KR20120080842A - Microfluidic device, method for controlling the same and method for controlling bubble - Google Patents

Abstract

PURPOSE: A microfluidic device, a method for controlling the same, and a bubble controlling method of the same are provided to cost effectively control the microfluidic device by injecting air into the reaction region of the microfluidic device. CONSTITUTION: A microfluidic device includes a first channel(120), a second channel(160), a third channel, and a discharging port. Sample fluid flows through the first channel. The first channel is in connection with the second channel. Air is injected into the second channel. The third channel is in connection with the second channel. A substrate solution flows through the third channel. A reaction region(130) is arranged in the third channel. The discharging port is in connection with the third channel. Sensors for detecting flowing materials are respectively installed at the first channel and the second channel.

Description

Microfluidic device, its control method and bubble control method {Microfluidic device, method for controlling the same and method for controlling bubble}

The present invention relates to a microfluidic device and its control method and bubble control method.

Recently, microfluidic devices have become increasingly interesting due to their wide variety of potential applications. For example, using very small volumes of samples, microfluidic devices can perform complex biochemical reactions to obtain important chemical and biological information.

Among other advantages, in particular, the microfluidic device reduces the requirements of samples and reagents, shortens the response time of the reaction, and reduces the amount of biohazardous waste for disposal.

Such microfluidic devices require an operation for transferring fluid located in an internal fluid channel for analysis, and various methods and systems for this are currently being developed.

The present invention solves the problem of performing a washing process to remove the residual antigen (Antigen) and unbound antibody (Antibody) in the reaction region.

The present invention,

A first channel through which the fluid of the sample can flow;

A second channel connected to the first channel and into which air is injected;

A third channel connected to the second channel and having a substrate solution flowing therein and having a reaction zone;

A microfluidic device is provided that includes an outlet port connected to the third channel.

A sensor for sensing a substance flowing through each of the first channel and the second channel is provided.

The third channel is also connected to a discharge chamber, which is connected to a vacuum pump through the discharge port.

The present invention,

Flowing a fluid of the sample into the first channel;

The sensing sensor installed in the first channel senses a substance flowing into the first channel, and when the substance sensed by the sensing sensor is determined to be a fluid of the sample, injecting air into a second channel connected to the first channel. Steps;

Detecting the air from the sensing sensor installed in the first channel and the sensing sensor installed in the second channel, and determining that the air has penetrated the first channel;

Detecting a fluid of the sample by a detection sensor installed in the first channel, and detecting the air by a detection sensor installed in the second channel to determine that an air bubble is generated in the fluid of the sample A control method is provided.

The present invention,

A first channel through which a fluid of a sample can flow, a second channel connected to the first channel, and an air injected therein, and a substrate connected to the second channel and a substrate solution flows and a reaction zone is provided. Preparing a microfluidic device comprising three channels, an evacuation chamber connected to said third channel, and an evacuation port connecting said evacuation chamber and a vacuum pump;

Injecting fluid of the sample into the first channel and reaching the reaction zone through the second channel and the third channel;

Injecting the substrate solution into the third channel to reach a region where the third channel and the second channel are connected, and injecting air into the second channel to form bubbles in the substrate solution, and Washing the area;

Terminating the injection of air into the second channel and passing the substrate solution through the reaction zone to detect a reaction of the fluid in the sample.

The connection region between the second channel and the third channel is a T-junction region.

In addition, an electrode for sensing is formed in the reaction region, and a first antibody is fixed to the electrode, and the fluid of the sample is in a state in which an antigen and a second antibody are reacted and bound.

In addition, the fluid of the sample is at least one of Blood, Urine, Serum and Saliva.

In addition, detecting the response of the fluid of the sample is detected by an electrochemical method or an optical method.

The size of the bubble is proportional to the channel width Wc and inversely proportional to the capillary number Ca.

The present invention provides an effect of controlling the microfluidic device at low cost by performing a washing process in which air injection removes residual antigens and unbound antibodies from the reaction region of the microfluidic device. There is.

