KR100471377B1 - Microfluidic Devices Controlled by Surface Tension - Google Patents

Abstract

The present invention relates to a microfluidic device controlled by the surface tension, the microfluidic device is coupled to the upper substrate and the lower substrate to control and react with the fluid, the lower substrate, the first fluid and the second fluid are respectively stored A first storage chamber and a second storage chamber, a sensing chamber connected with the first storage chamber and the second storage chamber, a first flow stop and a second flow stop to stop movement of the first or second fluid. And a flow delay unit for reducing the moving speed of the first fluid or the second fluid, a waste chamber in which the reaction of the first fluid or the second fluid is discarded and a connection between the flow delay unit and the waste chamber so that the fluid is moved. The upper substrate includes a sensing unit for measuring a biochemical reaction in the sensing chamber, and the first fluid is moved to the sensing chamber by capillary force, whereby a first biochemical reaction occurs. After the passage of time, when the second fluid enters the sensing chamber by capillary force, the first fluid is replaced and the secondary biochemical reaction occurs. Therefore, no additional device and power supply are required, so that the device can be miniaturized and portable, and the manufacturing cost can be lowered and the manufacturing yield can be increased.

Description

Microfluidic Devices Controlled by Surface Tension

The present invention relates to a microfluidic device applied to a biochip, and more particularly, to transfer, stop, and control a very small amount of fluid using only the surface tension of the fluid without using an external force such as a pump. The present invention relates to a microfluidic device controlled by surface tension that controls fluid flow such as exchange.

Microfluidic devices are the most basic and key components of biochips. That is, the microfluidic control device allows the fluid flow to be controlled for the biochemical action required for the biochip such as fluid transfer, mixing, reaction, and sensing. The microfluidic device can be implemented with various driving principles for such a function. Examples include a microactuating method (Microactuating Method) and a microchannel in which a micropump and a valve are processed on a microchannel and a chamber are formed on a channel or a chamber. Electrophoretic method (Electrophoretic Method), Electroosmotic Method (Electrosmotic Method), Capillary Flow Method (Capillary Flow Method) by capillary force is applied.

The fluid control device using the driving principle may be classified into an active microfluidic component and a passive microfluidic component. Active elements allow fluid control using micro pumps and valves driven by electric and mechanical external forces, and passive elements realize fluid control through natural force and surface modification or shape change of flow path or chamber. do. These fluid control devices can be applied in a variety of applications, including a variety of bio devices including protein chips, DNA chips, drug delivery systems, and microbiological / chemical reactors that require fine and accurate flow control. It is applied in the back.

Among them, the fluid control device using the capillary flow is a passive device, and the fluid stops, feeds, or further moves speeds by using a principle in which attraction or repulsion naturally occurs due to the surface tension between the inner surface of the fine flow path and the fluid. Make adjustments possible. In very small fluid systems, the ratio of surface area to volume increases, so that the forces associated with the surface play a relatively important role, especially when the liquid interface is exposed to gas and the surface tension occurs, and the contact angle when it encounters a solid wall. In the figure, capillary flow occurs when applied to a capillary tube.

1 is a view for explaining the shape of the droplets and the shape of the capillary flow caused by the difference in the relative magnitude of the surface tension between the liquid and the solid when the microdroplets are in contact with the solid surface or applied to the capillary. In this case, Figure 1 (a) shows the liquid droplets on the plate made of a hydrophilic material, Figure 1 (b) shows the shape of the tip of the liquid flowing through the hydrophilic capillary, Figure 1 (c ) Shows a shape in which a liquid drop is placed on a plate made of a hydrophobic material, and FIG. 1 (d) shows a tip shape of a fluid flowing through a hydrophobic capillary.

1 (a) and (b), when the contact angle θ is 90 degrees or less when the solid surface is hydrophilic, the liquid wets the solid surface and the liquid moves to the right in the channel. Referring to FIGS. 1 (c) and (d), when the contact angle θ is 90 degrees or more when the solid surface is hydrophobic, the solid pushes the liquid out so that the liquid moves to the left in the channel. Here, the contact angle θ is determined according to the Young's equation and can be expressed as Equation 1.

Σ _gl, σ _{gs and} σ _sl are the energy per unit area at the liquid-gas, solid-gas and solid-liquid interfaces, respectively. In particular, σ _gl is equal to the surface tension of the liquid.

2 is an exemplary view of various types of flow paths for explaining capillary flow. Figure 2 (a) is a tube having an arbitrary cross-section and the pressure acting by the surface tension at the front end of the fluid between the liquid and gas is expressed by the equation (2).

Where r ₁ and r ₂ are the two major axis radii of the fluid interface curvature.

2 (b), 2 (c) and 2 (d) show a circular tube, a two-dimensional channel and a three-dimensional square channel, respectively, and the pressure acting by the surface tension on the fluid tip between the liquid and the gas is represented by Equation 3 , 4 and 5.

