Multi-component monodisperse microdroplet digital electronic control system and method

Abstract

The application discloses a kind of multi-component monodisperse microdroplet digital electric control system and method, comprising: multi-component droplet generation module, for obtaining microdroplet by controlling the flow ratio between dispersed phase and continuous phase;Multi-component droplet digital electric control module is used to control the deformation, movement and fusion of the microdroplet by the combination electrode of several sharp electrodes and flat angle electrodes;The multi-component droplet generation module and multi-component droplet digital electric control module are connected by the flow channel of PVA solution injection, and are located on microdroplet chip.This application realizes the control of microdroplet component structure and the control of microdroplet size flow rate by adjusting flow ratio and adjusting overall flow rate through discrete droplet generation unit and multi-component droplet flow focusing structure, and finally forms a complex multi-component droplet independent generation system.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of microdroplet digital electric control, and particularly relates to a multi-component monodisperse microdroplet digital electric control system and method. BACKGROUND

[0002] Droplet microfluidics has become a research hotspot due to the large specific surface area, independent controllability of each droplet, and small amount of reagent, and is suitable for fields such as chemical synthesis, biological preparation, and drug transportation. At the same time, the droplet generation, classification, fusion, splitting, and capture technologies related thereto provide unparalleled fine control methods for the above-mentioned application practices, and meet the growing requirements of microfluidic control.

[0003] The generation of droplets is derived from the instability of fluid. In the passive generation method, one or more incompatible fluids (dispersed fluids) are introduced into another (continuous fluid), and the main flow modes formed include methods such as extrusion, dripping, jetting, and tip flow. In the active generation method, additional energy input changes the force balance on the interface, thereby manipulating the instability of the interface. Overall, in active control, the interface force balance can be changed by two basic strategies: (1) introducing additional forces such as electricity, magnetism, and centrifugal force; (2) changing the intrinsic parameters such as flow speed and material properties to change the viscous force, inertial force, and capillary force.

[0004] Droplet pair fusion represents a basic process of droplet microfluidics, which includes four steps: 1) droplet capture; 2) droplet proximity, collision, and deformation; 3) continuous phase discharge between droplets; and 4) droplet rupture and fusion. The method of droplet fusion can be passive or active, where the former fuses droplets without external driving, and the latter utilizes additional energy input to promote the interface instability of droplet fusion. Compared with the passive method, the regulation of droplet fusion with the aid of additional energy input shows some advantages. In particular, the active method provides additional processing and higher flexibility in controlling droplet fusion kinetics and fusion speed, which is crucial for understanding the basic physical mechanism and practical application of droplets.

[0005] In addition, in order to further analyze the microdroplets, it is necessary to develop screening, capture, and other methods to realize further real-time monitoring and research. At present, these technical means are still under research. Although there are still many problems in current microfluidic droplet technology, the technical form is basically still in the laboratory stage. Therefore, it is necessary to further develop highly controllable microdroplet manipulation technology.

[0006] In the current microdroplet control system, there are mainly two problems. First, the structural diversity of microdroplets is difficult to guarantee, and the dispersion system is relatively single. At present, the microdroplet generation system is usually a water / oil system, and the generated droplets are mainly single droplets, and it is difficult to realize the dispersion system of multi-component droplets, and the effective switching of water / oil (the dispersed phase is water, and the continuous phase is oil), oil / water and oil / oil system still exists. Second, the programmability, rapid response and flexibility of the control are insufficient. In the traditional microdroplet control system, passive control is mainly used, and the control means is mainly the flow condition and the change of fluid properties. The active control means uses heat, light, magnetic field and the like. The heating control response time is long, the optical control has a higher requirement for the fluid material, and the magnetic field control often needs to add magnetic nanoparticles in the solution, so as to realize the control of the flow state of the microdroplets. Therefore, at present, a programmable, rapid response and flexible multi-component droplet dynamic control system is needed, which can realize the microdroplet chip process method of various droplet dispersion systems, so as to meet the increasing demand for microdroplet control. SUMMARY

[0007] The purpose of the present application is to provide a multi-component monodisperse microdroplet digital electric control system and method. Relying on the current MEMS processing technology and non-contact electrode processing technology, a microdroplet system integrated chip is prepared. Relying on the physical mechanism of fluid shear and direct / alternating electric field, the behaviors of microdroplets are generated and controlled. Relying on the flow channel design and electrode design, the control of the specific behavior of complex structure droplets is realized. Compared with the existing microdroplet control system, the obtained droplet components are more diverse, the structure is more complex, the control system is more flexible, the programmability is richer, the response degree is faster, the integration, non-contact and high adjustability of microdroplet control can be realized, so as to solve the problems existing in the prior art.

