CN114317214A - A kind of micro liquid separation method based on interface contact and application of the method - Google Patents

Abstract

The invention discloses a micro-liquid separation method based on interface contact, comprising the following steps: 1. taking a container and a micro-pipeline with an opening, the micro-pipeline is filled with a first liquid, and the first liquid is a liquid containing biochemical substances , the micro-pipe is located above the container; ② the micro-pipe and the container move relative to each other, that is, the micro-pipe does not move, and the container moves upward, or the container does not move, the micro-pipe moves downward, and the first liquid is located at the opening of the micro-pipe 3. The first liquid at the opening of the micro-channel contacts the surface of the container, so that the first liquid at the opening of the micro-channel is separated from the micro-channel and remains on the container; 4. After the first liquid is left on the container, the micro-channel and the container are again A relative movement occurs, causing the micro-channels to move away from the container. Applications of this method include omics analysis of single cells, culture of single cells, and mass spectrometry analysis of single droplets. It has the advantages of simple equipment, simple operation and low cost.

Description

A kind of micro liquid separation method based on interface contact and application of the method

technical field

The invention relates to the field of micro liquid distribution, in particular to a micro liquid separation method based on interface contact and the application of the method.

Background technique

Injecting or jetting micro-liquids through microchannels such as capillaries to separate the liquids into the macroscopic world such as substrates, dishes, oil phase, water, etc., is a simple and convenient way of micro-liquid separation. When detached from the capillary, it is affected by various forces such as surface tension and adhesion, which makes it difficult to achieve natural dripping of trace liquids, and it is difficult to achieve accurate quantification of trace liquids. Usually, the existing technology uses piezoelectric ceramics, thermal shock expansion, high-voltage electrospray, ultrasonic and other special methods to excite the liquid to increase the kinetic energy of the liquid detaching from the surface of the microchannel to overcome the influence of surface tension, and through the microchannel outlet The special structure and silanization or coating treatment can reduce the adhesion of the liquid on the nozzle and realize the separation of trace liquids.

However, the above-mentioned method relies on relatively complex equipment and devices, and the operation is complicated and the cost is relatively high.

SUMMARY OF THE INVENTION

In the first aspect, the application provides a method for separating trace liquids based on interfacial contact, using the following technical solutions:

A method for separating trace liquids based on interfacial contact, comprising the following steps:

① Take a container and a micro-pipeline with an opening, the micro-pipe flow is filled with a first liquid, the first liquid is a liquid containing biochemical substances, and the micro-pipe is located above the container;

②The micro-pipe and the container move relative to each other, that is, the micro-pipe does not move, and the container moves upward, or the container does not move and the micro-pipe moves downward. At this time, the first liquid is located in the micro-pipe. opening;

3. the first liquid at the opening of the microchannel is in contact with the surface of the container, so that the first liquid at the opening of the microchannel is separated from the microchannel and remains on the container;

④ After the first liquid remains on the container, the micro-pipe and the container move relative to each other again, so that the micro-pipe and the container are kept away from each other.

By adopting the above technical solution, through steps ① to ④, the surface tension and adhesion force of the liquid at the outlet of the microchannel are overcome by utilizing the interfacial energy and fluid shear force of the trace liquid at the gas-liquid and gas-solid interface exchanges, The micro-liquid flowing out of the mouth of the micro-channel can be smoothly separated from the micro-channel and separated to a specific position. The method provided by the present application does not need to rely on particularly complicated equipment, is simple and feasible, can realize the transfer of a small amount of liquid to a specific container, realizes the purpose of separating a small amount of structure to a macro-scale equipment, and facilitates subsequent operations; and has equipment The structure is simple, the operation is easy, and the cost is greatly reduced.

Optionally, the microchannel is one of a single single-core capillary, a single multi-core capillary, an array capillary, a microfluidic single-channel or a microfluidic multi-channel array.

By adopting the above technical solution, the micro-channel can be selected according to the actual situation, so that the influence of the micro-channel on the separation of the micro-liquid can be reduced.