At this time, W represents the width of the channel, H represents the height of the channel.

2 (e) and 2 (f) are channels through which the height of the flow path expands and contracts, and the flow direction of the flow is determined as follows according to the reduction and expansion angles.

θ> 90 ° -β: go left

θ <90 ° -β: go right

θ = 90 ° -β: stop

Here, β is an angle enlarged or reduced counterclockwise with respect to the horizontal line.

2 (g) and 2 (h) are combinations of circular tubes having different radii and two-dimensional channels having different heights, respectively, and the change in pressure on the fluid during the flow of the fluid tip from left to right is represented by Equation 6, Same as 7.

At this time, r ₁ and r ₂ represent the radius, h ₁ and h ₂ represents the height. This value represents the additional pressure that must be applied to the fluid to continue the flow at the point of engagement of the channel.

2 (i) is a channel in which the height is extended and the pressure barrier at the starting point of expansion is shown in Equation 8.

Where α is the radius of curvature of the fluid tip.

2 (j) is a three-dimensional channel-coupled channel having different heights and widths, and a pressure change amount on the fluid in the process of moving the fluid tip from left to right is expressed by Equation 9.

Figure 2 (k) is a three-dimensional channel of increasing width and the maximum pressure barrier at the start of expansion is expressed by Equation 10.

If the wall surface of the channel is used as a dissimilar material, or if there is a treatment such as surface modification, the contact angle may be changed in the above equation.

As described above, the microfluidic system using only the surface tension as a driving force can be designed using the equations for capillary force. Examples of using surface tension in microsystems include micro stop valves, pressure sensors, accelerometers, micropumps, micromotors, fluid transfer, fluid filling, inkjet, robot probes, MOEMS devices, optical shutters, and micro switches. Do. Since the fluid control device using the capillary flow does not have a driving body, there is no need for an additional power supply device, so that the mother body including the biochip can be miniaturized, manufacturing costs and operating costs are reduced, and there is almost no failure.

However, depending on the application of the fluid control device, a very careful design process is required to realize a high performance biochip with pure capillary flow. In other words, since no external force is applied, if the flow path design is initially incorrect, there may be an operation problem in which a flow occurs at a part where flow is to be maintained or a flow is generated at a part to be stopped. In addition, there is no external force during operation, which makes precise time and position control of the fluid flow very difficult. In particular, when the detection method is optical, the buffer solution does not need to be reinserted.However, in the biochip using the electrochemical detection method, the injected sample undergoes a biochemical reaction on the detection electrode. The sample should be replaced with a buffer solution to suit the electrochemical measurements, while washing small particles suspended in the colloid, colloids, or reactants with weak coupling with the sensing electrode after the reaction. It is generally known that forced flow is required for the replacement of such buffer solutions. Due to the problems listed above, many microfluidic control devices essentially use an active device. However, if a fluid control device that replaces the role of an active device is manufactured through a careful and proper design process, the advantages of the passive fluid control device using the capillary force described above can be greatly emphasized, and a very difficult fluid replacement can be achieved. Can be.

A typical example of a fluid control device using capillary flow is U. S. Patent No. 6143248, “microscale devices and reactions in microscale devices,” registered November 7, 2000, using “capillary microvalve” as the name of the invention. No. 6,271,040, filed Aug. 7, 2001, entitled " Diagnostic Devices Method and Apparatus for the Controlled Movement of Reagents without Membranes, " US Patent No. 6,296,0020 B1 or "Devices Comprising Multiple Capillarity Inducing Surfaces", registered on October 2, 2001, entitled "Bluid Circuit Components Based upon Passive Fluid Dynamics," as the name of the invention. US Patent No. 6,113,855, issued September 5, 2000, and the like.

Here, "capillary microvalve" of U. S. Patent No. 6,614,48 discloses a microvalve that transfers a small amount of fluid from the micro storage chamber to the delivery channel with the size and centrifugal force of the channel using capillary principle and centrifugal force. U. S. Patent No. 6057149 proposes a microfluidic device that performs the movement and mixing of microdroplets through a microchannel by using a change in surface tension and contact angle of a fluid due to temperature change. U.S. Patent No. 6,271,040 B1, "Diagnostic Devices Method and Apparatus for the Controlled Movement of Reagents without Membranes," transfers a sample using only capillary flow and causes the sample to react on the chamber and flow path, thereby reacting the sample in an optical manner. A diagnostic biochip structure for determining the presence or absence of the present invention has been presented. U.S. Patent No. 6,296,0020 B1, "Fluid Circuit Components Based upon Passive Fluid Dynamics," proposes a structure capable of stopping flow by using a material having a rapid expansion or hydrophobicity of a flow path in a capillary tube. U.S. Patent No. 6,113,855, "Devices Comprising Multiple Capillarity Inducing Surfaces," discloses a technical idea of generating capillary forces by properly arranging hexagonal micro pillars in a chamber.

