A microfluidic chip for continuous phase recycling and a method for batch preparation of droplets

Abstract

This invention proposes a microfluidic chip for continuous phase recovery and reuse, and a method for mass droplet fabrication. The mass droplet fabrication method includes: injecting a dispersed phase into a series unit through a dispersed phase inlet; and allowing a continuous phase to enter the first-stage series unit through the continuous phase inlet, where it is reused stage by stage between series units. In each series unit, the dispersed phase is introduced through a dispersed phase branch channel and shears with the continuous phase in the intersection region to form droplets. After passing through an inertial separation bend and a guide island, the droplet product is discharged from the unit droplet product outlet and collected to the total droplet product outlet. A portion of the continuous phase enters the next-stage series unit through a narrow-slit guide channel and the unit continuous phase outlet to continue participating in droplet generation. This invention achieves the stage-by-stage reuse of the continuous phase within the chip through a series design, reducing continuous phase consumption and external liquid supply channels, lowering system complexity, and making it suitable for continuous and mass droplet fabrication.

Description

Technical Field

[0001] This invention belongs to the field of microfluidics technology, and particularly relates to a microfluidic chip for continuous phase recovery and reuse and a method for mass production of droplets. Background Technology

[0002] Microfluidics refers to a class of technologies that precisely manipulate fluids within micrometer-scale channels, and has been widely applied in fields such as food industry, fine chemicals, biomedical detection, and drug synthesis. As an important branch of microfluidics, droplet microfluidics can shear a dispersed phase within a continuous phase to form discrete droplets of controllable size, applicable to emulsion preparation, microsphere synthesis, and cell encapsulation. Existing droplet microfluidic chips typically use structures such as T-channels, flow focusing channels, or stepped emulsification channels to generate droplets. While these methods are relatively mature, the yield of a single traditional droplet generation unit is limited, making it difficult to meet the demands of mass production. To increase yield, existing technologies often employ parallel scaling up of multiple droplet generation units. However, this approach requires providing both continuous and dispersed phases to each generation unit separately, leading to complex supply channels, an increased number of chip interfaces, and a complex external pump system, while also requiring high levels of branch flow resistance balance and pressure stability. As the number of parallel channels increases, pressure losses and uneven flow distribution can easily occur between different branches, resulting in differences in droplet size and generation frequency. In addition, continuous phases in parallel structures are usually used once and discharged with droplet products. There is a lack of internal chip design for separating, recycling and reusing continuous phases, resulting in large consumption of continuous phases and high operating costs.

[0003] Existing patent CN121372540A discloses a microfluidic chip that employs a multi-point generation and tree-like splitting amplification method. It first generates larger droplets through multiple branching channels, then splits them into smaller droplets through a multi-level tree-like splitting structure. This technology has the following drawbacks: the continuous phase flows with the droplet products to the collection end; there is no structure to separate the continuous phase from the droplet-containing fluid and transport it to the next generation unit for continued use, resulting in low continuous phase utilization; the tree-like splitting structure becomes more complex with increasing levels, leading to more local turns and branches, increasing flow resistance and processing difficulty; simultaneously, it requires high symmetry and flow resistance consistency in the splitting structure, and processing deviations can easily affect the droplet splitting effect.

[0004] Existing patent CN202512010253 discloses a liquid-dispensing-converging integrated droplet microfluidic chip. This chip uses a multi-level splitting and converging network to ensure that the continuous and dispersed phases travel equal distances to each droplet generation unit, enabling high-throughput simultaneous preparation of multiple generation units. However, this technology has the following drawbacks: the continuous phase distribution network is complex, heavily reliant on channel symmetry and isopath design, and requires high processing precision; the arrangement of multiple collection ports complicates external collection interfaces and pipeline connections; and it also lacks a sequential reuse structure within the continuous phase chip, resulting in a high proportion of single-use continuous phase and significant consumption.