Optionally, the micropipe is arranged vertically, and the upper end of the micropipe is connected with a fluid driving device, the fluid driving equipment continuously or intermittently generates the first liquid flow, the opening of the micropipe is located at the lower end of the micropipe, and the opening of the micropipe is located at the lower end of the micropipe. The lower end can be in contact with the container surface.

By adopting the above technical solution, the fluid driving device can generate the first liquid, and at the same time, the first liquid can also have fluidity, so that the first liquid can enter and flow out of the microchannel.

Optionally, the fluid-driven device is one of a peristaltic pump, a syringe pump, a pressure-driven pump, a pneumatic-driven pump, or an electroosmotic-driven pump.

By adopting the above technical solution, the type of the fluid driving device can be selected as required, so that the flow speed of the first liquid can be more in line with the requirements.

Optionally, the size of the opening of the microchannel is between 0.1 micron and 1 mm.

By adopting the above technical solution, the micro-channel can be adapted to different types of first liquids, so that the first liquid can form droplets at the opening of the micro-channel.

Optionally, the openings of the micro-channels are treated with low surface energy.

By adopting the above technical solution, the opening of the micro-channel treated with low surface energy can increase the hydrophobicity at the opening of the micro-channel, so that the droplets formed by the first liquid can better escape from the micro-channel.

Optionally, the container is a liquid storage tank or a solid plate, and the second liquid is stored in the container.

When the container is a liquid storage tank for storing the second liquid, the second liquid in the liquid storage tank is an aqueous phase or an oil phase;

When the container is a solid plate, when the solid plate is a glass plate, agarose solid plate, or a metal plate, the first liquid is easily attached to the surface of the fixed plate.

By adopting the above technical solution, different types of containers and different types of second liquids can be selected according to the actual situation, so that the separated first liquid droplets are more likely to exist in the second liquid, and according to the subsequent needs, you can choose Use that kind of container.

Optionally, when the first liquid is an aqueous phase, the first liquid contains one or more biochemical substances among bacteria, cells, microspheres, nucleic acids, enzymes, and ions;

When the first liquid is an oil phase, the first liquid contains one or both of droplets and particles.

By adopting the above technical solution, when the first liquid is an aqueous phase, experimental operations such as single-cell isolation and culture, droplet PCR, enzyme activity screening, and protein crystallization can be realized for different biochemical substances in the aqueous solution; When a liquid is an oil phase, the droplets in the oil phase can be dispersed and separated into a single droplet for downstream analysis.

Optionally, in the steps ② and ④, the means for driving the micropipes or the container to move relative to each other is one of a moving operation, a manual translation stage operation or an automatic moving stage.

By adopting the above technical solution, there are various driving means that can be selected. In actual work, the existing equipment can be preferentially used to drive the movement of the micropipe or the container, and there is no need to purchase additional equipment, which can reduce the cost.

In the second aspect, the application provides a kind of application of the micro-liquid separation method based on interface contact, adopts the following technical scheme:

Application of an interfacial contact-based microfluidic separation method for single-cell omics analysis, single-cell culture, and single-droplet mass spectrometry.

By adopting the above technical solutions, the micro-liquid separation method can be applied to the omics analysis of a single cell, the culture of a single cell, and the mass spectrometry analysis of a single droplet, so that the application range of the micro-liquid separation method is wider.

In summary,

1. Using the interfacial energy and fluid shear force of the trace liquid at the gas-liquid, gas-solid interface exchange, it overcomes the surface tension and adhesion of the liquid at the outlet of the microchannel, so that the trace liquid flowing out of the mouth of the microchannel can be smoothly Detach the micropipette and separate to a specific location. Based on this method combined with simple chips and devices, the separation of single cells and the separation of single droplets can be achieved, and because the separation into the macroscopic world can be easily coupled with downstream operations, such as single-cell analysis, culture and other operations;

2. The micro-liquid separation method can be applied to the omics analysis of a single cell, the culture of a single cell, and the mass spectrometry analysis of a single droplet, so that the application range of the micro-liquid separation method is wider.