The above-mentioned U.S. patents only suggest means and methods for fluid to flow or stop due to the weakening of capillary forces by alteration of the flow path or surface treatment. That is, it was not possible to properly control the conveying speed of the fluid only by capillary flow or to completely replace the solution in the chamber.

Accordingly, the present invention has been made to solve the above problems, and not only transports and stops a small amount of fluid through natural flow by capillary force, but also changes the fluid's shape through surface change, surface modification, and temperature control. It is an object of the present invention to provide a microfluidic device capable of controlling the moving speed and realizing a total replacement of a solution.

In order to achieve the above object, the microfluidic device controlled by the surface tension according to the present invention, the upper substrate and the lower substrate is coupled to the microfluidic device to control and react the fluid, the lower substrate, the first fluid and the second A first storage chamber and a second storage chamber in which fluid is stored, a sensing chamber connected to the first storage chamber and a second storage chamber, a first flow stop for stopping movement of the first or second fluid, and A second flow stop, a flow retarder to reduce the moving speed of the first fluid or the second fluid, a waste chamber in which the first fluid or the second fluid is disposed of, and a flow retarder and waste to move the fluid A flow passage connecting the chambers, the upper substrate including a sensing unit for measuring the biochemical reaction in the sensing chamber, wherein the first fluid is moved to the sensing chamber by capillary force, Is taking place, it is preferable that when the second fluid is introduced into the detection chamber by capillary force that occurs is replaced and the secondary biochemical reaction of the first fluid after the lapse of a predetermined time.

In order to achieve the above object, the microfluidic device series array in which the plurality of microfluidic devices are arranged in series, the waste chamber of the N-1 th microfluidic device is connected to the sensing chamber of the N-th microfluidic device, each second Preferably, different second fluids are injected into the storage chamber so that biochemical reactions occur sequentially in the respective sensing chambers. The microfluidic parallel arrays in which a plurality of microfluidic elements are arranged in parallel are common to each sensing chamber. Preferably, the second fluid is connected to the first storage chamber, and different second fluids are injected into each of the second storage chambers so that a biochemical reaction occurs simultaneously in each sensing chamber.

The microfluidic device controlled by the surface tension according to the present invention is a device capable of fine control of a very small amount of fluid by purely relying on capillary force without the action of an external device such as a pump. Fluid control is to transfer and stop a small amount of fluid through surface tension control, to change the surface tension by surface or temperature control and to control the transfer speed by surface modification, to reflow the suspended fluid, and to heterogeneous fluid. Exchange transfer and the like. The microfluidic device controlled by the surface tension according to the present invention is configured in such a way that the upper substrate and the lower substrate are coupled, the lower substrate is a first storage chamber, a second storage chamber, a sensing chamber, a flow delay unit, a flow stop unit, It consists of isolation jaw, flow path and waste chamber. The upper substrate includes a sensing unit for electrochemical measurement, a first fluid inlet, a second fluid inlet, and an air hole of the waste chamber, and the air hole of the first fluid inlet, the second fluid inlet, and the waste chamber is not only an upper substrate. It may also be formed on the lower substrate. The first fluid and the second fluid injected through the first fluid inlet and the second fluid inlet stay in the reaction chamber at a predetermined time interval and are exchanged, and the whole process is performed by natural flow by capillary force.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the following embodiments are provided to those skilled in the art to fully understand the present invention, and may be modified in various forms, and the scope of the present invention is limited to the embodiments described below. It is not.

3 is a plan view of the lower substrate and the upper substrate of the microfluidic device controlled by the surface tension according to a preferred embodiment of the present invention, Figure 4 is a cross-sectional view when the upper substrate and the lower substrate shown in FIG.

3A is a plan view of the lower substrate, in which the lower substrate 100 includes a first storage chamber 102 in which a first fluid is stored, a second storage chamber 104 in which a second fluid is stored, and a sensing chamber 106. ), The sensing chamber connection 108, the isolation jaw 110 between the first storage chamber and the sensing chamber connection, the first flow stop 112, the second flow stop 114, the flow retardation 116, It consists of a flow path 118, a waste chamber 120, and a waste chamber structure 122. The difference in contrast shown in FIG. 3 (a) indicates the depth of the lower substrate 100 when combined with the upper substrate 130, and the higher the contrast, the greater the depth. 3 (b) is a plan view of the upper substrate, in which a sensing unit is formed in the upper substrate 130. The sensing unit is formed in a portion corresponding to the sensing chamber 106 by the outside of the sensing electrode 132. The electrode pad 134 transmits an electrical signal coming in from or to the outside, and an electrode wiring 136 transferring an electrical signal between the sensing electrode 19 and the electrode pad 17. The first fluid inlet 124, the second fluid inlet 126, and the air hole 128 of the waste chamber may be selectively formed in the lower substrate 100 or the upper substrate 130. Referring to 3 (b) has been illustrated a case formed on the upper substrate 130. On the other hand, the dotted line flow path and the chamber of the upper substrate 130 does not represent the shape to be actually processed, but as shown in Figure 4 helps to understand the shape of the flow path and chamber formed when bonded to the lower substrate 100 To give. 4 (a) and 4 (b) show the lines A-A 'and B-B' of FIG. 3 (a) when the lower and upper substrates of FIGS. 3 (a) and 3 (b) are combined, respectively. This is a cross section.

