CN116237095A - Microfluidic method for controllably preparing monodisperse emulsion based on infiltration principle - Google Patents
Microfluidic method for controllably preparing monodisperse emulsion based on infiltration principle Download PDFInfo
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- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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Abstract
The invention provides a microfluidic method for preparing monodisperse emulsion based on an infiltration principle, which adopts a microfluidic device for preparation and comprises the following steps: placing the continuous phase in a collection container to enable the liquid level of the continuous phase to be horizontal, placing the outlet of the injection tube above the liquid level of the continuous phase in the collection container, continuously injecting the disperse phase into the injection tube through an injection pump, and when the disperse phase flowing out of the outlet of the injection tube contacts the liquid level of the continuous phase, soaking the disperse phase into the continuous phase under the induction of three-phase interfacial tension differences of the air phase, the disperse phase and the continuous phase to generate monodisperse emulsion; the interfacial tension of the disperse phase and the continuous phase at the outlet of the injection tube should satisfy gamma AW >γ AO +γ WO . The invention can solve the problems of complex structure, complicated construction process, high requirements on fluid operation and control, multiple influence factors for preparing liquid drops, difficult preparation of high-viscosity liquid drops and the like in the existing microfluidic emulsion preparation technology.
Description
Technical Field
The invention belongs to the field of emulsion preparation, and relates to a microfluidic method for preparing monodisperse emulsion controllably based on an infiltration principle.
Background
Emulsions are mixtures of liquid phases in which one liquid phase is dispersed in another liquid phase which is immiscible with each other in the form of droplets, and emulsions having good size dispersibility have important uses in many fields such as chemical industry, medicine, food, cosmetics, and the like. Compared with the traditional emulsification methods such as high-speed stirring emulsification, ultrasonic homogenizing emulsification, membrane emulsification and the like, the microfluidic technology can accurately control the flow and dispersion of fluid in a microchannel, so that the method has unique advantages in controllable preparation of emulsion drops.
Traditional microfluidic technology mainly utilizes principles of liquid phase shearing, high-frequency vibration, high-speed centrifugation and the like to prepare monodisperse emulsion, and although the modes can prepare emulsion with uniform structural size, the structure and manufacturing process of a microfluidic device on which the traditional microfluidic technology depends are still complex, and operators are required to have professional microscale multiphase fluid manipulation skills. Meanwhile, the size and the size monodispersity of emulsion droplets prepared by the traditional microfluidic technology are also easily influenced by factors such as the geometric dimension of a micro-channel of a microfluidic device, the flowing condition of a continuous phase, physical parameters (such as viscosity, interfacial tension and the like) of fluid and the like, so that the emulsion droplet forming process is easily disturbed, and the size and the monodispersity of the emulsion droplets are influenced. For example, when emulsion droplets are prepared by conventional microfluidic technology, the emulsion droplet size will increase as the microchannel size increases and decrease as the continuous phase flow rate increases, and thus is susceptible to variations in production process conditions. When high viscosity fluids containing polymers, nanoparticles, and the like are involved, conventional microfluidic techniques often have difficulty emulsifying them into droplets, and even though high shear forces can be provided by greatly increasing the continuous phase flow rate, it has been difficult to shear the high viscosity fluid into monodisperse droplets, and a significant cost of the continuous phase is incurred. In addition, when the conventional microfluidic technology is used for synthesizing microparticles by using a droplet template, an online reaction between a dispersed phase droplet and a continuous phase in a droplet system in a channel is generally involved, and the process of converting the droplet into a solid particle is very easy to block the microchannel, so that continuous controllable preparation of the polymer microparticles in a microfluidic device is affected. Therefore, development of a novel microfluidic emulsification technology with convenient operation, simple device structure and strong robustness in the emulsification process has important significance for controllable preparation of monodisperse emulsion droplets, but challenges still exist.
