

10. The microfluidic chip according to claim 1, wherein The distance between the electrodes and the fusion channel is 10μm to 2mm.

11. The microfluidic chip according to claim 2, wherein The ratio of the cross-sectional area of the bulge to the cross-sectional area of the fusion channel is (1.5 to 4):

1.

12. The microfluidic chip according to claim 11, characterized in that, The bulges are evenly arranged on the fusion channel, and the distance between adjacent two bulges is 0.02 to 1mm.

13. The microfluidic chip according to claim 12, wherein, The aspect ratio of the bulge is (1 to 10):

1.

14. The microfluidic chip according to claim 1, characterized in that, It further includes a droplet supply region. The droplet supply region includes a generation region and / or a droplet introduction region, and the droplet introduction region further includes a filter column array for filtering the oil phase.

15. The microfluidic chip according to claim 14, wherein The number of the droplet supply regions is 2 or greater than 2.

16. The microfluidic chip according to claim 15, characterized in that, It further includes a moat for isolating the influence generated by the electrodes.

17. The microfluidic chip according to claim 16, characterized in that, The moat surrounds the chip in a circle and encloses all regions of the chip. The regions include a droplet supply region, an electrode region, a droplet pairing and fusion region, and an outlet region.

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