A generating device and method for improving micro-droplet volume proportion

Abstract

The present application relates to the technical field of microdroplet generation, and in particular to a generation device and method for improving microdroplet volume proportion, comprising: a liquid storage device, including a continuous phase liquid storage bottle for storing continuous phase fluid and a dispersed phase liquid storage bottle for storing dispersed phase fluid; a microfluidic chip, which is provided with a shallow channel, a cross microchannel, a micro-ladder structure and a deep channel in sequence according to the fluid flow sequence, and the shallow channel is connected with the continuous phase liquid storage bottle and the dispersed phase liquid storage bottle; a pressure pumping device, which is provided with a controller and is connected with the liquid storage device to provide power for fluid flow. The present application creates spatial mutation through the shallow channel and the deep channel based on the different deformation states of the two-phase fluid interface under different Laplace stresses, and amplifies the disturbance of the two-phase fluid interface, so that the dispersed phase fluid appears periodic extrusion and fracture, and high-volume-proportion microdroplets are formed, thereby solving the problems of complex operation, microdroplet product volume proportion and the like in the traditional microdroplet generation mode.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of microdroplet generation, and in particular to a generation device and a generation method for improving the volume proportion of microdroplets. BACKGROUND

[0002] Microfluidic partitioning technology has very wide application requirements in the fields of material synthesis, single cell analysis, rare mutation detection, medical testing, biochemical analysis, etc. The core of microfluidic partitioning technology is to divide milliliter or microliter level fluid into nanoliter or picoliter level independent units. One main branch of microfluidic partitioning technology is microdroplet generation method and technology.

[0003] Existing microdroplet generation methods and technologies include T-shaped shear method, flow focusing method, coaxial flow method, electrospraying method, and step emulsification method, etc. Among them, the step emulsification method, as the latest microdroplet generation technology, has good application prospects in terms of microdroplet generation simplicity and high proportion of microdroplet products. Generally, the step emulsification method makes the separate dispersed phase fluid cross the micro-step and enter the continuous phase fluid to generate microdroplets. However, this method requires continuous flow of the continuous phase fluid to collect microdroplets, and the volume proportion of microdroplets (volume of dispersed phase / volume of dispersed phase + volume of continuous phase) is less than 40%, which is still at a low level.

[0004] In addition, a microdroplet generation device is disclosed in CN113996354B and a microdroplet generation device is disclosed in CN110064452A, which can be used for microdroplet generation, but have the problems of complicated operation and high cost. SUMMARY

[0005] In view of the deficiencies of the prior art, the purpose of the present application is to provide a generation device and a generation method for improving the volume proportion of microdroplets. The present application is based on the deformation process of the interface between two-phase fluids under Laplace pressure, and the micro-step structure between the shallow channel and the deep channel induces the dispersed phase fluid to break into microdroplets, solving the problems of high production cost and complex operation of traditional microdroplet generation methods, and greatly improving the volume proportion of microdroplet products. In order to achieve the above purpose, the present application is implemented by the following technical solutions:

[0006] In a first aspect, the present application provides a generation device for improving the volume proportion of microdroplets, comprising:

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

[0008] The microfluidic chip is provided with a shallow channel, a cross-shaped microchannel, a micro-step structure and a deep channel in sequence according to the flow of fluid, and the shallow channel is communicated with the continuous phase storage bottle and the dispersed phase storage bottle.

[0009] The pressure pumping device is provided with a controller, and the controller is communicated with the storage device to provide power for the fluid flow.

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

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

[0012] In a second aspect, the present application provides a high-volume-ratio microdroplet generation method, which is generated by using the high-volume-ratio microdroplet generation device as described in the first aspect, and includes the following steps:

[0013] The pressure pumping device and its controller adjust the air pressure, and high-pressure gas is delivered to the dispersed phase storage bottle and the continuous phase storage bottle, and the dispersed phase fluid and the continuous phase fluid are pumped into the shallow channel in the microfluidic chip. The two-phase fluid moves respectively and intersects at the cross-shaped microchannel to form a synergistic flow of sheath flow. When the sheath flow crosses the micro-step structure and reaches the deep channel, the initial disturbance between the two-phase fluid interfaces is instantaneously amplified, generating an instant mutation Laplace pressure difference. The pressure squeezes the dispersed phase fluid to appear necking and break, and forms microdroplets after crossing the micro-step structure. With the continuous driving of high-pressure gas, microdroplets are continuously generated.