[0008] In order to achieve the above purpose, the present application provides a multi-component monodisperse microdroplet digital electric control system, comprising:

[0009] A multi-component droplet generation module is used to obtain microdroplets by controlling the flow ratio between the dispersed phase and the continuous phase;

[0010] A multi-component droplet digital electric control module is used to control the deformation, movement and fusion of the microdroplets through a combination of several sharp electrodes and flat angle electrodes;

[0011] The multi-component droplet generation module and the multi-component droplet digital electric control module are connected through a flow channel injecting PVA solution, and are located on the microdroplet chip.

[0012] Optionally, the multi-component droplet generation module comprises several discrete droplet generation units;

[0013] The discrete droplet generation unit comprises several groups of dispersed phases, and the proportion of the several groups of dispersed phases is controlled to adjust the component structure of the formed droplets.

[0014] The outside of the discrete droplet generation unit comprises several groups of continuous phase fluids, and the several groups of continuous phase fluids are used to shear the formed droplets to obtain microdroplets.

[0015] Optionally, the microdroplet digital electric control system further comprises a liquid input module and a voltage control module.

[0016] The liquid input module comprises several microinjectors, and the several microinjectors are connected with the several inlets of the multi-component droplet generation module through polytetrafluoroethylene conduits.

[0017] The voltage control module comprises a high-power amplifier and a signal generator, the positive electrode of the high-power amplifier is connected with the sharp-angle electrode, the negative electrode of the high-power amplifier is connected with the flat-angle electrode, and the voltage and frequency of the high-power amplifier are controlled through the signal generator.

[0018] The application further provides a multi-component monodisperse microdroplet digital electric control method, which comprises the following steps:

[0019] The microdroplet chip is placed on an inverted microscope and fixed, liquid is input into the microdroplet chip through the several microinjectors, the multi-component droplet generation module is brought to a stable state and microdroplets are generated, the parameters of the voltage control module are adjusted, the multi-component droplet digital electric control module controls the generated microdroplets, and the voltage control module comprises a high-power amplifier and a signal generator which are connected with each other.

[0020] Optionally, the preparation process of the microdroplet chip comprises the following steps: SU-8 glue is spin-coated on a silicon wafer as a positive film, after photoetching and developing are performed on the positive film, PDMS is poured into the positive film for casting and inverse molding, the peeled PDMS and the glass sheet are bonded to form the microdroplet chip based on a plasma activation process, and the flow electrode on the microdroplet chip is prepared based on molten metal indium.

[0021] Optionally, the preparation process of the microdroplet chip further comprises the following steps: PVA solution is input into the flow channel of the microdroplet chip, and a PVA coating layer is formed on the surface of the flow channel.

[0022] Optionally, the process in which the multi-component droplet generation module generates microdroplets comprises the following steps: the proportion of the several groups of dispersed phases in the multi-component droplet generation module is adjusted to obtain droplets, and then the several groups of continuous phase fluids in the multi-component droplet generation module are used to shear the droplets to obtain microdroplets.

[0023] Optionally, the process of controlling the generation of microdroplets by the multi-component droplet digital control module comprises placing the sharp-angle electrode and the flat-angle electrode in the multi-component droplet digital control module in different flow channel width flow areas respectively, and controlling the deformation, movement and fusion of the microdroplets.

[0024] Optionally, the process of adjusting the parameters of the voltage control module comprises adjusting the voltage and frequency of the high-power amplifier by the signal generator, and when the preset voltage value and frequency value are reached, the generated electric field acts on the multi-component droplet digital control module, and the generation of microdroplets is controlled based on the multi-component droplet digital control module.

