CN115845943A - Method for generating vacuum and filling continuous liquid phase in micro-fluidic chip by using liquid-transfer suction head - Google Patents

Abstract

The invention discloses a method for generating vacuum and filling continuous liquid phase in a microfluidic chip by using a liquid-transfer suction head, which is characterized in that the liquid-transfer suction head is used for carrying out vacuum treatment on the microfluidic chip, and then the same or the same liquid-transfer suction head is used for sucking various required reagents or liquid phases to be filled into the cavity of the microfluidic chip, so that the cavity of the microfluidic chip is sequentially filled with different liquid phases, and the rapid vacuum generation in the microfluidic chip and the simple and rapid filling of the continuous liquid phase can be realized.

Description

Method for generating vacuum and filling continuous liquid phase in micro-fluidic chip by using liquid-transfer suction head

Technical Field

The invention relates to a method for generating vacuum and filling continuous liquid phase in a microfluidic chip by using a liquid-transfering suction head, belonging to the technical field of microfluidic chips.

Background

The micro-fluidic chip is a hotspot field of the development of the current micro Total Analysis Systems (miniature Total Analysis Systems), takes the chip as an operation platform, simultaneously takes analytical chemistry as a basis, takes a micro-electromechanical processing technology as a support, takes a micro-pipeline network as a structural characteristic, takes life science as a main application object at present, is one of the leading-edge technologies which are rapidly developed at present, and is widely used for biochemical Analysis and detection at present. Its goal is to integrate the functions of the whole laboratory, including sampling, diluting, adding reagents, reacting, separating, detecting, etc., on a microchip, and to be used many times.

The micro-fluidic chip is a main platform for realizing the micro-fluidic technology. The device is characterized in that the effective structure (channels, reaction chambers and other functional parts) for containing the fluid is at least in one latitude in micron scale. Due to the micro-scale structure, the fluid exhibits and develops specific properties therein that differ from those of the macro-scale. Thus developing unique analytical yielding properties. The micro-fluidic chip has the characteristics of controllable liquid flow, extremely less consumption of samples and reagents, ten-fold or hundred-fold improvement of analysis speed and the like, can simultaneously analyze hundreds of samples in a few minutes or even shorter time, and can realize the whole processes of pretreatment and analysis of the samples on line.

The fluid sampling of the microfluidic chip is a key technology in the microfluidic chip, and different microfluidic chip fluid driving technologies are developed aiming at different application scenes, wherein the pressure driving technology, the electroosmotic flow driving technology, the interfacial tension driving technology, the braking variable driving technology and the like are adopted, and the pressure driving technology is the most common driving technology of the microfluidic chip. Pressure drive usually has malleation drive and negative pressure drive mode, and the malleation drive is simple, convenient, but the gaseous body can lead to flowing flow stability nature not enough in the chip, appears the bubble easily and blocks up the scheduling problem. The negative pressure driving is easier to control the filling of the fluid to the micro-fluidic chip cavity, and the stability is higher. The conventional negative pressure treatment method for the microfluidic chip is to place the whole chip into a vacuum chamber, vacuumize and degas the vacuum chamber through a vacuum specimen, and perform negative pressure treatment on the microfluidic chip, wherein the whole treatment process is complex, and a sample is inconvenient to be directly added into the microfluidic chip after the negative pressure treatment.

Disclosure of Invention

In view of the above, the present invention provides a method for generating vacuum and filling continuous liquid phase inside a microfluidic chip by using a liquid-transfer pipette tip, so as to solve the above problems in the prior art.

In order to achieve the purpose, the invention adopts the following technical scheme:

a method for generating vacuum and filling continuous liquid phase in a microfluidic chip by using a liquid-transfering sucker comprises the following steps:

(1) Communicating the power source with one air hole of the micro-fluidic chip cavity by using the first liquid-moving suction head, closing other air holes of the micro-fluidic chip cavity, and removing air in the micro-fluidic chip cavity by using negative pressure provided by the power source to enable the interior of the chip cavity to reach or approach a vacuum state;

(2) Closing an air hole connected with the micro-fluidic chip and the first liquid-transferring suction head, separating the first liquid-transferring suction head from the air hole of the micro-fluidic chip, and providing negative pressure through a power source to enable the first liquid-transferring suction head to suck a first liquid phase;