Description of drawings

Fig. 1 is a flow chart of cell separation in application example 1.

Fig. 2 is a flow chart of cell separation in Application Example 2.

FIG. 3 is a flow chart of cell separation in application example 3. FIG.

Description of reference numbers:

1. Quartz capillary; 2. First liquid; 3. PCR tube; 4. Second liquid; 5. Cell; 6. ITO glass.

Detailed ways

The embodiment of the present application discloses a method for separating trace liquids based on interface contact, comprising the following steps:

① Take a container and a micro-pipeline with an opening, the micro-pipe flow is filled with a first liquid 2, and the first liquid 2 is a liquid containing biochemical substances, and the micro-pipeline is located above the container;

② The micro-pipe and the container move relative to each other, that is, the micro-pipe does not move, and the container moves upward, or the container does not move and the micro-pipe moves downward, at this time, the first liquid 2 is located in the micro-pipe the opening;

③ The first liquid 2 at the opening of the microchannel is in contact with the surface of the container, so that the first liquid 2 at the opening of the microchannel is separated from the microchannel and remains on the container.

④ After the first liquid 2 remains on the container, the micro-pipe and the container move relative to each other again, so that the micro-pipe and the container are kept away from each other.

Through the above four steps, the interfacial energy and fluid shear force of the trace liquid at the gas-liquid and gas-solid interface exchange can be used to overcome the surface tension and adhesion of the liquid at the outlet of the microchannel, so that the flow out of the microchannel orifice can be achieved. The micro-liquid can be successfully separated from the micro-channel and separated to a specific position, realizing the separation of the micro world into the macro world, which is convenient for coupled downstream operations, such as the separation of a single cell 5, and the subsequent analysis and cultivation of a single cell 5 .

The microchannel in step ① can be one of a single single-core capillary, a single multi-core capillary, an array capillary, a microfluidic single-channel or a microfluidic multi-channel array; the use of the microchannel is based on the actual separation process. It needs to be selected to facilitate the separation operation.

The micro-pipe is vertically arranged directly above the container, and the upper end of the micro-pipe is connected with a fluid driving device. The fluid-driving device fills the micro-pipe with the first liquid 2, and the lower end of the micro-pipe is in contact with the container, so that the first liquid 2 and the container are in contact with each other. In contact, the first liquid 2 remains on the container in the form of droplets.

The fluid-driven device can be one of a peristaltic pump, a syringe pump, a pressure-driven pump, a pneumatic-driven pump, or an electroosmotic-driven pump, and is selected according to the actual situation of the first liquid 2. The fluid-driven device can indirectly or continuously generate the first fluid. The liquid 2 is poured into the micro-channel to realize the pouring of the first liquid 2 .

The size of the opening of the micro-channel is between 0.1 micron and 1 mm, so that the first liquid 2 can better produce drop-shaped first liquid 2 at the opening of the micro-channel; the opening of the micro-channel is treated with low surface energy, which can The hydrophobicity at the opening of the microchannel is improved, so that the droplet-shaped first liquid 2 can be better separated from the microchannel.

The surface energy treatment uses dimethyldichlorosilane solvent to fumigate the opening of the micropipe, so as to achieve the purpose of reducing the surface energy of the opening of the micropipe, so that the droplet-shaped first liquid 2 can be released from the micropipe more quickly. Separation at the opening.

The first liquid 2 in step 1 can be an aqueous phase or an oil phase. When the first liquid 2 is an aqueous phase, it can realize the separation and culture of single cells 5, droplet PCR, and different biochemical substances in the aqueous solution. Enzyme activity screening, protein crystallization and other experimental operations; when the first liquid 2 is the oil phase, the droplets in the oil phase can be dispersed and separated into a single droplet for downstream analysis. The first liquid 2 can be selected according to actual needs, which can better separate the trace liquid.

