Multi-volume emulsion droplet generation device and generation method

Abstract

The invention relates to the technical field of emulsion droplet generation, in particular to a multi-volume emulsion droplet generation device and method, and the device comprises a liquid storage device which comprises a continuous-phase liquid storage bottle for storing a continuous-phase fluid and a dispersed-phase liquid storage bottle for storing a dispersed-phase fluid; the micro-fluidic chip is provided with a shallow channel communicated with the continuous phase liquid storage bottle and the dispersed phase liquid storage bottle, a cross micro-channel for converging two-phase fluid, a central division column and a deep channel according to a fluid flowing sequence; and the pressure pumping device is provided with a controller and is communicated with the liquid storage device to provide power for fluid flowing. Based on different deformation states of a two-phase fluid interface under different Laplacian stresses, a central segmentation column structure is arranged at the tail end of a micro-channel to control the fluid resistance around an original emulsion droplet, so that the original emulsion droplet is forced to periodically deform and split, multiple-volume emulsion droplets are formed, and the multi-volume emulsion droplet is formed. The problems that a traditional multi-volume emulsion droplet generation mode is high in production cost, complex in operation and incapable of achieving synchronous generation are solved, and the multi-volume emulsion droplet generation efficiency is effectively improved.

Description

Technical Field

[0001] The invention relates to the technical field of emulsion droplet generation, in particular to a microfluidic device and a generation method capable of realizing synchronous generation of double-sized emulsion droplets. Background Art

[0002] Microfluidic segmentation technology has a wide range of application needs in the fields of material synthesis, single cell analysis, rare mutation detection, medical testing, biochemical analysis, etc. The core of microfluidic segmentation technology is to divide milliliter or microliter fluids into independent units at the nanoliter or picoliter level. A major technical branch of microfluidic segmentation technology is the emulsion droplet generation method and technology.

[0003] Existing emulsion droplet generation methods and technologies include T-shear method, flow focusing method, coaxial flow method, electrospray method and step emulsification method. Among them, multi-volume micro-droplet segmentation, as the latest emulsion droplet generation technology, has good application prospects in polydisperse encapsulation of active molecules and quantitative analysis of nucleic acid molecules with high dynamic range. For general multi-volume micro-droplet generation methods, it is often necessary to generate micro-droplets of different sizes in batches, which is relatively complicated to operate.

[0004] In addition, publication number CN115093961A discloses an emulsion droplet generation device, which can be used to generate multiple volume emulsion droplets, but involves a cumbersome ultrasonic oscillation process and requires an external power supply device, thus causing a high cost problem. Summary of the invention

[0005] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a device and method for generating multiple volume emulsion droplets. The present invention is based on the deformation process of the two-phase fluid interface under Laplace pressure, and induces the original emulsion droplets to break into large volume emulsion droplets and small volume emulsion droplets through a central dividing column, which solves the problems of high production cost and complex operation in the traditional multiple volume emulsion droplet generation method, and greatly improves the generation efficiency of multiple volume emulsion droplets. In order to achieve the above purpose, the present invention is implemented through the following technical solutions:

[0006] In a first aspect, the present invention provides a microfluidic device for generating multi-volume emulsion droplets, comprising:

[0007] A liquid storage device, comprising a continuous phase liquid storage bottle for storing a continuous phase fluid and a dispersed phase liquid storage bottle for storing a dispersed phase fluid;

[0008] A microfluidic chip, which is provided with a shallow channel connecting the continuous phase storage bottle and the dispersed phase storage bottle in the order of fluid flow, a cross microchannel for converging the two-phase fluid and shearing the dispersed phase fluid into original emulsion droplets, a central dividing column for dividing the original emulsion droplets into multiple emulsion droplets, and a deep channel;

[0009] The pressure pumping device is equipped with a controller and connected to the liquid storage device to provide power for the fluid flow.