[0014] As a further implementation, 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 a suitable ratio.

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

[0016] As a further implementation, the necking and broken dispersed phase fluid enters the deep channel and forms spherical microdroplets under the principle of minimum surface energy.

[0017] As a further implementation, under the condition that the pressure of the continuous phase storage bottle is maintained the same, the greater the pressure of the dispersed phase storage bottle, the larger the size of the generated microdroplets, showing a positive correlation.

[0018] As a further implementation manner, when the continuous phase fluid flow rate remains the same, the greater the dispersed phase fluid flow rate, the greater the generated microdroplet size, showing a positive correlation.

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

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

[0021] 1. The present application is based on the different deformation states of the two-phase fluid interface under different Laplace stresses, and the periodic necking and breaking of the sheath flow interface composed of the dispersed phase and the continuous phase are controlled by setting a micro-step structure between the shallow channel and the deep channel, so that high-volume-occupancy microdroplets are formed, solving the problems of high microdroplet production cost, complex operation of the traditional microdroplet generation method, and low volume occupancy of the traditional microdroplet generation product, and effectively improving the microdroplet generation efficiency.

[0022] 2. In the present application, when the sheath flow crosses the micro-step structure and enters the deep channel, the spatial mutation causes the disturbance on the two-phase fluid interface to be instantaneously amplified, thereby causing the interface curvature change to increase, that is, the Laplace pressure difference on both sides of the interface increases; the Laplace stress causes the interface bending degree to further increase, and the dispersed phase fluid is extruded by the continuous fluid on both sides and forms a contraction neck; the contraction neck breaks, and the broken dispersed phase fluid enters the deep channel and forms a spherical microdroplet under the principle of minimum surface energy. BRIEF DESCRIPTION OF DRAWINGS

[0023] The drawings accompanying the specification of the present application form a part thereof and serve to provide further understanding of the present application, the illustrative embodiments of the present application and its description serve to explain the present application, and do not constitute an improper limitation on the present application.

[0024] Figure 1 is a structure schematic diagram of the high-volume-occupancy microdroplet generation device in embodiment one of the present application.

[0025] Figure 2 is a process schematic diagram of generating microdroplets by using the high-volume-occupancy microdroplet generation device in embodiment one.

[0026] Figure 3 is a continuous phase and dispersed phase gas pressure curve diagram in embodiment two of the present application.

[0027] Figure 4 is a microdroplet generated by embodiment two of the present application.

[0028] Figure 5 is a continuous phase and dispersed phase gas pressure curve diagram in embodiment three of the present application.

[0029] Figure 6is the microdroplet generated in the embodiment three of the present application.

[0030] Figure 7 is the flow rate curve of the continuous phase and the dispersed phase in the embodiment four of the present application.

[0031] Figure 8 is the microdroplet generated in the embodiment four of the present application.

[0032] Figure 9 is the flow rate curve of the continuous phase and the dispersed phase in the embodiment five of the present application.

[0033] Figure 10 is the microdroplet generated in the embodiment five of the present application.

[0034] In the figure, the mutual distance or size is exaggerated for showing the position of each part, and the schematic diagram is only illustrative.

[0035] Wherein: 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, sheath flow; 13, microdroplet. DETAILED DESCRIPTION

[0036] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used in the present application have the same meaning as generally understood by those skilled in the art to which the present application belongs.

[0037] Embodiment one

[0038] In a typical embodiment of the present application, referring to Figure 1 Fig. 1, a generating device for improving the proportion of microdroplet volume, comprising a liquid storage device, a microfluidic chip 9 and a pressure pumping device.

