This U.S. non-provisional patent application claims priority under 35 U.S.C. §119 of Korean Patent Application No. 10-2008-0131856, filed on Dec. 23, 2008, the entire contents of which are hereby incorporated by reference.
The present invention disclosed herein relates to a method of controlling a fluid flow in a microfluidic device and a microfluidic analysis apparatus.
Typical biochips quickly detect analytes such as biomaterials or environmental materials using membranes or hygroscopic papers. For example, biochips may be used for pregnancy diagnostic apparatuses, apparatuses for measuring hormones such as human chorionic gonadotropin (HCG), and alpha fetoprotein (AFP) (this is used as a liver cancer biomarker) measurements, which are currently commercialized. Biochips realized using membranes are disadvantageous for adjusting the flow of microfluid. The membranes may be formed of a polymeric material having a predetermined thickness and pores. Thus, the membranes are used for a simple test that determines whether an analyte is present at a previously set concentration or more. However, uniformity of sizes of the pores formed in the membranes is below the level required for an accurate test. In addition, if the sizes of the pores within the membrane are determined, strength of a capillary force is also determined. As a result, since it is impossible to adjust a microfluidic flow velocity in the membrane, the biochip realized using the membrane is not suitable for testing to accurately quantify the concentration of an analyte.
Alternatively, to overcome such limitations, there is a method which uses a microchannel as a passage for transferring a fluid. Based on hydrodynamics, a technology is widely used, which adjusts microfluidic flow velocity using microchannels with different widths and depths, and configurations of the microchannels are controlled to increase and decrease capillary force. There are many limitations in a typical biochip field in which a constant transfer velocity of the fluid in a microchannel, a constant reaction time in a reaction region, and a transfer stopping ability of fluid are necessary for quantifying analytes. Biochips using only capillary action are limited in that only the configuration and size of a channel are adjusted to accurately control fluid flow. Although a method in which an inner wall of the channel is surface-treated to have a hydrophilic property or a hydrophobic property to control the fluid was attempted, it is difficult to realize a biochip having a function that stops the fluid at a desired position and transfers the fluid to a desired position. For example, there is a technique in which a hydrophilic region of a capillary is defined to prevent the fluid from flowing so as to maintain constant reaction time. When the fluid reaches the hydrophilic region, the fluid flow is stopped due to a property in which the inner wall of the channel pushes the fluid. In general, most materials tend to have the hydrophilic property at the initial stage. However, if the materials contact the fluid for a long time, the materials tend to convert to the hydrophobic property. Thus, the fluid passes through the hydrophilic region at a very slow speed. During this time, the fluid is stopped in the channel in proportion to the surface area of the hydrophilic region. When the reaction time is controlled using such a method, a specific section of the channel should have the hydrophobic property. Thus, a suitable material and a processing method should be contrived in consideration of a physicochemical property of the fluid to be used. Also, in the case where the hydrophilic region of the channel is defined to prevent the fluid from flowing so as to maintain constant reaction time, there is a limitation that the hydrophilic property is insecure in the hydrophilic region due to absorption of atmospheric moisture, the amount of a reaction material, and inertial force of fluid flow in the reaction region. As a result, the reaction material within the reaction region may flow into the hydrophilic region.
There is a method in which pressure and electric energy are used to transfer and treat a fluid within a microfluidic device. In the case where pressure is used, a separate pressure regulator (e.g., a syringe pump or a peristaltic pump) is required, and the volume of a diagnosis system including a microfluidic device increases. In addition, the system price is affected by the pressure regulator more than the microfluidic device. Thus, this technique is unsuited for a point of care system (POCS) market in which a microfluidic device having a small size and a low price is required. On the other hand, it is advantageous that a relatively small system may be used in a method in which a fluid flow is controlled using an electrokinetic technique when compared to the method using pressure. However, a method for controlling the fluid using the electric energy may be used very limitedly. To apply the electric energy, an electrode should be provided in the microfluidic device. Accordingly, a unique configuration and method should be provided according to a property of the fluid, and various devices for transferring an electrical signal into the microfluidic device should be disposed in combination. Thus, it is complicated to manufacture and realize the system even if the system is small. Specifically, when many reaction processes are performed in one microfluidic device, the electric energy should be adjusted for each process in the case where the electrical property of the fluid is changed in each process. Therefore, the above-described method may be very complicated and difficult.
The present invention provides a method of controlling a fluid flow in a microfluidic device that can simply and accurately control the fluid flow.