1 is a conceptual plan view for explaining a microfluidic device applied to the present invention.
2A-2E are conceptual views illustrating how a bubble is formed that is applied to the microfluidic device of the present invention.
3A to 3C are conceptual views for explaining a bubble control method applied to the microfluidic device of the present invention.
4A to 4D are conceptual top views for explaining a method of controlling a microfluidic device of the present invention.
5A through 5C are conceptual views for explaining a method of controlling a microfluidic device of the present invention.

Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings.

1 is a conceptual plan view for explaining a microfluidic device applied to the present invention.

The microfluidic device is in the form of a chip or cartridge having a first channel 120 through which fluid can flow and an air injection passage 150 connected to the first channel 120.

In addition, a reaction region 130 may be located in the first channel 120, and a reaction inducing substance capable of reacting with a fluid flowing in the first channel 120 may be located in the reaction region 130. have.

In addition, electrodes may be positioned in the reaction region 130 to measure the degree of reaction electrochemically.

Here, the electrodes are a reference electrode, a counter electrode, and a working electrode.

In addition, the first channel 120 may be connected to the inlet 110 for injecting the fluid and the outlet (not shown) for discharging the fluid.

In addition, the air injection passage 150 is connected to one end of the second channel 160, and the other end of the second channel 160 is connected to the first channel 120, and thus, the first channel 120. ) And the connection region A of the second channel 160 form a 'T-junction' region.

Here, the 'T-junction' region may be defined as a region formed in a 'T' shape.

Therefore, when the fluid of the sample (Sample) for the measurement to the second channel 160 flows in the inlet 110, the fluid can flow to the reaction region 130 under pressure control.

In this case, the air injected from the air injection passage 150 reaches the connection area A of the first channel 120 and the second channel 160 through the second channel 160 and is connected to the fluid. In the fluid, an air bubble is generated in the fluid to perform a washing process to remove residual fluid such as an antigen and unbound antibody remaining in the reaction region 130. You can do it.

Accordingly, the present invention can control the microfluidic device at low cost by performing a washing process that removes residual antigens and unbound antibodies from the reaction region of the microfluidic device by air injection. There is an advantage.

2A-2E are conceptual diagrams for explaining how a bubble is formed that is applied to the microfluidic device of the present invention.

As described above, in order to perform the washing process of the microfluidic device, the present invention injects air into a channel through which the fluid flows to generate bubbles.

That is, as shown in FIG. 2A, the second channel 160 into which the air 151 is injected is connected to the first channel 120 through which the fluid 111 of the sample to be measured flows.

At this time, when the fluid 111 of the sample to be measured flows in the first channel 120, when the air 151 is injected into the second channel 160 at a predetermined pressure, the air 151 is shown in FIG. As shown in FIG. 2A, the first channel 120 and the second channel 160 reach the area where the second channel 160 is connected, and as shown in FIG. 2B, the first channel 120 penetrates into the first channel 120.

In this case, when the air 151 penetrates into the first channel 120, as shown in FIG. 2B, 'T−, which is a connection region between the first channel 120 and the second channel 160. The partial pressure of the 'a' region of the junction 'region is lowered so that the air 151 penetrates into the first channel 120.

Thereafter, as shown in FIG. 2C, the air 151 travels in the flowing direction of the fluid 111 by the flow velocity of the fluid 111. As shown in FIG. 2D, the first channel 120 and the After reaching the edge b of the region where the second channel 160 is connected, as shown in FIG. 2E, the air 152 of the first channel 120 is discharged from the air 151 of the second channel 160. It is separated and becomes a bubble.

The size of the bubble is proportional to the channel width Wc and inversely proportional to the capillary number Ca.

Where capillary number = uV / r, u is the viscosity of the fluid, V is the flow rate of the fluid and r is the surface tension of the fluid.

