KR20060017701A - Microfluidic device and diagnostic and analysis device having the same - Google Patents

Abstract

The present invention relates to a microfluidic device and a diagnostic and analytical device having the same. The microfluidic device according to the present invention is a microfluidic device having a microchannel through which a microfluid flows. An inlet having a predetermined section length having one cross section; The microfluid is disposed adjacent to the inlet, and the microfluid discharged from the inlet is introduced, and when the microfluid flows by the capillary force, the curvature of the interface is reduced than the inlet, thereby decreasing the flow rate. A flow delay unit having a second section having an area larger than that of the cross section and having a predetermined section length in a direction in which the microfluid flows; And a flow recovery part of a predetermined section length disposed adjacent to the flow delay part and having a third cross-section having a smaller cross-sectional area than a second end surface of the flow delay part, and having a microfluid discharged from the flow delay part. Characterized in that. Thereby, through the shape design of the flow path in the natural flow by the capillary force, not only can additionally quantitatively control the small amount of fluid flow without additional manipulation and energy, but also is easy to manufacture and simple to use.

Microfluidics, microchannels, capillary flow, diagnostic devices, analytical devices

Description

Microfluidic Device and Apparatus for Diagnosing and Analyzing Having the Same}

1 is a schematic diagram of a typical microchannel;

2 is a graph showing the change over time of the pressure distribution of the capillary flow,

3 is a conceptual diagram of a flow delay model in consideration of a change in interfacial curvature;

4A is a simplified diagram of a microfluidic device according to a first embodiment of the present invention;

4b is a simplified diagram of a microfluidic device according to a second embodiment of the present invention;

4C is a simplified diagram of a microfluidic device according to a third embodiment of the present invention;

5a to 5f show various cross-sectional views of the microfluidic device according to the present invention;

Figure 6 is a photograph of the change in flow in the flow delay model of Figure 5a,

7A is a schematic diagram of a flow acceleration model when the capillary primary length is kept constant and the ratio of the secondary lengths is increased;

FIG. 7B is a schematic diagram of a flow acceleration model in which an inner wall is inserted into an area where an interface is located in FIG. 7A;

8A is a graph showing the change over time of the pressure distribution in the case of expanding the flow passage cross-sectional area,                 

8B is a graph showing a change in velocity for each section in the case of enlarged flow passage cross section,

FIG. 8C is a graph showing the results of change over time of the D ₁ region velocity in the case where the wall is inserted into the flow acceleration model to increase the magnitude of the interfacial pressure. FIG.

8d is a graph showing the effect of the number of internal walls inserted on the speed;

9A is a schematic diagram of a microfluidic device of the flow acceleration model according to the first embodiment of the present invention;

9b to 9c are schematic views of a flow acceleration model according to the second and third embodiments of the present invention, including structures of various shapes to increase capillary force;

10 is a schematic diagram of a diagnostic and analysis device according to a first embodiment of the present invention applying a flow delay model and a flow acceleration model according to the present invention;

11 is a schematic diagram of a diagnostic and analysis device according to a second embodiment of the present invention with a flow branch model using a flow delay model;

12 is a schematic diagram of an apparatus for multiple diagnosis and analysis according to a third embodiment of the present invention using the flow delay model, the flow acceleration model, and the flow branch model of the present invention.

* Explanation of symbols for main parts of the drawings

 1: Diagnostic and analysis device with microfluidic device

10 microfluidic element of the flow delay model 11 inlet

12: delay boundary area 13: flow delay unit

14: recovery boundary zone 15: flow recovery                 

20: microfluidic device of the flow acceleration model 21: inlet

22: cross-sectional expansion portion 23: flow acceleration portion

24: acceleration wall 25: tip of acceleration wall

26: acceleration passage 30: gas passage

31: inlet 32: outlet

40: branch control furnace 41: suspension furnace

42: flow delay unit 43: flow recovery unit

50: discharged fine flow path 60: flow stop

70: discharge pipe 71: air outlet

The present invention relates to a microfluidic device and a diagnostic and analysis device having the same, and more particularly, to a microfluidic device capable of quantitatively controlling the flow of a very small amount of fluid in a natural capillary flow by capillary force. (microfluidic device) and a diagnostic and analysis device having the same.

The microfluidic technology of flow generation and control for transporting and controlling very small amounts of fluid is a key element technology enabling the operation of diagnostic and analytical devices, which can be implemented with various driving principles. Among them, a pressure-driven method for applying pressure to the fluid injection portion, an electrophoretic method for transferring fluid by applying a voltage between the microchannels, an electroosmotic method, and a capillary force The capillary flow method used is representative.

A representative example of a microfluidic device of a pressure-driven microfluidic device by artificial pressure is U.S. Patent No. 6,296,020. U.S. Patent No. 6,296,020 uses a manual valve such as control of a cross-sectional area of a hydrophobic fluid element and hydrophobic control of a flow path. A fluid circuit element is disclosed. In addition, U.S. Patent No. 6,637,463 discloses a microfluidic device for uniformly distributing fluid into a plurality of flow paths by designing a flow path having a pressure gradient.

On the other hand, the capillary flow method takes advantage of the capillary phenomenon that occurs naturally in the micro-channel, so that an extremely small amount of fluid placed in the fluid injection portion without additional device moves naturally and immediately along a given channel, which is currently utilized. There is an active research on the design of a microfluidic system. U.S. Patent No. 6,271,040 discloses a diagnostic biochip that detects a specific substance in a sample by an optical method by transferring the sample using a natural capillary flow in a microchannel without using a porous material and causing a reaction of the sample. It is starting. In addition, US Patent No. 6,113,855 discloses a device for generating capillary force by properly arranging hexagonal pillars for transporting a sample between two points away from the diagnostic device.

However, in a conventional microfluidic device and a diagnostic and analysis device having the same, a section in which a reaction occurs in order to provide a sufficient reaction time for a reaction between samples while minimizing the overall time required in the diagnostic and analysis device. Although there is little research on this technique, although it is important to design a flow path in which a flow rate is reduced only at a specific time point at which a sample is reached, or a flow rate is increased only at a specific time point for a cleaning effect for selectivity of the reaction. There was this. In consideration of these problems, a method of changing the equilibrium contact angle by partially strengthening or weakening the interfacial tension or partially changing the surface energy of the capillary wall may be considered. However, such a method may require additional devices or additional work.

