A controllable generation device and method of a high-throughput core-shell composite droplet with a converging inlet flow

Abstract

The application provides a shrinkable inlet flow focusing high-flux core-shell composite droplet controllable generation device and method, which comprises a first fluid pipeline for inputting core fluid; a second fluid pipeline below the first fluid pipeline, the second fluid pipeline being used for inputting shell fluid and outputting shell droplets wrapping core droplets; a third fluid pipeline at one end of the second fluid pipeline away from the first fluid pipeline, the third fluid pipeline being used for inputting external phase fluid; a collection pipeline below the third fluid pipeline, the collection pipeline being used for collecting composite droplets; and a fluid focusing structure between the third fluid pipeline and the collection pipeline, the fluid focusing structure being used for extruding and accelerating the shell droplets. The application can improve the fluid flow rate, promote the uniformity of the generated core-shell composite droplets, improve the generation quality of the core-shell composite droplets, and realize the generation of micron-level core-shell composite droplets; meanwhile, the fluid flow rate and the collection pipeline are regulated to ensure the collection quality of the core-shell composite droplets.

Description

Technical Field

[0001] The present invention relates to the field of microfluidics technology, and in particular to a device and method for controllably generating high-throughput core-shell composite droplets with contraction-type inlet flow focusing. Background Art

[0002] Composite droplets typically consist of a core (polymer) matrix and a (polymer) shell. The intermediate fluid acts as a protective shell or semipermeable barrier, separating the internal aqueous phase from the external phase. This makes composite droplets suitable for a wide range of applications, most notably in the food industry, cosmetics, controlled delivery, and encapsulation. Research on the generation of composite droplets is therefore of particular interest. Encapsulation of drugs and other substances is a key application of composite droplets. Encapsulation helps isolate unstable components from corrosive environments, prevents the decomposition of unstable polymers due to exposure to specific atmospheres, and delivers a given material to specific receptors, thereby delivering the drug. Sometimes, the shell may contain multiple cores encapsulated in smaller droplets within a larger droplet, with the shell fluid acting as a barrier separating the core fluid from the external matrix fluid, thus having significant practical applications.

[0003] Currently, composite droplet production primarily utilizes double-cross and T-shaped structures, primarily focusing on a two-step process. However, these processes present challenges such as low generation efficiency, poor droplet stability, and clogging issues within microfluidic chip structures. Furthermore, after core-shell droplets are generated, they can shift relative to the shell droplets as they move through the collection pipeline. While core-shell droplet quality is maintained within a certain travel distance, exceeding this distance can lead to composite droplet deflection and breakage, resulting in a decrease in the quality of the resulting core-shell composite droplets. Summary of the Invention

[0004] In view of this, the present invention proposes a device and method for controllable generation of high-throughput core-shell composite droplets with a contraction-type inlet flow focusing to solve the problems in the prior art of poor stability of core-shell composite droplets and quality reduction due to motion deviation during the generation process.

[0005] The technical solution of the present invention is achieved as follows:

[0006] In a first aspect, the present invention provides a device for controllably generating high-throughput core-shell composite droplets by focusing a contraction-type inlet flow, comprising a first fluid conduit, a second fluid conduit, a third fluid conduit, and a collection conduit.

[0007] The first fluid conduit is used to input nucleoplasmic fluid;

[0008] The second fluid conduit is located below the first fluid conduit, and is used to input chitin fluid and output composite droplets. The composite droplets are chitin droplets that wrap the core droplets.

[0009] The third fluid pipe is located at one end of the second fluid pipe away from the first fluid pipe, and is used for inputting an external phase fluid,

[0010] The collecting pipe is located below the third fluid pipe, and is used for collecting the composite droplets;

[0011] A fluid focusing structure is arranged between the third fluid pipe and the collecting pipe, and is used for extruding the composite droplets.

[0012] On the basis of the above technical scheme, preferably, the fluid focusing structure comprises a first protruding part and a second protruding part,

[0013] The first protruding part and the second protruding part are arranged in parallel, and one end of each of the first protruding part and the second protruding part is connected with the inner wall of the collecting pipe,

[0014] A flow channel is arranged between the first protruding part and the second protruding part, and the width of the flow channel is smaller than the width of the collecting pipe.

[0015] On the basis of the above technical scheme, preferably, the first fluid pipe and the second fluid pipe are both arranged in a tapered shape, and the angle of the tapered shape ranges from 30 to 90 degrees.

[0016] On the basis of the above technical scheme, preferably, the device further comprises a connecting part, one end of the connecting part is connected with the collecting pipe, and the other end of the connecting part is arranged around the first fluid pipe, the second fluid pipe, the third fluid pipe and the fluid focusing structure.

