A gravity-driven automatic single-droplet generation device and method based on three-way valve control.

Abstract

This invention provides a gravity-driven automatic single-droplet generation device and method based on three-way valve control, comprising: a liquid level control module, a three-way valve switching control module, a whole-machine control system, three containers, a three-way valve, and a microfluidic chip; the liquid level control module is used to control the liquid level of the oil / water two-phase system, including three control units, one of which controls the liquid level of one group of water phases, and the other two control units control the liquid level of two groups of oil phases respectively; the three-way valve switching control module uses an electric device or an electromagnetic control structure to control the switching of the three-way valve; this invention overcomes the technical difficulty of generating microdroplets at a relatively slow speed in existing technologies, and also solves the problem that existing droplet microfluidic technology cannot generate only one microdroplet at a time as needed.

Description

Technical Field

[0001] This invention relates to the field of droplet microfluidics and its biological applications, and in particular to a gravity-driven automatic single droplet generation device and method based on a three-way valve control. Background Technology

[0002] Microdroplets have a wide range of applications in fields such as biology, chemistry, materials science, and engineering. Examples include commercially available microdroplet digital PCR systems and droplet microfluidic systems that use microdroplets as microreactors to detect and screen chemical substances.

[0003] In different applications, people have different requirements for droplet generation speed, droplet size, and the practicality of droplet generation system. In some applications, it is often necessary for the droplet generation system to generate microdroplets at a relatively slow speed and to control the generation of only a single droplet at a certain time as needed, so as to combine with other technologies.

[0004] Traditional pump-driven microdroplet preparation systems are cumbersome to operate and typically generate a large number of microdroplets very quickly, leaving them helpless when the requirement is to generate only one microdroplet at a given time. Summary of the Invention

[0005] To overcome the shortcomings of the prior art, the present invention provides a gravity-driven automatic single droplet generation device and method based on three-way valve control, which overcomes the technical problem that the prior art cannot generate microdroplets at a relatively slow speed, and at the same time solves the problem that the existing droplet microfluidic technology cannot generate only one microdroplet at a certain time as needed.

[0006] The technical solution adopted by this invention to solve the above-mentioned technical problems is: a gravity-driven automatic single droplet generation device and method based on three-way valve control, wherein:

[0007] A gravity-driven automatic single-droplet generation device based on a three-way valve control includes:

[0008] Liquid level control module, three-way valve switching control module, whole machine control system, three containers, three-way valve and microfluidic chip;

[0009] The liquid level control module is used to control the liquid level of the oil / water two-phase system. It includes three control units, one of which controls the liquid level of one group of water phases, and the other two control units control the liquid level of the two groups of oil phases respectively.

[0010] As an example, the oil / water two-phase liquid surface can also be replaced by oil / gas or water / gas, two mutually incompatible phases.

[0011] As an example, the liquid level control module adopts one of the following: an electric linear guide, a pneumatic device, or a hydraulic cylinder.

[0012] The three-way valve switching control module uses an electric actuator or electromagnetic control structure to control the switching of the three-way valve.

[0013] As an example, the three-way valve switching control module can also use a multi-way control valve device to control the switching of the three-way valve.

[0014] The overall control system is used to control the liquid level control module and the three-way valve switching control module, and to power the entire device;

[0015] Of the three containers, one container is used to store the medium water, and the other two containers are used to store the medium oil.

[0016] One port of the three-way valve is used to connect to one container for storing oil, and the other port is used to connect to another container for storing oil. By switching the three-way valve, the level of the oil phase can be controlled to cut off the water phase. Alternatively, the level of the water phase can be controlled by the three-way valve and cut off by the oil phase. The third port of the three-way valve is used to connect to the tail end of the microfluidic chip's T-port.

[0017] The left front end of the microfluidic chip T-port is connected to a water storage container, and the right front end of the microfluidic chip T-port is used for the discharge of micro-droplets.

[0018] Control method for a gravity-driven automatic single-droplet generation device based on a three-way valve:

[0019] Step 1: Adjust the liquid level of the oil and water phases using the liquid level control module, thereby controlling the pressure of the oil and water phases.

[0020] Step 2: When the three-way valve is switched to one oil phase, the oil pressure at the T port of the microfluidic chip is greater than the water pressure, and the water phase cannot flow through the T port.