The present invention also provides a microfluidic analysis apparatus that can simply and accurately control a fluid flow to accurately analyze a fluid.
Embodiments of the present invention provide methods of controlling a fluid flow in a microfluidic device having an upper plate, a lower plate facing the upper plate, and a flow path defined between the upper plate and the lower plate, the methods including: adjusting an inclination of the microfluidic device with respect to a horizontal direction to control the fluid flow.
In some embodiments, the methods may further include inclining the microfluidic device so that an end of the microfluidic device is disposed downward from a direction in which the fluid flows along the flow path to accelerate the fluid flow.
In other embodiments, the methods may further include inclining the microfluidic device so that an end of the microfluidic device is disposed upward from a direction in which the fluid flows along the flow path to decelerate or stop the fluid flow.
In still other embodiments, the lower plate may further include a detection part disposed in a predetermined region of the flow path to detect a specific material contained in the fluid, and the methods may further include: inclining the microfluidic device so that an end of the microfluidic device is disposed downward from the fluid flow direction to accelerate the fluid flow until the fluid reaches the detection part to fully fill the detection part; and when the detection part is fully filled with the fluid, inclining the microfluidic device so that an end of the microfluidic device is disposed upward from a direction in which the fluid flows along the flow path to decelerate or stop the fluid flow.
In even other embodiments, the inclining of the microfluidic device so that an end of the microfluidic device is disposed upward from a direction in which the fluid flows along the flow path to decelerate or stop the fluid flow when the detection part is fully filled with the fluid may proceed until an reaction for detecting the specific material is completed in the detection part.
In yet other embodiments, after the reaction for detecting the specific material is completed in the detection part, the methods may further include inclining the microfluidic device so that an end of the microfluidic device is disposed downward from the fluid flow direction to accelerate the fluid flow.
In further embodiments, the lower plate may further include a reaction part coated with a reaction material reacting with a predetermined material contained in the fluid to generate a specific material to be detected by the detection part, and the method may further include: inclining the microfluidic device so that an end of the microfluidic device is disposed downward from the fluid flow direction to accelerate the fluid flow until the fluid reaches the reaction part to fully fill the reaction part; and when the reaction part is fully filled with the fluid, inclining the microfluidic device so that an end of the microfluidic device is disposed upward from a direction in which the fluid flows along the flow path to decelerate or stop the fluid flow.
In still further embodiments, the inclining of the microfluidic device so that an end of the microfluidic device is disposed upward from a direction in which the fluid flows along the flow path to decelerate or stop the fluid flow when the detection part is fully filled with the fluid may proceed until an reaction of the predetermined material and the reaction material is completed in the reaction part.
In other embodiments of the present invention, microfluidic analysis apparatuses include: a microfluidic device including an upper plate, a lower plate facing the upper plate, a flow path defined between the upper plate and the lower plate, and a detection part disposed in a predetermined region of the flow path on a surface of the lower plate to detect a specific material contained in a fluid: a microfluidic device receiving part receiving the microfluidic device; an inclination operation unit causing an inclination change of the microfluidic device receiving part with respect to a horizontal plane; an inclination control part controlling an operation of the inclination operation unit; and a reading part reading a data value with respect to a specific material in the detection part.
In some embodiments, the inclination operation unit may include an elevating actuator respectively supporting at least both ends of the microfluidic device or a hinge disposed at a central portion of the microfluidic device receiving part.
In other embodiments, the microfluidic analysis apparatuses a fixing unit fixing the microfluidic device. At this time, the fixing unit may include a robot arm, a belt, or an adhesive.
In still other embodiments, the microfluidic device may further include a lower plate electrode electrically connected to the detection part and disposed in a predetermined region of the lower plate, and the microfluidic analysis apparatuses may further include a receiving part electrode disposed in a predetermined region of the microfluidic device receiving part, contacting with the lower plate electrode, and electrically connected to the reading part.
The accompanying figures are included to provide a further understanding of the present invention, and are incorporated in and constitute a part of this specification. The drawings illustrate exemplary embodiments of the present invention and, together with the description, serve to explain principles of the present invention. In the figures:
Preferred embodiments of the present invention will be described below in more detail with reference to the accompanying drawings. The present invention may, however, be embodied in different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the present invention to those skilled in the art.