[0025] The technical effects of the present application are:

[0026] The present application realizes the control of the component structure of microdroplets and the control of the size and flow rate of microdroplets by adjusting the flow ratio and adjusting the overall flow rate through the discrete droplet generation unit and the flow focusing structure of multi-component droplets, and finally forms a complex multi-component droplet independent generation system.

[0027] The present application realizes the control of the dynamic behavior of complex component structure droplets through the design of different types of electrodes, such as flat-angle electrodes, sharp-angle electrodes, special-shaped electrodes and combined electrodes between each other, etc.

[0028] The present application realizes the controllable switching of water / oil, oil / water and oil / oil systems by coating the PVA coating, and maximizes the stability of the dispersion system. BRIEF DESCRIPTION OF DRAWINGS

[0029] The accompanying drawings, which form a part of this application, are included to provide a further understanding of the application, and are incorporated herein for purposes of explanation and are not intended to limit the application. In the drawings:

[0030] Figure 1 A schematic diagram is designed for the multi-component monodisperse microdroplet digital control system in the embodiments of the present application;

[0031] Wherein, 1.1-continuous phase A1; 1.2-dispersed phase A1; 1.3-dispersed phase A2; 1.4-dispersed phase A3; 1.5-continuous phase A2; 1.6-continuous phase B1; 1.7-dispersed phase B1; 1.8-dispersed phase B2; 1.9-dispersed phase B3; 1.10-continuous phase B2; 1.11-continuous phase C1; 1.12-dispersed phase C1; 1.13-dispersed phase C2; 1.14-dispersed phase C3; 1.15-continuous phase C2; 1.16-continuous phase D1; 1.17-dispersed phase D1; 1.18-dispersed phase D2; 1.19-dispersed phase D3; 1.20-continuous phase D2; 1.21-continuous phase E1; 1.22-dispersed phase E1; 1.23-dispersed phase E2; 1.24-dispersed phase E3; 1.25-continuous phase E2; 1.26-design electrode; 1.27-droplet control area; 1.28-droplet generation area;

[0032] Figure 2 For the electrode type of the multi-component monodisperse microdroplet digital electric control system in the embodiment of the application;

[0033] Figure 3 For the design drawing of the multi-component monodisperse microdroplet digital electric control system in the embodiment of the application;

[0034] Wherein, 3.1-continuous phase inlet 1; 3.2-continuous phase inlet 2; 3.3-outlet; 3.4-sharp corner electrode 1; 3.5-sharp corner electrode 2; 3.6-flat corner electrode 1; 3.7-flat corner electrode 2; 3.8-continuous phase 1; 3.9-continuous phase 2; 3.10-dispersed phase inlet 1; 3.11-dispersed phase inlet 2; 3.12-dispersed phase inlet 3; 3.13-dispersed phase inlet 4; 3.14-dispersed phase 1; 3.15-dispersed phase 2; 3.16-dispersed phase 3; 3.17-dispersed phase 4; 3.18-droplet generation area; 3.19-electric field control area;

[0035] Figure 4 For the schematic diagram of the multi-component monodisperse microdroplet digital electric control in the embodiment of the application;

[0036] Figure 5 For the process flow chart of the processing side of the multi-component monodisperse microdroplet digital electric control system in the embodiment of the application;

[0037] Figure 6 For the schematic diagram of the connection mode of the multi-component monodisperse microdroplet digital electric control system in the embodiment of the application;

[0038] Wherein, 6.1-high precision syringe pump 1; 6.2-high precision syringe pump 2; 6.3-high precision syringe pump 3; 6.4-Hamilton microsyringe 1; 6.5-Hamilton microsyringe 2; 6.6-Hamilton microsyringe 3; 6.7-Hamilton microsyringe 4; 6.8-Hamilton microsyringe 5; 6.9-Hamilton microsyringe 6; 6.10-signal generator; 6.11-high voltage power amplifier; 6.12-high speed camera; 6.13-microscope; 6.14-liquid reservoir; 6.15-data acquisition system; 6.16-polytetrafluoroethylene conduit. DETAILED DESCRIPTION

[0039] It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict. The present application will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0040] It should be noted that the steps shown in the flowchart of the accompanying drawings can be executed in a computer system such as a set of computer executable instructions, and although the logical order is shown in the flowchart, in some cases, the steps shown or described herein can be executed in an order different from that shown herein.