[0005] Therefore, there is an urgent need to provide a new microfluidic mass production structure for droplets that differs from traditional parallel amplification methods. By splitting, recovering, and reusing the continuous phase within the chip, multiple droplet generation units can participate in the droplet preparation process sequentially. This reduces the number of independent liquid supply channels for the continuous phase, lowers the consumption of the continuous phase and the complexity of the external pump circuit, improves the chip integration, and provides a new microfluidic amplification method for the continuous and mass production of droplets. Summary of the Invention

[0006] The purpose of this invention is to solve the technical problems of existing droplet microfluidic chips, such as limited output of a single generation unit, complex parallel amplification structure, large continuous phase consumption, large number of external interfaces, and lack of continuous phase reuse path within the chip. The invention provides a microfluidic chip for continuous phase recovery and reuse and a method for batch preparation of droplets, which is suitable for continuous and batch preparation of droplets.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: A continuous phase cascaded multiplexing type tandem droplet microfluidic chip includes a chip substrate and a chip cover plate; the chip cover plate covers the chip substrate and is sealed to the chip substrate. The chip substrate is provided with a dispersed phase inlet, a continuous phase inlet, a remaining dispersed phase outlet, a continuous phase outlet, a droplet product outlet, and multiple series-connected units. The series unit includes a dispersed phase main channel, a dispersed phase introduction branch channel, a unit continuous phase inlet, a unit continuous phase outlet, a unit droplet product outlet, an inertial separation bend, a guide island, and a narrow slit guide channel; One end of the dispersed phase main channel is connected to the dispersed phase inlet branch channel and the dispersed phase main channel of the next-level series unit; the dispersed phase inlet branch channel is connected to the unit continuous phase inlet, the unit continuous phase inlet is connected to the inertial separation bend, and two narrow slot guide channels are formed between the guide island and the surrounding channel wall. One end of the narrow slot guide channel is connected to the inertial separation bend, and the other end of the narrow slot guide channel is connected to the unit continuous phase outlet. The unit continuous phase outlet is connected to the unit continuous phase inlet of the next-level series unit.

[0008] Furthermore, the dispersed phase is introduced into the branch channel to form a droplet generation region between the unit continuous phase inlet and the branch channel.

[0009] Furthermore, the width of the narrow slit guide channel is equal to half the width of the dispersed phase main channel.

[0010] Furthermore, the number of series units is at least two.

[0011] Furthermore, one end of the dispersed phase main channel of the first-stage series unit is connected to the dispersed phase main inlet, and the other end of the dispersed phase main channel 1 of the first-stage series unit is connected to the dispersed phase main channel of the adjacent next stage; the dispersed phase main channel of the last-stage series unit is connected to the dispersed phase outlet.

[0012] Furthermore, one end of the continuous phase inlet of the first-stage series unit is connected to the continuous phase total inlet, and the other end is connected to the inertial separation bend.

[0013] Furthermore, the continuous phase outlet of the last-stage series unit is connected to the total continuous phase outlet.

[0014] A method for preparing droplets using a continuous-phase, cascaded droplet microfluidic chip, characterized by comprising the following steps: The dispersed phase fluid is injected into the main dispersed phase channel through the main dispersed phase inlet, causing the dispersed phase to flow downstream along the main dispersed phase channel and split into the corresponding dispersed phase inlet branch channel at each series unit, entering the droplet generation region. The continuous phase fluid is injected into the unit continuous phase inlet through the continuous phase total inlet and flows toward the droplet generation region; In the droplet generation region of each series unit, the continuous phase contacts and shears the dispersed phase to form droplets, which then enter the inertial separation bend in the series unit. The droplet-containing fluid flows sequentially through the inertial separation bend and the guide island. Under the action of the narrow slit guide channel, the droplets and part of the continuous phase flow out through the unit droplet product outlet, and the remaining continuous phase flows into the continuous phase inlet of the next stage series unit through the unit continuous phase outlet. The continuous phase is reused stepwise among multiple series units, and the droplets generated by each series unit flow into the corresponding unit droplet product outlet and are discharged through the corresponding unit droplet product outlet.

[0015] The beneficial effects of this invention are as follows: 1. This invention achieves continuous phase reuse and centralized droplet product output by arranging multiple series units on a chip substrate and integrating structures such as dispersed phase introduction, droplet generation, inertial bend guidance, flow island diversion, narrow slit guidance, reused continuous phase output, and droplet product output in each series unit. This technical solution can solve the technical problems of limited yield of a single generation unit, complex parallel amplification structure, large continuous phase consumption, large number of external interfaces, and lack of continuous phase reuse path within the chip in existing droplet microfluidic chips, and is suitable for continuous and batch preparation of droplets.

[0016] 2. Compared to microfluidic chips with only a single droplet generation structure, this invention increases the number of droplet generation positions through the integrated arrangement of multiple series units, thereby improving the overall droplet generation capability of the chip. Therefore, this invention can alleviate the problem of limited yield of a single droplet generation unit, making it difficult to meet the needs of continuous and batch droplet fabrication.