3 (a) and 3 (b) and 4 (a) and 4 (b), the first fluid is introduced into the first fluid inlet 124, and the first fluid is introduced by capillary force. It moves beyond the isolation jaw 110 and passes through the sensing chamber connection 108 to the sensing chamber 106. And, the first fluid stops at the first flow stop 112 and the second flow stop 114, respectively. The first fluid may be a sample. A second fluid flows into the second fluid inlet 126 to fill the second storage chamber 104 by capillary force, and is stopped at the second flow stop 114 to stand by. Here, the second fluid may be a buffer solution, and the injection of the buffer solution may be performed in advance at the time of diagnosis or at the time when the chip is manufactured. The first fluid enters the flow retardation portion 116 laterally connected to the sensing chamber connection 108 by capillary force and moves to the second flow stop 114 and the flow path 118. Here, the first fluid moving through the sensing chamber to the second flow stop 114 rather than reaching the first flow stop 112 with a difference in flow path reaching the first flow stop 112. Allow the fluid to arrive at the second flow stop 114 naturally first. The first fluid passes through the flow delay unit 116 for a predetermined time, and the first fluid that reaches the second flow stop 114 before the first flow stop 112 is the second storage chamber 104. And a first fluid and a second fluid stopped at the second flow stop 114 from the sensing chamber 106, and the combined fluid flows through the flow path 118 by capillary force of the fluid moving to the flow path 118. Will continue to run). The first fluid then passes through the first storage chamber 102-the isolation 110-the sensing chamber connection 108 and the path of the sensing chamber 106-the second flow stop 114-the flow path 118. It is moved in the path of the flow retardation portion 116-the flow path 118, and the second fluid is moved to the second storage chamber 104-the second flow stop 114-flow path 118. The mixed fluid of the first fluid and the second fluid along the flow path 118 meets the first fluid stopped at the first flow stop 112 and moves to the waste chamber 120 to be stored. A separate air hole 128 is formed in the upper substrate 130 in order to smoothly transport the waste fluid. The structure 122 formed in the waste chamber serves to increase the surface tension to maintain a smooth flow. The main flow thereafter consists of the path of the first storage chamber 102-the isolation 110-the sensing chamber connection 108-the first flow stop 112-the waste chamber 120 in the case of the first fluid. Second storage chamber 104-second flow stop 114-sensing chamber 106-sensing chamber connection 108-first flow stop 112-disposal chamber in the case of a second fluid. 120). At this time, the main flow path of the second fluid forms a straight path in a curved path (second storage chamber 104-second flow stop 114-flow path 118-first flow stop 112-waste). Compared to the case of moving to the path of the chamber 120, it has a relatively small flow resistance by the height difference and the path difference.

Through the above process, the sensing chamber 106 is initially filled with a sample which is the first fluid to perform biochemical coupling and reaction, and after a predetermined time, the sensing electrode 132 after the reaction is filled with the second fluid buffer solution. At the same time as washing the weakly bound reactants, the sample is replaced with a buffer solution suitable for electrochemical measurements. Therefore, in the sensing chamber 106, a full exchange of the fluid from the existing first fluid to the second fluid occurs, and all of these processes are characterized by only the naturally occurring surface tension.

The lower substrate 100 may include polymethylmethacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), polydimethylsiloxane (PDMS), polyamide (PA), polyethylene (PE), polypropylene (PP), and polyphenylene ether (PPE). , Polystyrene (PS), polyoxymethylene (POM), polyetheretherketone (PEEK), polytetrafluoroethylene (PEEK), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutyleneterephthalate (PBT), fluorinated ethylenepropylene (FEP), and perfluoralkoxyalkane (PFA) In addition to a variety of polymers, or a variety of metals including aluminum, copper, iron, etc., a single material such as silicon, glass, printed circuit board (PCB), or a heterogeneous material may be used. The lower substrate 100 may be formed by hot embossing, injection molding, casting, stereolithography, laser ablation, rapid prototyping, and silk screen. It can be manufactured by conventional machining methods such as NC (Numerical Control) machining or semiconductor processing methods using deposition and etching. In addition, the upper substrate 130 may be a material and a manufacturing method that can be used to fabricate the lower substrate 100 described above. The upper part of the sensing electrode 132 may be immobilized with various biochemicals such as antigens, proteins, or DNA including antibodies, and surface treatments such as a self-assembled monolayer. If desired, various chemicals, including surfactants, may be pre-formed.