Therefore, the smaller the wall of the microfluidic device is hydrophilic, the narrower the channel, the higher the viscosity of the fluid, the smaller the bubble size.

And, if the fluids are the same and the flow rate is constant, the degree of hydrophilicity can be a variable.

3A to 3C are conceptual views for explaining a bubble control method applied to the microfluidic device of the present invention.

The bubble control method applied to the microfluidic device of the present invention is characterized by detecting sensors (1) in each of the first channel 120 through which the fluid 111 of the sample flows and the second channel 160 through which the air 151 is injected 171 and 172 are installed and the detection sensors 171 and 172 detect the presence or absence of the fluid 111 and the air 151, and the air pressure is controlled to smoothly form bubbles.

Here, the sensing sensor 171 detects a material flowing in the first channel 120, and the sensing sensor 172 detects a material flowing in the second channel 160.

First, the fluid 111 of the sample flows through the first channel 120.

Subsequently, when the material flowing into the first channel 120 is sensed by the detection sensor 171, and the material sensed by the detection sensor 171 is determined as the fluid 111, the second channel 160 is detected. The air 151 is injected into the furnace.

3A, the fluid 111 of the sample is detected by a material flowing in the first channel 120 in the sensing sensor 171, and the second channel (in the sensing sensor 172). The air 151 is detected as a material flowing in the 160.

Next, as shown in FIG. 3B, when the air 151 penetrates to the first channel 120 to some extent, the fluid 111 and the air 151 of the sample are detected by the detection sensor 171. Only the air 151 is detected by the detection sensor 172.

When the air 151 penetrated into the first channel 120 becomes a bubble 152 included in the fluid 111 of the sample, the fluid 111 of the sample is detected by the detection sensor 171. The air 151 is detected by the detection sensor 172.

4A to 4D are conceptual top views for explaining the method of controlling the microfluidic device of the present invention.

First, a first channel 520 through which a fluid of a sample can flow, a second channel 540 connected with the first channel 120, a second channel 540 through which air is injected, and a second channel 540 connected with each other. A third channel 560 in which a substrate solution flows and is provided with a reaction zone K, an discharge chamber 571 connected to the third channel 560, the discharge chamber 571 and a vacuum pump ( Prepare a microfluidic device that includes an outlet port 570 that connects (not shown).

Here, the second channel 540 and the third channel 560 form a 'T-junction'.

Next, as shown in FIG. 4A, the fluid of the sample is injected into the first channel 520, and as shown in FIG. 4B, the fluid of the sample is injected through the second channel 540 and the third channel 560. The reaction zone K (shown in FIG. 4C) is reached.

In this case, a substrate solution may be injected into the third channel 560 simultaneously with or after the fluid of the sample is injected into the first channel 520.

The first channel 520 is connected to the port 510, the second channel 540 is connected to the port 530, and the third channel 560 is connected to the port 550. It is.

When the port 530 and the port 550 are sealed and the discharge chamber 571 is operated and suctioned, the fluid of the sample injected into the first channel 520 is separated from the reaction zone (see FIG. 4B). Pass K).

Here, an electrode for sensing is formed in the reaction region K, and a first antibody is fixed to the electrode.

In addition, the fluid of the sample is in a state in which an antigen such as blood and a second antibody are reacted and bound.

In addition, the fluid of the sample may be a biological material such as blood, urine, serum, saliva, or the like.

Therefore, the antigen bound to the second antibody, which is the fluid of the sample, is captured by the sandwich ELISA (enzyme-linked immunosorbent assay) method to the first antibody immobilized in the reaction region (K).

At this time, depending on the state inside the microfluidic device, a phenomenon occurs in which the input pressure is not solved and accumulates. To compensate for this, feedback control may be performed to maintain a constant pressure condition by checking the current pressure in the pressure sensor.

Subsequently, as shown in FIG. 4C, the substrate solution is injected into the third channel 560 to reach an area where the third channel 560 and the second channel 540 are connected, and the second Air is injected into the channel 540 to form bubbles in the substrate solution, and the reaction zone K is washed.