[0010] As a further implementation, the pressure pumping device is a pressure pump, and the pressure pump is a vane pump, a positive displacement pump, or an electromagnetic pump.

[0011] As a further implementation, the continuous phase liquid storage bottle and the dispersed phase liquid storage bottle are connected to the continuous phase inlet and the dispersed phase inlet of the microfluidic chip.

[0012] In a second aspect, the present invention provides a method for generating multi-volume emulsion droplets, which is generated using the multi-volume emulsion droplet generation device as described in the first aspect, comprising the following steps:

[0013] The pressure pumping device and its controller adjust the air pressure, deliver the high-pressure gas to the dispersed phase storage bottle and the continuous phase storage bottle, pump the dispersed phase fluid and the continuous phase fluid into the shallow channel in the microfluidic chip, and the two phases of fluid move separately and meet at the cross microchannel. The dispersed phase fluid is sheared by the continuous phase fluid, thereby generating original emulsion droplets. When the original emulsion droplets move along the microchannel and reach the central dividing column, they are squeezed and deformed, split into large-volume emulsion droplets and small-volume emulsion droplets and enter the deep channel behind. With the continuous drive of high-pressure gas, multiple-volume emulsion droplets are continuously generated.

[0014] As a further implementation, the controller may control the unit flow rates of the dispersed phase fluid and the continuous phase fluid, and control the flow rates of the dispersed phase fluid and the continuous phase fluid to be in an appropriate ratio by controlling the pressure of the driving gas.

[0015] As a further implementation method, the dispersed phase fluid and the continuous phase fluid are squeezed by the high-pressure gas, and the dispersed phase fluid and the continuous phase fluid are respectively transported to the dispersed phase inlet and the continuous phase inlet of the microfluidic chip through the liquid pipeline.

[0016] As a further implementation method, the dispersed phase fluid is sheared by the continuous phase fluid into original emulsion droplets, and when impacting the central dividing column, it breaks into large-volume emulsion droplets and small-volume emulsion droplets, that is, multiple-volume emulsion droplets.

[0017] As a further implementation method, when the pressure in the continuous phase storage bottle is maintained at the same, the greater the pressure in the dispersed phase storage bottle, the larger the size of the generated multi-volume emulsion droplets, showing a positive correlation.

[0018] As a further implementation method, when the flow rate of the continuous phase fluid remains the same, the greater the flow rate of the dispersed phase fluid, the larger the size of the generated multi-volume emulsion droplets, showing a positive correlation.

[0019] As a further implementation, the other pressure of the pressure pumping device is 0 to 100 kPa, and the pressure adjustment range of the controller is 0 to 100 kPa.

[0020] The beneficial effects of the present invention are as follows:

[0021] 1. Based on the different deformation states of the two-phase fluid interface under different Laplace stresses, the present invention sets a central dividing column structure at the end of the microchannel to control the fluid resistance around the original emulsion droplets, thereby forcing the original emulsion droplets to deform and split periodically, thereby forming multiple-volume emulsion droplets. This solves the problems of high production cost, complex operation and inability to generate synchronously in traditional multiple-volume emulsion droplet generation methods, and effectively improves the efficiency of multiple-volume emulsion droplet generation.

[0022] 2. In the present invention, when the original emulsion droplets reach the central dividing column and split into multiple-volume emulsion droplets, the multiple-volume emulsion droplets enter the deep channel at the rear and move in two directions respectively, which do not interfere with each other and can be collected and used separately. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0024] Figure 1 It is a schematic diagram of the structure of a multi-volume emulsion droplet generating device in Example 1 of the present invention.

[0025] Figure 2 It is a schematic diagram of the process of generating emulsion droplets using the multi-volume emulsion droplet generating device in Example 1.

[0026] Figure 3 It is a graph of the continuous phase and dispersed phase gas pressures in Example 2 of the present invention.

[0027] Figure 4 These are the multi-volume emulsion droplets generated in Example 2 of the present invention.