[0017] 3. To address the issue that in traditional droplet generation structures, the continuous phase is typically discharged along with the droplet products after participating in droplet generation, resulting in low continuous phase utilization, especially in multi-unit high-throughput fabrication, which leads to a significant increase in continuous phase consumption, this invention incorporates a second continuous phase outlet in each series unit. After the droplet-containing fluid passes through an inertial separation bend, a guide island, and a narrow-slit guide channel, a portion of the continuous phase is guided to the second continuous phase outlet and continues into the continuous phase inlet of the next-stage series unit. This structure allows the continuous phase to be utilized at multiple stages within the chip, rather than being completely discharged after one droplet generation cycle. Therefore, this invention improves continuous phase utilization, reduces continuous phase consumption, and helps lower reagent consumption and operating costs. Furthermore, it reduces the number of independent continuous phase supply channels and external interfaces, lowering the complexity of the continuous phase supply network within the chip. Compared to traditional parallel supply structures, this invention eliminates the need for a separate, complex continuous phase allocation branch for each droplet generation unit, thus simplifying the chip structure and facilitating system integration.

[0018] 4. Traditional parallel droplet microfluidic chips typically increase throughput by increasing the number of parallel channels. However, differences in channel length, width, number of turns, or manufacturing errors can easily lead to variations in liquid resistance between parallel branches. These resistance differences result in uneven flow distribution across different branches, affecting the operational status of each droplet generation unit. This invention employs a series-based method with continuous phase multiplexing. The continuous phase enters each series unit sequentially along the series direction, rather than being simultaneously distributed to multiple units through a complex parallel distribution network. This structure reduces the design requirement for strict flow resistance matching between multiple continuous phase supply branches in traditional parallel amplification. Therefore, this invention can, to a certain extent, reduce the design difficulty of flow balancing caused by multiple parallel supply branches, providing a batch amplification path for droplet microfluidic chips that differs from traditional parallel expansion. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the overall chip structure provided by the present invention; Figure 2 This is an exploded view of the chip structure provided by the present invention; Figure 3 This is a schematic diagram of the chip planar structure provided by the present invention; Figure 4 This is a partially enlarged structural diagram of the series unit provided by the present invention.

[0020] Reference numerals: 1: Chip substrate, 1-1: Dispersed phase main inlet, 1-2: Continuous phase main inlet, 1-3: Remaining dispersed phase outlet, 1-4: Continuous phase main outlet, 1-5: Droplet product main outlet; 2: Chip cover plate, 3: Series unit, 3-1: Dispersed phase main channel, 3-2: Dispersed phase introduction branch channel, 3-3: Unit continuous phase inlet, 3-4: Unit continuous phase outlet, 3-5: Unit droplet product outlet, 3-6: Inertial separation bend, 3-7 Guide island, 3-8: Narrow slit guide channel. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0022] The application principle of the present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0023] Please refer to Figure 1 and Figure 2 A continuous-phase, cascaded droplet microfluidic chip includes a chip substrate 1 and a chip cover plate 2. The chip cover plate 2 covers the chip substrate 1 and is sealed to the chip substrate 1 by thermo-press bonding, thereby closing the open microfluidic channel structure on the chip substrate 1 to form a closed microfluidic channel that allows for stable fluid flow.

[0024] The chip substrate 1 is provided with a dispersed phase inlet 1-1, a continuous phase inlet 1-2, a residual dispersed phase outlet 1-3, a continuous phase outlet 1-4, and a droplet product outlet 1-5. The chip substrate 1 also has multiple series-connected units 3, with at least two series-connected units 3. The dispersed phase inlet 1-1, continuous phase inlet 1-2, residual dispersed phase outlet 1-3, continuous phase outlet 1-4, and droplet product outlet 1-5 are connected by the series-connected units 3. Each series-connected unit 3 is a complete droplet generation-droplet separation-continuous phase reuse functional unit. Multiple series-connected units 3 are arranged sequentially along the fluid flow direction, allowing the continuous phase to enter the next series-connected unit 3 from the previous one to continue participating in droplet generation.