Disclosure of Invention
Aiming at the problems of complex structure and construction process of the device, high requirements on fluid operation and control, multiple influence factors of droplet preparation, difficulty in preparing high-viscosity (> 1 Pa.s) droplets and the like in the existing microfluidic emulsion preparation technology, the invention provides a microfluidic method for controllably preparing monodisperse emulsion based on a liquid phase interface infiltration principle, which is used for simplifying the structure of the microfluidic device and the construction process thereof, simplifying the emulsion preparation operation process, ensuring that the emulsion preparation process is not easily influenced by factors such as liquid phase flowing condition, liquid phase viscosity, microchannel size and the like, improving the robustness of the emulsion preparation process, and realizing convenient and efficient controllable preparation of the monodisperse emulsion.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the microfluidic method for preparing the monodisperse emulsion based on the infiltration principle comprises the steps of:
placing the continuous phase in a collection container to enable the liquid level of the continuous phase to be horizontal, placing the outlet of the injection tube above the liquid level of the continuous phase in the collection container, continuously injecting the disperse phase into the injection tube through an injection pump, and when the disperse phase flowing out of the outlet of the injection tube contacts the liquid level of the continuous phase, soaking the disperse phase into the continuous phase under the induction of three-phase interfacial tension differences of the air phase, the disperse phase and the continuous phase to generate monodisperse emulsion;
the interfacial tension of the disperse phase and the continuous phase at the outlet of the injection tube should satisfy gamma AW >γ AO +γ WO ，γ AW Gamma, the interfacial tension between the air phase and the dispersed phase AO Is the interfacial tension between the air phase and the continuous phase, gamma WO As a dispersed phaseInterfacial tension between the continuous phases;
in the preparation process, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase, the distance between the outlet of the injection tube and the liquid level of the continuous phase is L+/(1% -5%), L is a constant value which is more than or equal to 50 mu m.
In the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the disperse phase is a water phase and the continuous phase is an oil phase.
Furthermore, in the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the continuous phase can also contain an interface stabilizing agent, wherein the interface stabilizing agent comprises a surfactant or/and nanoparticles for stabilizing the interface. The surfactant is dissolved in the continuous phase, and the nanoparticles for stabilizing the interface are uniformly dispersed in the continuous phase. A preparation method of a feasible continuous phase comprises the step of dissolving or uniformly dispersing a reagent for stabilizing an interface in an oil phase solvent to obtain the continuous phase.
In the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the disperse phase contains at least one of a functional polymer, a monomer, a thickener, a salt and functional nano particles which can be dissolved in an aqueous phase solvent. A preparation method of a feasible disperse phase comprises the step of dissolving at least one of a functional polymer, a monomer, a thickener, a salt and functional nano particles which can be dissolved in an aqueous phase solution in the aqueous phase solvent to obtain the disperse phase.
When the dispersed phase fluid contains functional polymer or monomer, the monodisperse emulsion liquid drops prepared by the technical scheme can obtain functionalized monodisperse polymer microspheres after solidification; when the dispersed phase fluid contains functional nano particles and functional polymers or monomers, the monodisperse emulsion liquid drops prepared by the technical scheme can obtain the functionalized monodisperse polymer microspheres containing the nano particles after solidification.
In practical applications, the formulations of the dispersed and continuous phases may be determined according to specific application requirements, and the formulations of the dispersed and continuous phases may be determined with reference to the prior art.
In the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the injection tube is a tube with a conical port or a cylindrical port at the outlet. The material of the injection tube can be metal, polymer or glass, etc.
Further, in the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the outer diameter of the outlet of the injection tube is 10-1000 μm.
Furthermore, in the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, L is a constant value between 50 and 1000 mu m.
In the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, along with the process of preparing the monodisperse emulsion, the liquid level of the continuous phase can rise, and in the preparation process, the outlet of the injection tube is ensured to be above the liquid level of the continuous phase and the distance between the outlet of the injection tube and the liquid level of the continuous phase is kept at L+/-1% -5% L by adjusting the position of the injection tube upwards, or adjusting the position of the collecting container downwards, or adjusting the liquid level in the collecting container downwards (for example, taking out part of the monodisperse emulsion from the collecting container).
In the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the injection tube is provided with one fluid channel or more than one fluid channels which are consistent in shape and parallel to each other. When the injection tube is provided with more than one fluid channel, the fluid channels which are consistent in shape and parallel to each other of the injection tube are communicated with different liquid outlets of the injection pump. For example, when a syringe has two fluid channels that are identical in shape and parallel to each other, janus-type emulsion droplets can be prepared using the method of the present invention.
The diameter of the monodisperse emulsion droplets prepared by the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is mainly determined by the distance between the outlet of the injection tube and the liquid level of the continuous phase in the preparation process. In practical applications, where the structure of the syringe of the microfluidic device, the formulation of the dispersed and continuous phases, and the flow rate of the dispersed phase are determined, the distance between the outlet of the syringe and the liquid surface of the continuous phase may be determined experimentally to ensure that the dispersed phase can shear off from the outlet of the syringe to form droplets.
According to the technical scheme of the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the diameter of the liquid drops of the prepared monodisperse emulsion can be flexibly adjusted by adjusting the distance between the outlet of the injection tube and the liquid level of the continuous phase in the preparation process. In general, the monodisperse emulsion droplets prepared by the above technical scheme have any diameter between 50 and 1000 μm.