[0021] When the three-way valve is switched to the second oil phase, the oil pressure at the T port of the microfluidic chip is less than the water pressure, and the water phase flows through the T port. When the three-way valve is switched back to the first oil phase, the oil pressure at the T port is once again greater than the water pressure, which will cut off the water flow through the T port and form a microdroplet.

[0022] By controlling the height of the oil and water phases and switching the three-way valve, it is possible to easily meet the needs of generating a microdroplet at a certain moment, as well as the needs of generating microdroplets at a slower speed.

[0023] Step 3: The parameter settings for the aqueous phase, the first oil phase, and the second oil phase must meet the following requirements:

[0024] The pressure of the oil phase in the second channel is less than the pressure of the water phase, which is less than the pressure of the oil phase in the first channel.

[0025] Pw = ρw﹒ g﹒ △hw;

[0026] Where: Pw is the water phase pressure, ρw is the density of water, and Δhw is the height of the water phase liquid level;

[0027] Po1 = ρo﹒ g﹒ △ho1;

[0028] Where: Po1 is the oil phase pressure of one path, ρo is the density of the oil, and Δho1 is the oil phase liquid level height of one path;

[0029] Po2 = ρo﹒ g﹒ △ho2;

[0030] Where: Po2 is the pressure of the two oil phases, ρo is the density of the oil, and Δho2 is the liquid level of the two oil phases;

[0031] As an example, the medium oil used in the first and second oil phases is the same.

[0032] The beneficial effects of this invention are:

[0033] 1. The liquid level control module and the three-way valve switching control module are the key to generating a single droplet at a certain moment. The above structure is simple, reliable and ingeniously designed.

[0034] 2. Only one microdroplet can be generated at any given time, depending on actual needs.

[0035] 3. By using gravity to drive the generation of microdroplets at a relatively slow speed, the technical challenge of generating microdroplets has been overcome. Attached Figure Description

[0036] Figure 1 This is an overall structural diagram of the gravity-driven automatic single-droplet generation device based on three-way valve control of the present invention.

[0037] Figure 2 This is a schematic diagram illustrating the principle of the gravity-driven automatic single-droplet generation device based on three-way valve control of the present invention.

[0038] Figure 3 This is a schematic diagram of the oil-water critical surface of the gravity-driven automatic single-droplet generation device based on a three-way valve control according to the present invention.

[0039] Figure 4 This is an experimental data diagram of the gravity-driven single droplet formation process controlled by a three-way valve in the control method of the gravity-driven single droplet automatic generation device based on the three-way valve control of the present invention.

[0040] Figure 5 This invention relates to a control method for a gravity-driven automatic single-droplet generation device based on a three-way valve, where a three-way valve controls gravity drive combined with optical tweezers to form single-cell droplet encapsulation. Detailed Implementation

[0041] The preferred embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0042] Reference Figures 1 to 5 As shown, a gravity-driven automatic single-droplet generation device and method based on three-way valve control is disclosed, wherein:

[0043] A gravity-driven automatic single-droplet generation device based on a three-way valve control includes:

[0044] Liquid level control module 101, three-way valve switching control module 102, whole machine control system 103, three containers, three-way valve 204, and microfluidic chip 205;

[0045] The liquid level control module 101 is used to control the liquid level of the oil / water two-phase system. It includes three control units, one of which is used to control the liquid level of a group of water phases 201, and the other two control units are used to control the height of the two groups of oil phases respectively.

[0046] As an example, the oil / water two-phase liquid surface can also be replaced by oil / gas or water / gas, two mutually incompatible phases.

[0047] As an example, the liquid level control module 101 adopts one of the following: an electric linear guide, a pneumatic device, or a hydraulic cylinder.

[0048] The three-way valve switching control module 102 uses an electric device or an electromagnetic control structure to control the switching of the three-way valve 204.

[0049] As an example, the three-way valve switching control module 102 can also use a multi-way control valve device to control the switching of the three-way valve 204.

[0050] The overall control system is used to control the liquid level control module and the three-way valve switching control module, and to power the entire device;

[0051] Of the three containers, one container is used to store the medium water, and the other two containers are used to store the medium oil.

[0052] One port of the three-way valve 204 is used to connect to one container for storing oil, and the other port is used to connect to another container for storing oil. By switching the three-way valve 204, the level of the oil phase can be controlled to cut off the water phase. Alternatively, the level of the water phase can be controlled by the three-way valve 204 and cut off by the oil phase. The third port of the three-way valve is used to connect to the tail end of the microfluidic chip 205T port.