[0025] In this invention, the dispersed phase inlet 1-1 is used to introduce a dispersed phase, such as an aqueous phase or other liquid to be dispersed, into the chip; the continuous phase inlet 1-2 is used to introduce a continuous phase, such as paraffin oil containing surfactants, mineral oil, silicone oil, fluorinated oil, or other liquids that can serve as a continuous phase, into the chip. The remaining dispersed phase outlet 1-3 is used to discharge the dispersed phase that has not been consumed by each series unit 3; the continuous phase outlet 1-4 is used to discharge the remaining continuous phase that has not been discharged with the droplet products after passing through multiple series units 3; and the droplet product outlet 1-5 is used to output the droplet products generated and collected by each series unit 3. The overall structure of this chip is not a simple parallel connection of multiple droplet generation units, but rather a series connection of multiple series units 3. The continuous phase separated from the previous series unit 3 can enter the next series unit 3 and continue to be used as a continuous phase, thereby forming a step-by-step reuse path for the continuous phase within the chip. Through this structure, continuous integrated operation of multiple droplet generation locations can be achieved while reducing the number of independent liquid supply channels for the continuous phase.

[0026] like Figure 3 and Figure 4 As shown, each of the series units 3 includes a dispersed phase main channel 3-1, a dispersed phase introduction branch channel 3-2, a second continuous phase inlet 3-3, a second continuous phase outlet 3-4, a second droplet product outlet 3-5, an inertial separation bend 3-6, a guide island 3-7, and a narrow slit guide channel 3-8.

[0027] The dispersed phase main channel 3-1 is arranged along the length of the chip and is connected to the dispersed phase main channel 3-1 of the adjacent next-level series unit 3. One end of the dispersed phase main channel 3-1 of the first-level series unit 3 is connected to the dispersed phase inlet 1-1, and the other end is connected to the dispersed phase main channel 3-1 of the adjacent next-level unit. The dispersed phase main channel 3-1 of the last-level series unit 3 is connected to the dispersed phase outlet 1-3.

[0028] The dispersed phase introduction branch channel 3-2 originates from the dispersed phase main channel 3-1 and extends to the droplet generation region. Both ends of the dispersed phase introduction branch channel 3-2 are connected to the dispersed phase main channel 3-1 and the unit continuous phase inlet 3-3, respectively. The unit continuous phase inlet 3-3 is located at the continuous phase inlet end of the series unit 3 and is used to introduce the continuous phase into the series unit 3. The dispersed phase introduction branch channel 3-2 and the continuous phase inlet 3-3 are correspondingly arranged so that the dispersed phase and the continuous phase can meet in the local convergence region.

[0029] A step-T type confluence structure, i.e., the droplet generation region, is formed between the dispersed phase inlet 3-2 and the unit continuous phase inlet 3-3. The continuous phase enters through the unit continuous phase inlet 3-3 and flows along the main flow direction, while the dispersed phase enters the step-T type confluence through the dispersed phase inlet 3-2. Under the shearing action of the continuous phase, the dispersed phase breaks at the confluence, forming discrete droplets. These droplets then enter the downstream inertial separation bend 3-6 along with the continuous phase.

[0030] The unit continuous phase inlet 3-3 is connected to the inertial separation bend 3-6, and one end of the unit continuous phase inlet 3-3 of the first-stage series unit 3 is connected to the continuous phase total inlet 1-2, while the other end is connected to the inertial separation bend 3-6. The inertial separation bend 3-6 is located downstream of the droplet generation region. This inertial separation bend 3-6 is an arc-shaped flow channel structure with a bending and deflecting function. The inertial separation bend 3-6 is used to change the flow direction of the droplet-containing fluid, so that the droplets are subjected to streamline deflection, inertial offset, and geometric constraint caused by the curved flow channel before entering the subsequent diversion region. This structure can provide pre-guiding conditions for the subsequent guide island 3-7 and narrow slit guide channel 3-8 to achieve the diversion of droplet product flow and reused continuous phase flow.

[0031] The guide island 3-7 is located in the downstream diversion region of the inertial separation bend 3-6. Two narrow-slit guide channels 3-8 are formed between the guide island 3-7 and the surrounding channel walls, with one end of each narrow-slit guide channel 3-8 connected to the inertial separation bend 3-6. The other end of each narrow-slit guide channel 3-8 is connected to the unit continuous phase outlet 3-4, which is connected to the unit continuous phase inlet 3-3 of the adjacent next-level series unit 3. The unit continuous phase outlet 3-4 of the last series unit 3 is connected to the total continuous phase outlet 1-4. The guide island 3-7 is used to spatially separate and streamline the droplet-containing fluid entering the diversion region, causing the droplets and a portion of the continuous phase near them to tend to enter the second droplet product outlet 3-5, while the remaining continuous phase enters the next-level series unit 3 via the reused unit continuous phase outlet 3-4.