[0028] Figure 5 It is a graph of the continuous phase and dispersed phase gas pressures in Example 3 of the present invention.

[0029] Figure 6 These are the multi-volume emulsion droplets generated in Example 3 of the present invention.

[0030] Figure 7 It is a flow velocity curve diagram of the continuous phase and the dispersed phase in Example 4 of the present invention.

[0031] Figure 8These are the multi-volume emulsion droplets generated in Example 4 of the present invention.

[0032] Fig. 9 It is a flow velocity curve diagram of the continuous phase and the dispersed phase in Example 5 of the present invention.

[0033] Fig.10 These are the multi-volume emulsion droplets generated in Example 5 of the present invention.

[0034] In the figure: the distances or sizes between parts are exaggerated to show the positions of various parts, and the schematic diagram is for reference only.

[0035] Among them: 1. pressure pump; 2. controller; 3. gas pipeline; 4. continuous phase storage bottle; 5. dispersed phase storage bottle; 6. continuous phase fluid; 7. dispersed phase fluid; 8. fluid pipeline; 9. microfluidic chip; 10. shallow channel; 11. deep channel; 12. central dividing column; 13. original emulsion droplets; 14. small volume emulsion droplets; 15. large volume emulsion droplets. DETAILED DESCRIPTION

[0036] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0037] Embodiment 1

[0038] In a typical embodiment of the present invention, reference is made to Figure 1 As shown, a multi-volume emulsion droplet generation device includes a liquid storage device, a microfluidic chip 9 and a pressure pumping device.

[0039] The pressure pumping device is equipped with a controller 2, which is connected to the liquid storage device to provide power for the fluid flow. The pressure pumping device is a pressure pump 1, which is a vane pump, a volumetric pump or an electromagnetic pump.

[0040] The liquid storage device comprises a continuous phase liquid storage bottle 4 for storing a continuous phase fluid 6 and a dispersed phase liquid storage bottle 5 for storing a dispersed phase fluid 7 . The controller 2 is connected to the continuous phase liquid storage bottle 4 and the dispersed phase liquid storage bottle 5 through a gas pipeline 3 .

[0041] The microfluidic chip 9 is provided with a shallow channel 10 connecting the continuous phase liquid storage bottle 4 and the dispersed phase liquid storage bottle 5, a cross microchannel that intersects the two-phase fluid and forms the original emulsion droplet 13, a central dividing column 12, and a deep channel 11 according to the fluid flow sequence. The microfluidic chip 9 is connected to the continuous phase liquid storage bottle 4 and the dispersed phase liquid storage bottle 5 through a fluid pipeline 8, and the fluids in the continuous phase liquid storage bottle 4 and the dispersed phase liquid storage bottle 5 are pumped into the microfluidic chip 9.

[0042] The gas pipeline 3 and the fluid pipeline 8 are made of glass, silicone or plastic.

[0043] In this embodiment, the continuous phase fluid 6 and the dispersed phase fluid 7 are pumped into the microfluidic chip 9 by high-pressure gas. The two-phase fluids meet at the cross microchannel, and the dispersed phase fluid is sheared into original emulsion droplets 13, which move in the shallow channel 10. When the original emulsion droplet 13 moves to the terminal position, it hits the central partition column 12 and deforms. The central partition column 12 divides the shallow channel 10 into two outlets with different cross-sectional areas, resulting in different flow resistances for the original emulsion droplet 13, which is then unevenly divided and forms small-volume emulsion droplets 14 and large-volume emulsion droplets 15 after entering the deep channel 11. With the continuous driving of the high-pressure gas, multiple-volume emulsion droplets 14 and 15 are continuously generated.