Therefore, the object of the present invention, in order to solve this problem of the prior art, through the shape design of the flow path in the natural flow by the capillary force can not only quantitatively control the very small amount of fluid flow without additional manipulation and energy The present invention also provides a microfluidic device that is easy to manufacture and simple to use, and a diagnostic and analysis device having the same.

According to the present invention, there is provided a microfluidic device having a microchannel through which a microfluid flows, the inlet having a predetermined section length having a first cross section through which the microfluid flows; The microfluid is disposed adjacent to the inlet, and the microfluid discharged from the inlet is introduced, and when the microfluid flows by the capillary force, the curvature of the interface is reduced than the inlet, thereby decreasing the flow rate. A flow delay unit having a second section having an area larger than that of the cross section and having a predetermined section length in a direction in which the microfluid flows; And a flow recovery part of a predetermined section length disposed adjacent to the flow delay part and having a third cross-section having a smaller cross-sectional area than a second end surface of the flow delay part, and having a microfluid discharged from the flow delay part. It is achieved by a microfluidic device characterized in that.

Here, the length of the predetermined section of the flow delay unit is preferably shorter than the width of the flow delay unit.

The first end face of the inflow part, the second end face of the flow delay part, and the third end face of the flow recovery part may be configured so that each cross-sectional area is constant at each section length.

In addition, the angle formed by the wall portion in the longitudinal direction of the inflow portion and the horizontal wall portion in the longitudinal direction of the flow delay portion is preferably 45 degrees or more and 90 degrees or less.

The second cross section may have the same height as the first cross section, but may be configured to have a larger width. The width of the second cross section may be configured to be three times larger than the width of the first cross section.

In addition, the second cross section may be configured to have the same width as the first cross section, but a greater height, wherein the height of the second cross section is twice as large as the height of the first cross section, and the second cross section and the first cross section. The upper surface of one end surface can be comprised so that it may be coplanar.

The first cross section and the third cross section are preferably the same.                     

In addition, according to the present invention, there is provided a diagnostic and analysis device having the aforementioned microfluidic device.

On the other hand, an object of the present invention, a diagnostic and analysis device having a microfluidic device having a microfluidic passage through which the microfluid flows, comprising: a gas passage through which the microfluid flows; And a plurality of branch regulating furnaces connected to the oil passages and branching the microfluid flowing from the oil into a plurality of the microfluidic elements, wherein each branch control passage is connected to the oil passages. A floating furnace having a first cross-section having a smaller cross-sectional area than that of the furnace; The microfluids are connected to the floating path and discharged from the floating path, and when the microfluid flows by capillary force, the curvature of the interface is reduced in the floating path, so that the flow rate is reduced. A flow delay unit having a second section having an area larger than the area and having a predetermined section length in a direction in which the microfluid flows; And a flow recovery part having a third cross-section having a smaller cross-sectional area than a second cross-section of the flow delay part, wherein the microfluid discharged from the flow delay part flows in. Diagnosis and analysis with a microfluidic device comprising a It is also achieved by the device.

Wherein a cross-sectional area of the floating passage upstream of the flow direction of the microfluid in the filling passage is such that the microfluid flowing in the filling passage reaches the respective microfluidic elements at about the same time. It is preferred to be larger than the cross-sectional area of the float furnace downstream.

And the number of branch regulating furnaces upstream of the flow direction of the microfluid in the main flow passage so that the microfluid flowing through the main flow passage reaches the respective microfluidic elements at about the same time is the flow of the microfluid. Preferably more than the number of branching furnaces downstream of the direction.

Further, the length of a predetermined section of the floating passage upstream of the flow direction of the microfluid in the filling passage so that the microfluid flowing in the filling passage reaches the respective microfluidic elements at about the same time, the flow of the microfluid It is preferred to be longer than the length of the predetermined section of the floating furnace downstream of the direction.

In addition, at least one acceleration wall disposed along the longitudinal direction is installed in the gas passage so that the capillary force increases as the microfluid flows in the gas passage, thereby reaching the microfluidic elements at substantially the same time. It is preferable.

In addition, the discharge micro flow path connected to the microfluidic device, a flow stop passage connected to the discharge micro flow path to stop the microfluid at the end of the discharge micro flow path, and connected to each of the flow stop passages, respectively, inside the microfluidic device. It may be configured to further include a discharge pipe for discharging the air present in the outside through the discharge micro-path.

Each of the microfluidic elements may include an inflow passage having a fourth cross section through which the microfluid discharged from the floating passage flows; A cross-sectional extension part in which the microfluid discharged from the inflow path is introduced and gradually extends from the fourth end face to a fifth end face having an area larger than that of the fourth end face; And a flow accelerator having a cross section substantially the same as the fifth cross section.

Here, the flow acceleration unit, it is preferable to have at least one acceleration wall arranged in the longitudinal direction at a predetermined interval horizontally in the longitudinal direction in which the microfluid flows to form a plurality of flow paths therein.

In addition, it is preferable that the end portion of the cross-sectional extension portion side of the acceleration wall is pointed so that the fine liquid flowing into the flow acceleration portion from the cross-sectional expansion portion flows separately into the plurality of flow paths.

And, the acceleration wall may be a thin plate formed in the longitudinal direction of the flow acceleration portion.

In addition, the surface of the flow path of the flow acceleration portion may be hydrophilic.

The inflow path may be a flow path connected to a detection unit in which the microfluid introduced from the suspension path reacts with a fixed antibody present therein.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

The present invention effectively reduces or increases the velocity of a fluid flowing through a capillary effect in a specific region. First, the flow equation is used to summarize the model equations for pressure difference and contact angle at the interface, which is the root cause of capillary flow, and to delay the flow using the capillary effect. The design principle of the delay module and the flow acceleration module will be described.