[0032] The inertial separation bend 3-6 is connected to the second droplet product outlet 3-5. Two narrow slit guide channels 3-8 are located on both sides of the guide island 3-7. The narrow slit guide channel 3-8 is a locally contracting channel with a width equal to half the width of the dispersed phase main channel 3-1. It is used to limit the distribution path of the fluid in the split region and to guide the continuous phase and the droplet-containing fluid.

[0033] The width and depth of the dispersed phase main channel 3-1 and the dispersed phase inlet branch channel 3-2 are both 200 micrometers. The width and depth of the dispersed phase main inlet 1-1, continuous phase main inlet 1-2, remaining dispersed phase outlet 1-3, continuous phase main outlet 1-4, and droplet product main outlet 1-5 are both 1.1 mm and 1.1 mm, respectively, and are designed for insertion into flat-tipped needles with an outer diameter of 1 mm.

[0034] In this invention, after the droplet-containing fluid enters the inertial separation bend 3-6 from the droplet generation region, the fluid flow direction changes. Under the geometric constraints, local inertia, and streamline deflection of the bend, the droplets form a certain motion deflection before entering the splitting region. Subsequently, the droplet-containing fluid enters the splitting region where the guide island 3-7 is located. The guide island 3-7 is located downstream of the inertial separation bend 3-6 and forms a narrow slit guide channel 3-8 between itself and the surrounding channel walls. Because the guide island 3-7 has the function of separating and reconstructing local streamlines, the fluid entering the splitting region is divided into two parts: one part carries droplets along the mainstream direction to the unit droplet product outlet 3-5, while the other part of the continuous phase enters the unit continuous phase outlet 3-4 through the narrow slit guide channel 3-8 between the guide island 3-7 and the channel wall.

[0035] The width of the narrow-slit guide channel 3-8 is half the width of the dispersed phase main channel 3-1, thus exhibiting different passage characteristics for droplets and the continuous phase. The continuous phase, being a continuous fluid, can enter the narrow-slit guide channel 3-8 under the influence of pressure difference or flow resistance distribution on the unit continuous phase outlet 3-4, and is then transported to the next-stage series unit 3 via the unit continuous phase outlet 3-4. Droplets, being a discrete phase, require interfacial deformation upon entering the narrow-slit guide channel 3-8, accompanied by changes in droplet surface area and interfacial curvature, resulting in additional capillary pressure resistance and deformation resistance. Therefore, compared to the continuous phase, droplets are less likely to enter the narrow-slit guide channel 3-8, and tend to enter the unit droplet product outlet 3-5 along a path with less resistance and a wider channel space.

[0036] Meanwhile, the guide island 3-7 positions the narrow slit guide channel 3-8 laterally within the diversion region, enabling it to primarily function as a continuous phase stripper and guide. The unit droplet product outlet 3-5 is located in the main direction of movement of the droplet-containing fluid, serving to receive droplets and part of the continuous phase. Thus, the inertial separation bend 3-6, the guide island 3-7, and the narrow slit guide channel 3-8 together form a passive diversion structure, enabling path separation of the droplet product flow and the reused continuous phase flow without the need for external electric fields, magnetic fields, acoustic fields, or valve-controlled structures.

[0037] It should be noted that the narrow slit guide channel 3-8 is not intended to completely block droplets from entering the unit continuous phase outlet 3-4. Instead, it reduces the probability of droplets entering the reused continuous phase flow path by narrowing the local channel width, increasing the interfacial deformation resistance required for droplets to enter the narrow slit, and cooperating with the guiding effect of the guide island 3-7 on the streamlines, thereby improving the availability of reused continuous phase entering the next stage series unit.

[0038] Through this connection method, an overall flow path structure is formed inside the chip: "multi-stage supply of dispersed phase - stage-by-stage reuse of continuous phase - centralized output of droplet products". This structure allows the continuous phase to be utilized stage by stage along the series direction, without having to be supplied to each series unit 3 by multiple independent inlets.

[0039] The present invention also provides a method for preparing droplets using the above-mentioned continuous phase stepwise multiplexing type cascaded droplet microfluidic chip, comprising the following steps: Step 1: Introduce the dispersed phase.