[0017] On the other hand, the application provides a composite droplet generation method of a contraction type inlet flow focusing high-throughput core-shell composite droplet controllable generation device, comprising the following steps:

[0018] Step one: pumping a core-liquid fluid into the first fluid pipe, and pumping a shell-liquid fluid into the second fluid pipe, so as to make the shell-liquid fluid wrap the core-liquid fluid;

[0019] Step two: injecting an external phase fluid into the third fluid pipe, and outputting the core-shell composite droplets from the fluid focusing structure to the collecting pipe after the external phase fluid wraps the shell-liquid fluid-core-liquid fluid;

[0020] Step three: calculating the offset rate of the core droplet according to the offset distance of the core droplet when the composite droplet moves in the collecting pipe;

[0021] Step four: calculating the critical value of the predicted moving distance of the composite droplet in the collecting pipe before the composite droplet breaks according to the initial relative offset rate of the core droplet and the shell droplet, and calculating the critical value of the length of the collecting pipe according to the critical value of the predicted moving distance.

[0022] Step five: when the length of the collection pipeline is fixed, the length of the collection pipeline and the flow rate ratio of the nuclear and shell fluids are feedback adjusted according to the length critical value of the collection pipeline, so as to optimize the generation quality of the nuclear-shell composite droplets.

[0023] On the basis of the above technical scheme, preferably, the calculation formula of the initial relative offset rate of the core droplet and the shell droplet is

[0024] V 偏移 = V 核 -V 壳 ,

[0025] V 核 = L 核 / T,

[0026] V 壳 = L 壳 / T;

[0027] wherein V 偏移 represents the initial relative offset rate of the core droplet and the shell droplet, V 核 represents the moving rate of the core droplet, V 壳 represents the moving rate of the shell droplet, T represents the initial time period of the generation of the nuclear-shell composite droplets; L 核 represents the moving distance of the core droplet within the T time period, and L 壳 represents the moving distance of the shell droplet within the T time period.

[0028] On the basis of the above technical scheme, preferably, the calculation formula of the predicted moving distance critical value is

[0029] L * = T * × V 壳 ,

[0030] T * = L0 / V 偏移 ,

[0031] wherein L * represents the moving predicted critical value before the composite droplet breaks, T * represents the predicted critical time before the composite droplet breaks, and L0 represents the initial distance from the core droplet boundary to the shell droplet boundary.

[0032] On the basis of the above technical scheme, preferably, the length critical value of the collection pipeline is calculated according to the predicted moving distance critical value in step four, and specifically includes:

[0033] When the generation state of the nuclear-shell composite droplets is droplet-like, the length critical value of the collection pipeline is When the length of the collection pipeline is approximately When the length of the collection pipe (4) is approximately equal to the critical value, the collection quality of the core-shell droplet is good.

[0034] The function relationship between the different core-liquid phase / shell-liquid phase flow rate ratio and the critical value of the length of the collection pipe (4) is as follows:

[0035]

[0036] U1 is the pumping speed of the core-liquid phase, and U2 is the pumping speed of the shell-liquid phase.

[0037] The function relationship between the different collection pipe diameters and the critical value of the length of the collection pipe (4) is as follows:

[0038]

[0039] W is the diameter of the collection pipe (4).

[0040] When the length of the collection pipe (4) is approximately equal to the critical value, the collection quality of the core-shell droplet is good.

[0041] On the basis of the above technical scheme, preferably, in the step four, the critical value of the length of the collection pipe is calculated according to the critical value of the predicted moving distance, and specifically, when the generation state of the core-shell composite droplet is jet-like,

[0042] The function relationship between the different core-liquid phase / shell-liquid phase flow rate ratio and the critical value of the length of the collection pipe (4) is as follows:

[0043]

[0044] U1 is the pumping speed of the core-liquid phase, and U2 is the pumping speed of the shell-liquid phase.

[0045] The function relationship between the different collection pipe diameters and the critical value of the length of the collection pipe (4) is as follows:

[0046]

[0047] W is the diameter of the collection pipe (4).

[0048] When the length of the collection pipe (4) is approximately equal to the critical value, the collection quality of the core-shell droplet is good.

[0049] On the basis of the above technical scheme, preferably, in the step five, the length of the collection pipe is not fixed, and the length of the collection pipe to be designed is determined according to the flow rate ratio or the channel diameter at this time, so as to optimize the generation quality of the core-shell composite droplet.