Capillary flow generation is due to a discontinuous change in pressure occurring at the gas-liquid interface and is manifested when the interface is curved and curved. The cause of the interfacial curvature is the contact angle (θ) between the interface and the wall at the triple point where the gas-liquid interface and the solid wall meet. In general, the contact angle is defined as the angle toward the liquid at the interface between the wall and the surface, where 0 <θ <π / 2 if the wall is more intimate with the liquid than gas, and vice versa π / 2 <θ <π. Neglecting the edge effect of the tube in the case where the cross section of the fluid flow path is rectangular, the pressure change excluding the flow effect can be expressed as follows.

------ (수학식 1)

------ (Equation 1)

FIG. 1 is a schematic diagram of a general microchannel, as shown here, where the general microchannel is manufactured to have a depth and width of several tens to hundreds of micrometers (μm). In Equation 1, depth is represented by b and width is represented by c. In most cases, it is manufactured under the condition of b <c. Therefore, b may be referred to as primary length and c as secondary length according to the contribution to ΔP generation. The pressure change occurring at the interface is connected to the position (a) of the interface to generate a pressure gradient of ΔP / a, which produces the motion of the fluid. The generated flow is included in the laminar flow region, and the resistive terms (?) And the flow rate (v) due to the pressure gradient term and the flow path wall surface have the following relationship.

---------- (수학식 2)

---------- (Equation 2)

In the case of a rectangular flow passage cross section, the resistive term is given as follows for the primary length (b) and the secondary length (c) of FIG.

---------- (수학식 3)

---------- (Equation 3)

Assuming a pseudo steady state, the following ordinary differential equation for the interface position can be obtained.

--------- (수학식 4)

--------- (Equation 4)

As shown in FIG. 1, if the flow passage cross section is rectangular and constant, a theoretical solution regarding the interface position, flow velocity, and pressure distribution can be obtained. In FIG. 2, the time-dependent change in the pressure distribution of the capillary flow is shown when 2b = 50 μm, 2c = 200 μm, Υ = 0.07 N / m, and θ = π / 3. In FIG. 2, a negative pressure gradient is a liquid phase region, a pressure free interval is a gas phase region, and a sudden change in slope corresponds to a position of an interface. The flow generated by the amount of pressure change in the liquid phase region shifts the position of the interface, and as the position of the interface moves, the slope of the pressure change gradually decreases, and thus the speed of the interface movement decreases with time.

The key idea of constructing the flow retardation model of the present invention is to reduce the ΔP and to retard the flow in a specific region by effectively adjusting the interface curvature by bending the wall with respect to the primary length or the secondary length. 3 is a conceptual diagram of a flow retardation model considering a change in interfacial curvature. As shown in this figure, in the case of a hemispherical interface, the curvature of the interface causing the pressure (ΔP) generated at the interface is at the contact point where the interface and the wall surface meet. It is proportional to the cosine of the angle between the straight line contacting the interface and the forward direction e _i of the interface. In this case, in the case of a simple straight wall surface having a constant wall shape, the wall surface coincides with the contact angle θ formed between the interface and the wall surface. Method of changing the surface curvature, that is, how to give way to the interface change the advancing direction (e _i) angle of the forming of the straight line and the interface in contact with the contact point changes in δθw In Figure 3 the method of varying the δθi divided into I can think of it. In this case, the method of changing δθi is to change the thermodynamic state of the wall constituent material. Therefore, additional work on the specific wall surface must be performed when designing the flow path. On the other hand, giving a change in δθw by bending the wall does not require additional work when manufactured using a technique such as photolithography. In addition, the change in interfacial curvature through δθi is possible only in a limited range related to the physical properties of the wall, while the change in interfacial curvature through δθw is possible in a wider range. In the present invention, the latter method is adopted.

4A is a simplified diagram of the microfluidic device of the flow delay model according to the first embodiment of the present invention, and FIG. 4B is a simplified diagram of the microfluidic device of the flow delay model according to the second embodiment of the present invention. The microfluidic device of the flow retardation model according to the first embodiment of the present invention is a flow retardation model having wall curvatures varying the secondary length of the microchannel, and the microfluidic device of the flow retardation model according to the second embodiment of the present invention Flow retardation model with wall curvature with varying primary length of flow path. As shown therein, the microfluidic elements 10 and 10a according to the first and second embodiments of the present invention have inlet portions 11 and 11a having a predetermined section length having a first cross section through which the microfluid flows. ) And the microfluids discharged from the inlets 11 and 11a are disposed adjacent to the inlets 11 and 11a and the interface is more interfacing at the inlets 11 and 11a when the microfluid flows due to capillary force. Flow delay parts 13 and 13a having a second section having an area larger than the area of the first section and having a predetermined section length in the direction in which the microfluid flows so that the curvature of the filter decreases and the flow velocity decreases. The microfluids are disposed adjacent to the delay parts 13 and 13a and discharged from the flow delay parts 13 and 13a and have a third cross section having a smaller cross-sectional area than the second cross sections of the flow delay parts 13 and 13a. It has flow recovery parts 15 and 15a of predetermined section length.

The supplied capillary flow generates a flow delay effect in the delay boundary regions 12 and 12a, which are boundary regions between the inflow portions 11 and 11a and the flow delay portions 13 and 13a. The delay effect lasts for the duration of the passage. The capillary flow passing through the delay boundary regions 12 and 12a passes through the flow delay portions 13 and 13a and is a recovery boundary region which is a boundary region between the flow delay portions 13 and 13a and the flow recovery portions 15 and 15a. Interfacial curvature increases while contacting (14, 14a) to restore the previous flow rate. The flow rate gradually recovered is returned to the previous flow rate while being transferred to the flow recovery units 15 and 15a to continue the flow.

In the present embodiments, the fluid passage cross-sectional area is designed to be the same as the inflow portions 11 and 11a in the flow recovery portions 15 and 15a corresponding to the position where the wall bending ends. This allows the capillary flow passing through the flow retardation model to recover at a rate prior to passage, for the purpose of the flow retardation model that temporarily retards the flow at a particular location, at a specific time. As emphasized above, this flow retardation effect can be controlled by changing the wall angle.