Subsequently, the injection of air into the second channel 540 is terminated, and the substrate solution is passed through the reaction zone K to sense the reaction of the fluid in the sample (FIG. 4D).

In this case, detecting the response of the fluid of the sample may be detected by an electrochemical method or an optical method.

5A to 5C are conceptual views for explaining a method of controlling a microfluidic device of the present invention.

An electrode 800 for sensing is formed in the reaction region K of the microfluidic device, and a first antibody 810 is fixed to the electrode 800.

In this state, when the fluid of the sample in which the antigen 820 and the second antibody 830 are coupled to flow into the reaction region K flows, as shown in FIG. 5A, the antigen ( 820 is coupled between the first antibody 810 and the second antibody 830 and captured by sandwich enzyme-linked immunosorbent assay (ELISA).

Thereafter, a substrate solution having an air bubble is injected into the reaction zone K to wash the antigen 820 and the second antibody 830a and 830b which are not bound to the first antibody 810. Washing) process is performed (FIG. 5B).

Here, the antigen 820 and the second antibody 830 which are not bound to the first antibody 810 are components that are undesirably attached to the solution of the residual sample.

Subsequently, an air bubble-free substrate solution is injected into the reaction zone K to react with the antigen 820, and then the reaction state is measured electrochemically or optically (FIG. 5C).

It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims (10)

A first channel through which the fluid of the sample can flow;
A second channel connected to the first channel and into which air is injected;
A third channel connected to the second channel and having a substrate solution flowing therein and having a reaction zone;
A microfluidic device comprising an outlet port connected to said third channel.
The method according to claim 1,
And a sensor for sensing a substance flowing in each of the first channel and the second channel.
The method according to claim 1,
The third channel is connected to a discharge chamber, and the discharge chamber is connected to a vacuum pump through the discharge port.
Flowing a fluid of the sample into the first channel;
The sensing sensor installed in the first channel senses a substance flowing into the first channel, and when the substance sensed by the sensing sensor is determined to be a fluid of the sample, injecting air into a second channel connected to the first channel. Steps;
Detecting the air from the sensing sensor installed in the first channel and the sensing sensor installed in the second channel, and determining that the air has penetrated the first channel;
Detecting a fluid of the sample by a detection sensor installed in the first channel, and detecting the air by a detection sensor installed in the second channel to determine that an air bubble is generated in the fluid of the sample Control method.
A first channel through which a fluid of a sample can flow, a second channel connected to the first channel, and an air injected therein, and a substrate connected to the second channel and a substrate solution flows and a reaction zone is provided. Preparing a microfluidic device comprising three channels, an evacuation chamber connected to said third channel, and an evacuation port connecting said evacuation chamber and a vacuum pump;
Injecting fluid of the sample into the first channel and reaching the reaction zone through the second channel and the third channel;
Injecting the substrate solution into the third channel to reach a region where the third channel and the second channel are connected, and injecting air into the second channel to form bubbles in the substrate solution, and Washing the area;
Terminating the injection of air into the second channel and passing the substrate solution through the reaction zone to detect a reaction of the fluid in the sample.
The method according to claim 5,
And the connection region of the second channel and the third channel is a T-junction region.
The method according to claim 5,
An electrode for sensing is formed in the reaction region, and a first antibody is fixed to the electrode, and the fluid of the sample is a microfluidic device in which an antigen and a second antibody are reacted and bound. Control method.
The method according to claim 5,
The fluid of the sample,
A method of controlling a microfluidic device that is at least one of blood, urine, serum, and saliva.
The method according to claim 5,
The method of controlling a microfluidic device is to sense the response of the fluid in the sample by an electrochemical or optical method.
The method according to claim 5,
The size of the bubble,
A method of controlling a microfluidic device in which the channel width Wc is proportional and inversely proportional to the capillary number Ca.

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