[0050] The function relationship between the diameter of the collection pipe and the radius of the shell droplet is as follows:

[0051] R 壳= 0.30973 x W 1.01572 , R 壳 represents the shell droplet radius, W represents the collection pipe diameter;

[0052] The functional relationship between the collection pipe diameter and the core droplet radius is:

[0053] R 核 = 0.15W-2.3, R 核 represents the core droplet radius, W represents the collection pipe diameter

[0054] The converging inlet flow focusing high-flux core-shell composite droplet controllable generation device and method of the present application has the following beneficial effects relative to the prior art:

[0055] (1) By setting the first fluid pipe and the second fluid pipe to be conical, the acceleration effect of the core fluid and the shell fluid can be achieved, the fluid flow rate is improved, the generated core-shell composite droplets are excellent in uniformity, the size difference is small, the generation quality of the core-shell composite droplets is improved, and the generation of micron-level core-shell composite droplets is realized;

[0056] (2) By setting the fluid focusing structure between the third fluid pipe and the collection pipe, the three-phase flow can be further accelerated, the generation of the core-shell composite droplets is accelerated, and the efficiency is improved; (3) By adjusting the conical angle size of the first fluid pipe and the second fluid pipe, and adjusting the diameter of the collection pipe, the droplet generation size can be further controlled, the single flow rate control method is changed, the micro-control method of the generated composite droplets is supplemented, and the composite droplet size in a specific range is met;

[0057] (4) By calculating the critical collection pipe length S * 预测 under different conditions, the data is fitted, and the length of the collection pipe under a specific flow rate and different collection pipe diameters, and the appropriate flow rate and collection pipe diameter under a fixed collection pipe length are better predicted, so as to ensure the collection quality of the generated core-shell droplets. BRIEF DESCRIPTION OF DRAWINGS

[0058] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor.

[0059] Figure 1 It is a front view of the converging inlet flow focusing high-flux core-shell composite droplet controllable generation device of the present application;

[0060] Figure 2 It is a cross-sectional view in the EE direction of the device for controllably generating high-throughput core-shell composite droplets with a contraction-type inlet flow focusing according to the present invention;

[0061] Figure 3 Composite droplets prepared under different tapered angles of the first fluid conduit and the second fluid conduit of the present invention;

[0062] Figure 4 A flow chart of a method for controllable generation of high-throughput core-shell composite droplets by focusing a contraction-type inlet flow;

[0063] Figure 5 The graph shows the relationship between the critical value of the collection pipe length before the shell droplet breaks up and the flow rate ratio of the core fluid and the shell fluid in the drop state;

[0064] Figure 6 This is a graph showing the relationship between the critical value of the collection pipe length before the shell droplet breaks in the dripping state and the collection pipe diameter.

[0065] Figure 7 The graph shows the relationship between the critical value of the collection pipe length before the shell droplet breaks up in the jet-like state and the flow rate ratio of the core fluid and the shell fluid;

[0066] Figure 8 This is a graph showing the relationship between the critical value of the collection pipe length before the shell droplet breaks up in the jet-like state and the collection pipe diameter.

[0067] Figure 9 is a graph showing the relationship between the radius of the core droplet and the diameter of the collection tube;

[0068] Figure 10 is a graph showing the relationship between the shell droplet radius and the collection pipe diameter;

[0069] Figure 11 Composite droplets collected under different collection pipe diameters.

[0070] Reference numerals

[0071] 1. First fluid conduit; 2. Second fluid conduit; 3. Third fluid conduit; 4. Collection conduit; 5. Fluid focusing structure; 6. Connecting part; 7. Composite droplet. DETAILED DESCRIPTION

[0072] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0073] like Figure 1-2 As shown, the present invention provides a controllable generation device for high-throughput core-shell composite droplets with a contraction-type inlet flow focusing, comprising a first fluid pipeline 1, a second fluid pipeline 2, a third fluid pipeline 3 and a collection pipeline 4, wherein the first fluid pipeline 1 is used to input core-cytoplasm fluid to generate core-cytoplasm droplets; the second fluid pipeline 2 is located below the first fluid pipeline 1, and the second fluid pipeline 2 is used to input chitin fluid, and generate and output composite droplets 7 through interfacial tension and shear force, and the composite droplets 7 are chitin droplets that wrap the inner core droplets; the third fluid pipeline 3 is located at one end of the second fluid pipeline 2 away from the first fluid pipeline 1, and the third fluid pipeline 3 is used to input external phase fluid, apply shear force, and accelerate the generation of composite droplets 7; the collection pipeline 4 is located below the third fluid pipeline 3, and the collection pipeline 4 is used to collect composite droplets 7; a fluid focusing structure 5 is also provided between the third fluid pipeline 3 and the collection pipeline 4, and the fluid focusing structure 5 is used to squeeze the composite droplets 7 to increase the multiphase flow pressure, increase the fluid flow rate, and accelerate the multiphase fluid to extend downstream. The first fluid conduit 1 , the second fluid conduit 2 , the third fluid conduit 3 , the fluid focusing structure 5 and the collecting conduit 4 are all located on the same central axis.