Referring to
where the force F is equal to the product of the mass m and the change in velocity V over time t, as shown in Equation 1. Thus, if the microfluidic device 10 is inclined downward from the fluid flow direction, the resultant force acting on the fluid 3 increases from F1 to F2. As a result, the fluid flow velocity increases. Accordingly, when the microfluidic device 10 is inclined downward from the fluid flow direction, the fluid flow velocity may increase.
A contrary case will be described below with reference to
If the microfluidic device 10 is inclined at +90°, the resultant force F4 applied to the fluid 3 is a difference value between the capillary force Fc and the gravity Fg. If the capillary force Fc is equal to the gravity Fs, a force applied to the fluid 3 is zero to stop the fluid flow.
Therefore, the inclination of the microfluidic device 10 may be adjusted with respect to the horizontal direction to control the flow velocity of the fluid 3 within the microfluidic device 10.
A method of controlling a flow velocity of a fluid within a microfluidic device according to an embodiment will be described in detail with reference to
Referring to
A detection part 70 to which a capture antibody 75 for capturing the detection antibody 65 is fixed may be disposed in a predetermined region of the flow path 80 spaced apart from the reaction part 60. In the microfluidic device 100, the fluid 90 is injected into the storage chamber 40 through the fluid injection hole 35. In this embodiment, a length direction of the flow path 80 is parallel to a length direction L of a bottom surface of the lower plate 20. At this time, the microfluidic device 100 may be in a horizontal state. That is, a horizontal direction (X-axis) is equal to the length direction L of the bottom surface of the lower plate 20.
Referring to
Referring to
Referring to
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Referring to
According to the above-described processes, fluid conveyance may be completely controlled, and the antigen-antibody immunity reaction may be realized using only a small amount of sample. In addition, the processes may be manually performed by a user. That is, the user may identify a position of the fluid with the naked eye and adjust the inclination of the microfluidic device 100 using a user's finger to control the fluid flow velocity. In this case, the upper plate 30 may be formed of a transparent material.
In the inclination of the microfluidic device 100 described with reference to
A microfluidic analysis device in which a fluid flow velocity can be automatically adjusted, but manually adjusted, will be described with reference to
Referring to
Referring to
A process for utilizing the microfluidic analysis apparatus 200 will be described below.
The microfluidic device 100 in which a fluid 90 illustrated in
The microfluidic analysis apparatus 300, to which the same microfluidic device 100 as that of
Referring to
Although the microfluidic analysis apparatuses 200 and 300 detect and read the specific material using the electrochemical method, the present invention is not limited thereto. For example, the microfluidic analysis apparatuses 200 and 300 may detect and read the specific material using a laser-induced fluorescence detection. That is, the microfluidic analysis apparatus adopting the laser-induced fluorescence detection, e.g., a fluorescent scanner may include a fixing unit for fixing the microfluidic device according to the present invention, an inclination operation unit for changing an inclination of a receiving part with respect to a horizontal direction, and an inclination control part for controlling an operation state of the inclination operation unit.
In the method of controlling the fluid flow in the microfluidic device according to an embodiment of the present invention, the inclination of the microfluidic device with respect to the horizontal direction can be adjusted to control a correlation between the capillary force and the effective gravity, which act on the microfluid within the flow path. Thus, the fluid flow can be simply and accurately controlled in the microfluidic device. In addition, the fluid conveyance may be completely controlled, and the inspection can be performed using only a small amount of sample. The method of controlling the fluid flow in the microfluidic device can be manually performed by the user. That is, the user can identify a position of the fluid with the naked eye and adjust the inclination of the microfluidic device 100 using the user's finger to control the fluid flow velocity. Thus, since a power is not required, the method of controlling the fluid flow in the microfluidic device can be economical and simple.
The microfluidic analysis apparatus according to another embodiment of the present invention can include the inclination operation unit for causing the inclination change of the receiving part of the microfluidic device with respect to the horizontal plane and the inclination control part for controlling the operation of the inclination operation unit to simply and accurately control the fluid flow, thereby to accurately analyze the fluid.
The above-disclosed subject matter is to be considered illustrative, and not restrictive, and the appended claims are intended to cover all such modifications, enhancements, and other embodiments, which fall within the true spirit and scope of the present invention. Thus, to the maximum extent allowed by law, the scope of the present invention is to be determined by the broadest permissible interpretation of the following claims and their equivalents, and shall not be restricted or limited by the foregoing detailed description.
Number | Date | Country | Kind |
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10-2008-0131856 | Dec 2008 | KR | national |