(3) Opening the air hole connected with the first liquid-moving suction head of the micro-fluidic chip, connecting the air hole of the first liquid-moving suction head and the cavity of the micro-fluidic chip again, and enabling the first liquid phase to enter the cavity of the micro-fluidic chip by providing positive pressure through a power source or utilizing negative pressure in the chip;

(4) Discarding the first liquid-transfering sucker, connecting the second liquid-transfering sucker with power source, and providing negative pressure to suck the second liquid phase by power source;

(5) And the second liquid-transferring suction head for sucking the second liquid phase is connected with one air hole of the cavity of the microfluidic chip, the air hole and the other air hole are opened, and positive pressure is provided by a power source to enable the second liquid phase to enter the cavity of the microfluidic chip.

On the basis of the technical scheme, the invention can be further improved as follows:

furthermore, the microfluidic chip is provided with at least one communicated chamber, and the chamber is provided with at least 2 air holes and is connected with the external atmosphere through the air holes.

Further, the air vent is hermetically connected with the first and second pipetting tips.

Further, the air holes are controlled to be opened and closed through micro valves.

Further, the first liquid phase and the second liquid phase are immiscible.

Further, the volume of the first liquid phase and the volume of the second liquid phase are not less than the volume of the chamber of the microfluidic chip.

The invention also provides another method for generating vacuum and filling continuous liquid phase in the microfluidic chip by using the liquid-transfering sucker, which comprises the following steps:

(1) Communicating the power source with one air hole of the micro-fluidic chip cavity by using the first liquid-moving suction head, closing other air holes of the micro-fluidic chip cavity, and removing air in the micro-fluidic chip cavity by using negative pressure provided by the power source to enable the interior of the chip cavity to reach or approach a vacuum state;

(2) Closing the air hole of the micro-fluidic chip connected with the first liquid-transferring suction head, separating the first liquid-transferring suction head from the air hole of the micro-fluidic chip, and providing negative pressure through a power source to enable the first liquid-transferring suction head to absorb a first liquid phase; continuously sucking a second liquid phase which is immiscible with the first liquid phase;

(3) And opening the air hole of the micro-fluidic chip connected with the first liquid-removing suction head, connecting the air hole of the first liquid-removing suction head and the air hole of the cavity of the micro-fluidic chip again, enabling the second liquid phase to enter the cavity of the micro-fluidic chip under the negative pressure action of the micro-fluidic chip, and enabling the first liquid phase to enter the cavity of the micro-fluidic chip by providing positive pressure through the power source.

The invention has the beneficial effects that: the most common liquid-transfering suction head is used for carrying out vacuum treatment on the microfluidic chip, the efficiency of the vacuum treatment on the chip is higher than that of the existing vacuum chamber, and the control and the automatic operation are easier; meanwhile, the suction head is used for filling liquid phase in the chip, so that other systems are prevented from being polluted by reagents.

Drawings

FIG. 1 shows a first pipette tip evacuating a microfluidic chip according to example 1 of the present invention;

FIG. 2 shows a state where a first reagent is aspirated by a first pipette tip in example 1 of the present invention;

FIG. 3 shows a state where the first pipetting tip injects the first liquid phase into the chamber of the microfluidic chip in example 1 of the present invention;

FIG. 4 shows a state where the second liquid phase is aspirated by the second pipette tip in example 1 of the present invention;

FIG. 5 shows a state where the second pipetting tip injects a second liquid phase into the chamber of the microfluidic chip in example 1 of the present invention;

FIG. 6 is a state where the first liquid phase is aspirated by the first pipette tip and the second liquid phase is further aspirated by the first pipette tip in example 2 of the present invention;

FIG. 7 shows the state where the second liquid phase and the first liquid phase are injected into the chamber of the microfluidic chip by the first pipette tip aspiration in example 2 of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. It is specifically noted that the number of the air holes of the microfluidic chamber may not only be two, but also be one or more, the number of the pipette tips used in the whole process of evacuating and sampling the microfluidic chip may not only be 1 or two, and more pipette tips may be used to achieve the same effect.