[0074] As a preferred embodiment, both the first fluid conduit 1 and the second fluid conduit 2 are configured as conical shapes, with the minimum diameter of the conical inlet being smaller than the channel width. By configuring the first fluid conduit 1 as a conical shape, the formation of core-shell droplets can be accelerated. The conical portion is located within the second fluid conduit 2 and contacts the chitin fluid within the second fluid conduit 2. This, on the one hand, encourages the core-shell droplets to be simultaneously enveloped by the chitin fluid upon exiting. On the other hand, due to interfacial tension and other effects, the core-shell fluid undergoes a corresponding morphological change, achieving a primary acceleration of the core-shell fluid. By configuring the second fluid conduit 2 as a conical shape, the formation of chitin droplets can be accelerated. The conical inlet portion is located within the third fluid conduit 3 and contacts the external phase fluid within the third fluid conduit 3. The core-shell phase fluid and the chitin phase fluid contact at the first fluid conduit 1. Within the conical inlet of the second fluid conduit 2, due to interfacial tension and other effects, the chitin fluid envelopes the core-shell fluid. Simultaneously, core-shell composite droplets 7 are discharged from the inlet of the second fluid conduit 2, achieving a secondary acceleration of the two-phase fluid, enabling the formed composite droplets 7 to accelerate their downstream movement.

[0075] Specifically, the taper angle range of the first fluid conduit 1 and the second fluid conduit 2 is 30-90°. The minimum diameter of the first fluid conduit 1 is 45-55 μm, the minimum diameter of the second fluid conduit 2 is 35-45 μm, and the minimum diameter of the third fluid conduit 3 is 35-45 μm.

[0076] As a preferred embodiment, the fluid focusing structure 5 includes a first protrusion and a second protrusion, wherein the first protrusion and the second protrusion are arranged in parallel and opposite to each other, one end of the first protrusion is connected to the inner wall of the collection pipe 4, and the end of the second protrusion away from the first protrusion is connected to the inner wall of the collection pipe 4, and a flow channel is provided between the first protrusion and the second protrusion, and the width of the flow channel is smaller than the width of the collection pipe 4. Preferably, the width of the flow channel is 35 to 45 μm and the length is 45 to 55 μm. In the present application, through the flow focusing structure, the three parts of the fluid phase passing through the flow focusing structure are prompted to generate core-shell droplets under interfacial tension (hindering fracture), shear force (promoting fracture), Laplace pressure (promoting fracture), momentum force (promoting fracture) and pressure drop force (promoting fracture), and enter the collection pipe 4 part of the pipe body. The core-shell droplets enter the collection device connected to the pipe under the action of the external phase fluid.

[0077] As a preferred embodiment, it also includes a connecting portion 6, one end of which is connected to the collection pipe 4, and the other end is arranged around the first fluid pipe 1, the second fluid pipe 2, the third fluid pipe 3 and the fluid focusing structure 5. A connecting tube connected to the second fluid pipe 2 and the third fluid pipe 3 is provided in the connecting portion 6. The end of the first fluid pipe 1 away from the second fluid pipe 2 is connected to the connecting tube. The inlet ends of the above three connecting tubes are all sealed. Fine steel needle capillaries are respectively inserted into the sealing tubes of the connecting tubes until they are inserted into the first fluid pipe 1, the second fluid pipe 2 and the third fluid pipe 3. The other end of the fine steel needle capillary is connected to the injection pump for the input of each part of the fluid.

[0078] The connecting portion 6 is made of PDMS material, which has excellent chemical stability. PDMS has good stability to most common solvents and chemicals, is not easily corroded or dissolved, and can be safely used in a variety of different environments. At the same time, the material also has a certain plasticity. Due to its excellent softness and elasticity, it can be stretched, compressed and bent without breaking.

[0079] Specifically, the collection pipe 4 is made of glass and is bonded or threaded to the connection portion 6. The pipe wall contact angle of the collection pipe 4 is 90°, and the pipe diameter is preferably 300-600 μm to meet the requirements of different droplet sizes. The end of the collection pipe 4 away from the focusing structure is connected to the collection device. The collection device is pre-set with a portion of external phase fluid to help maintain the morphology of the generated core-shell droplets and facilitate the collection and storage of the generated core-shell composite droplets 7, which is stable and reliable. It should be noted that the diameter and length of the collection pipe 4 in this application are adjustable and can be adjusted according to user needs.