Referring to FIG. 4, which shows a fluid control device in which the lower substrate 100 and the upper substrate 130 are joined by a bonding material, the bonding material used in the bonding may be a powder or paper as well as a liquid adhesive material. The same thin plate adhesive material may also be used. In particular, when bonding at room temperature or low temperature is required in order to prevent denaturation of biochemicals during bonding, Ultrasonic Bonding is performed by using pressure sensitive adhesive, which is bonded only by pressure, or by locally melting a substrate using ultrasonic energy. ) Method can be used. One of the things to consider when joining two substrates is to ensure that the injected solution does not flow out or flow into the other chamber through tiny gaps or voids without passing through the already formed flow path. The junction must be made. In addition, the lower substrate 100 and the upper substrate 130 are forcibly fastened using a clip-shaped additional structure, or an embossed groove is formed in one of the lower substrate 100 and the upper substrate 130 and the other The two substrates can be joined by making and inserting an indented groove, and when using such a joint, an elastic polymer layer can be added to the contact surface so that a small gap does not occur.

Hereinafter, the features and roles of each part of the fluid control element will be described in detail following the overall description of the movement of each fluid in the fluid control element.

The first storage chamber 102 should be large enough so that the sample, the first fluid injected through the first fluid inlet 124, can reach the sensing chamber 106 sufficiently, and the volume of the first storage chamber 102 is In general, the isolation jaw 110, the sensing chamber connection 108, the sensing chamber 106, the flow retardation unit 116 and the flow path 118 are preferably at least twice the combined volume. The second storage chamber 104 should be large enough that the buffer solution, the second fluid injected through the second fluid inlet 126, can sufficiently wash the sensing chamber 106, and the volume of the second storage chamber 104 is reduced. It is generally preferred to be at least five times the combined volume of the second flow stop 114, the sensing chamber 106, the sensing chamber connection 108, and the flow path 118. In addition, the first storage chamber 102 and the second storage chamber 104 preferably has a shape in which the width of the storage chamber is narrowed in a direction in which the flow of fluid proceeds in order to allow smooth flow to occur by surface tension. Do. This is because the larger the width of the chamber, the smaller the pressure due to the surface tension and the smaller the amount of surface tension acting in the reverse direction of the flow process. The force acting in the reverse direction of the process is minimized to keep the smooth flow.

The isolation jaw 110 separates the first storage chamber 102 and the sensing chamber 106 to define the size of each chamber, and at the same time, the sample reacted in the sensing chamber 106 is spread by the first storage chamber 102. ) To minimize backflow. In addition, the isolation jaw 110 prevents the second fluid from flowing back into the first storage chamber 102 by convection during the cleaning process, and the flow rate of the first fluid in the sensing chamber connection 108 is the flow rate of the second fluid. It does less.

The first flow stop part 112 and the second flow stop part 114 allow the sample, which is the first fluid introduced, to stop in the sensing chamber 106 and to stay for a predetermined time so that a reaction occurs in the sensing chamber 106. In addition, the second flow stop 114 also serves to stop the buffer solution, which is the second fluid. In the prior art, a stop valve in which a sudden outlet enlargement or additional hydrophobic material is formed in a flow path is used. However, only a sudden outlet enlargement is used in the upper and lower surfaces of the channel when the channel is a strong hydrophilic material and the height of the channel is shallow compared to the width. It is impossible to stop due to hydrophilic surface tension driving force, and the formation of additional hydrophobic material has the disadvantage that an additional process is required in manufacturing. Accordingly, the present invention proposes a type of stop valve illustrated in FIG. 5 to allow the flow to stop at a specific portion.

Flow stops 112 and 114 are described in more detail. 5 is a view for explaining a flow stop unit for stopping the flow of the fluid through the rapid expansion of the outlet and the increase in the channel height. 5 (a) is a plan view of the flow stop, FIG. 5 (b) is a sectional view, and FIG. 5 (c) is a perspective view, and each β is an angle of exit enlargement.

In the case of using a mold manufacturing by semiconductor processing or small machining for forming a substrate, it is generally difficult to form a channel having a gradual increase or decrease in the depth direction and have a step shape. Therefore, the increase in the channel depth can generally be manufactured in the form illustrated in (a), (b) and (c) of FIG. 7 shows an example of rapid expansion of the outlets of the flow stops 112 and 114. The angle β of the expansion of the outlet is appropriately adjusted according to the magnitude of the fluid surface tension, the contact angle according to the hydrophilicity of the channel wall, and the depth of the channel. Flow stops can be implemented. The larger the surface tension of the fluid, the stronger the hydrophilicity of the channel wall surface, the smaller the contact angle, and the smaller the depth of the channel, the larger the value of β. In particular, the pointed shape at the end of the expansion outlet in the example shown in Figure 7 is a shape that can serve as a stable stop valve as an example that can be very large β. In this case, however, the flow path may be disturbed and processing may be difficult.