[0044] This embodiment is based on the fact that the deformation states of the two-phase fluid interface are different under different Laplace stresses. A central dividing column 12 is set between the shallow channel 10 and the deep channel 11 to create two outlets with different flow resistances, thereby forcing the original emulsion droplets 13 to deform and split periodically, thereby forming multiple-volume emulsion droplets 14 and 15. This solves the problem that the traditional preparation process of multiple-volume emulsion droplets is complicated and cannot be generated synchronously, and effectively improves the generation efficiency of multiple-volume emulsion droplets.

[0045] The gas pressure in the pressure pump 1 is 0-100 kPa, such as 80 kPa, 85 kPa, 90 kPa, 95 kPa or 100 kPa, but is not limited to the listed values, and other values ​​not listed within the numerical range are also applicable.

[0046] The pressure adjustment range of the controller 2 is 0 to 100 kPa, such as 80 kPa, 85 kPa, 90 kPa, 95 kPa or 100 kPa, but is not limited to the listed values, and other values ​​not listed within the range are also applicable.

[0047] The size of the emulsion droplets generated by the generating device of this embodiment is 10nm-1mm, such as 50μm, 100μm, 200μm or 500μm, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0048] The frequency of the emulsion droplets generated by the generating device of this embodiment is 1 Hz to 2000 Hz, such as 50 Hz, 200 Hz, 500 Hz or 1000 Hz, but is not limited to the listed values, and other values ​​not listed within the numerical range are also applicable.

[0049] Embodiment 2

[0050] This embodiment provides a method for generating multi-volume emulsion droplets, which uses the microfluidic device provided in the first embodiment to generate multi-volume emulsion droplets, and specifically includes the following steps:

[0051] (1) The pressure pump 1 compresses the external air and delivers it to the controller 2;

[0052] (2) The controller 2 adjusts the gas pressure and delivers 550Pa and 300Pa of compressed gas to the continuous phase storage bottle 4 and the dispersed phase storage bottle 5 respectively through the gas hose (e.g. Figure 3 shown);

[0053] (3) The continuous phase fluid 6 and the dispersed phase fluid 7 are squeezed by the high-pressure gas, and the two-phase fluids are respectively transported to the dispersed phase inlet and the continuous phase inlet of the microfluidic chip 9 through the fluid pipeline 8, and enter the shallow channel 10;

[0054] (4) The continuous phase fluid 6 and the dispersed phase fluid 7 meet at the cross microchannel position, and the continuous phase fluid 6 is sheared into original emulsion droplets 13 and moves forward in the shallow channel 10;

[0055] (5) When the original emulsion droplet 13 reaches the central dividing column 12, the spatial mutation causes the original emulsion droplet 13 to be subjected to uneven flow resistance, which in turn leads to an increase in the change in interface curvature, that is, an increase in the Laplace pressure difference on both sides of the interface; the Laplace stress causes the degree of interface curvature to be further enhanced, which manifests itself macroscopically as the original emulsion droplet 13 being squeezed and deformed by the central dividing column 12.

[0056] (6) When the original emulsion droplet 13 is deformed to the limit state, it splits into two parts and enters the deep channel 11, and forms a small-volume emulsion droplet 14 and a large-volume emulsion droplet 15 under the principle of minimum surface energy;

[0057] (7) Steps (5) and (6) are repeated alternately. Driven by the pressure source, the original emulsion droplets 13 are continuously generated, continuously hit the central partition column 12, and break into small-volume emulsion droplets 14 and large-volume emulsion droplets 15. The macroscopic manifestation is the high-frequency oscillation of the original emulsion droplets 13 at the outlet of the shallow channel 10, and the continuous ejection of multiple-volume emulsion droplets (such as Figure 4 shown).

[0058] Embodiment 3

[0059] This embodiment provides a method for generating multi-volume emulsion droplets. The difference from the second embodiment is that the pressures of the continuous phase storage bottle 4 and the dispersed phase storage bottle 5 are 550Pa and 400Pa respectively (e.g. Figure 5As shown in FIG. 1 , the high-pressure gas pushes the dispersed phase fluid 7 and the continuous phase fluid 6 into the microfluidic chip 9 and generates the original emulsion droplets 13. Under the action of the central dividing column 12, the original emulsion droplets 13 are split into small-volume emulsion droplets 14 and large-volume emulsion droplets 15 (as shown in FIG. 1 ). Figure 6 shown).