The invention is based on three-phase interfacial tension difference (gamma) of gas (A) -water (W) -oil (O) AW >γ AO +γ WO ) The air micro-fluidic technology for automatically generating water-in-oil (W/O) single emulsion by soaking the disperse phase can solve the problem that the stability and the repeatability of the droplet production are affected due to the large number of droplet preparation influencing factors in the existing micro-fluidic emulsion technology, and can realize the high-viscosity fluid droplet>1 Pa.s). Meanwhile, the structure and the construction process of the microfluidic device relied on by the method are simple, the microchannel is not required to be constructed by means of a complex micro-manufacturing process, and the dependence on the professional operation skills of the fluid is lower.
Compared with the prior art, the technical scheme provided by the invention has the following beneficial technical effects:
1. the invention provides a microfluidic method for preparing monodisperse emulsion based on an infiltration principle, which can continuously prepare the disperse phase fluid pumped into a syringe by a syringe pump into monodisperse emulsion droplets by selecting disperse phase fluid and continuous phase fluid and controlling the distance between the outlet of the syringe and the liquid level of the continuous phase fluid to be above the liquid level of the continuous phase fluid in the preparation process, wherein the structure and the construction process of a required microfluidic device are simple, and the construction of the microfluidic device does not need a complex microfabrication process.
2. According to the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle, the size and the monodispersity of the prepared emulsion are not influenced by physical parameters of fluid, so that the problem that the stability and the repeatability of droplet production are influenced due to a plurality of droplet preparation influencing factors in the conventional microfluidic emulsion technology can be solved, the preparation of the monodisperse emulsion droplets can be realized within a wide viscosity range (for example, 1-2500 mPa.s), and the preparation of the monodisperse emulsion droplets of high-viscosity fluid (> 1 Pa.s) can be realized.
3. When the emulsion prepared by the method is used as a template to synthesize polymer microparticles, the microfluidic device is not in direct contact with the cross-linking agent due to the existence of air in the preparation process of the polymer microparticles, so that the device blockage can be effectively avoided, and the preparation process is more stable. Can solve the problems of easy blockage of the microfluidic channel and limitation of continuous preparation of polymer microparticles caused by liquid solidification in the reaction of dispersed phase liquid drops and continuous phase in the microchannel in the prior art.
Drawings
FIG. 1 is a schematic diagram of a microfluidic device for preparing monodisperse emulsions, in which a 1-syringe, a 2-collection vessel, and a 3-syringe pump are shown.
Fig. 2 is a schematic structural diagram of a syringe of the microfluidic device according to example 2.
FIG. 3 a) is an optical microscope photograph of the W/O emulsions prepared in examples 3 to 6, and FIGS. 3 b) to d) are graphs of the droplet diameter of the W/O emulsion prepared in example 7, respectively, as a function of the distance H between the outlet of the injection tube and the continuous phase liquid level, and the dispersed phase flow rate Q d And an inner diameter D at the outlet of the syringe o Is a variation graph of (a).
FIG. 4 a) is an optical microscope photograph of the W/O emulsions prepared in examples 8 to 11, and FIGS. 4 b) to c) are, respectively, droplet diameters of the W/O emulsions prepared in example 12 as a function of the viscosity μ of the dispersed phase fluid d And a distribution of the diameter of the droplets of the W/O emulsion.
FIGS. 5 a) to c) are laser confocal microscopy pictures of calcium alginate particles prepared in examples 13 to 15 in the bright field, dark field and superimposed field, respectively.
Detailed Description
The method for preparing the monodisperse emulsion based on the infiltration principle provided by the invention is further described below by way of examples and with reference to the accompanying drawings. It is to be noted that the following examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, since numerous insubstantial modifications and variations of the present invention may be made by those skilled in the art in light of the above teachings, and still fall within the scope of the invention.
In the following examples, the continuous phase liquid level gradually increases as the monodisperse emulsion preparation proceeds, and in the preparation in the following examples, the position of the syringe may be adjusted upward, or the position of the collection vessel may be adjusted downward, or a portion of the monodisperse emulsion may be removed from the collection vessel, so as to ensure that the outlet of the syringe is above the continuous phase liquid level and that the distance between the outlet of the syringe and the continuous phase liquid level is maintained at l±5%.
Example 1
In this embodiment, a structure of a microfluidic device for preparing monodisperse emulsion is provided, the microfluidic device comprises a syringe 1, a collection container 2 and a syringe pump 3, an inlet of the syringe is communicated with a liquid outlet of the syringe pump through a pipe fitting, and a schematic structural diagram of the microfluidic device is shown in fig. 1.
The injection tube 1 is a circular tube with a conical outlet, in particular a quartz glass capillary with a conical tail, and the inner diameter of the outlet of the injection tube is 10-1000 mu m. In particular, two types of microfluidic devices are provided in this embodiment, the two types differing only in the size at the outlet of the syringe.