[0040] The dispersed phase fluid is injected into the chip substrate 1 through the dispersed phase main inlet 1-1, allowing the dispersed phase to enter the dispersed phase main channel 3-1. The dispersed phase flows downstream along the dispersed phase main channel 3-1, and enters the corresponding dispersed phase inlet branch channel 3-2 when passing through each series unit 3. Each dispersed phase inlet branch channel 3-2 introduces a portion of the dispersed phase into the droplet generation region of the corresponding series unit 3. The droplet generation region refers to the intersection of the dispersed phase inlet branch channel 3-2 and the unit continuous phase inlet 3-3, which is the Step-T type intersection region mentioned above. The remaining dispersed phase that does not enter the droplet generation region continues to flow along the dispersed phase main channel 3-1 and is eventually discharged from the remaining dispersed phase outlet 1-3.

[0041] Step two: Introduce a continuous phase.

[0042] A continuous phase fluid is injected into the chip substrate 1 through the continuous phase main inlet 1-2, allowing the continuous phase to first enter the unit continuous phase inlet 3-3 of the series unit 3. Within the series unit 3, the continuous phase flows along the unit continuous phase inlet 3-3 towards the droplet generation region, where it meets the dispersed phase introduced by the dispersed phase introduction branch channel 3-2 at the convergence region. The continuous phase can be an oil phase containing surfactants, and the dispersed phase can be an aqueous phase or other liquids immiscible with the continuous phase.

[0043] Step 3: Forming droplets.

[0044] In the droplet generation region of each series unit 3, the dispersed phase comes into contact with the continuous phase. Since the continuous and dispersed phases are immiscible and differ in viscosity, interfacial tension, and flow velocity, the dispersed phase necks and breaks down under the shearing action of the continuous phase, thus forming discrete droplets. The generated droplets continue to flow downstream with a portion of the continuous phase, entering the inertial separation bends 3-6 within the series unit 3.

[0045] Step four: The droplets and the continuous phase are passively separated within the cell.

[0046] After the droplet-containing fluid enters the inertial separation bend 3-6, its flow direction changes, and it is guided into the flow-dividing region where the guide island 3-7 is located. The guide island 3-7 and the surrounding flow channel walls together form a narrow slit guide channel 3-8, causing the droplet-containing fluid to undergo path distribution within the flow-dividing region. Among them, the droplets and part of the continuous phase flow out through the unit droplet product outlet 3-5 and enter the droplet product collection channel; the other part of the continuous phase flows out through the unit continuous phase outlet 3-4 and is used as the continuous phase input for the next stage series unit 3.

[0047] Step 5: The continuous phase enters the next series unit for continued use.

[0048] The continuous phase outlet 3-4 of the first-stage series unit 3 is connected to the continuous phase inlet 3-3 of the next-stage series unit 3, thus the continuous phase diverted from the first-stage series unit 3 continues to enter the next-stage series unit 3. In the next-stage series unit 3, the reused continuous phase comes into contact again with the new dispersed phase introduced from the main dispersed phase channel 3-1 via the corresponding dispersed phase introduction branch channel 3-2, and forms new droplets under the shearing action of the continuous phase. Subsequently, the newly generated droplets and part of the continuous phase are output through the unit droplet product outlet 3-5 of this stage series unit 3, while the remaining continuous phase continues to enter the next-stage series unit 3 through the reused unit continuous phase outlet 3-4 of this stage series unit 3.

[0049] Step six: Multi-stage repeating droplet generation and continuous phase reuse process.

[0050] Steps three through five are repeated, with the continuous phase being reused sequentially among multiple series units 3. Each series unit 3 receives new dispersed phase replenishment from the main dispersed phase channel 3-1 and sequentially completes droplet generation, inertial bend guidance, flow island diversion, narrow slot guidance, and continuous phase reuse output. The remaining continuous phase in the last series unit 3 that does not flow out with the droplet products is discharged from the continuous phase main outlet 1-4, or connected to an external recovery device as needed.

[0051] Step 7: Collect the droplet products.

[0052] The droplets generated in each series unit 3 enter the droplet product collection channel through the corresponding unit droplet product outlet 3-5, and finally converge to the droplet product total outlet 1-5 for discharge. Thus, droplets generated by multiple series units 3 can be collected centrally through the same droplet product total outlet 1-5, realizing continuous and batch preparation of droplets.