[0060] Combination Figure 4 and Figure 6 It can be found that when the pressure in the continuous phase storage bottle 4 is maintained at the same, the greater the pressure in the dispersed phase storage bottle 5 is, the larger the generated multi-volume emulsion droplets 14 and 15 are, showing a positive correlation.

[0061] Embodiment 4

[0062] This embodiment provides a method for generating multi-volume emulsion droplets, which uses the microfluidic device provided in the first embodiment to generate multi-volume emulsion droplets, and specifically includes the following steps:

[0063] (1) The pressure pump 1 compresses the external air and delivers it to the controller 2;

[0064] (2) The controller 2 adjusts the gas pressure, and the compressed gas is delivered to the continuous phase liquid storage bottle 4 and the dispersed phase liquid storage bottle 5 through the gas hose;

[0065] (3) The continuous phase fluid 6 and the dispersed phase fluid 7 are squeezed by the high-pressure gas, and the two-phase fluids are respectively transported to the dispersed phase inlet and the continuous phase inlet of the microfluidic chip 9 through the fluid pipeline 8, and enter the shallow channel 10;

[0066] (4) The controller 2 can control the unit flow rate of the continuous phase fluid 6 and the dispersed phase fluid 7. By controlling the pressure of the driving gas, the flow rates of the continuous phase fluid 6 and the dispersed phase fluid 7 are controlled to be in an appropriate ratio. The flow rate of the continuous phase fluid 6 is 5 cm / s, and the flow rate of the dispersed phase fluid 7 is 3 cm / s (e.g. Figure 7 As shown). The two-phase fluids meet at the cross microchannel position in the microfluidic chip 9, and the continuous phase fluid 6 is sheared into original emulsion droplets 13 and moves forward in the shallow channel 10;

[0067] (5) When the original emulsion droplet 13 reaches the central partition column 12, the spatial mutation causes the original emulsion droplet 13 to be subjected to uneven flow resistance, which in turn causes the interface curvature to increase, that is, the Laplace pressure difference on both sides of the interface increases; the Laplace stress causes the interface curvature to be further enhanced, which is manifested macroscopically as the original emulsion droplet 13 is squeezed and deformed by the central partition column 12;

[0068] (6) When the original emulsion droplet 13 is deformed to the limit state, it splits into two parts and enters the deep channel 11, and forms a small-volume emulsion droplet 14 and a large-volume emulsion droplet 15 under the principle of minimum surface energy;

[0069] (7) Steps (5) and (6) are repeated alternately. Driven by the pressure source, the original emulsion droplets 13 are continuously generated, continuously hit the central partition column 12, and break into small-volume emulsion droplets 14 and large-volume emulsion droplets 15. The macroscopic manifestation is the high-frequency oscillation of the original emulsion droplets 13 at the outlet of the shallow channel 10, and the continuous ejection of multiple-volume emulsion droplets (such as Figure 8 shown).

[0070] Embodiment 5

[0071] This embodiment provides a method for generating multi-volume emulsion droplets, which is different from the fourth embodiment in that the flow rates of the continuous phase fluid 6 and the dispersed phase fluid 7 are 5 cm / s and 3.5 cm / s respectively (e.g. Fig. 9 As shown in FIG. 1 , the high-pressure gas pushes the continuous phase fluid 6 and the dispersed phase fluid 7 into the microfluidic chip 9 and generates the original emulsion droplets 13. Under the action of the central dividing column 12, the original emulsion droplets 13 are split into small-volume emulsion droplets 14 and large-volume emulsion droplets 15 (as shown in FIG. 1 ). Fig.10 shown).