In the first type of microfluidic device, the syringe is made of a quartz glass capillary having an inner diameter of 500 μm and an outer diameter of 960 μm, and the tail of the quartz glass capillary is drawn by a needle puller and processed into a conical flat port having an inner diameter of about 50 μm and an outer diameter of about 80 μm, i.e., an inner diameter of about 50 μm and an outer diameter of about 80 μm at the outlet of the syringe.
In the second type of microfluidic device, the syringe is made of a quartz glass capillary having an inner diameter of 500 μm and an outer diameter of 960 μm, and the tail of the quartz glass capillary is drawn by a needle puller and processed into a conical flat port having an inner diameter of about 65 μm and an outer diameter of about 100 μm, i.e., an inner diameter of about 65 μm and an outer diameter of about 100 μm at the outlet of the syringe.
Example 2
In this embodiment, a structure of a microfluidic device for preparing a monodisperse emulsion is provided, the microfluidic device includes a syringe 1, a collection container 2 and a syringe pump 3, a schematic structure of the syringe is shown in fig. 2, two fluid channels are provided in the syringe 1, inlets of the two fluid channels of the syringe are respectively communicated with different liquid outlets of the syringe pump through a pipe fitting, and the structure of the microfluidic device is similar to that of fig. 1.
The preparation method of the injection tube 1 comprises the following steps: two 34G stainless steel needles were inserted into a quartz glass capillary tube, the inner diameter of the stainless steel needles was 110 μm and the outer diameter thereof was 244 μm, the inner diameter of the quartz glass capillary tube was 500 μm and the outer diameter thereof was 960 μm, and the tail portions of the quartz glass capillary tube into which the two stainless steel needles were inserted were drawn by a needle drawing machine and processed into conical flat mouths, the inner diameter of the conical mouths being about 65 μm and the outer diameter thereof being about 100. Mu.m.
The inlets of the two stainless steel needles are respectively communicated with different liquid outlets of the injection pump, and the liquid outlets of the two stainless steel needles are positioned in the section of the quartz glass capillary tube.
Example 3
In this embodiment, taking a preparation process of a monodisperse water-in-oil (W/O) emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) Preparing a disperse phase and a continuous phase fluid
Deionized water is used as a disperse phase fluid; the oil-soluble surfactant is polyisobutenyl succinimide (T154) dissolved in tetradecane to obtain a continuous phase fluid, wherein the concentration of T154 in the continuous phase fluid is 0.04g/mL.
(2) Preparation of monodisperse W/O emulsions
Use in example 1The first type of microfluidic device was prepared. Placing the continuous phase fluid in a collecting container, placing the collecting container horizontally to make the liquid level of the continuous phase fluid be horizontal, placing the outlet of the injection tube above the liquid level of the continuous phase fluid in the collecting container, continuously injecting the disperse phase fluid into the injection tube by means of injection pump at a flow rate of 4mL/h, when the disperse phase fluid flowing out from the outlet of the injection tube contacts with the continuous phase fluid, the disperse phase is separated in the three-phase interfacial tension difference (gamma AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form a monodisperse W/O emulsion.
In the preparation process, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept within the range of 350+/-17.5 mu m.
Example 4
In this embodiment, taking the preparation process of the monodisperse W/O emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) The preparation of the dispersed and continuous phase fluids was the same as in example 3.
(2) Preparation of monodisperse W/O emulsions
The preparation was carried out using the microfluidic device of the first type in example 1. Placing the continuous phase fluid in a collecting container, placing the collecting container horizontally to make the liquid level of the continuous phase fluid be horizontal, placing the outlet of the injection tube above the liquid level of the continuous phase fluid in the collecting container, continuously injecting the disperse phase fluid into the injection tube by means of injection pump at a flow rate of 4mL/h, when the disperse phase fluid flowing out from the outlet of the injection tube contacts with the continuous phase fluid, the disperse phase is separated in the three-phase interfacial tension difference (gamma AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form a monodisperse W/O emulsion.
In the preparation process, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept in the range of 400+/-40 mu m.
Example 5
In this embodiment, taking the preparation process of the monodisperse W/O emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) The preparation of the dispersed and continuous phase fluids was the same as in example 3.
(2) Preparation of monodisperse W/O emulsions
The preparation was carried out using the microfluidic device of the first type in example 1. Placing the continuous phase fluid in a collecting container, placing the collecting container horizontally to make the liquid level of the continuous phase fluid be horizontal, placing the outlet of the injection tube above the liquid level of the continuous phase fluid in the collecting container, continuously injecting the disperse phase fluid into the injection tube by means of injection pump at a flow rate of 4mL/h, when the disperse phase fluid flowing out from the outlet of the injection tube contacts with the continuous phase fluid, the disperse phase is separated in the three-phase interfacial tension difference (gamma AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form a monodisperse W/O emulsion.