[0080] like Figure 3 As shown, in this embodiment, by combining different tapered angles of the first fluid conduit 1 and the second fluid conduit 2, the average droplet radius of multiple groups of core droplets and the average droplet radius of shell droplets are measured, and the obtained droplet sizes are shown in Table 1.

[0081] Table 1

[0082]

[0083] As can be seen from Table 2, the generated core-shell composite droplets 7 also have certain differences. Compared with changing the diameter of the four collection pipes, it achieves smaller size differences and realizes micro-control of the generated core-shell composite droplets 7. The coverage rate of the core-shell composite droplets 7 obtained in the entire simulation process is 100%. The obtained composite droplets 7 are relatively uniform in size and have good morphology.

[0084] During the collection process of the core-shell composite droplets 7, as the composite droplets 7 move in the collection pipe 4, a relative offset phenomenon will occur between the core droplets and the shell droplets. The relative stability of the core droplets and the shell droplets can be guaranteed within a certain distance. Beyond a certain distance, the shell droplets will rupture, thereby generating single-phase droplets, affecting the generation quality of the core-shell droplets. Based on this problem, a method for generating composite droplets 7 based on a controllable generation device of high-throughput core-shell composite droplets 7 with a contraction-type inlet flow focusing is proposed. Through research, it is found that in the initial fracture generation stage of the composite droplets 7, the relative offset distance of the core droplets is large, and the relative speed of the core droplets and the shell droplets reaches a maximum value (the core droplet speed is large). As the composite droplets 7 continue to move downstream, the relative speed of the core droplets and the shell droplets gradually decreases, which is a variable speed motion. To ensure the quality of the prepared composite droplets 7 to a greater extent, the relative velocity is assumed to be constant at its maximum value in the initial stage. This relative velocity is used to determine the predicted critical time (this critical time is less than the critical time for actual shell droplet rupture), and further the predicted critical movement distance (this critical distance is less than the critical distance for actual shell droplet rupture). The predicted critical pipe length is the sum of the maximum jet length in the collection pipe 4 and the predicted critical movement distance. This collection pipe 4 length can ensure the high-quality production of core-shell composite droplets 7 while simultaneously reducing the length of the collection pipe 4 and saving costs while ensuring the integrity of the composite droplets 7. By fitting the data and inferring the required collection pipe 4 length based on the offset rate at the multiphase flow rate and fluid properties, the quality of the core-shell composite droplets 7 can be better guaranteed.

[0085] like Figure 4-11 As shown, the present invention provides a method for generating composite droplets 7 of a device for controlling generation of high-throughput core-shell composite droplets with a contraction-type inlet flow focusing, comprising the following steps:

[0086] Step 1: injecting core-plasma fluid into the first fluid conduit 1 and injecting chitin fluid into the second fluid conduit 2, so that the chitin fluid wraps the core-plasma fluid.

[0087] The core-plasma fluid enters through the inlet of the first fluid conduit 1. After being squeezed by the first fluid conduit 1, the local pressure increases. At the same time, the flow rate of the core-plasma fluid in the first fluid conduit 1 increases, prompting the core-plasma fluid to accelerate downstream, achieving a primary acceleration of the core-plasma fluid and promoting the formation of core droplets. The chitin fluid enters the second fluid conduit 2 through the inlet of the second fluid conduit 2. After being squeezed by the second fluid conduit 2, the local pressure increases. At the same time, the velocity in the second fluid conduit 2 also increases accordingly. The core-plasma fluid and chitin fluid are accelerated to move downstream, achieving a secondary acceleration of the core-plasma fluid and a primary acceleration of the chitin fluid, promoting the formation of shell droplets.

[0088] Step two: inject an external phase fluid into the third fluid channel, the external phase fluid wraps the shell-core fluid output core-shell composite droplet 7 to the collection pipeline 4 through the fluid focusing structure 5.

[0089] The core fluid and shell fluid through the first fluid pipeline 1 and the second fluid pipeline 2 move downstream along the pipeline, the external phase fluid enters the third fluid channel through the third fluid channel inlet, contacts the shell fluid, and all three parts of the fluid move downstream into the flow focusing structure, realizing three accelerations of the core fluid, two accelerations of the shell fluid, and one acceleration of the external phase fluid, and further promoting the generation of the core-shell composite liquid.

[0090] Step three: calculate the offset rate of the core liquid droplet according to the offset distance of the core liquid droplet when the composite droplet 7 moves in the collection pipeline 4.