When the first liquid 2 is an aqueous phase, the first liquid 2 contains one or more biochemical substances among bacteria, cells 5, microspheres, nucleic acids, enzymes, and ions; when the first liquid 2 is an oil phase, the first liquid 2 Contains one or both of droplets and particles.

The container in step 1. can be a liquid storage tank or a solid plate, and the second liquid 4 is stored in the container. When the container is a liquid storage tank for storing the second liquid 4, the second liquid 4 in the liquid storage tank is an aqueous phase or an oil phase. ;

When the container is a solid plate, when the solid plate is a glass plate, agarose solid plate, or a metal plate, the first liquid 2 is easily attached to the surface of the fixed plate; when the container is a liquid storage tank, the second liquid in the liquid storage tank When 4 is an aqueous phase, such as a liquid medium, by this method, the single cell 5 in the first liquid 2 can be separated into the liquid medium for the cultivation of the single cell 5; when the second liquid 4 in the liquid storage tank is an oil phase , by this method, the single cells 5 in the first liquid 2 can be separated into oil, so as to facilitate the subsequent single cell 5 omics analysis. When the container is a solid plate, such as an agarose solid plate, the cells 5 in the first liquid 2 can be dispersed to a specific position on the solid plate for subsequent culture; when the solid plate is a metal plate, the first A liquid 2 is separated onto a metal plate for subsequent mass spectrometry analysis.

In ② and ④, to drive the movement of the micropipe or container, the means used can be manual operation, manual translation stage operation or automatic moving stage operation control mode. Purpose.

Application example 1: The micro-liquid separation method based on interface contact is applied to the 5-omics analysis of single cells. The specific method is as follows;

① Selection: Quartz capillary 1 is selected for the micro-channel, cell 5 suspension is selected for the first liquid 2, the container is a liquid storage tank, and the PCR tube 3 is used as a liquid storage tank. Fluid driven equipment employs a syringe pump. In this application example, the relative motion of the micro-pipe and the container is realized by driving the container to move, so a three-dimensional moving platform, ie, an automatic moving platform, is used to drive the container to move.

②Assembly: There is also a microfluidic chip between the quartz capillary 1 and the syringe pump, and the syringe pump is connected to the sample inlet of the microfluidic chip through a hose; the upper end of the quartz capillary 1 is connected to the sample outlet of the microfluidic chip.

③Experiment preparation: place the quartz capillary 1 above the PCR tube 3, the PCR tube 3 is filled with 10 microliters of mineral oil, the PCR tube 3 is placed on the three-dimensional mobile platform, the microfluidic chip is placed on the chip rack, and the microfluidic The inside of the chip and the quartz capillary 1 is filled with an aqueous solution driven by a syringe pump.

④Separation of single cell 5: The microfluidic chip obtains a single cell 5. Driven by the fluid, the single cell 5 will flow into the quartz capillary 1 through the microfluidic sample outlet; the aqueous solution containing the single cell 5 reaches At the end of the quartz capillary 1, the three-dimensional moving platform drives the PCR tube 3 to move upward, causing the micropipe and the container, that is, the relative movement between the quartz capillary 1 and the PCR tube 3, and the aqueous solution containing the single cell 5 escapes from the quartz capillary 1 and enters the mineral oil. , to complete the isolation of single cells 5 .

⑤ Omics analysis: The single cells 5 are separated through steps ① to ④, and the single cells 5 are separated into a macroscopic container, which is easy to connect to the subsequent single cell 5 omics analysis. The genetic information of a single cell 5 can be obtained by sequencing.

In step 1, the second liquid 4 selects mineral oil, the density of mineral oil is smaller than that of water, the first liquid 2 separated into the liquid storage tank can sink to the bottom of the PCR tube 3, and the existence of the oil phase can prevent pollution and liquid. evaporation.