Example 1

Referring to fig. 1-5, in a sample introduction of a microfluidic chip, a power source is firstly communicated with the tail of a first liquid-moving suction head, then the tip of the first liquid-moving suction head is inserted into a first air hole of the microfluidic chip, at the moment, the first air hole is in an open state, a chamber of the microfluidic chip is communicated with the power source through the liquid-moving suction head, a second air hole or more other air holes of the microfluidic chip are closed by a micro valve, at the moment, the chamber of the microfluidic chip forms a closed space, then, the power source starts a negative pressure mode, and air in the chamber of the microfluidic chip is pumped out, so that the interior of the microfluidic chip is changed into a vacuum state. The vacuum treatment of the micro-fluidic chip chamber directly by using the suction head reduces the operation complexity of the conventional sealing bin on the vacuum treatment of the chip. The suction head after the vacuum treatment of the micro-fluidic chip can also be used for sucking liquid phase and filling the liquid phase into the cavity of the micro-fluidic chip, so that the utilization efficiency of the suction head is improved, and the reagent pollution to other systems can be reduced.

Then, the first micro valve is closed, so that the vacuum in the cavity of the micro-fluidic chip can be maintained, and the first liquid-removing sucker is removed from the first air hole of the micro-fluidic chip.

And inserting the first liquid transferring suction head connected with the power source into the first liquid phase, and sucking the first liquid phase into the first liquid transferring suction head under the action of negative pressure.

Then inserting the first liquid-transfering suction head after absorbing the first liquid phase into a first air hole of the microfluidic chip, and opening a first micro valve, wherein the first liquid phase in the first liquid-transfering suction head can rapidly enter a chamber of the microfluidic chip under the driving of negative pressure in the microfluidic chip until the whole chamber of the microfluidic chip is filled with the first liquid phase; in addition, a positive pressure can be applied to the first liquid phase by the power source, so that the speed of the first liquid phase entering the cavity of the microfluidic chip is increased.

Then, the first liquid-transfering suction head is withdrawn from the first air hole and withdrawn from the power source, the tail part of the second suction head is connected to the power source, the tip end of the second suction head is inserted into the second liquid phase, the second liquid phase is sucked under the action of negative pressure of the power source, then the second suction head which sucks the second liquid phase is inserted into the first air hole, the second micro valve is opened, the second liquid phase enters the micro-fluidic chip chamber under the driving of positive pressure of the power source, the first liquid phase on the main flow channel in the micro-fluidic chip is pushed to flow out from the second air hole, the main flow channel is filled with the second liquid phase, and partial micro-chambers of the micro-fluidic chip chamber cannot be pushed out by the second liquid phase due to the dead-mustache structure, and the first liquid phase in the micro-fluidic chip is remained in the micro-fluidic chip and is divided by the second liquid phase and sealed in the micro-fluidic chip.

In particular, when the first liquid phase is an aqueous phase and the second liquid phase is an oil phase reagent immiscible with water, droplets of the first liquid phase separated by the second liquid phase and the micro-chambers of the chip are formed in the 'cul-de-sac' structure in the chip.

Example 2

Referring to fig. 6 and 7, in a sample introduction of a microfluidic chip, a power source is firstly communicated with the tail part of a first liquid-moving suction head, then the tip end of the first liquid-moving suction head is inserted into a first air hole of the microfluidic chip, at the moment, the first air hole is in an open state, a chamber of the microfluidic chip is communicated with the power source through the liquid-moving suction head, a second air hole or more other air holes of the microfluidic chip are closed by using a micro valve, at the moment, the chamber of the microfluidic chip forms a closed space, then, the power source starts a negative pressure mode, and air in the chamber of the microfluidic chip is pumped out, so that the interior of the microfluidic chip is changed into a vacuum state.

Then, the first micro valve is closed, so that the vacuum in the cavity of the micro-fluidic chip can be maintained, and the first liquid-removing sucker is removed from the first air hole of the micro-fluidic chip.

The first liquid-transferring suction head connected with the power source is inserted into the first liquid phase, the first liquid phase is sucked into the first liquid-transferring suction head under the action of negative pressure, then the first liquid phase is inserted into the second liquid phase, the second liquid phase is continuously sucked into the first suction head under the action of negative pressure, the second liquid phase and the first liquid phase are not mutually fused, and the specific gravity of the first liquid phase is lower than that of the second liquid phase. By the mode, only one suction head is needed, so that the vacuum treatment of the microfluidic chip can be completed, and different continuous phases can be added into the chamber of the microfluidic chip.