[0041] Embodiment one

[0042] The present embodiment provides a multi-component monodisperse microdroplet digital control system and method, the microdroplet digital control system of the present embodiment is composed of two parts, the first part is a multi-component droplet generation module (such as the area shown in Figure 3 3.18), the second part is a multi-component droplet digital control module (such as the area shown in Figure 3 3.19), the multi-component droplets are first generated on the multi-component droplet generation module, and then flow into the area of the multi-component droplet digital control module through the microchannel, and are deformed, moved, fused and the like under the influence of the electric field force (such as the droplet movement, deformation and droplet fusion shown in Figure 4 ), the two systems are designed together and integrated on chip, and the droplet transmission is connected through the microchannel, all of which are located on the finally processed PDMS microfluidic chip.

[0043] In the generation of multi-component monodisperse microdroplets, the scheme of the present embodiment adopts a discrete flow focusing type multi-component microdroplet generation method. Independent droplet generation units are designed for different types of microdroplets, such as Figure 1 shown in the figure, there are different component inlets (such as Figure 1The number of components is controllable, the ratio between components is controlled to correspond to different flow ratios, the required microdroplet components are mixed, the droplet generation mode uses flow focusing, and the shear force between fluids is used for droplet generation (e.g. Figure 1 The different droplet generation units are used to independently control the generation of microdroplets of different components, and a multi-component monodisperse microdroplet generation system is finally formed.

[0044] Specifically, the multi-component droplet generation module in the microdroplet digital control system of the embodiment uses two separate droplet generation units, each of which has two dispersed phases (e.g. Figure 3 3.14 and 3.15, 3.16 and 3.17), and the component structure of the formed droplets can be adjusted by controlling the ratio of the two dispersed phases. The outer part is sheared by a continuous phase fluid (e.g. Figure 3 3.8 and 3.9) to finally form microdroplets, and the relative size of the final microdroplets is controlled by the flow ratio between the dispersed phase and the continuous phase. The microdroplet digital control system also includes a liquid input module, which includes a plurality of high-precision syringe pumps, and the connection mode is that six Hamilton microsyringes (e.g. Figure 6 6.1-6.3) on three high-precision syringe pumps (each syringe pump has two independent control channels) are connected to six inlets (four dispersed phase inlets and two continuous phase inlets) in the multi-component droplet generation module (e.g. Figure 6 6.17) through polytetrafluoroethylene tubes (e.g. Figure 6 6.16) and multi-component droplet generation modules (e.g. Figure 6 6.17) (four dispersed phase inlets and two continuous phase inlets) (e.g. Figure 3 3.1, 3.2, 3.10-3.13), and the syringe pumps (e.g. Figure 6 6.1-6.3) are opened during the generation process, and multi-component droplets can be generated when the fluid interface is stable. The component ratio and relative size of the droplets are controlled by adjusting the flow of the syringe pumps. In addition, the outlet of the microdroplet (e.g. Figure 3 3.3) is also connected to a liquid storage tank (e.g. Figure 6 6.14) through a polytetrafluoroethylene tube (e.g. Figure 6 6.16), so as to realize the collection of droplets.

[0045] In the design and integration of different types of electrodes, the scheme of the embodiment uses multiple types of electrode design and integration, including flat electrodes, sharp electrodes, and special-shaped electrodes, such as Figure 2 and as shown in Figure 1 1.26, a field control region (e.g. Figure 1The electrode includes, but is not limited to, a single-tip electrode, a double-tip electrode, a three-tip electrode, and other multi-tip electrode designs, a wave electrode, and other electrode forms, and various special-shaped electrodes designed to meet different control requirements, and a combination electrode therebetween. Meanwhile, in the processing technology of the electrode, a MEMS photolithography technology is used together with a microchannel to design and process an electrode channel, a low-melting-point liquid metal (solid at room temperature, including but not limited to metal indium) is used to fill the electrode channel, and a wire is used to connect out, and finally different types of multipurpose design electrodes are formed.