When the bend is made at right angles as shown in FIGS. 4A and 4B, capillary flow may be maintained by maintaining a plane on at least one of four surfaces surrounding the fluid to prevent the flow from completely stopping. On the other hand, in general, the section length of the flow delay unit (13, 13a) must be shorter than the width of the flow delay unit (13, 13a) to continue the flow, so in general, the section length of the flow delay unit (13, 13a) than the width It is short. In addition, the first end face of the inflow parts 11 and 11a, the second end face of the flow delay parts 13 and 13a, and the third end face of the flow recovery parts 15 and 15a are configured such that each cross-sectional area is gradually changed in each section length. In this embodiment, however, each section length is configured to remain constant. In addition, the angle formed by the wall portion in the longitudinal direction of the inflow portions 11 and 11a and the horizontal wall portion in the longitudinal direction of the flow delay portions 13 and 13a is formed at 90 degrees. The height of the first section is the same as the first section, but the width of the second section is about three times larger than the width of the first section. In the second embodiment, the second section has the same width as the first section but the height of the second section is the height of the first section. It is larger than 2 times but the upper surface of the second cross section and the first cross section is configured to be in the same plane.

In particular, in the case of the wall curved surface of the primary length of FIG. 4b, the curvature flow is maintained only when one surface is bent and the plane is maintained on the other three surfaces, but the wall surface is sufficiently hydrophilic to ensure continuous capillary flow. Therefore, in order to ensure a continuous capillary flow, it is necessary to manufacture the flow delay part by changing the secondary length to make the wall curved and maintaining the primary length as shown in FIG. 4A. By controlling the size of each region, the flow delay effect can be controlled. If the delay boundary regions 12 and 12a are long lasting, the flow delay effect is increased due to the influence of the flow passage cross-sectional area increase. Therefore, when forming the wall bend, it is advantageous to repeatedly generate the flow retardation effect by periodically forming the bend instead of reducing the length of the section where the wall is opened. In other words, when designing the flow retardation model, it is necessary to repeatedly make small bends rather than give large bends to the wall and to create a quantitative effect of flow retardation by the number of total bends.

4C is a schematic diagram of a microfluidic device according to a third exemplary embodiment of the present invention. In the microfluidic device according to the third exemplary embodiment of the present invention, two flow delay models are connected in series, corresponding to the first exemplary embodiment. The element is indicated by the addition of 'b'. Therefore, the capillary flow supplied from the inlet inlet 11b is delayed by the second flow delay model 17 after the flow is delayed by the first flow delay model 16. At this time, the flow recovery part 15b of the first flow retardation model 16 becomes the inflow part of the second flow retardation model 17. By continuously connecting the flow delay models 16 and 17 in this way, the flow delay effect is adjusted by the number of connected flow delay models.

5A to 5F are various cross-sectional views of a microfluidic device according to still another exemplary embodiment of the present invention. The flow delay effect is controlled by changing the shape and dimensions of the delay boundary region, the flow delay portion, and the recovery boundary region with respect to the rectangular microchannel. The flow delay model of FIG. 5A is a case where the delay boundary regions are vertically connected to both walls of the inflow portion as shown in FIGS. 4A to 4C of the first to third embodiments described above, and the shape of the flow delay portion is a quadrangle. On the other hand, the flow delay model of FIG. 5B has a delay boundary region vertically connected to one wall of the inlet so that the capillary flow supplied to the inlet is delayed in the delay boundary region, but the opposite wall does not interfere with the flow of the flow. Thus, the delay effect is lower than the flow delay model of FIG. 5A. In the flow retardation model of FIG. 5C, a delay boundary region is connected to one wall of the inflow portion, and the shape of the flow retardation model is trapezoidal when the angle formed by the inflow portion and the delay boundary region is acute. Since the angle formed by the inlet and the delay boundary region is an acute angle, the delay effect is superior to the flow delay model of FIG. 5B. The flow delay model of FIGS. 5D to 5F is a case where the width of the flow delay unit is narrow in the flow delay model of FIGS. 5A to 5C. That is, in the case where the expanded cross-sectional area of the flow delay portion is reduced than that of FIGS. 5A to 5C, the flow of the flow delay model of FIGS. 5D to 5F in which the expanded cross-sectional area is reduced when compared with the flow delay model of FIGS. 5A to 5C, respectively. Low delay effect

FIG. 6 is an embodiment of the flow retardation model of FIG. 5 (a) manufactured by bonding a first plate including a pattern formed in a negative shape to a flat second plate. More specifically, after fabricating an embossed mold plate including a shape corresponding to the flow retardation model, a polydimethylsiloxane (PDMS) is cast on the mold plate to prepare a first plate including an intaglio pattern. The first plate manufactured is drilled with holes for the inlet through which the fluid can be injected from the outside and the outlet through which the fluid can be discharged to the outside. After treating the surface of the first plate and the second plate made of polymethylmethacrylate (PMMA) to control hydrophilicity, the second plate and the first plate are bonded. After the surface treatment, the contact angle of water of the first plate was 56 degrees, and the contact angle of water of the second plate made of PMMA was 75 degrees.

The Procion Red MX-5B (Aldrich Chemical Company, Inc.) chromophore was dissolved in ultra pure water and supplied to a flow delay model. As described above, the fluid supplied to the flow delay model passes through each flow delay model and generates a delay effect. As shown in FIG. 6, the fluid reaching the delay boundary region past the inlet of the flow delay model has a significant decrease in the flow velocity (see FIG. 6). The fluid maintains the delay effect while passing through the delay boundary (FIG. 6. 1 minute 40 seconds, 2 minutes 7.57 seconds), while contacting the recovery boundary areas 14 and 14a, the fluid loses the delay effect and flows into the flow at the inlet. Recovery (Fig. 6. 2 minutes 7.60 seconds, 2 minutes 7.63 seconds). At this time, the fluid transferred through the recovery boundary regions 14 and 14a to the flow recovery part took 0.5 seconds from 2 minutes 7.63 seconds in FIG. 6 to 2 minutes 13 seconds. Comparing this with the delay time in the flow delay part, 2 minutes 7.57 seconds, the effect of the flow delay part can be confirmed.

In the flow delay model of FIG. 6, the fluid moves to the recovery boundary region without passing through the flow delay portion, and air is trapped in the bend. In general, trapped air does not affect the flow, but in the case of the flow retardation model as shown in FIG.