The shape between the isolation jaw 110 and the sensing chamber connection 108 preferably has the shape shown in FIG. 8. 8 (a), 8 (b) and 8 (c) show a plan view, a sectional view and a perspective view, respectively. The isolation jaw 110 should be shallow in depth for the above-described function, and the sensing chamber connection 108 should be relatively deep in order to minimize flow resistance during cleaning. As described in Equation 9, when the fluid is hydrophilic, if the depth of the channel suddenly increases, it becomes impossible to move to the deep channel by acting as a stop valve. In this case, if a deep channel is reduced in width as in the example shown in Fig. 8 between the shallow channel and the deep channel as a proposal to continue the flow, the surface tension in the flow direction at the end of the added channel is reduced. It works great to prevent the flow from stopping. The reduced angle β should depend on the relative depth difference of the channels, and the larger the depth difference, the smaller β will ensure flow persistence.

Flow delay unit 116 serves to significantly reduce the flow rate of the sample in order to ensure a sufficient reaction time between the sample and the biochemical made in the sensing chamber 106. For example, the sample moving rapidly by the capillary force flows slowly through the flow retardation unit 116 over about 2 to 10 minutes. Typical flow rate control methods include controlling the shape of the channel, controlling the temperature for changing the surface tension of the fluid, and adding various surfactants for changing the contact angle of the solid surface.

9 is a plan view illustrating the flow delay unit 116 as an example of controlling the shape of the channel to delay flow. 9 (a) is a case of a two-dimensional linear channel, the delay time t for the traveling distance L in the flow in the channel due to the surface tension is expressed by Equation 11 below.

Where h is the height of the channel, σ is the surface tension, θ is the contact angle, and μ is the viscosity coefficient. When the height is gradually expanded, the flow delay time is represented by the following equation (12).

Equations 11 and 12 represent the length and time from the inlet when driven by surface tension alone without the pressure difference between the inlet and outlet. In practice, due consideration should be given to the roughness at the wall of the channel and to changes in viscosity and velocity boundary conditions in very small channels. In addition, consideration should be given to the structure and flow resistance of the channel in front of the flow retarder unless the flow retarder 116 is at the inlet. FIG. 7 (b) shows the shape of retarding the flow rate through the diffuser effect. The diffuser effect means that the driving pressure is increased while reducing the flow velocity by widening the channel width. FIG. 7 (c) shows a shape in which expansion and contraction channels are connected, and FIGS. 7 (d) and 7 (e) show a shape in which the shape of FIG. 7 (c) is concentrated. In this way, the width, length, and height of the channel can be adjusted appropriately to allow the flow to stall for the desired time.

10 is a view for explaining a method of delaying the flow by using the change in the surface tension of the fluid through temperature control. 10 (a) shows the change in the surface tension σ of the fluid according to the change in temperature T. In general, the higher the temperature, the lower the surface tension. As described in Equation 11, the flow delay time is inversely proportional to the magnitude of the surface tension. FIG. 10 (b) is a view for explaining a method of changing a flow rate by changing a temperature gradually or in various forms by inserting a structure capable of temperature change such as an electrode on a bottom surface of a square channel. Since the surface tension acts at the tip of the fluid, by adjusting the temperature of the heat generating patch 140 at the position where the tip of the fluid reaches, it is possible to control the speed by making the surface tension. Figure 10 (c) is an illustration of a microvalve using the surface tension change through the temperature change, by giving the temperature change and the surface tension change by the heating patch 142 to the end of the fluid stopped by expansion can be a valve function. have.

11 is an exemplary view for explaining the waste chamber 120. The waste chamber 120 should have a sufficient volume to include both volumes of the first fluid and the second fluid injected through the first fluid inlet 124 and the second fluid inlet 126. In addition, since the cleaning process is caused by the capillary force acting in the waste chamber, it should have a structure that generates sufficient driving force. To this end, the present invention proposes a shape in which the diffuser-type chamber and the diffuser shape and the structure are combined, and the width gradually decreases. The diffuser chamber is a square, triangular and circular chamber as shown in FIGS. 11 (a), 11 (b) and 11 (c), and a shape in which multiple chambers as shown in FIGS. 11 (d) and 11 (e) are combined. f), a gradually decreasing shape such as 11 (g), and a shape in which a diffuser type and a width reducing type are combined as shown in FIG. 11 (h) may be used.

FIG. 12 is an exemplary diagram for describing a shape of a structure that may be installed in the diffuser type waste chamber of FIG. 11. This structure is shaped to sufficiently increase the surface tension using an increase in surface area. Each shape does not have to be the same as the height of the channel, and may vary in size, direction, and arrangement, and may combine heterogeneous patterns or may be placed throughout or at the diffuser waste chamber. In addition, the structure may be used to uniformize the overall tip shape of the fluid during the flow to prevent the appearance of fine air bubbles that may be caused by the local flow rate difference.