[0053] The left front end of the microfluidic chip 205T port is connected to a water storage container, and the right front end of the microfluidic chip T port is used for the discharge of micro-droplets.

[0054] Control method for a gravity-driven automatic single-droplet generation device based on a three-way valve:

[0055] Step 1: Adjust the liquid level of the oil and water phases through the liquid level control module 101, thereby controlling the pressure of the oil and water phases;

[0056] Step 2: When the three-way valve 204 switches to one oil phase 202, the oil pressure at the T port of the microfluidic chip 205 is greater than the water pressure, and the water phase cannot flow through the T port.

[0057] When the three-way valve 204 is switched to the second oil phase 203, the oil pressure at the T port of the microfluidic chip 205 is less than the water pressure, and the water phase flows through the T port; when the three-way valve 204 is switched to the first oil phase 202, the oil pressure at the T port is once again greater than the water pressure, which will cut off the water flow through the T port and form a microdroplet.

[0058] By controlling the height of the oil and water phases and switching the three-way valve 204, it is possible to easily meet the needs of generating a microdroplet at a certain moment and the needs of generating microdroplets at a slower speed.

[0059] Step 3: The parameter settings for aqueous phase 201, first-stage oil phase 202, and second-stage oil phase 203 must meet the following requirements:

[0060] The pressure of the oil phase in the second channel is less than the pressure of the water phase, which is less than the pressure of the oil phase in the first channel.

[0061] Pw = ρw﹒ g﹒ △hw;

[0062] Where: Pw is the water phase pressure, ρw is the density of water, and Δhw is the height of the water phase liquid level;

[0063] Po1 = ρo﹒ g﹒ △ho1;

[0064] Where: Po1 is the oil phase pressure of one path, ρo is the density of the oil, and Δho1 is the oil phase liquid level height of one path;

[0065] Po2 = ρo﹒ g﹒ △ho2;

[0066] Where: Po2 is the pressure of the two oil phases, ρo is the density of the oil, and Δho2 is the liquid level of the two oil phases;

[0067] As an example, the medium oil used in the first oil phase 202 and the second oil phase 203 is the same.

[0068] To better illustrate the working principle of the present invention, specific embodiments are provided below:

[0069] Example 1: The slow generation of droplets is illustrated by controlling the height of the oil and water phases and switching the three-way valve;

[0070] First, the operator places water and oil into three containers, which are then placed vertically and connected to the liquid level control module 101.

[0071] Secondly, one port of the three-way valve 204 is used to connect to one oil storage container, and the other port is used to connect to another oil storage container. By switching the three-way valve 204, the level of the oil phase can be controlled to cut off the water phase. Alternatively, the level of the water phase can be controlled by the three-way valve 204 and cut off by the oil phase. The third port of the three-way valve is used to connect to the tail end of the microfluidic chip 205T port.

[0072] The liquid level control module 101 controls the oil and water levels so that the pressure generated by one oil phase is higher than that of water, and the pressure generated by the second oil phase is lower than that of water.

[0073] Finally, by controlling the switching three-way valve 204, this can be achieved. Figure 4 The microdroplet generation process is shown; the mechanical switching of the three-way valve requires a time response. By repeatedly controlling the switching of the three-way valve 204, the stable generation of droplets at a minimum rate of 1 droplet / s can be achieved.

[0074] Example 2: Taking the control of the oil and water phase heights, the switching of the three-way valve, and the combination of optical tweezers technology to encapsulate single-cell droplets as an example;

[0075] First, the user should refer to Example 1 for preliminary preparations;

[0076] Secondly, cell fluid is added to the aqueous phase, and the target single cell is clamped by optical tweezers and moved to the oil-water interface in the flow channel. During this process, the oil phase pressure is kept higher than the aqueous phase pressure.

[0077] Finally, by controlling the switching three-way valve 204 to make the oil phase pressure lower than the aqueous phase pressure, the aqueous phase will continue to move forward. At the same time, the optical tweezers are controlled to manipulate the cells to follow the aqueous phase forward. When the cells reach the T-port, the three-way valve 204 is switched again, thus achieving the desired effect. Figure 5 The diagram illustrates the process of microdroplets encapsulating single cells during cell generation.

[0078] In this second embodiment, by using the real-time switching control of the three-way valve 204 in conjunction with optical tweezers technology, it is possible to achieve the encapsulation of a single cell by a single droplet.