Another main object of the present invention is to provide a flow acceleration model that increases the flow rate of capillary flow in a particular region. As can be seen from Equation 2, the capillary flow velocity increases at the position (a) of the interface as the flow proceeds. Therefore, when ΔP is fixed, the moving speed of the interface decreases with time, and the only way to accelerate it again is to increase ΔP as a increases, but the implementation thereof is very limited. However, when it is necessary to accelerate the velocity of a specific position inside the passage rather than the movement speed of the interface in the flow passage design of the diagnostic apparatus, the flow acceleration model developed in the present invention exhibits a powerful effect. The flow relation utilized in the present invention is the following mass conservation formula for the case where two flow paths having different fluid passage sections are connected.

-------------- (수학식 5)

-------------- (Equation 5)

In Equation 5, V ₁ is the velocity of the region D ₁ to be accelerated and V ₂ corresponds to the flow velocity of the region D _{2 at} which the interface is located. In Equation 5, it can be seen that the method of increasing V _{1 is} to increase V ₂ or increase the ratio of the capillary primary length (b ₂ / b ₁ ) or the ratio of the secondary length (c ₂ / c ₁ ). have. At this time, since V ₂ is a variable controlled by Equation 2, it is very limited to increase it, but the ratio of the capillary primary or secondary lengths can be changed relatively freely. A feature of the design of the flow acceleration model of the present invention is the intensive use of the effect of b ₂ / b ₁ or c ₂ / c ₁ on V ₁ .

7A is a schematic diagram of a flow acceleration model when the capillary primary length is kept constant and the ratio of the secondary lengths is increased. The reason for keeping the capillary primary length constant is to minimize the flow retardation effect experienced by the interface at the moment the position of the interface moves to the secondary length increasing region. It should be noted that the capillary pressure at the interface decreases due to an increase in c ₂ / c ₁ , which causes a flow rate reducing effect. In the present invention, as a countermeasure, a flow acceleration model in which an inner wall is inserted into a region where an interface is located is illustrated and illustrated in FIG. 7B. At this time, the increase in the number of the inner wall inserted in Figure 7b increases the flow rate by the effect of increasing ΔP, but the inner wall inserted in any number of more increases the wall resistance force, thereby reducing the flow rate. In other words, there is an optimal number of walls to maximize V ₁ for the thickness of the inner wall to be inserted. In this case, using Equation 5 can theoretically predict the optimal number of walls according to the thickness of the wall to be inserted.

In FIG. 8A, the change over time of the pressure distribution in the case of a ₁ = 2000 μm, 2b ₁ = 50 μm, 2c ₁ = 200 μm, 2b ₂ = 50 μm, 2c ₂ = 2000 μm, Υ = 0.07 N / m, θ = π / 3 Indicated. That is, it corresponds to a condition in which the calculation condition of FIG. 2 for the simple straight flow path is maintained up to a ₁ = 2000 μm and the length is increased ten times in the capillary secondary length direction. In FIG. 8A, the pressure rapidly changes in a region D ₁ having a small cross-sectional area of fluid passage, and changes with a gentle slope in a region D ₂ having a large cross-sectional area. The ratio of the slope of the pressure change in the two regions D ₁ and D ₂ is inversely proportional to the ratio of the cross-sectional area of the fluid passage and the ratio of the resistive term. The calculation condition of FIG. 8A corresponds to a case where the change in the resistive term is relatively small, so that the ratio of the slope of the pressure change is given by approximately 10: 1. Since the velocity ratio of the two regions is inversely proportional to the area ratio, the velocity of the region D ₁ having a small cross-sectional area is maintained at ten times the velocity of the region D ₂ having a large cross-sectional area. Compared with the results of FIG. 2, the size of the interfacial pressure was reduced due to the expansion of the fluid passage cross-sectional area under the conditions of FIG. 8A, and the slope of the pressure change was gentle in D ₂ , but rather, the slope of the pressure change rapidly increased in D ₁ . Can be.

8B is a result of time-dependent change in velocity for each region. The dotted line in the figure is the calculation result for the condition of FIG. 2 with no change in the cross section of the fluid passage, and the solid line is the result for the condition of FIG. Therefore, the cross-sectional area enlargement reduces the moving speed (V ₂₎ of the surface speed (V ₁₎ of the D ₁ can know the clearance made relative to the effect of maintaining a large value. In other words, the flow passage cross-sectional enlargement effect in the capillary flow can be said to suppress the decrease of the small cross-sectional area velocity.

FIG. 8C is a graph showing a result of change in time of the D ₁ region velocity with respect to the case where the wall is inserted inside the flow acceleration model to increase the magnitude of the interfacial pressure. Calculation conditions are the same as in the case of Fig. 8A, and n inner walls having a thickness of 10 μm are inserted in the area D ₂ . In FIG. 8C, it can be seen that the insertion of the inner wall increases the magnitude of the interface generating pressure and increases the speed V ₁ of the D ₁ region. In the case of excessive insertion of the inner wall, the resistance of the wall increases and thus the capillary flow rate decreases. As can be seen in FIG. 8C, the insertion of 20 inner walls increases the speed of all time intervals, while the 40 insertions of the inner walls increase the initial velocity at which the interface enters the flow acceleration model, but the speed is increased due to the increase of internal wall resistance. Suddenly decreasing again, the velocity at t = 1 [s] is smaller than without the inner wall.

In the present invention, using the mathematical model used, it is possible to calculate the optimal value of the number of interior walls to be inserted in a given condition, and the results are shown in FIG. 8D. The calculation condition used is the same as that of Fig. 8C and corresponds to the result of t = 1 [s]. In FIG. 8D, there is an optimal number of walls for maximizing V ₁ for each inner wall thickness, and as the thickness of the inserted wall is thinner, the effect of increasing the velocity increases. From the theoretical analysis results of the present invention, it can be seen that the insertion of the inner wall having the thinnest thickness possible is the most effective in accelerating the flow because it increases the amount of interfacial pressure and minimizes the internal resistance. However, since the production of a thin wall is limited according to the fabrication method, the present invention designed a flow acceleration model in consideration of the ease of fabrication of the actual microchannel.