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

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

[0041] The microfluidic chip 9 is provided with a shallow channel 10, a cross microchannel, a micro-step structure and a deep channel 11 in sequence according to the fluid flow sequence, the shallow channel 10 is connected with the continuous phase storage bottle 4 and the dispersed phase storage bottle 5, the cross microchannel intersects the two-phase fluid to form a sheath flow 12, the microfluidic chip 9 is connected to the continuous phase storage bottle 4 and the dispersed phase storage bottle 5 through the fluid pipeline 8, and the fluid in the continuous phase storage bottle 4 and the dispersed phase storage bottle 5 is pumped into the microfluidic chip 9.

[0042] The material of the gas pipeline 3 and the fluid pipeline 8 includes glass, silica gel or plastic.

[0043] In the embodiment, the high-pressure gas pumps the dispersed phase fluid 7 and the continuous phase fluid 6 into the shallow channel 10 in the microfluidic chip 9, the two-phase fluids move respectively and intersect at the cross microchannel to form a sheath flow 12, when the sheath flow 12 crosses the micro-step structure and reaches the deep channel 11, the initial disturbance between the two-phase fluid interfaces is instantaneously amplified, a sudden Laplace pressure difference is generated, the pressure squeezes the dispersed phase fluid 7 to appear necking and break, and the micro-droplet 13 is formed after crossing the micro-step structure, and the micro-droplet 13 is continuously generated with the continuous driving of the high-pressure gas.

[0044] In the embodiment, based on the different deformation states of the two-phase fluid interfaces under different Laplace stresses, the periodic necking and breaking of the sheath flow 12 interface composed of the dispersed phase and the continuous phase are controlled by setting the micro-step structure between the shallow channel 10 and the deep channel 11, the dispersed phase fluid 7 spontaneously breaks based on static instability, and does not need the shearing of the external continuous phase fluid 6, thereby forming the micro-droplet 13 with a high volume ratio (up to 92%), solving the problem of low volume ratio of the generated product of the traditional micro-droplet 13, and effectively improving the generation efficiency of the micro-droplet 13.

[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 in the value range are also applicable.

[0046] The pressure adjustment range of the controller 2 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 in the value range are also applicable.

[0047] The micro-droplet generated by the generation device in the embodiment has a size of 10 nm-1 mm, such as 50 μm, 100 μm, 200 μm or 500 μm, but is not limited to the listed values, and other values not listed in the value range are also applicable.

[0048] The microdroplet generation device of the present embodiment generates microdroplets at a frequency of 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 within the range are also applicable.

[0049] The sheath flow has a flow rate of 10 μm / s to 10 m / s, such as 100 μm / s, 1 mm / s, 1 cm / s, 1 dm / s, or 1 m / s.

[0050] Embodiment 2

[0051] The present embodiment provides a method for generating microdroplets with a high volume ratio, which uses the microdroplet generation device of Embodiment 1 to generate microdroplets, and specifically includes the following steps:

[0052] (1) The pressure pump 1 compresses external air and delivers it to the controller 2;

[0053] (2) The controller 2 adjusts the gas pressure and delivers compressed gas at 550 Pa and 300 Pa, respectively, to the continuous phase reservoir 4 and the dispersed phase reservoir 5 through the gas hose (as shown in Figure 3

[0054] (3) The continuous phase fluid 6 and the dispersed phase fluid 7 are extruded by high-pressure gas and delivered to the dispersed phase inlet and the continuous phase inlet of the microfluidic chip 9 through the fluid pipeline 8, respectively, and enter the shallow channel 10;

[0055] (4) The continuous phase fluid 6 and the dispersed phase fluid 7 meet at the cross microchannel position and form a sheath flow 12, which advances cooperatively towards the right outlet position;

[0056] (5) When the sheath flow crosses the micro-step structure and enters the deep channel 11, the spatial mutation causes the disturbance on the interface of the two-phase fluid to be amplified instantaneously, resulting in an increase in the change in the interface curvature, i.e., an increase in the Laplace pressure difference on both sides of the interface; the Laplace stress causes the interface to bend further, and the dispersed phase fluid 7 is extruded by the continuous phase fluid 6 on both sides and forms a constriction neck;

[0057] (6) The constriction neck breaks, and the broken dispersed phase fluid 7 enters the deep channel 11 and forms a spherical microdroplet 13 under the principle of minimum surface energy;