[0046] Specifically, the multi-component droplet digital control module in the microdroplet digital control system of the embodiment adopts a combination electrode between two pairs of sharp-angle electrodes (such as Figure 3 3.4 and 3.5) and flat-angle electrodes (such as Figure 3 3.6 and 3.7), wherein the sharp-angle electrodes are connected to the positive electrode, the flat-angle electrodes are connected to the negative electrode, and are respectively located in flow regions with different flow channel widths, to control the deformation, movement, fusion and other behaviors of the microdroplets (as shown in Figure 4 ), the spacing between the two pairs of electrodes is different, and the flow channel width in the middle is also different, so that different electric control modes can be formed. The connection mode is that the positive and negative electrodes of the electrode (such as Figure 3 3.4-3.7) formed by connecting the metal indium and the wire are connected to the high-voltage power amplifier (such as Figure 6 6.11), the input signal of the high-voltage power amplifier is controlled by the signal generator (such as Figure 6 6.10), and the voltage and frequency can be adjusted on the signal generator, so as to control the frequency and voltage of the electric field between the electrodes.

[0047] In the design and processing of various dispersion systems, the scheme of the embodiment adopts whether to integrate a PVA coating to act on different dispersion systems. For a water / oil system, the surface of the microchannel is a hydrophobic PDMS surface, for an oil / water or oil / oil system, the surface of the microchannel needs to be integrated with a PVA coating, so that the channel surface can be changed from the original hydrophobicity to hydrophilicity, which is beneficial to the formation of an oil / water or oil / oil droplet dispersion system. By whether to integrate the PVA coating, different dispersion systems can be finally designed and prepared.

[0048] Specifically, as shown in Figure 5As shown, the processing design of the microdroplet chip of the embodiment is that SU-83050 is used as a positive film, MEMS high-precision ultraviolet lithography is used to process the shape, finally PDMS is used to cast a negative mold, a microdroplet chip is formed by using plasma activation process and glass sheet bonding, finally molten metal indium is used as a flow channel electrode, a wire is connected to an external electric field control system, and finally a microdroplet digital control system is formed. For the oil / water system and the oil / oil system, PVA solution is introduced into the microchannel, and after heating and evaporation, a PVA film is formed on the surface of the channel, so as to promote the stability of the oil / water and oil / oil system. The specific steps are as follows:

[0049] SU-83050 positive film processing flow

[0050] Step one: spin-coat 4-inch 500-μm-thick silicon wafer with SU-83050 for 50 μm, and obtain SU-8 patterned mask by using patterned lithography.

[0051] PDMS experimental part processing flow

[0052] Step one: pour PDMS onto the SU-8 positive film, and after baking at 80°C for 2 h, peel off the PDMS from the SU-8 positive film.

[0053] Step two: punch the peeled PDMS, and after cleaning, bond the PDMS and the glass sheet by using plasma activation process.

[0054] Step three: introduce metal indium into the prepared electrode channel for melting and filling, and then use a wire to lead out to the external power system.

[0055] PVA coating processing flow

[0056] Step one: prepare a PVA solution with a mass fraction of 10%, introduce the solution into the microchannel of the chip, blow off the excess liquid after standing for about 30 min, and bake at 120°C to form a PVA coating on the surface of the channel, which is beneficial to the stability of the oil / water and oil / oil dispersion system.

[0057] As Figure 6As shown, the connection relationship and logical relationship of the microdroplet digital control system of the microdroplet chip are as follows: first, place the completed microdroplet chip on the inverted microscope 6.13, observe the droplet generation area and droplet control area and fix them, and continue to record through the high-speed camera 6.12, and upload the acquired droplet conditions to the data acquisition system 6.15 in real time. Then, connect the multiple inlets of the microdroplet chip with the corresponding liquid in the syringe through the polytetrafluoroethylene conduit 6.16, place the syringe on the high-precision syringe pump, and use the polytetrafluoroethylene conduit 6.16 for droplet collection at the outlet, and collect into the liquid storage tank 6.14. The electrode part of the microdroplet chip is connected with the high-voltage power amplifier 6.11 through a wire, the input end of the high-voltage power amplifier 6.11 is connected with the output end of the signal generator 6.10, so as to complete the connection of the digital control system. At the beginning of the experiment, first open the high-precision flow pump for parameter setting, so that the liquid is introduced into the chip, and after the fluid interface is stable, the multi-component droplet generation module reaches a stable state, then open the signal generator 6.10 and the high-voltage power amplifier 6.11, set the voltage, frequency and amplification multiple, start the voltage control module, the electric field starts to act, and the multi-component droplet digital control module starts to act on the generated droplets, through the adjustment of various parameters, the change of droplet components, the control of droplet size, the action of behavior, etc. can be realized, and finally the multi-component monodisperse microdroplet digital control system is realized.