In step 4, the single cell 5 is obtained by dragging a single cell 5 using optical tweezers in the microfluidic chip to obtain the single cell 5. The obtained single cell 5 can flow with the fluid, that is, the aqueous solution, and the single cell 5 passes through the microfluidic chip. The sample outlet of the fluid control chip enters the quartz capillary 1. When a single cell 5 flows in the quartz capillary 1, the position of the single cell 5 can be judged by auxiliary optical means. When the aqueous solution containing the single cell 5 is in the quartz capillary 1 When a drop of cell 5 is formed at the end, that is, the lower end, the three-dimensional moving platform moves upward so that the mineral oil in the PCR can contact the drop-shaped aqueous solution at the end of the quartz capillary 1, that is, the drop of cell 5, and even make the quartz capillary 1 enter the liquid level of the mineral oil. Next, let the aqueous solution enter the mineral oil. During this movement, because of the interfacial energy and fluid shear force at the gas-liquid interface exchange, the aqueous solution at the end of the quartz capillary 1 can be successfully separated from the quartz capillary 1 and separated into the PCR tube. In the mineral oil in 3, a single cell 5 is contained in the aqueous solution at this time, and because the two phases of water and oil are incompatible, the trace liquid containing a single cell 5 will form a droplet in the PCR tube 3, which is driven by a three-dimensional moving platform. The PCR descends back to the initial position, thus accomplishing the purpose of separating individual cells 5 into macroscopic vessels.

If multiple single cells 5 need to be obtained, a new PCR tube 3 can be installed and replaced on the three-dimensional mobile platform, and then the new PCR tube 3 is controlled to repeat the above steps to complete the purpose of obtaining multiple single cells 5 .

Application example 2: The method of micro-liquid separation based on interface contact is applied to the culture of single cell 5, and the specific method is as follows;

①Select: Quartz capillary 1 is selected for the micro-pipeline, cell 5 suspension is selected for the first liquid 2, the container is a liquid storage tank, the PCR tube 3 is used as the liquid storage tank, and the second liquid 4 is selected from a liquid culture medium, which is separated into the second liquid medium. The single cells 5 in the liquid 4 can be directly cultured. The fluid driving device adopts a syringe pump. In this application example, the relative motion of the micro-pipe and the container is realized by driving the container to move. Therefore, a three-dimensional moving platform, that is, an automatic moving platform, is used to drive the container to move.

②Assembly: There is also a microfluidic chip between the quartz capillary 1 and the syringe pump, and the syringe pump is connected to the sample inlet of the microfluidic chip through a hose; the upper end of the quartz capillary 1 is connected to the sample outlet of the microfluidic chip.

③Experiment preparation: place the quartz capillary 1 above the PCR tube 3, the PCR tube 3 is filled with 10 microliters of culture medium, the PCR tube 3 is placed on the three-dimensional mobile platform, the microfluidic chip is placed on the chip rack, and the microfluidic control The inside of the chip and the quartz capillary 1 is filled with an aqueous solution driven by a syringe pump.

④Separation of single cell 5: The microfluidic chip obtains a single cell 5. Driven by the fluid, the single cell 5 will flow into the quartz capillary 1 through the microfluidic sample outlet; the aqueous solution containing the single cell 5 reaches At the end of the quartz capillary 1, the three-dimensional moving platform drives the PCR tube 3 to move upward, so that the micropipe and the container, that is, the quartz capillary 1 and the PCR tube 3, produce relative motion, and the aqueous solution containing the single cell 5 is separated from the quartz capillary 1 and enters the culture medium. , to complete the isolation of single cells 5 .

⑤Cultivation: A single tube of single cell 5 is realized, the single cell 5 is separated into a macroscopic container, and the PCR tube 3 only needs to be placed in an environment suitable for the growth of the single cell 5 for cultivation.