Then inserting the first liquid-transferring suction head absorbing the first liquid phase and the second liquid phase into a first air hole of the microfluidic chip, and opening a first micro valve, wherein the second liquid phase in the first liquid-transferring suction head can rapidly enter a chamber of the microfluidic chip under the driving of negative pressure in the microfluidic chip until the whole chamber of the microfluidic chip is filled with the second liquid phase; and opening the second micro valve, wherein the first liquid phase enters the micro-fluidic chip chamber and can push the second liquid phase on the main flow channel in the micro-fluidic chip to flow out of the second air hole under the driving of positive pressure of the power source, the main flow channel is filled with the first liquid phase, and the micro-chamber of the micro-fluidic chip chamber is partially filled with the second liquid phase.

In particular, when the second liquid phase is an aqueous phase and the first liquid phase is an oil phase reagent immiscible with water, droplets of the second liquid phase separated by the first liquid phase and the micro-chambers of the chip are formed in the "cul-de-sac" structure in the chip.

Claims (7)

1. A method for generating vacuum and filling continuous liquid phase in a microfluidic chip by using a liquid transfer suction head is characterized by comprising the following steps:

(1) Communicating the power source with one air hole of the micro-fluidic chip cavity by using the first liquid-moving suction head, closing other air holes of the micro-fluidic chip cavity, and removing air in the micro-fluidic chip cavity by using negative pressure provided by the power source to enable the interior of the chip cavity to reach or approach a vacuum state;

(2) Closing the air hole of the micro-fluidic chip connected with the first liquid-transferring suction head, separating the first liquid-transferring suction head from the air hole of the micro-fluidic chip, and providing negative pressure through a power source to enable the first liquid-transferring suction head to absorb a first liquid phase;

(3) Opening the air hole of the micro-fluidic chip connected with the first liquid-transferring sucker, connecting the air hole of the first liquid-transferring sucker and the cavity of the micro-fluidic chip again, and providing positive pressure through a power source or utilizing negative pressure in the chip to enable the first liquid phase to enter the cavity of the micro-fluidic chip;

(4) Discarding the first liquid-transferring sucker, connecting the second liquid-transferring sucker with a power source, and providing negative pressure to suck a second liquid phase through the power source;

(5) And the second liquid-transfering suction head for sucking second liquid phase is connected with one air hole of the chamber of the microfluidic chip, the air hole and another air hole are opened, and positive pressure is provided by a power source to make the second liquid phase enter the chamber of the microfluidic chip.

2. The method of claim 1, wherein the microfluidic chip comprises at least one chamber in communication with the pipette tip, wherein the chamber comprises at least 2 air vents and is connected to the outside atmosphere through the air vents.

3. The method for generating vacuum and continuous liquid phase filling inside a microfluidic chip with a pipette tip according to any one of claims 1 to 2, wherein the air vent is sealingly connected to the first and second pipette tips.

4. The method for generating vacuum and continuous liquid phase filling inside a microfluidic chip with a pipette tip according to claim 1, wherein the air holes are controlled to be opened and closed by a micro valve.

5. The method of claim 1, wherein the first liquid phase and the second liquid phase are immiscible.

6. The method for generating vacuum and filling continuous liquid phase in the microfluidic chip by using the pipetting tip as recited in claim 1 or 5, wherein the volumes of the first liquid phase and the second liquid phase are not less than the volume of the chamber of the microfluidic chip.

7. A method for generating vacuum and filling continuous liquid phase in a microfluidic chip by using a liquid transfer suction head is characterized by comprising the following steps:

(1) Communicating the power source with one air hole of the micro-fluidic chip cavity by using the first liquid-moving suction head, closing other air holes of the micro-fluidic chip cavity, and removing air in the micro-fluidic chip cavity by using negative pressure provided by the power source to enable the interior of the chip cavity to reach or approach a vacuum state;

(2) Closing the air hole of the micro-fluidic chip connected with the first liquid-transferring suction head, separating the first liquid-transferring suction head from the air hole of the micro-fluidic chip, and providing negative pressure through a power source to enable the first liquid-transferring suction head to absorb a first liquid phase; continuously sucking a second liquid phase which is immiscible with the first liquid phase;

(3) And opening the air hole of the micro-fluidic chip connected with the first liquid-removing suction head, connecting the air hole of the first liquid-removing suction head and the air hole of the cavity of the micro-fluidic chip again, enabling the second liquid phase to enter the cavity of the micro-fluidic chip under the negative pressure action of the micro-fluidic chip, and enabling the first liquid phase to enter the cavity of the micro-fluidic chip by providing positive pressure through the power source.

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