[0079] The liquid level control module 101 and the three-way valve switching control module 102 are key to generating a single droplet at a certain moment. The above structure is simple, reliable and ingeniously designed. By driving with gravity, the technical challenge of generating microdroplets at a relatively slow speed is achieved.

[0080] The above description is only a preferred embodiment of the present invention. It should be understood that the above description of the embodiments is only for the purpose of helping to understand the method and core idea of ​​the present invention, and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, etc. made within the idea and principle of the present invention should be included within the scope of protection of the present invention.

Claims

1. A gravity-driven automatic single-droplet generation device based on a three-way valve control, characterized in that, include: Liquid level control module, three-way valve switching control module, whole machine control system, three containers, three-way valve and microfluidic chip; The liquid level control module is used to control the liquid level of the oil / water two-phase system. It includes three control units, one of which controls the liquid level of one group of water phases, and the other two control units control the liquid level of the two groups of oil phases respectively. The three-way valve switching control module uses an electric device to control the switching of the three-way valve; The overall control system is used to control the liquid level control module and the three-way valve switching control module, and to power the entire device; Of the three containers, one container is used to store the medium water, and the other two containers are used to store the medium oil. One port of the three-way valve is used to connect to a container for storing oil, and the other port of the three-way valve is used to connect to another container for storing oil. The water phase is cut off by controlling the oil phase level by switching the three-way valve; the three ports of the three-way valve are used to connect to the tail end of the microfluidic chip T port. The left front end of the microfluidic chip T-port is connected to a water storage container, and the right front end of the microfluidic chip T-port is used for the discharge of micro-droplets. The two sets of oil phases include: one oil phase and two oil phases. When the three-way valve is switched to the one oil phase, the oil pressure at the T port of the microfluidic chip is greater than the water pressure, and the water phase cannot flow through the T port. When the three-way valve is switched to the second oil phase, the oil pressure at the T port of the microfluidic chip is less than the water pressure, and the water phase flows through the T port. When the three-way valve is switched back to the first oil phase, the oil pressure at the T port is once again greater than the water pressure, which will cut off the water flow through the T port and form a microdroplet.

2. The gravity-driven automatic single-droplet generation device based on three-way valve control according to claim 1, characterized in that, The oil / water two-phase liquid surface is replaced by two immiscible phases, oil / gas or water / gas.

3. The gravity-driven automatic single-droplet generation device based on three-way valve control according to claim 1, characterized in that, The liquid level control module adopts one of the following: an electric linear guide, a pneumatic device, or a hydraulic cylinder.

4. The gravity-driven automatic single-droplet generation device based on three-way valve control according to claim 1, characterized in that, The three-way valve switching control module adopts a multi-way control valve device.

5. The control method for the gravity-driven automatic single-droplet generation device based on a three-way valve control as described in claim 1, characterized in that, Includes the following steps: Step 1: Adjust the liquid level of the oil and water phases using the liquid level control module, thereby controlling the pressure of the oil and water phases. Step 2: When the three-way valve is switched to one oil phase, the oil pressure at the T port of the microfluidic chip is greater than the water pressure, and the water phase cannot flow through the T port. When the three-way valve is switched to the second oil phase, the oil pressure at the T port of the microfluidic chip is less than the water pressure, and the water phase flows through the T port. When the three-way valve is switched back to the first oil phase, the oil pressure at the T port is once again greater than the water pressure, which will cut off the water flow through the T port and form a microdroplet. By controlling the height of the oil and water phases and switching the three-way valve, it is possible to easily meet the needs of generating a microdroplet at a certain moment and the needs of generating microdroplets at a slower speed. Step 3: The parameter settings for the aqueous phase, the first oil phase, and the second oil phase must meet the following requirements: The pressure of the oil phase in the second channel is less than the pressure of the water phase, which is less than the pressure of the oil phase in the first channel. Pw = ρw﹒ g﹒ △hw; Where: Pw is the water phase pressure, ρw is the density of water, and Δhw is the height of the water phase liquid level; Po1 = ρo﹒ g﹒ △ho1; Where: Po1 is the oil phase pressure of one path, ρo is the density of the oil, and Δho1 is the oil phase liquid level height of one path; Po2 = ρo﹒ g﹒ △ho2; Where: Po2 is the pressure of the two oil phases, ρo is the density of the oil, and Δho2 is the liquid level of the two oil phases.

6. The control method according to claim 5, characterized in that: The first and second oil phases use the same medium oil.

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