In step 4, the single cell 5 is obtained by dragging a single cell 5 using optical tweezers in the microfluidic chip to obtain the single cell 5. The obtained single cell 5 can flow with the fluid, that is, the aqueous solution, and the single cell 5 passes through the microfluidic chip. The sample outlet of the fluid control chip enters the quartz capillary 1. When a single cell 5 flows in the quartz capillary 1, the position of the single cell 5 can be judged by auxiliary optical means. When the aqueous solution containing the single cell 5 is in the quartz capillary 1 When a drop-shaped aqueous solution is formed at the lower end, the three-dimensional moving platform moves upward so that the medium in the PCR can contact the drop-shaped aqueous solution at the end of the quartz capillary 1, and even make the quartz capillary 1 enter below the liquid level of the medium, so that the aqueous solution enters the culture medium. In the base, during this movement, the aqueous solution at the end of the quartz capillary 1 can be successfully separated from the quartz capillary 1 and separated into the medium in the PCR tube 3 because of the interfacial energy and fluid shear force during the gas-liquid interface exchange. , at this time, the aqueous solution contains a single cell 5, and because the water and oil phases are incompatible, a small amount of liquid containing a single cell 5 will form a droplet in the PCR tube 3, and the three-dimensional mobile platform drives the PCR to descend back to the initial position , thus accomplishing the purpose of separating individual cells 5 into macroscopic vessels.

If multiple single cells 5 need to be obtained, a new PCR tube 3 can be installed and replaced on the three-dimensional mobile platform, and then the new PCR tube 3 is controlled to repeat the above steps to complete the purpose of obtaining multiple single cells 5 .

Application example 3: The micro-liquid separation method based on interfacial contact is applied to single-droplet mass spectrometry analysis, and the specific method is as follows;

① Selection: Quartz capillary 1 is selected for the micro-pipeline, oil phase is selected for the first liquid 2, the container is a solid flat plate, and ITO (indium tin oxide) glass plate is used, the second liquid 4 is selected from the cell liquid 5, and the fluid driving equipment adopts a syringe pump. The application example adopts the method of driving the container to move to realize the relative motion of the micro-pipe and the container, so a three-dimensional mobile platform, ie, an automatic mobile platform, is used to drive the container to move.

②Assembly: There is also a microfluidic chip between the quartz capillary 1 and the syringe pump, and the syringe pump is connected to the sample inlet of the microfluidic chip through a hose; the upper end of the quartz capillary 1 is connected to the sample outlet of the microfluidic chip.

③Experiment preparation: Place the quartz capillary 1 on the top of the ITO glass plate 6, the PCR tube 3 is filled with 10 microliters of culture medium, the PCR tube 3 is placed on the three-dimensional mobile platform, the microfluidic chip is placed on the chip rack, and the microfluidic The inside of the control chip and the quartz capillary 1 is filled with an aqueous solution driven by a syringe pump.

④Single droplet separation: The microfluidic chip obtains a single droplet with a single cell 5. Driven by the fluid, the single droplet will flow into the quartz capillary 1 through the microfluidic sample outlet; When the aqueous solution of the droplets reaches the end of the quartz capillary 1, the three-dimensional moving platform drives the PCR tube 3 to move upward, causing relative movement between the micropipe and the container, that is, the quartz capillary 1 and the PCR tube 3, and the aqueous solution containing a single droplet is separated from the quartz capillary. 1 Enter the medium to complete the separation of single droplets.

⑤ The single droplet separated on the ITO glass 6 is subjected to standard sample processing, and the subsequent time-of-flight mass spectrometry (MALDI-TOF MS) can be docked, and the mass spectrometry analysis of the substances in the single droplet can be realized.

In step (4), the acquisition of a single droplet is the controllable acquisition of a single droplet by the microfluidic chip. The obtained single droplet can flow with the fluid, that is, the oil phase, and the single droplet passes through the sample outlet of the microfluidic chip. Entering into the quartz capillary 1, when a single droplet flows in the quartz capillary 1, the droplet position of the oil phase containing the single droplet can be judged by auxiliary optical means. When the oil phase containing the single droplet is in the quartz capillary 1 When a drop-shaped oil droplet is formed at the end, that is, the lower end, the three-dimensional moving platform moves upward so that the ITO glass 6 plate can contact the drop-shaped oil at the end of the quartz capillary 1, and the surface energy of the ITO glass 6 plate is higher than that at the end of the quartz capillary 1. The surface energy makes the oil phase droplets containing the cell 5 liquid at the end of the quartz capillary 1 separate from the quartz capillary 1 and separate to the ITO glass 6 plate, and the single droplet in the oil phase is naturally also separated to the ITO glass 6 plate. The three-dimensional moving platform drives the ITO glass 6 plate to descend back to the initial position, so as to complete the purpose of separating single droplets into macroscopic containers.