9A is a schematic diagram of the microfluidic device of the flow acceleration model according to the first embodiment of the present invention. As shown therein, the microfluidic device 20 of the flow acceleration module according to the present invention is a microfluidic device in which a microfluid flows. An inlet portion 21 having a first cross section and a microfluid discharged from the inlet portion 21 flow in and gradually extend from the first cross section to a second cross section having an area larger than that of the first cross section. At least one having a cross-sectional extension 22 and a cross-section substantially the same as the second cross-section and are arranged along the longitudinal direction at predetermined intervals in a horizontal direction in the longitudinal direction in which the microfluid flows; And a flow accelerator 23 having an acceleration wall 24.

Here, the tip portion 25 of the cross-sectional extension portion 22 side of the acceleration wall 24 has a pointed shape so that the fine liquid of the cross-sectional extension portion 22 is separated and flows into a plurality of flow paths, and the acceleration for increasing the capillary force is increased. The wall 24 is a thin plate formed long in the longitudinal direction of the flow acceleration 23. In addition, the acceleration accelerator 24 forms the at least two acceleration passages 26 by the acceleration walls 24. On the other hand, the surface of the flow path of the flow acceleration part 23 can be hydrophilic.

In such a configuration, the capillary flow supplied to the inlet 21 is transferred to the plurality of acceleration passages 26 through the cross-sectional extension 22. One acceleration flow path has a large capillary force because of its small cross-sectional area, and by arranging a plurality of acceleration flow paths, the cross-sectional area through which the entire flow moves increases and capillary force increases. Therefore, the flow rate transferred from the cross-sectional extension part 22 to the acceleration flow path 26 is increased compared to the case where the acceleration flow path 26 is absent, which significantly increases the flow speed of the inflow portion 21.

 On the other hand, the thinner the thickness of the acceleration wall 24 inserted in order to minimize the resistance to capillary flow is better, the tip portion 25 of the wall at the point where the cross-sectional extension portion 22 and the acceleration flow path 26 is connected Maintaining a pointed triangular shape is effective. In addition, in order not to give resistance to the capillary flow, the point where the inlet portion 21 and the cross-sectional extension portion 22 are connected, and the point where the cross-sectional extension portion 22 and the acceleration flow passage 26 are manufactured are curved.

9B and 9C are schematic views of a flow acceleration model according to the second and third embodiments of the present invention including structures of various shapes to increase capillary force. The components corresponding to the first embodiment of FIG. 9A are indicated by adding 'a' and 'b', respectively, as shown in these figures, instead of the acceleration wall 24 of FIG. Increase the capillary force of the flow acceleration model by inserting the various structures of. In this case, the structure may be manufactured by selecting a suitable height from the bottom surface of the flow path to the top or a height between the top surface and the bottom surface of the flow path.

10 is a schematic diagram of a diagnostic and analysis device according to a first embodiment of the present invention applying a flow delay model and a flow acceleration model according to the present invention, and the diagnostic and analysis device 1 according to the first embodiment of the present invention. The sample includes a sample introducing unit 101, a reaction unit 102, a flow delay model 110, a detector 103, and a flow acceleration model 120 to which a sample to be diagnosed is supplied from the outside.

The reaction unit 102 includes a combination of a detection antibody and a fluorescent dye in advance, and the detection unit 103 is fixed to the surface in advance. The sample supplied through the sample introduction unit of the diagnostic and analysis device 1 is transferred to the reaction unit 102 through the microchannel. In the reaction unit 102, an antigen in a sample reacts with a combination of a detection antibody and a fluorophore to form an antigen-antibody-fluorescence chromophore conjugate. At this time, the flow delay models 110 and 111 are introduced to secure the reaction time, and the reaction time in the reaction unit 102 may be adjusted according to the design of the flow delay models 110 and 111. Since the detection antibody-fluorescence chromophore conjugate previously included in the reaction unit 102 is not fixed to this device, the antigen-antibody-fluorescence chromophore conjugate in the reaction unit 102 is transferred to the detection unit 103 through the microchannel. . The immobilized antibody is immobilized on the surface of the detector 103 so that the antigen-antibody-fluorescent chromophore conjugate reacts with the immobilized antibody of the detector 103 and is immobilized to the detector 103. At this time, the reaction time of the detector 103 is adjusted using the flow delay models 110 and 111. After the reaction in the detector 103 is completed, the sample moves to the flow acceleration model 120. The flow rate of the sample in the microchannel before the flow acceleration model 120 is increased by the action of the flow acceleration model 120, through which the unnecessary substance or non-specifically bound antigen-antibody-fluorescence present in the detector 103 is increased. The chromophore conjugate is removed.

It is yet another object of the present invention to provide a flow divergence model that uniformly diverges very small amounts of fluid into a number of microfluidic devices, using the flow delay technique described above. As described above, bending may be inserted into the microchannel to quantitatively delay the capillary flow. Therefore, when one fluid is branched into a plurality of micro-channels, the longer the delay time of the flow branched to the micro-channels is, the closer to the point from which the fluid is supplied.

FIG. 11 is a schematic diagram of a diagnostic and analysis device 1a according to a second embodiment of the present invention having a flow branch model using a flow delay model, as shown therein. The diagnostic and analysis device 1a having a fluid element includes a plurality of microfluidic devices that supply a microfluidic flow path through which the microfluid flows, and a microfluid flowing from the main flow path 30 in connection with the main flow path 30. It is provided with a plurality of branch control furnace 40 to branch to. Here, each branch control passage 40 is connected to the oil passage 30 and is connected to the floating passage 41 and the floating passage 41 having a first cross-section having a smaller cross-sectional area than that of the oil passage 30. Areas larger than the area of the first cross-section are such that the microfluid discharged from the float passage 41 flows in and the microfluid flows through the capillary force so that the curvature of the interface decreases than the float passage 41 and the flow velocity is reduced. Flow delay portion 42 having a second section having a predetermined length in the direction in which the microfluid flows, and the microfluid discharged from the flow delay portion 42 is introduced and the second of the flow delay portion 42 And a flow recovery portion 43 having a third cross section having a smaller cross section than the cross section.                     