During the preparation, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept within the range of 450+/-22.5 mu m.
Example 6
In this embodiment, taking the preparation process of the monodisperse W/O emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) The preparation of the dispersed and continuous phase fluids was the same as in example 3.
(2) Preparation of monodisperse W/O emulsions
The preparation was carried out using the microfluidic device of the first type in example 1. The continuous phase fluid is contained in a collecting container, the collecting container is horizontally placed so that the liquid level of the continuous phase fluid is horizontal,placing the outlet of the syringe above the liquid level of the continuous phase fluid in the collection vessel, continuously injecting the dispersion phase fluid into the syringe at a flow rate of 4mL/h by a syringe pump, and when the dispersion phase fluid flowing out of the outlet of the syringe contacts the continuous phase fluid, the dispersion phase is separated by a three-phase interfacial tension difference (gamma) between the air phase (A) -the dispersion phase (W) -the continuous phase (O) AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form a monodisperse W/O emulsion.
In the preparation process, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept within the range of 500+/-25 mu m.
The graph a) of FIG. 3 shows the optical microscope pictures of the W/O emulsions prepared in examples 3 to 6, and it is clear from the graph that the W/O emulsions prepared in examples 3 to 6 have uniform droplet sizes.
Example 7
In this embodiment, the diameter of the emulsion droplet is controlled by controlling the distance between the outlet of the injection tube and the liquid level of the continuous phase fluid, the flow rate of the disperse phase fluid, and the outer diameter of the outlet of the injection tube, specifically as follows:
(1) The preparation method of the disperse phase and continuous phase fluids is the same as that of example 6, and the first type of microfluidic device described in example 1 is used, and the operation is similar to that of example 6, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid in the preparation process is controlled to be respectively kept in the ranges of 350+/-17.5, 400+/-20, 416+/-20.8, 450+/-22.5 and 500+/-25 mu m under the condition that the flow rates of the disperse phase fluid are respectively 2, 4, 6 and 8mL/H.
The diameter of the monodisperse W/O emulsion thus prepared is shown in fig. 3 b), which shows that the diameter of the droplets of the W/O emulsion gradually increases as the distance (H) from the outlet of the syringe to the surface of the continuous phase fluid increases with a fixed flow rate of the disperse phase fluid.
(2) The preparation method of the disperse phase and continuous phase fluids was the same as in example 6, using the first type of microfluidic device described in example 1, and the operation was similar to that of example 6, with the distances (H) between the outlet of the syringe and the liquid surface of the continuous phase fluid during the preparation being controlled to be maintained at 350.+ -. 17.5, 400.+ -. 20, 450.+ -. 22.5 and 500.+ -. 25 μm, respectively, and the flow rates of the disperse phase fluid being controlled to be 1, 2, 4, 6 and 8mL/H, respectively.
The diameter of the monodisperse W/O emulsion thus prepared is shown in FIG. 3 c), which shows that the diameter of the W/O emulsion droplets remains substantially unchanged as the flow rate of the disperse phase fluid increases, with the distance (H) between the outlet of the syringe and the surface of the continuous phase fluid being fixed.
(3) Referring to the preparation method of the injection tube in example 1, the tail parts of quartz glass capillaries with the inner diameters of 500 μm and the outer diameters of 960 μm are respectively drawn by a needle drawing instrument and processed into conical flat mouths, so as to obtain injection tubes with various conical mouths with different sizes (namely, different outer diameters at the outlet), and specifically five injection tubes with the outer diameters at the outlet of 40, 60, 80, 100 and 120 μm are prepared. The following experiments were performed using these syringes instead of the syringes in the microfluidic device described in example 1.
The preparation method of the disperse phase fluid and the continuous phase fluid is similar to that of example 6, the flow rate of the disperse phase fluid is controlled to be 4mL/H, and the W/O emulsion is prepared by adopting micro-fluidic devices with the outer diameters of 40, 60, 80, 100 and 120 mu m at the outlet of the injection tube under the conditions that the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is respectively kept at 400+/-20, 450+/-22.5, 500+/-25 and 550+/-27.5 mu m in the preparation process.
The diameter of the monodisperse W/O emulsion thus prepared is shown in FIG. 3 d), and it is shown that the diameter of the W/O emulsion droplets remains substantially unchanged as the outer diameter of the syringe outlet increases with a constant flow rate of the dispersed phase.