Auxiliary optical means can use photodiode, photomultiplier tube (PMT), microscopic imaging and so on. The position of a single cell can be judged conveniently and quickly.

The above are all preferred embodiments of the present application, and are not intended to limit the protection scope of the present application. Therefore: all equivalent changes made according to the structure, shape and principle of the present application should be covered within the scope of the present application. Inside.

Claims (11)

1. a micro-liquid separation method based on interface contact, is characterized in that: comprise the following steps: ① Take a container and a micro-pipeline with an opening, the micro-pipe flow is filled with a first liquid, the first liquid is a liquid containing biochemical substances, and the micro-pipe is located above the container; ②The micro-pipe and the container move relative to each other, that is, the micro-pipe does not move, and the container moves upward, or the container does not move and the micro-pipe moves downward. At this time, the first liquid is located in the micro-pipe. opening; 3. the first liquid at the opening of the microchannel is in contact with the surface of the container, so that the first liquid at the opening of the microchannel is separated from the microchannel and remains on the container; ④ After the first liquid remains on the container, the micro-pipe and the container move relative to each other again, so that the micro-pipe and the container are kept away from each other. 2. A kind of micro-liquid separation method based on interface contact according to claim 1, it is characterized in that: described micro-pipeline is a single single-core capillary, single multi-core capillary, array capillary, microfluidic single-channel or One of the microfluidic multi-channel arrays. 3. A method for separating trace liquids based on interface contact according to claim 1, characterized in that: the micro-pipes are arranged vertically, and the upper ends of the micro-pipes are connected with fluid-driven equipment, and the fluid-driven equipment continuously or intermittently The first liquid flow is generated, the opening of the micro-channel is located at the lower end of the micro-channel, and the lower end of the micro-channel can be in contact with the surface of the container. 4. a kind of micro-liquid separation method based on interface contact according to claim 3, is characterized in that: described fluid-driven equipment is peristaltic pump, syringe pump, pressure-driven pump, pneumatic-driven pump or electroosmotic drive pump in A sort of. 5 . The method for separating trace liquids based on interface contact according to claim 1 , wherein the size of the openings of the micro-channels is between 0.1 μm and 1 mm. 6 . 6 . The method for separating trace liquids based on interfacial contact according to claim 1 , wherein the openings of the micro-channels are treated with low surface energy. 7 . 7 . The method for separating trace liquids based on interface contact according to claim 1 , wherein the container is a liquid storage tank or a solid plate, and the container stores the second liquid. 8 . 8. When the container is a storage tank for storing the second liquid, the second liquid in the storage tank is an aqueous phase or an oil phase; When the container is a solid plate, when the solid plate is a glass plate, agarose solid plate, or a metal plate, the first liquid is easily attached to the surface of the fixed plate. 9 . A method for separating trace liquids based on interface contact according to claim 1 , wherein: when the first liquid is an aqueous phase, the first liquid contains bacteria, cells, microspheres, nucleic acids, enzymes, One or more biochemical substances in the ion; When the first liquid is an oil phase, the first liquid contains one or both of droplets and particles. 10. a kind of micro-liquid separation method based on interface contact according to claim 1, it is characterized in that: in described step 2., 4., the means that drive micro-pipe or container to produce relative motion are moving operation, manual translation stage operation or one of the automatic mobile stations. 11. An application of the method for separating trace liquids based on interfacial contact according to any one of claims 1-9, characterized in that: for omics analysis of single cells, culture of single cells, mass spectrometry of single droplets analyze.

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