By such a configuration, the fluid supplied through the inlet portion 31 from another microfluidic element or the outside is transferred to the oil passage 30. The fluid transferred to the main flow passage 30 is sequentially branched to each branch control passage 40 connected to the main flow passage 30 and flows into the microfluidic device through the branch control passage 40 configured based on the flow delay model. The fluid is transferred. At this time, since the branch control passage 40 has a greater delay effect as it moves away from the inlet portion 31, when the fluid reaches the discharge portion 32 through the oil passage 30, the respective floating passages 41 The fluid supplied to) is placed in the same position before being transferred to the microfluidic device. Therefore, using the present flow branching model, one fluid introduced from the inlet portion 31 is uniformly branched into a plurality of fine flow paths. That is, in this embodiment, the number of branch control paths upstream of the flow direction of the microfluid in the main flow path 30 is such that the microfluids flowing in the main flow path 30 reach each microfluidic element at about the same time. More than the number of branching furnaces downstream of the flow direction. However, the cross-sectional area of the floating passage 41 upstream of the flow direction of the microfluid in the main passage 30 is such that the microfluid flowing in the main passage 30 reaches each microfluidic element approximately simultaneously with the flow of the microfluid. It may be configured to be larger than the cross-sectional area of the floating passage 41 downstream of the direction, and also, the length of the predetermined section of the floating passage 41 upstream of the flow direction of the microfluid in the oil passage 30 is fine. Naturally, it may be configured to be longer than a predetermined section length of the floating passage 41 downstream of the flow direction of the fluid. In addition, at least one acceleration wall disposed along the longitudinal direction is installed in the oil passage 30 so that the capillary force increases as the micro fluid flowing in the oil passage 30 reaches the microfluidic element at about the same time. Of course it can.

12 is a schematic diagram of a multiple diagnosis and analysis apparatus according to a third embodiment of the present invention using the flow delay model, the flow acceleration model, and the flow branch model of the present invention, and the diagnostic and analysis device according to the third embodiment of the present invention. 1b includes a sample introduction part 301 to which a sample is supplied, a gas passage 330, a floating passage 341 connected to the oil passage 330, a diagnostic unit 310 corresponding to a microfluidic element, A discharge micro-channel 50 connected to the microfluidic device, a flow delay model 310 positioned between the floating path 341 and the diagnostic unit 310, and a discharge micro-channel 50 connected to the discharge micro-channel 50. Flow stop passage (60) for stopping the microfluid at the end of the, and discharge pipe passage connected to each flow stop passage (60) for discharging air existing in each microfluidic element to the outside through the discharge micro-channel 50 70 is provided.

Here, each microfluidic element corresponding to the diagnosis unit 310 may be provided with a flow acceleration model. That is, an inflow path having a fourth cross section through which the microfluid discharged from the floating path 341 flows, and a microfluid discharged from the inflow path is introduced and has an area larger than the area of the fourth cross section from the fourth cross section. A cross-sectional extension portion gradually extending with a predetermined section length up to 5 cross sections, and having substantially the same cross section as the fifth cross section, are aligned along the longitudinal direction at a predetermined interval in the horizontal direction in the longitudinal direction in which the microfluid flows. It may be configured to include a flow acceleration having at least one acceleration wall forming a plurality of flow paths.

In this configuration, the sample supplied through the sample introduction unit 301 is transferred to the oil passage 330. The sample transferred to the gas passage 330 is supplied to each of the microfluidic elements diagnostic unit 310 through the floating passage 341. The microchannel extending from the flow retardation model 310 is connected to the inlet of the diagnostic unit 310, and the outlet 343 of the diagnostic unit 310 is connected to the discharge microchannel 50. At this time, when the sample transferred to the gas passage 330 reaches the distal end 332 of the gas passage 330, the samples transferred to each floating passage 341 are placed in the same position, a plurality of diagnostic units 310 ) Uniformly supplied. On the other hand, the discharge passage 70 is connected to the discharge micro-path 50 so that the air existing in the diagnostic unit 310 is discharged to the outside through the air outlet (71). At this time, in order to prevent the sample of the diagnostic unit 310 from flowing into the discharge pipe (70), the flow stop passage 60 is inserted between the discharge micro-path 50 and the discharge pipe (70). The sample stops in the flow stop passage 60 because the width of the discharge micro-channel 50 is narrow and the cross-sectional area is rapidly expanded in the flow stop passage 60.

Meanwhile, the plurality of diagnostic units 310 may be replaced with different microfluidic elements to simultaneously perform various functions such as an immune reaction, a polymerase chain reaction (PCR), and a DNA hybridization reaction from one fluid. Multiple microfluidic device implementations are possible.

The micro-channel manufactured in the present invention is formed by covering the plate including the pattern of the intaglio flat or embossed or engraved plate. The plate may be made of various materials such as polymer, metal, silicon, glass, printed circuit board (PCB), and preferably includes a polymer material. For example, PMMA (polymethylmethacrylate), PC (polycarbonate), COC (cycloolefin copolymer), PDMS (polydimethylsiloxane), PA (polyamide), PE (polyethylene), PP (polypropylene), PPE (polyphenylene ether), PS (polystyrene), It refers to plastics such as polyoxymethylene (POM), polyetherketone (PEEK), polytetrafluoroethylene (PTFE), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutyleneterephthalate (PBT), and fluorinated ethylenepropylene (FEP). Such materials are widely used in mold molding such as injection molding, hot embossing or casting. In particular, such materials are generally inert and are preferred for the gastric flow path due to their ease of manufacture, low cost and one-off.

According to the present invention, a method for manufacturing a micro-channel includes manufacturing a mold plate formed with an embossed shape corresponding to the micro-channel, and imitating a negative plate on the template, and then adjusting the hydrophilicity of the surface of each plate and the second plate. And, the negative plate is bonded to the second plate.

In the above-described embodiments, the acceleration wall is provided in the flow acceleration section, but the acceleration wall is not installed in the flow acceleration section if the flow velocity of the inflow section can be sufficiently increased by extending the cross-sectional area of the flow acceleration section than the inflow section. Of course it can.