Example 8
In this embodiment, taking the preparation process of the monodisperse W/O emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) Preparing a disperse phase and a continuous phase fluid
Deionized water is used as a disperse phase fluid; t154 was dissolved in tetradecane to give a continuous phase fluid, the concentration of T154 in the continuous phase fluid was 0.04g/mL.
(2) Preparation of monodisperse W/O emulsions
The preparation was carried out using the microfluidic device of the first type in example 1. Placing the continuous phase fluid in a collecting container, horizontally placing the collecting container to make the liquid level of the continuous phase fluid be horizontal, placing the outlet of the injection tube above the liquid level of the continuous phase fluid in the collecting container, continuously injecting the disperse phase fluid into the injection tube by means of injection pump at a flow rate of 0.5mL/h, when the disperse phase fluid flowing out from the outlet of the injection tube is contacted with the continuous phase fluid, the disperse phase is separated by three-phase interfacial tension difference (gamma) of air phase (A) -disperse phase (W) -continuous phase (O) AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form a monodisperse W/O emulsion.
During the preparation, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept within the range of 450+/-22.5 mu m.
Example 9
In this embodiment, taking the preparation process of the monodisperse W/O emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) Preparing a disperse phase and a continuous phase fluid
Dissolving sodium carboxymethyl cellulose in deionized water to obtain a disperse phase fluid, wherein the concentration of sodium carboxymethyl cellulose in the disperse phase fluid is 0.003g/mL; t154 was dissolved in tetradecane to give a continuous phase fluid, the concentration of T154 in the continuous phase fluid was 0.04g/mL.
(2) The procedure for preparation of monodisperse W/O emulsion was the same as in step (2) of example 8.
Example 10
In this embodiment, taking the preparation process of the monodisperse W/O emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) Preparing a disperse phase and a continuous phase fluid
Dissolving sodium carboxymethyl cellulose in deionized water to obtain a disperse phase fluid, wherein the concentration of sodium carboxymethyl cellulose in the disperse phase fluid is 0.005g/mL; t154 was dissolved in tetradecane to give a continuous phase fluid, the concentration of T154 in the continuous phase fluid was 0.04g/mL.
(2) The procedure for preparation of monodisperse W/O emulsion was the same as in step (2) of example 8.
Example 11
In this embodiment, taking the preparation process of the monodisperse W/O emulsion as an example, the microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is described as follows:
(1) Preparing a disperse phase and a continuous phase fluid
Dissolving sodium carboxymethylcellulose in deionized water to obtain a disperse phase fluid, wherein the concentration of sodium carboxymethylcellulose in the disperse phase fluid is 0.008g/mL; t154 was dissolved in tetradecane to give a continuous phase fluid, the concentration of T154 in the continuous phase fluid was 0.04g/mL.
(2) The procedure for preparation of monodisperse W/O emulsion was the same as in step (2) of example 8.
The graph a) of FIG. 4 shows the optical microscope pictures of the W/O emulsions prepared in examples 8 to 11, and it is clear from the graph that the W/O emulsions prepared in examples 8 to 11 have uniform droplet sizes.
Example 12
In this embodiment, the concentration of sodium carboxymethylcellulose in the dispersed phase fluid is adjusted to adjust the viscosity of the dispersed phase fluid, and the influence of the viscosity of the dispersed phase fluid on the preparation of the emulsion is examined.
(1) Preparing a disperse phase and a continuous phase fluid
T154 was dissolved in tetradecane to give a continuous phase fluid, the concentration of T154 in the continuous phase fluid was 0.04g/mL.
Dissolving sodium carboxymethyl cellulose in deionized water to obtain a disperse phase fluid, and obtaining disperse phase fluids with different sodium carboxymethyl cellulose concentrations; the concentration of sodium carboxymethyl cellulose in each of the dispersed phase fluids was 0, 0.003, 0.005, 0.008, 0.01, 0.013 and 0.02g/mL, respectively, and the viscosity (. Mu.s) of each of the dispersed phase fluids was correspondingly determined d ) 1, 44.3, 92.6, 236.7 respectively,501.9、1041.8、2408.0mPa·s。
(2) Preparation of monodisperse W/O emulsions
A W/O emulsion was prepared by the procedure of step (2) of example 8, respectively.
The diameter and the diameter distribution of the monodisperse W/O emulsion prepared by using the disperse phase fluid with different viscosities are shown in fig. 4 b) and fig. 4 c), and it can be seen from the graph that the diameter of the droplets of the W/O emulsion remains unchanged basically along with the increase of the viscosity of the disperse phase fluid under the condition that the distance between the outlet of the injection tube and the liquid surface of the continuous phase fluid is constant and the flow rate of the disperse phase fluid is fixed; meanwhile, the diameter distribution of the droplets of the W/O emulsion prepared with the dispersion phase fluids with different viscosities in this example is normal distribution, and the average diameter of the emulsion droplets is 450 μm. The experimental results show that the method for preparing the monodisperse emulsion provided by the invention is not limited by the viscosity of the disperse phase fluid, and is suitable for not only low-viscosity disperse phase fluid but also high-viscosity disperse phase fluid.