[0091] The moving distance of the core liquid droplet and the shell liquid droplet is measured respectively in a certain time after the generation of the composite droplet 7, and the moving rate of the core liquid droplet and the shell liquid droplet is calculated respectively, and the specific calculation formula is:

[0092] V 偏移 = V 核 -V 壳 ,

[0093] V 核 = L 核 / T,

[0094] V 壳 = L 壳 / T;

[0095] Wherein, V 偏移 represents the relative offset rate of the core liquid droplet and the shell liquid droplet, V 核 represents the moving rate of the core liquid droplet, V 壳 represents the moving rate of the shell liquid droplet, and T represents the initial time period of the generation of the core-shell composite droplet 7; L 核 represents the moving distance of the core liquid droplet in the T period, and L 壳 represents the moving distance of the shell liquid droplet in the T period.

[0096] Step four: calculate the predicted moving distance critical value of the composite droplet 7 before breaking in the collection pipeline 4 according to the offset rate of the core liquid droplet, and calculate the length critical value of the collection pipeline 4 according to the predicted moving distance critical value.

[0097] The initial distance from the core boundary to the shell boundary in the core-shell liquid droplet is measured, and the critical time of the shell liquid droplet breaking is calculated according to the initial distance, and the maximum distance of the core-shell liquid droplet moving along the pipeline before breaking after generation, i.e. the predicted moving distance critical value, is obtained by comprehensively considering the shell liquid droplet speed and the critical breaking time, and the calculation formula is

[0098] L* =T * ×V 壳 ,

[0099] T * =L0 / V 偏移 ,

[0100] Among them, L * represents the critical value of the composite droplet 7 before its breakup, T * represents the predicted critical time before the composite droplet 7 breaks up, and L0 represents the initial distance from the core droplet boundary to the shell droplet boundary.

[0101] There are two cases when calculating the critical value of the length of the collecting pipe 4: (1) the critical length of the collecting pipe 4 in the drop-like mode is the actual designed length of the collecting pipe 4; (2) the actual length of the collecting pipe 4 in the jet-like mode is the sum of the length of the multiphase flow neck breaking point and the predicted critical length of the collecting pipe 4.

[0102] When the composite droplet 7 is in a drop-like state, there is no need to consider the elongation of the composite droplet 7. The critical value of the length of the collecting pipe 4 is the critical value of the length of the collecting pipe 4, that is, in Indicates the critical length of collection pipe 4. When the collection pipe 4 length is fixed, the collection channel diameter or flow rate ratio is adjusted to ensure that the critical length of collection pipe 4 meets the required collection pipe length. When the collection pipe length is not fixed, the droplet mass is controlled by adjusting the collection pipe length.

[0103] Among them, the functional relationship between the flow rate ratio of different core phase / shell phase and the critical value of the length of the collection pipe (4) is:

[0104]

[0105] Among them, U1 is the pumping speed of the core fluid, and U2 is the pumping speed of the chitin fluid;

[0106] The functional relationship between the critical value of the length of the collecting pipe (4) and the diameter of the collecting pipe (4) is as follows:

[0107]

[0108] Wherein, W is the diameter of the collecting pipe (4);

[0109] When the length of the collection pipe (4) ≈ When , the core-shell droplet collection quality is good.

[0110] When the composite droplet 7 is in a jet-like state, the elongation of the composite droplet 7 needs to be considered. At this time, the critical length of the collecting pipe 4 is L 伸长It represents the elongation of the multiphase flow in the pipe when the composite droplet 7 is generated, and the maximum movement distance of the core-droplet is measured under different conditions, and the critical value of the length of the collection pipe 4 under different conditions is calculated.

[0111] Among them, the functional relationship between the flow rate ratio of different core-cytoplasm phase / shell phase and the critical value of the length of the collection pipe 4 is:

[0112]

[0113] Among them, U1 is the pumping speed of the core fluid, and U2 is the pumping speed of the chitin fluid;

[0114] When the flow rate ratio of the core phase to the shell phase is adjustable, the length of the collection pipe 4 is ≈ When , the integrity of the shell droplets is good, which can ensure the collection quality of the core-shell droplets;

[0115] The functional relationship between the critical value of the length of the collecting pipe 4 and the diameter of the collecting pipe 4 is as follows:

[0116]

[0117] Wherein, W is the diameter of the collection pipe 4;

[0118] When the diameter of the collecting pipe 4 is adjustable, the length of the collecting pipe 4 ≈ When , the shell droplets have good integrity, which can ensure the collection quality of core-shell droplets.

[0119] Step 5: When the length of the collecting pipe 4 is fixed, the diameter of the collecting pipe 4 and the flow rate ratio of the core-shell fluid to the shell-shell fluid are feedback-adjusted according to the critical value of the length of the collecting pipe 4 to optimize the generation quality of the core-shell composite droplets 7.