 In addition, in the above-described embodiments, the cross-sectional shape of the microfluidic device has been described above as a quadrangular shape. However, the cross-sectional shape of the microfluidic device may be various shapes such as a circular shape.

As described above, according to the present invention, through the shape design of the flow path in the natural flow by the capillary force can not only quantitatively control the very small amount of fluid flow without additional operation and energy, but also easy to manufacture and use A microfluidic device and a diagnostic and analysis device having the same are provided for simplicity.

Claims (22)

In a microfluidic device having a microchannel through which microfluid flows, An inlet of a predetermined section length having a first cross section through which the microfluid flows; The microfluid is disposed adjacent to the inlet, and the microfluid discharged from the inlet is introduced, and when the microfluid flows by the capillary force, the curvature of the interface is reduced than the inlet, thereby decreasing the flow rate. A flow delay unit having a second section having an area larger than that of the cross section and having a predetermined section length in a direction in which the microfluid flows; And It includes a flow recovery portion of a predetermined section length disposed adjacent to the flow delay portion flows in the microfluid discharged from the flow delay portion has a third cross-sectional area smaller than the second cross section of the flow delay portion; Microfluidic device, characterized in that. The method of claim 1, The length of the predetermined section of the flow delay portion is a microfluidic device, characterized in that shorter than the width of the flow delay portion. The method of claim 1, The first cross section of the inlet, the second cross section of the flow delay portion, and the third cross section of the flow recovery portion are each microfluidic device, characterized in that the respective cross-sectional area is maintained at each section length. The method of claim 1, And the angle formed by the wall portion in the longitudinal direction of the inflow portion and the horizontal wall portion in the longitudinal direction of the flow delay portion is 45 degrees or more and 90 degrees or less. The method of claim 1, The second end face is the same height as the first end but the microfluidic device, characterized in that the width is larger. The method of claim 5, And the width of the second cross section is three times greater than the width of the first cross section. The method of claim 1, The second cross section is a microfluidic device, characterized in that the width is the same as the first cross section, but the height is larger. The method of claim 7, wherein The height of the second cross-section is greater than the height of the first cross-section, the microfluidic device, characterized in that the second cross-section and the upper surface of the first cross-section is in the same plane. The method of claim 1, The first cross section and the third cross section is a microfluidic device, characterized in that the same. Diagnostic and analysis device comprising the microfluidic device according to claim 1. A diagnostic and analysis device having a microfluidic device having a microfluidic passage through which microfluids flow, An oil supply passage through which the microfluid flows; And And a plurality of branch regulating furnaces connected to the oil passages and branching the microfluid introduced from the oil passages into a plurality of the microfluidic elements. As for each said branch control, A floating passage connected to the main passage and having a first end surface having a cross-sectional area smaller than that of the main passage; The microfluids are connected to the floating path and discharged from the floating path, and when the microfluid flows by capillary force, the curvature of the interface is reduced in the floating path, so that the flow rate is reduced. A flow delay unit having a second section having an area larger than the area and having a predetermined section length in a direction in which the microfluid flows; And And a flow recovery part having a third cross section having a cross-sectional area smaller than a second cross section of the flow delay part and having a microfluid discharged from the flow delay part. . The method of claim 11, The cross-sectional area of the floating passage upstream of the flow direction of the microfluid in the filling passage so that the microfluids flowing in the filling passage reach the respective microfluidic elements at about the same time is downstream of the flow direction of the microfluid. Diagnostic and analysis device with a microfluidic device, characterized in that it is larger than the cross-sectional area of the floating furnace. The method of claim 11, The number of branch regulating passages upstream of the flow direction of the microfluid in the filling passage is such that the microfluids flowing in the filling passage reach the respective microfluidic elements approximately simultaneously with the flow direction of the microfluid. Diagnostic and analysis device with a microfluidic element characterized by more than the number of branching furnaces downstream. The method of claim 11, The length of the predetermined section of the floating passage upstream of the flow direction of the microfluid in the filling passage so that the microfluid flowing in the filling passage reaches the respective microfluidic elements at about the same time as the flow direction of the microfluid Diagnostic and analysis device with a microfluidic element, characterized in that it is longer than a predetermined section length of the floating furnace downstream. The method of claim 11, At least one acceleration wall disposed along the longitudinal direction is installed in the oil passage so that the capillary force increases as the microfluid flows in the oil passage, thereby reaching each of the microfluidic elements at about the same time. Diagnostic and analysis device provided with a microfluidic device. The method of claim 11, A discharge micro flow path connected to the microfluidic device, a flow stop connected to the discharge micro flow path to stop the microfluid at the end of the discharge micro flow path, and connected to each of the flow stop paths to be inside the microfluidic devices. And a discharge pipe for discharging the existing air to the outside through the discharged micro flow path. The method of claim 11, Each of the microfluidic elements, An inflow passage having a fourth cross section through which the microfluid discharged from the floating passage flows; A cross-sectional extension part in which the microfluid discharged from the inflow path is introduced and gradually extends from the fourth end face to a fifth end face having an area larger than that of the fourth end face; And And a flow accelerator having a cross section substantially the same as the fifth cross section. The method of claim 17, The flow accelerating portion has a microfluid, characterized in that it has at least one acceleration wall arranged in the longitudinal direction at a predetermined interval horizontally in the longitudinal direction in which the microfluid flows to form a plurality of flow paths therein Diagnostic and analysis device equipped with an element. The method of claim 18, Diagnosis and analysis device having a microfluidic device characterized in that the end portion of the cross-sectional extension portion of the acceleration wall is pointed so that the micro-liquid flowing into the flow acceleration portion from the cross-sectional expansion portion flows into the plurality of flow paths. . The method of claim 18, The acceleration wall is a diagnostic and analysis device having a microfluidic device, characterized in that the thin plate formed in the longitudinal direction of the flow acceleration portion. The method of claim 17, Diagnosis and analysis device having a microfluidic device, characterized in that the surface of the flow path of the flow acceleration portion is hydrophilic. The method of claim 17, The inflow path is a diagnostic and analysis device having a microfluidic device, characterized in that the flow path is connected to the detection unit that reacts with the immobilized antibody present in the microfluid flow from the suspension passage.

Images