FIG. 13 is a plan view of a lower substrate for explaining a state in which the reaction chamber 150 is added to the microfluidic device controlled by the surface tension of FIG. 3. Referring to FIG. 13, an example in which a sample is not directly moved to the sensing chamber 106 as illustrated in FIG. 3, and an reaction chamber 150 that causes an additional reaction is added on the lower substrate. In the added reaction chamber 150, a biochemical / chemical compound in a powder, colloid, gel, or solution state may be previously formed on the reactant attachment structure 152 to react with the injected sample. Various surfactants may be added to aid the reaction between the biochemical and the biochemical or to control the flow rate of the reacted sample. Referring to FIG. 13, a time delay unit 154 may be introduced, which is an additional isolation barrier that serves as a time delay for the reaction in the added reaction chamber. A tip-shaped holding protrusion 156 is introduced on the side wall of the time delay part 154, which is the isolation jaw, to make the velocity of the fluid tip constant at the time delay part. The protrusion structure 156 serves to hold the liquid tip that has arrived first to help the fluid tip to move uniformly in the axial direction.

14 is a plan view of a lower substrate for explaining another embodiment of the microfluidic device controlled by the surface tension shown in FIG. 13. Referring to FIG. 14, an embodiment in which a reaction chamber 150 is added to the shape of the microfluidic device illustrated in FIG. 3, and another form of the second storage chamber 104 and the waste chamber 120 is used. . As such, the reaction chamber may be added and removed or the size and shape of the shape may be changed according to the purpose.

FIG. 15 is a view for explaining an embodiment in which microfluidic devices controlled by the surface tension of FIG. 3 are arranged in series or in parallel. 15A illustrates an embodiment in which the microfluidic devices of FIG. 3 are arranged in series. In this case, different samples and buffers may be injected into the second storage chamber so that different reactions occur sequentially in the sensing chamber. FIG. 15B illustrates an embodiment in which the microfluidic devices of FIG. 3 are arranged in parallel. In this case, different samples and buffers may be injected into the second storage chamber so that different reactions may occur simultaneously in the sensing chamber.

FIG. 16 is a plan view of a lower substrate for explaining an embodiment in which the microfluidic device controlled by the surface tension of FIG. 3 has multiple electrode strings. Referring to FIG. 16, a plurality of sensing units are arranged in parallel in order to enable generation of different reactions in each sensing chamber. The sensing electrode of each sensing unit may be previously attached to a specific biochemical material so that different biochemical coupling occurs.

As described above, the microfluidic device controlled by the surface tension according to the present invention not only transfers and stops a small amount of fluid through natural flow by capillary force, but also changes in shape of the flow path, surface modification, and temperature control. By providing a microfluidic control element that can control the moving speed of the fluid and realize a total replacement of the solution through the need, no additional device and power supply is required, making the device compact and portable, lowering the manufacturing cost and at the same time manufacturing In addition to increasing the yield, there is almost no effect in use. In addition, the microfluidic device controlled by the surface tension according to the present invention includes a protein chip, a DNA chip, a drug delivery system, and a microbiological / chemical reactor, which require fine and accurate flow control. It can be applied to various bio devices.

As mentioned above, although preferred embodiment of this invention was described in detail, this invention is not limited to the said embodiment, A various deformation | transformation by a person of ordinary skill in the art within the scope of the technical idea of this invention is carried out. This is possible.

1 is a view for explaining the shape change of the droplet and the form of the capillary flow when the microdroplet is in contact with the solid surface or applied to the capillary.

2 is an exemplary view of various types of flow paths for explaining capillary flow.

3 is a plan view of the lower substrate and the upper substrate of the microfluidic device controlled by the surface tension according to a preferred embodiment of the present invention.

4 is a cross-sectional view when the upper substrate and the lower substrate shown in FIG. 3 are combined.

5 is a view for explaining a flow stop unit for stopping the flow of the fluid through the rapid expansion of the outlet and the increase in the channel height.

6 is a cross-sectional view for explaining a modification of the flow stop.

7 is a plan view of a modification of the sudden exit enlarged shape of the flow stop.

8 is a view for explaining the shape between the isolation jaw and the sensing chamber connection.

9 is a plan view for explaining the flow delay unit.

10 is a view for explaining a method of delaying the flow by using the change in the surface tension of the fluid through temperature control.

11 is an exemplary view for explaining a waste chamber.

FIG. 12 is an exemplary diagram for describing a shape of a structure that may be installed in the diffuser type waste chamber of FIG. 11.

FIG. 13 is a plan view of a lower substrate for explaining a state in which a reaction chamber is added to the microfluidic device controlled by the surface tension of FIG. 3.