[0058] (7) Steps (5) and (6) are alternately repeated, and the sheath flow 12 body retracts into the shallow channel 10 and, under the driving of the pressure source, starts the next microdroplet generation process (as shown in Figure 2 Figure 4 The macroscopic performance is the high-frequency oscillation of the dispersed phase fluid 7 at the micro-step position, and the continuous ejection of microdroplets (as shown in

[0059] ​​Example Three

[0060] The embodiment provides a high-volume-ratio microdroplet generation method, and the difference from the embodiment two is that the pressures of the dispersed phase storage bottle 5 and the continuous phase storage bottle 4 are 400 Pa and 550 Pa respectively (as shown in the figure), and the high-pressure gas pushes the dispersed phase fluid 7 and the continuous phase fluid 6 to form the sheath flow 12. Figure 5 Under the continuous driving of the above high-pressure gas, the microdroplet 13 (as shown in the figure) is formed. Figure 6

[0061] In combination with Figure 4 and Figure 6 It can be found that, under the condition that the pressure of the continuous phase storage bottle 4 is maintained to be the same, the greater the pressure of the dispersed phase storage bottle is, the greater the size of the generated microdroplet is, and the positive correlation is presented.

[0062] Example Four

[0063] The embodiment provides a high-volume-ratio microdroplet generation method, and the difference from the embodiment two is that the pressures of the dispersed phase storage bottle 5 and the continuous phase storage bottle 4 are 400 Pa and 550 Pa respectively (as shown in the figure), and the high-pressure gas pushes the dispersed phase fluid 7 and the continuous phase fluid 6 to form the sheath flow 12.

[0064] (1) The pressure pump 1 compresses external air and delivers it to the controller 2;

[0065] (2) The controller 2 adjusts the gas pressure and delivers the compressed gas to the continuous phase storage bottle 4 and the dispersed phase storage bottle 5 through the gas hose respectively;

[0066] (3) The continuous phase fluid 6 and the dispersed phase fluid 7 are extruded by the high-pressure gas, and the two-phase fluid is delivered to the dispersed phase inlet and the continuous phase inlet of the microfluidic chip 9 through the fluid pipeline 8 respectively;

[0067] (4) The controller 2 can control the unit flow rate of the dispersed phase fluid 7 and the continuous phase fluid 6, control the flow rate of the dispersed phase fluid 7 and the continuous phase fluid 6 to be in a suitable proportion by controlling the pressure of the driving gas. The flow rate of the continuous phase fluid 6 is 5 cm / s, the flow rate of the dispersed phase fluid 7 is 3 cm / s, and the two fluids meet at the cross microchannel position in the microfluidic chip 9 and cooperatively advance to the right outlet position in the form of sheath flow (as shown in the figure); Figure 7

[0068] (5) When the sheath flow 12 crosses the micro-step structure and enters the deep channel 11, the spatial mutation causes the disturbance on the interface of the two-phase fluid to be instantaneously amplified, so that the change of the interface curvature is increased, that is, the Laplace pressure difference on both sides of the interface is increased; the Laplace stress causes the bending degree of the interface to be further enhanced, and the dispersed phase fluid 7 is extruded by the continuous phase fluid 6 on both sides and forms a contraction neck;

[0069] ​​(6) the neck contracts and breaks, the broken dispersed phase fluid 7 enters the deep channel, and forms spherical microdroplets under the principle of minimum surface energy;

[0070] (7) steps (5) and (6) are alternately repeated, the sheath flow 12 body retracts into the shallow channel, and starts the next microdroplet generation process under the driving of the pressure source, macroscopically showing high-frequency oscillation of the dispersed phase fluid 7 at the micro-step position, and continuous ejection of microdroplets (as shown in Figure 8 ).

[0071] Example Five

[0072] This embodiment provides a high-volume-ratio microdroplet generation method, which is different from example four in that the flow rates of the dispersed phase fluid 7 and the continuous phase fluid 6 are 3.5 cm / s and 5 cm / s respectively (as shown in Figure 9 ), and the high-pressure gas pushes the dispersed phase fluid 7 and the continuous phase fluid 6 to form a sheath flow 12, under the movement condition of the above fluid flow rates, the microdroplets 13 (as shown in Figure 10 ) are formed.