Example 13
In this example, janus calcium alginate droplets were prepared by the method of the present invention, and calcium alginate particles were prepared based on the prepared Janus calcium alginate droplets, as follows:
(1) Preparing dispersed phase and continuous phase fluid and collecting liquid
Fully dispersing sodium alginate and nano calcium carbonate particles in water to obtain a disperse phase fluid, wherein the mass ratio of deionized water to sodium alginate to nano calcium carbonate particles in the disperse phase fluid is 1:0.015:0.001. And adding a small amount of green fluorescent silica nanoparticles and red fluorescent silica nanoparticles into the disperse phase fluid respectively to obtain a disperse phase fluid containing the green fluorescent silica nanoparticles and a disperse phase fluid containing the red fluorescent silica nanoparticles.
Dissolving T154 and glacial acetic acid in tetradecane to obtain a continuous phase fluid, wherein the mass ratio of the tetradecane to the T154 to the glacial acetic acid in the continuous phase fluid is 1:0.04:0.004.
Fully mixing n-octanol and soybean oil according to the volume ratio of 1:4, then adding calcium iodide, fully mixing to obtain a collecting liquid, and carrying out secondary crosslinking reaction on calcium alginate liquid drops by the collecting liquid, wherein the concentration of the calcium iodide in the collecting liquid is 0.8% (w/v).
(2) Preparation of monodisperse Janus calcium alginate droplets
The microfluidic device described in example 2 was used for preparation. Placing continuous phase fluid in a collecting container, placing the collecting container horizontally to make the liquid level of continuous phase fluid be horizontal, placing the outlet of injection tube above the liquid level of continuous phase fluid in the collecting container, respectively continuously injecting the disperse phase fluid containing green fluorescent silica nano particles and disperse phase fluid containing red fluorescent silica nano particles into two fluid channels of injection tube by means of different liquid outlets of injection pump at the flow rate of 0.1mL/h and 0.1mL/h, when the disperse phase fluid discharged from outlet of injection tube is contacted with continuous phase fluid, the disperse phase is separated by three-phase interfacial tension difference (gamma) of air phase (A) -disperse phase (W) -continuous phase (O) AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form monodisperse Janus calcium alginate droplets.
During the preparation, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept within the range of 450+/-22.5 mu m.
(3) Preparation of monodisperse calcium alginate particles
And (3) placing the dispersed Janus calcium alginate droplets prepared in the step (2) into a collection liquid to carry out secondary crosslinking reaction, so as to obtain the monodisperse calcium alginate particles.
Example 14
In this example, janus calcium alginate droplets were prepared by the method of the present invention, and calcium alginate particles were prepared based on the prepared Janus calcium alginate droplets, as follows:
(1) The dispersed and continuous phase fluids and the collection fluid were formulated as in step (1) of example 13.
The microfluidic device described in example 2 was used for preparation. Placing the continuous phase fluid in a collecting container, and horizontally placing the collecting container to make continuous phase fluidThe liquid level of the phase fluid is horizontal, the outlet of the injection tube is arranged above the liquid level of the continuous phase fluid in the collecting container, the disperse phase fluid containing the green fluorescent silica nano particles and the disperse phase fluid containing the red fluorescent silica nano particles are respectively and continuously injected into two fluid channels of the injection tube through different liquid outlets of the injection pump at the flow rate of 0.05mL/h and 0.15mL/h, when the disperse phase fluid flowing out from the outlet of the injection tube contacts the continuous phase fluid, the disperse phase is in the three-phase interfacial tension difference (gamma AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form monodisperse Janus calcium alginate droplets.
During the preparation, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept within the range of 450+/-22.5 mu m.
(3) Preparation of monodisperse calcium alginate particles
And (3) placing the dispersed Janus calcium alginate droplets prepared in the step (2) into a collection liquid to carry out secondary crosslinking reaction, so as to obtain the monodisperse calcium alginate particles.
Example 15
In this example, janus calcium alginate droplets were prepared by the method of the present invention, and calcium alginate particles were prepared based on the prepared Janus calcium alginate droplets, as follows:
(1) The dispersed and continuous phase fluids and the collection fluid were formulated as in step (1) of example 13.