[0053] Using the above method, the continuous phase is not completely discharged with the droplet products after one droplet generation. Instead, it continues to enter the next stage of the series unit 3 through the unit continuous phase outlet 3-4 within each stage of the series unit 3, thereby achieving the cascaded reuse of the continuous phase within the chip. Simultaneously, each stage of the series unit 3 can receive dispersed phase replenishment through the dispersed phase main channel 3-1, and the generated droplets are uniformly channeled into the total droplet product outlet 1-5. Therefore, this method can achieve cascaded batch preparation of droplets while reducing the independent liquid supply requirements and consumption of the continuous phase.

[0054] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A continuous phase stepwise multiplexing type serial droplet microfluidic chip, characterized by, Includes a chip substrate and a chip cover plate; the chip cover plate covers the chip substrate and is sealed to the chip substrate. The chip substrate is provided with a dispersed phase inlet, a continuous phase inlet, a remaining dispersed phase outlet, a continuous phase outlet, a droplet product outlet, and multiple series-connected units. The series unit includes a dispersed phase main channel, a dispersed phase introduction branch channel, a unit continuous phase inlet, a unit continuous phase outlet, a unit droplet product outlet, an inertial separation bend, a guide island, and a narrow slit guide channel; One end of the dispersed phase main channel is connected to the dispersed phase inlet branch channel and the dispersed phase main channel of the next-level series unit; the dispersed phase inlet branch channel is connected to the unit continuous phase inlet, the unit continuous phase inlet is connected to the inertial separation bend, and two narrow slot guide channels are formed between the guide island and the surrounding channel wall. One end of the narrow slot guide channel is connected to the inertial separation bend, and the other end of the narrow slot guide channel is connected to the unit continuous phase outlet. The unit continuous phase outlet is connected to the unit continuous phase inlet of the next-level series unit.

2. The continuous-phase, step-by-step multiplexing tandem droplet microfluidic chip according to claim 1, characterized in that, The dispersed phase is introduced into the branch channel to form a droplet generation region between the unit continuous phase inlet and the branch channel.

3. The continuous-phase, step-by-step multiplexing tandem droplet microfluidic chip according to claim 1, characterized in that, The width of the narrow slit guide channel is equal to half the width of the main dispersed phase channel.

4. The continuous-phase, step-by-step multiplexing tandem droplet microfluidic chip according to claim 1, characterized in that, The number of series units must be at least two.

5. The continuous-phase, step-by-step multiplexing tandem droplet microfluidic chip according to claim 1, characterized in that, One end of the dispersed phase main channel of the first-stage series unit is connected to the dispersed phase main inlet, and the other end of the dispersed phase main channel 1 of the first-stage series unit is connected to the dispersed phase main channel of the next adjacent stage; the dispersed phase main channel of the last-stage series unit is connected to the dispersed phase outlet.

6. The continuous-phase, step-by-step multiplexing tandem droplet microfluidic chip according to claim 1, characterized in that, One end of the continuous phase inlet of the first-stage series unit is connected to the continuous phase total inlet, and the other end is connected to the inertial separation bend.

7. The continuous-phase, step-by-step multiplexing tandem droplet microfluidic chip according to claim 1, characterized in that, The continuous phase outlet of the last-stage series unit is connected to the total continuous phase outlet.

8. A method for preparing droplets using a continuous-phase stepwise multiplexing tandem droplet microfluidic chip according to any one of claims 1 to 7, characterized in that, Includes the following steps: The dispersed phase fluid is injected into the main dispersed phase channel through the main dispersed phase inlet, causing the dispersed phase to flow downstream along the main dispersed phase channel and split into the corresponding dispersed phase inlet branch channel at each series unit, entering the droplet generation region. The continuous phase fluid is injected into the unit continuous phase inlet through the continuous phase total inlet and flows toward the droplet generation region; In the droplet generation region of each series unit, the continuous phase contacts and shears the dispersed phase to form droplets, which then enter the inertial separation bend in the series unit. The droplet-containing fluid flows sequentially through the inertial separation bend and the guide island. Under the action of the narrow slit guide channel, the droplets and part of the continuous phase flow out through the unit droplet product outlet, and the remaining continuous phase flows into the continuous phase inlet of the next stage series unit through the unit continuous phase outlet. The continuous phase is reused stepwise among multiple series units, and the droplets generated by each series unit flow into the corresponding unit droplet product outlet and are discharged through the corresponding unit droplet product outlet.

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