[0058] The above is only the preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto, any person skilled in the art can easily think of changes or replacements within the technical range disclosed in the present application, which should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A multi-component monodisperse microdroplet digital electronic control system, characterized by, The system comprises: a multi-component droplet generation module for obtaining microdroplets by controlling the flow ratio between the dispersed phase and the continuous phase; a multi-component droplet digital control module for controlling the deformation, movement and fusion of the microdroplets by a combination of several pointed electrodes and flat electrodes; the multi-component droplet generation module and the multi-component droplet digital control module are connected through a flow channel filled with PVA solution and are both located on a microdroplet chip; the multi-component droplet generation module comprises several discrete droplet generation units; the discrete droplet generation unit comprises several groups of dispersed phase, and the proportion of the several groups of dispersed phase is controlled to adjust the component structure of the formed droplets; the outside of the discrete droplet generation unit comprises several groups of continuous phase fluid, and the several groups of continuous phase fluid are used to obtain microdroplets by shearing the formed droplets; the microdroplet digital control system further comprises a liquid input module and a voltage control module; the liquid input module comprises several microinjectors, and the several microinjectors are respectively connected to the several inlets of the multi-component droplet generation module through polytetrafluoroethylene conduits; the voltage control module comprises a high-power amplifier and a signal generator, the positive electrode of the high-power amplifier is connected to the pointed electrode, and the negative electrode of the high-power amplifier is connected to the flat electrode; the voltage and frequency of the high-power amplifier are controlled by the signal generator.

2. A multi-component monodisperse microdroplet digital electronic control method, characterized in that, The system according to claim 1, comprising the following steps: placing the microdroplet chip on an inverted microscope and fixing it, passing liquid into the microdroplet chip through several microinjectors, so that the multi-component droplet generation module reaches a stable state and generates microdroplets; adjusting the parameters of the voltage control module to control the generated microdroplets by the multi-component droplet digital control module; the voltage control module comprises a high-power amplifier and a signal generator connected to each other; the preparation process of the microdroplet chip further comprises passing PVA solution into the flow channel of the microdroplet chip to form a PVA coating on the surface of the flow channel; the process of generating microdroplets by the multi-component droplet generation module comprises adjusting the proportion of the several groups of dispersed phase in the multi-component droplet generation module to obtain droplets, and then shearing the droplets by the several groups of continuous phase fluid in the multi-component droplet generation module to obtain microdroplets; the process of controlling the generated microdroplets by the multi-component droplet digital control module comprises placing the pointed electrode and the flat electrode in the multi-component droplet digital control module in different flow regions with different flow channel widths to control the deformation, movement and fusion of the microdroplets; the process of adjusting the parameters of the voltage control module comprises adjusting the voltage and frequency of the high-power amplifier by the signal generator, and when the preset voltage and frequency values are reached, the generated electric field acts on the multi-component droplet digital control module, and the generated microdroplets are controlled based on the multi-component droplet digital control module.

3. The multi-component monodisperse microdroplet digital control method according to claim 2, characterized in that, The preparation process of the microdroplet chip comprises the following steps: spin-coating SU-8 glue on a silicon wafer as a positive film; after photoetching and developing on the positive film, pouring PDMS into the positive film for casting and inverse molding; finally, based on a plasma activation process, bonding the peeled PDMS and the glass wafer to form a microdroplet chip, and based on molten metal indium, preparing a flow channel electrode on the microdroplet chip.

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