The microfluidic device described in example 2 was used for preparation. Placing continuous phase fluid in a collecting container, horizontally placing the collecting container to make the liquid level of continuous phase fluid be horizontal, placing the outlet of injection tube above the liquid level of continuous phase fluid in the collecting container, respectively continuously injecting the disperse phase fluid containing green fluorescent silica nano particles and disperse phase fluid containing red fluorescent silica nano particles into two fluid channels of injection tube by means of different liquid outlets of injection pump at the flow rate of 0.025mL/h and 0.175mL/h, when the flow rate is changed fromWhen the disperse phase fluid flowing out of the outlet of the injection tube contacts with the continuous phase fluid, the disperse phase generates three-phase interfacial tension difference (gamma) between the air phase (A) -the disperse phase (W) -the continuous phase (O) AW >γ AO +γ WO ) Is immersed in the continuous phase fluid to form monodisperse Janus calcium alginate droplets.
During the preparation, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase fluid, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase fluid, and the distance (H) between the outlet of the injection tube and the liquid level of the continuous phase fluid is kept within the range of 450+/-22.5 mu m.
(3) Preparation of monodisperse calcium alginate particles
And (3) placing the dispersed Janus calcium alginate liquid drops prepared in the step (2) into a collection liquid to carry out secondary crosslinking reaction, so as to obtain the dispersed calcium alginate particles.
FIG. 5 is a photograph of laser confocal microscopy of calcium alginate particles of examples 13-15 in bright field, dark field and superimposed field, respectively, Q d1 :Q d2 The flow ratio of the dispersion fluid containing green fluorescent silica nanoparticles to the dispersion fluid containing red fluorescent silica nanoparticles was shown, and it was found that the calcium alginate particles prepared in examples 13 to 15 were uniform in size and had an average diameter of about 450. Mu.m.
Claims (10)
1. The microfluidic method for controllably preparing the monodisperse emulsion based on the infiltration principle is characterized by comprising the following steps of:
placing the continuous phase in a collection container to enable the liquid level of the continuous phase to be horizontal, placing the outlet of the injection tube above the liquid level of the continuous phase in the collection container, continuously injecting the disperse phase into the injection tube through an injection pump, and when the disperse phase flowing out of the outlet of the injection tube contacts the liquid level of the continuous phase, soaking the disperse phase into the continuous phase under the induction of three-phase interfacial tension differences of the air phase, the disperse phase and the continuous phase to generate monodisperse emulsion;
disperse phaseAnd the interfacial tension of the continuous phase at the outlet of the syringe should be such that gamma AW >γ AO +γ WO ，γ AW Gamma, the interfacial tension between the air phase and the dispersed phase AO Is the interfacial tension between the air phase and the continuous phase, gamma WO Interfacial tension between the dispersed phase and the continuous phase;
in the preparation process, the injection tube is controlled to be perpendicular to the liquid level of the continuous phase, the outlet of the injection tube is controlled to be positioned above the liquid level of the continuous phase, the distance between the outlet of the injection tube and the liquid level of the continuous phase is L+/(1% -5%), L is a constant value which is more than or equal to 50 mu m.
2. The microfluidic method for controllably preparing a monodisperse emulsion based on the infiltration principle according to claim 1, wherein the disperse phase is an aqueous phase and the continuous phase is an oil phase.
3. The microfluidic method for the controlled preparation of monodisperse emulsions according to claim 2, wherein the continuous phase contains a reagent with a stable interface.
4. A microfluidic method for the controlled preparation of monodisperse emulsions based on the wetting principle according to claim 3, wherein the agent for stabilizing the interface comprises a surfactant or/and nanoparticles for stabilizing the interface.
5. The microfluidic method for controllably preparing a monodisperse emulsion based on the wetting principle according to claim 2, wherein the dispersed phase contains at least one of a functional polymer, a monomer, a thickener, a salt and a functional nanoparticle which is soluble in an aqueous solvent.
6. The microfluidic method for the controlled preparation of monodisperse emulsions according to any of claims 1 to 5, wherein the syringe is a tube with a conical or cylindrical outlet.
7. The microfluidic method for controllably preparing monodisperse emulsion according to the infiltration principle of claim 6, wherein the outer diameter of the outlet of the injection tube is 10-1000 μm.
8. The microfluidic method for the controlled preparation of monodisperse emulsions according to claim 7, wherein L is a constant value between 50 and 1000 μm.
9. The microfluidic method for controllably preparing a monodisperse emulsion based on the wetting principle according to claim 6, wherein the syringe has one fluid channel or more than one fluid channels which are uniform in shape and parallel to each other.
10. The microfluidic method for controllably preparing a monodisperse emulsion according to the infiltration principle of claim 9, wherein when the syringe has more than one fluid channel, the fluid channels of the syringe are consistent in shape and mutually parallel are communicated with different liquid outlets of the syringe pump.
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