[0073] In combination with Figure 8 and Figure 10 , it can be found that under the condition that the flow rate of the continuous phase fluid 6 remains the same, the greater the flow rate of the dispersed phase fluid 7, the larger the size of the generated microdroplets 13, showing a positive correlation.

[0074] The above only describes the preferred embodiments of the present application and is not used to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A device for generating microdroplets to increase their volume ratio, characterized in that, The application relates to a microfluidic chip and a pressure pumping device. The application 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; a microfluidic chip, which is provided with, in sequence according to the fluid flow, a shallow channel connected with the continuous phase liquid storage bottle and the dispersed phase liquid storage bottle, a cross microchannel for intersecting the two phase fluids to form a sheath flow, a micro-step structure and a deep channel; the two phase fluids move respectively and intersect at the cross microchannel to form a sheath flow, the micro-step structure is arranged between the shallow channel and the deep channel, when the sheath flow crosses the micro-step structure and reaches the deep channel, initial disturbance between the two phase fluid interfaces is instantaneously amplified, instantaneously mutated Laplace pressure difference is generated, the dispersed phase fluid is squeezed to appear necking fracture, and microdroplets are formed after crossing the micro-step structure; 2.The device of claim 1, wherein, a pressure pumping device, which is provided with a controller and is connected with the liquid storage device to provide power for fluid flow. 3.The device of claim 1, wherein, The pressure pumping device is a pressure pump, and the pressure pump is a vane pump, a positive displacement pump or an electromagnetic pump.

4. A method for generating high-volume-fraction microdroplets, using the high-volume-fraction microdroplet generating device according to any one of claims 1-3, wherein, The continuous phase liquid storage bottle and the dispersed phase liquid storage bottle are connected with a continuous phase inlet and a dispersed phase inlet of the microfluidic chip. The application comprises the following steps:

5. The method of claim 4, wherein the microdroplet generation device is a microfluidic chip. the pressure pumping device and the controller regulate air pressure, high-pressure gas is delivered into the dispersed phase liquid storage bottle and the continuous phase liquid storage bottle, the dispersed phase fluid and the continuous phase fluid are pumped into the shallow channel in the microfluidic chip, the two phase fluids move respectively and intersect at the cross microchannel to form a sheath flow, when the sheath flow crosses the micro-step structure and reaches the deep channel, initial disturbance between the two phase fluid interfaces is instantaneously amplified, instantaneously mutated Laplace pressure difference is generated, the dispersed phase fluid is squeezed to appear necking fracture, and microdroplets are formed after crossing the micro-step structure, and the microdroplets are continuously generated with continuous driving of the high-pressure gas.

6. The method of claim 4, wherein the microdroplets have a volume fraction of greater than 50%. The controller can control the unit flow rate of the dispersed phase fluid and the continuous phase fluid, the pressure of the driving gas is controlled, and the flow rate of the dispersed phase fluid and the flow rate of the continuous phase fluid are located at a proper ratio.

7. The method of claim 4, wherein the microdroplets have a volume fraction of greater than 50%. 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 delivered to a dispersed phase inlet and a continuous phase inlet of the microfluidic chip through liquid pipelines.

8. The method of claim 4, wherein the microdroplets have a volume fraction of greater than 50%. The necking fractured dispersed phase fluid enters the deep channel and forms spherical microdroplets under the principle of minimum surface energy.

9. The method of claim 4, wherein the microdroplets have a volume fraction of greater than 50%. When the pressure of the continuous phase liquid storage bottle is kept unchanged, the greater the pressure of the dispersed phase liquid storage bottle is, the greater the size of the generated microdroplets is, and the positive correlation is presented.

10. The method of claim 4, wherein the microdroplet generation method is a high volume fraction microdroplet generation method. When the flow rate of the continuous phase fluid is kept unchanged, the greater the flow rate of the dispersed phase fluid is, the greater the size of the generated microdroplets is, and the positive correlation is presented. The pressure of the pressure pumping device is 0-100 kPa, and the pressure adjustment range of the controller is 0-100 kPa.

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