[0120] When the length of the collection pipe 4 is fixed, the current length of the collection pipe 4 is set as the critical value of the collection pipe length. According to the functional relationship between the flow rate ratio of different core-cytoplasm fluid phase / shell fluid phase and the critical value of the collection pipe 4 length or the functional relationship between different collection pipe 4 diameters and the critical value of the collection pipe 4 length, the diameter of the collection pipe 4 and the flow rate ratio of the core-cytoplasm fluid and the shell fluid are respectively adjusted to ensure the collection quality of the core-shell composite droplets 7.

[0121] When the length of the collection channel 4 is not fixed, the collection channel length to be designed is determined according to the flow rate ratio or channel diameter at that time to optimize the generation quality of the core-shell composite droplets 7 .

[0122] As the channel diameter increases, the core droplet radius and the shell droplet radius have a consistent linear increase law. Among them, the functional relationship between the diameter of the collection channel 4 and the shell droplet radius is:

[0123] R壳 =0.30973×W 1.01572 , R 壳 represents the shell droplet radius, W represents the diameter of the collection pipe 4;

[0124] The functional relationship between the diameter of the collection pipe 4 and the radius of the nuclear droplet is:

[0125] R 核 =0.15W-2.3, R 核 represents the radius of the nuclear droplet, and W represents the diameter of the collection pipe 4.

[0126] like Figure 9 As shown, in this embodiment, the generation of 20 groups of core-shell composite droplets 7 under six different channel diameters is simulated. From the simulation results, it can be seen that the sizes of the obtained core-shell composite droplets 7 have certain differences. The sizes of the generated core-shell composite droplets 7 are measured using Image J software, and the average value is shown in Table 2.

[0127] Table 2

[0128]

[0129] Table 2 shows that when the collection channel diameter is 300 μm, the core droplet radius is the smallest at 41.98 μm, while the shell droplet radius is 97.8 μm. When the collection channel diameter is 600 μm, the core droplet radius is the largest at 86.06 μm, while the shell droplet radius is 199.98 μm. Channel diameters of 300 to 360 μm are considered small, 460 to 510 μm are considered medium-sized core-shell composite droplets, and 510 to 600 μm are considered large. These size results demonstrate microscopic control of core-shell composite droplets, changing the traditional single-mode flow rate-based droplet size control to meet industrial and high-precision production requirements.

[0130] By comparing the predicted values ​​with the actual measured values, it was found that the average error of the predicted value of the core droplet radius was about 4%, and the average error of the predicted value of the shell droplet radius was about 4.8%. The errors of the obtained results were within an acceptable range, and the predicted values ​​can be used as a reference for the core droplet radius.

[0131] 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, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for generating composite droplets using a device for controlling the generation of high-throughput core-shell composite droplets with a constricted inlet flow focusing system, characterized by: The following steps are involved: Step 1: pumping a core-plasma fluid into the first fluid conduit (1) and pumping a chitin fluid into the second fluid conduit (2), so that the chitin fluid wraps the core-plasma fluid; Step 2: injecting an external phase fluid into the third fluid conduit, wherein the external phase fluid wraps the chitin-core fluid and outputs the core-shell composite droplets to the collection conduit (4) through the fluid focusing structure (5); Step 3: Calculating the displacement rate of the core droplet according to the displacement distance of the core droplet when the composite droplet (7) moves in the collection pipe (4); Step 4: Calculate the critical value of the predicted moving distance of the composite droplet in the collection pipe (4) before it breaks based on the initial relative displacement rate of the core droplet and the shell droplet, and calculate the critical value of the length of the collection pipe (4) based on the predicted moving distance critical value; Step 5: When the length of the collection pipe (4) is fixed, feedback adjustment is performed on the collection pipe (4) and the flow rate ratio of the core-shell fluid and the shell-shell fluid according to the critical value of the length of the collection pipe (4) to optimize the generation quality of the core-shell composite droplets; The controllable generation device is used to implement a composite droplet generation method, comprising a first fluid conduit (1), a second fluid conduit (2), a third fluid conduit (3) and a collection conduit (4). The first fluid conduit (1) is used for inputting nucleoplasmic fluid; The second fluid conduit (2) is located below the first fluid conduit (1), and the second fluid conduit (2) is used to input chitin fluid and output shell droplets that wrap the core droplets. The third fluid conduit (3) is located at one end of the second fluid conduit (2) away from the first fluid conduit (1), and the third fluid conduit (3) is used to input external phase fluid. The collecting pipe (4) is located below the third fluid pipe (3), and the collecting pipe (4) is used to collect the composite droplets (7); A fluid focusing structure (5) is provided between the third fluid conduit (3) and the collecting conduit (4), and the fluid focusing structure (5) is used to squeeze the shell droplets to accelerate the extension of the fluid downstream; In step 4, the calculation formula for the initial relative offset rate of the core droplet and the shell droplet is: V 偏移 =V 核 -V 壳 , V 核 =L 核 / T, V 壳 =L 壳 / T; Among them, V 偏移 represents the initial relative displacement rate of the core droplet and the shell droplet, V 核 represents the moving velocity of the nuclear droplet, V 壳 represents the migration rate of the shell droplet, T represents the initial time period of the core-shell composite droplet generation; L 核 The distance the core droplet moves during the T time period, L 壳 represents the distance the shell droplet moves during the time period T; In step 4, the calculation formula for the predicted moving distance critical value is: L * =T * ×V 壳 , T * =L0 / V 偏移 , Among them, L * represents the critical value of the composite droplet (7) before its breakup, T * represents the predicted critical time before the composite droplet (7) breaks up, L0 represents the initial distance from the core droplet boundary to the shell droplet boundary; In step 4, the critical value of the length of the collection pipeline (4) is calculated based on the predicted critical value of the moving distance, which specifically includes: When the core-shell composite droplet is in drop-like state, the critical length of the collection channel (4) is When the collection pipe (4) When , the collection quality of core-shell composite droplets is good; The functional relationship between the flow rate ratio of different core fluid / shell fluid and the critical value of the length of the collection pipe (4) is: Among them, U1 is the pumping speed of the core fluid, and U2 is the pumping speed of the chitin fluid; The functional relationship between the critical value of the length of the collecting pipe (4) and the diameter of the collecting pipe (4) is as follows: Wherein, W is the diameter of the collecting pipe (4); When the collection pipe (4) When , the core-shell composite droplets are collected with good quality.