[0072] Combination Figure 8 and Fig.10 It can be found that when the flow rate of the continuous phase fluid 6 remains the same, the greater the flow rate of the dispersed phase fluid 7 is, the larger the generated multi-volume emulsion droplets 14 and 15 are, showing a positive correlation.

[0073] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A multi-volume emulsion droplet generation device, characterized in that: include: A liquid storage device, comprising a continuous phase liquid storage bottle for storing a continuous phase fluid and a dispersed phase liquid storage bottle for storing a dispersed phase fluid; A microfluidic chip, which is provided with a shallow channel connecting the continuous phase storage bottle and the dispersed phase storage bottle in the order of fluid flow, a cross microchannel for converging the two-phase fluid and shearing the dispersed phase fluid into original emulsion droplets, a central dividing column for dividing the original emulsion droplets into multiple emulsion droplets, and a deep channel; The pressure pumping device is equipped with a controller and connected to the liquid storage device to provide power for the fluid flow.

2. A device for increasing the volume ratio of emulsion droplets according to claim 1, characterized in that: The pressure pumping device is a pressure pump, and the pressure pump is a vane pump, a positive displacement pump, or an electromagnetic pump.

3. A device for increasing the volume ratio of emulsion droplets according to claim 1, characterized in that: The continuous phase liquid storage bottle and the dispersed phase liquid storage bottle are connected to the continuous phase inlet and the dispersed phase inlet of the microfluidic chip.

4. A method for generating multi-volume emulsion droplets, using the multi-volume emulsion droplet generation device according to any one of claims 1 to 3, characterized in that: The following steps are involved: The pressure pumping device and its controller adjust the air pressure, deliver the high-pressure gas to the dispersed phase storage bottle and the continuous phase storage bottle, pump the dispersed phase fluid and the continuous phase fluid into the shallow channel in the microfluidic chip, and the two phases of fluid move separately and meet at the cross microchannel. The dispersed phase fluid is sheared by the continuous phase fluid, thereby generating original emulsion droplets. When the original emulsion droplets move along the microchannel and reach the central dividing column, they are squeezed and deformed, split into large-volume emulsion droplets and small-volume emulsion droplets and enter the deep channel behind. With the continuous drive of high-pressure gas, multiple-volume emulsion droplets are continuously generated.

5. A method for generating multi-volume emulsion droplets according to claim 4, characterized in that: The controller can control the unit flow rate of the dispersed phase fluid and the continuous phase fluid, and by controlling the pressure of the driving gas, the flow rate of the dispersed phase and the flow rate of the continuous phase fluid are controlled to be in an appropriate ratio.

6. A method for generating multi-volume emulsion droplets according to claim 4, characterized in that: The dispersed phase fluid and the continuous phase fluid are squeezed by the high-pressure gas, and are respectively transported to the dispersed phase inlet and the continuous phase inlet of the microfluidic chip through the liquid pipeline.

7. A method for generating multi-volume emulsion droplets according to claim 4, characterized in that: The dispersed phase fluid is sheared by the continuous phase fluid into original emulsion droplets, and when it hits the central dividing column, it breaks into large-volume emulsion droplets and small-volume emulsion droplets, namely, multiple-volume emulsion droplets.

8. A method for generating multi-volume emulsion droplets according to claim 4, characterized in that: When the pressure in the continuous phase storage bottle remains the same, the greater the pressure in the dispersed phase storage bottle, the larger the size of the generated multi-volume emulsion droplets, showing a positive correlation.

9. A method for generating multi-volume emulsion droplets according to claim 4, characterized in that: When the flow rate of the continuous phase fluid remains the same, the greater the flow rate of the dispersed phase fluid, the larger the size of the generated multi-volume emulsion droplets, showing a positive correlation.

10. A method for generating multi-volume emulsion droplets according to claim 4, characterized in that: The other pressure of the pressure pumping device is 0~100kPa, and the pressure adjustment range of the controller is 0~100kPa.

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