14 is a plan view of a lower substrate for explaining another embodiment of the microfluidic device controlled by the surface tension shown in FIG. 13.

FIG. 15 is a view for explaining an embodiment in which microfluidic devices controlled by the surface tension of FIG. 3 are arranged in series or in parallel.

FIG. 16 is a plan view of a lower substrate for explaining an embodiment in which the microfluidic device controlled by the surface tension of FIG. 3 has multiple electrode strings.

<Explanation of symbols for the main parts of the drawings>

100: lower substrate 102: first storage chamber

104: second storage chamber 106: detection chamber

108: detection chamber connection 110: isolation jaw

112: first flow stop 114: second flow stop

116: flow delay unit 118: flow path

120: waste chamber 122: waste chamber structure

124: first fluid inlet 126: second fluid inlet

128: air hole in the waste chamber

130: upper substrate 132: sensing electrode

134: electrode pad 136: electrode wiring

Claims (15)

In the microfluidic device that the upper substrate and the lower substrate is combined to control and react with the fluid, The lower substrate, A first storage chamber and a second storage chamber in which the first fluid and the second fluid are respectively stored; At least one sensing chamber in communication with the first storage chamber and the second storage chamber; A first flow stop and a second flow stop to stop movement of the first or second fluid; A flow delay unit for reducing a moving speed of the first fluid or the second fluid; A waste chamber in which the first fluid or the second fluid in which the reaction is completed is discarded; And A flow path connecting the flow retardation unit and the waste chamber to move the fluid, The upper substrate is At least one sensing unit for measuring the biochemical reaction in the sensing chamber, When the first fluid moves to the sensing chamber by capillary force, a first biochemical reaction occurs, and after a predetermined time, when the second fluid enters the sensing chamber by capillary force, the first fluid is replaced and the second biochemistry. Microfluidic device controlled by the surface tension, characterized in that the reaction takes place. The method of claim 1, wherein the lower substrate And a isolation jaw and a sensing chamber connection portion between the first storage chamber and the sensing chamber. The method of claim 2, wherein the isolation jaw and the sensing chamber connecting portion Surface tension-controlled microfluidic device, characterized in that the flow of the fluid by the surface tension through the stepped increase in the channel height and the decrease in the channel width, respectively. The method of claim 1, wherein the first storage chamber and the second storage chamber is And a first fluid inlet and a second fluid inlet through which the first fluid and the second fluid are injected, respectively. The method of claim 1, wherein the first storage chamber and the second storage chamber is The microfluidic device controlled by the surface tension of the first fluid and the second fluid by the surface tension has a shape that narrows in the direction in which the movement proceeds. The method of claim 1, wherein the detection unit A sensing electrode formed at a portion corresponding to the sensing chamber; An electrode pad transferring an electrical signal through coupling with an outside; And The microfluidic device is controlled by the surface tension comprising an electrode wiring for connecting between the sensing electrode and the electrode pad. The method of claim 6, wherein the sensing electrode A microfluidic device controlled by surface tension, characterized in that a biochemical such as protein or DNA is fixed. The method of claim 1, wherein the lower substrate And a reaction chamber in which a pretreatment biochemical reaction with respect to the first fluid occurs between the first storage chamber and the sensing chamber. The method of claim 1, wherein the waste chamber is Surface tension-controlled microfluidic device having a structure for increasing the surface area in the waste chamber to increase the surface tension. The method of claim 1, wherein the waste chamber is Surface tension-controlled microfluidic device characterized in that it has a form of gradual enlargement or gradual reduction of the channel width to increase the surface tension and ensure sufficient volume. The method of claim 1, wherein the first flow stop and the second flow stop A microfluidic device controlled by surface tension, characterized by stopping the movement of the fluid by using a stepped enlargement of the channel width and a stepped increase of the channel height or by controlling the surface tension of the fluid with temperature. The method of claim 11, wherein the first flow stop and the second flow stop are Surface tension-controlled microfluidic device, characterized in that the flow is resumed by dissipating the surface tension barrier through the combination of different fluids. The method of claim 1, wherein the flow delay unit Surface tension, characterized by changing the shape of the channel, changing the surface tension of the fluid by changing the temperature of the channel wall, or by adding a surfactant to change the contact angle of the channel wall, reducing the speed of fluid movement. Microfluidic device controlled by. In the microfluidic device series array in which a plurality of microfluidic devices according to claim 1 are arranged in series, A waste chamber of the N-1 th microfluidic device is connected to the sensing chamber of the N th microfluidic device, and a different second fluid is injected into each second storage chamber so that biochemical reactions occur sequentially in each sensing chamber. Microfluidic device series array, characterized in that. In the microfluidic device parallel array in which a plurality of microfluidic devices according to claim 1 are arranged in parallel, Each sensing chamber is connected to a common first storage chamber, and a different second fluid is injected into each of the second storage chambers so that a biochemical reaction occurs simultaneously in each sensing chamber. .