2. The composite droplet generation method of the device for controlling the generation of high-throughput core-shell composite droplets with a contraction-type inlet flow focusing according to claim 1, characterized in that: The fluid focusing structure (5) comprises a first protrusion and a second protrusion, The first protrusion and the second protrusion are arranged parallel to each other, and one end of the first protrusion and the second protrusion are respectively connected to the inner wall of the collecting pipe (4). A flow channel is provided between the first protrusion and the second protrusion, and the width of the flow channel is smaller than the width of the collecting pipe (4).

3. The composite droplet generation method of the device for controlling the generation of high-throughput core-shell composite droplets with a contraction-type inlet flow focusing according to claim 2, characterized in that: The first fluid conduit (1) and the second fluid conduit (2) are both configured to be conical, with the angle of the conic being in the range of 30 to 90°.

4. The composite droplet generation method of the device for controlling the generation of high-throughput core-shell composite droplets with a contraction-type inlet flow focusing according to claim 1, characterized in that: It also includes a connecting portion (6), one end of which is connected to the collecting pipe (4), and the other end of which is arranged around the first fluid pipe (1), the second fluid pipe (2), the third fluid pipe (3) and the fluid focusing structure (5).

5. The composite droplet generation method of the device for controlling the generation of high-throughput core-shell composite droplets with a contraction-type inlet flow focusing according to claim 1, characterized in that: The step 4 calculates the critical value of the length of the collection pipe (4) according to the critical value of the predicted moving distance, specifically including: when the generation state of the core-shell composite droplet (7) is a jet-like state, the critical value of the length of the collection pipe (4) is L 伸长 represents the elongation of the multiphase flow in the pipe when the composite droplet (7) is generated, The functional relationship between the flow rate ratio of different core fluid / shell fluid and the critical value of the length of the collection pipe (4) is: Among them, U1 is the pumping speed of the core fluid, and U2 is the pumping speed of the chitin fluid; The functional relationship between the critical value of the length of the collecting pipe (4) and the diameter of the collecting pipe (4) is as follows: Wherein, W is the diameter of the collecting pipe (4); When the collection pipe (4) When , the core-shell composite droplets are collected with good quality.

6. The composite droplet generation method of the device for controlling the generation of high-throughput core-shell composite droplets with a contraction-type inlet flow focusing according to claim 1, characterized in that: The step five further comprises: when the length of the collection pipe (4) is not fixed, determining the length of the collection pipe (4) to be designed according to the flow rate ratio or the diameter of the collection pipe (4) at this time, so as to optimize the generation quality of the core-shell composite droplets (7); The functional relationship between the diameter of the collecting pipe (4) and the radius of the shell droplet is: R 壳 =0.30973×W 1.01572 , R 壳 represents the shell droplet radius, W represents the collection pipe (4) diameter; The functional relationship between the diameter of the collecting pipe (4) and the radius of the nuclear droplet is: R 核 =0.15W-2.3, R 核 represents the radius of the core droplet, and W represents the diameter of the collection pipe (4).

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