KR100883658B1 - Centrifugal force-based microfluidic device and microfluidic system including the same - Google Patents

Abstract

Disclosed are a centrifugal force-based microfluidic device capable of centrifuging a fluid sample containing particles and quantitatively dispensing the separated fluid and a microfluidic system including the same. Microfluidic device according to the present invention, the rotatable disk-like platform; A sample inlet disposed on one side of the platform; One end is connected to the sample inlet, and extends to the outside of the disk-shaped platform, a space for centrifuging the sample containing particles injected through the sample inlet with particles and fluid by the rotation of the disk-shaped platform Providing a fluid separator; And at least one outlet connected to the fluid separator, each driven separately, and disposed at a position capable of discharging a predetermined volume of fluid among the separated fluids in the fluid separator by rotation of the disk-like platform. It includes a valve.

Microfluidic Device, Microfluidic System, Lab-on-a Disk, Centrifugation

Description

Centrifugal force-based microfluidic device and microfluidic system including the same}

1 is a plan view showing an embodiment of a microfluidic device according to the present invention.

FIG. 2A is a cross-sectional view illustrating a II-II 'cross section showing a fluid separator in FIG. 1.

FIG. 2B is a cross-sectional view illustrating a modification of the bottom of the fluid separator shown in FIG. 2A.

3 is a plan view showing another embodiment of a microfluidic device according to the present invention.

4A is a cross-sectional view illustrating a IV-IV 'cross section showing the fluid separation unit of FIG. 3.

4B is a cross-sectional view illustrating a modified example of the bottom of the fluid separator shown in FIG. 4A.

5 is a plan view showing another embodiment of a microfluidic device according to the present invention.

Figure 6a is a plan view showing another embodiment of a microfluidic device according to the present invention.

FIG. 6B is an experimental photograph showing the centrifugal velocity in the case where various angles of the fluid separator with respect to the radial direction are arranged in the embodiment of FIG.

FIG. 7 is a plan view illustrating an opening valve employed in the microfluidic devices of FIGS. 1, 3, 5, and 6.

FIG. 8 is a cross-sectional view illustrating a cross-sectional view of the open valve of FIG. 7.

9 is a series of high-speed photographs showing the operation of the opening valve of FIG.

FIG. 10 is a graph showing a relationship between a volume ratio of a magnetic fluid included in a valve plug and a valve reaction time in the opening valve of FIG. 7.

FIG. 11 is a graph showing a relation between a valve reaction time and a power of a laser light source used as an external energy source when the opening valve of FIG. 7 is driven.

12 is a perspective view showing an embodiment of a microfluidic system including the microfluidic device of any one of FIGS. 1, 3, 5, and 6.

FIG. 13 is a perspective view illustrating another embodiment of the microfluidic system including the microfluidic device of any one of FIGS. 1, 3, 5, and 6.

14A to 14B are photographs showing an experimental example of separating and quantitatively distributing plasma from blood using the microfluidic device shown in FIG. 5.

Explanation of symbols on the main parts of the drawings

21: disc platform 211: bottom plate

212: top plate 30: sample storage unit

31: sample inlet 40, 44: fluid separation unit

411, 412: fluid separator bottom 42: particle separator

421: stepped portions 49 and 59: exhaust channel

491, 591: exhaust port 50: excess fluid collection part

82: test unit 100 to 103: microfluidic device

130L, 130P: External energy source 140: Rotating drive part

150: light detector 221L, 221R: flow path

222L, 222R: Drain Chamber 223: Valve Plug

231, 232, 233: open valve

The present invention relates to a centrifugal force-based microfluidic device, and more particularly, to separate fluids and particles using centrifugal force from a sample containing fluids and particles in a disk-shaped platform, and to quantitatively distribute the separated fluids. A microfluidic device is provided.

In general, the microfluidic structure constituting the microfluidic device has a chamber capable of trapping a small amount of fluid, a channel through which the fluid can flow, a valve that can control the flow of the fluid, and a fluid to receive a predetermined function. Various functional units and the like. The functional unit also includes a base structure such as a chamber, a channel or a valve as described above, and can be made through a combination thereof. Placing these microfluidic structures on chip-like substrates to perform tests involving biochemical reactions on a small chip is called a biochip, and in particular, several steps of processing and manipulation are performed on one chip. The device manufactured to do this is called a lab-on-a chip.

In order to transfer fluid in the microfluidic device, a driving pressure is required. As a driving pressure, a capillary pressure may be used, or a pressure by a separate pump may be used. Recently, microfluidic devices have been proposed for disposing microfluidic structures on a compact disc shaped platform and driving fluid using centrifugal force. This is also known as a Lab CD or a Lab-on a disk. In this case, however, the microfluidic device is rotated without being fixed to the frame, and thus is different in many respects from a lab-on-a-chip operating while being fixed to the floor. While centrifugal separation using centrifugal force is easy, it is difficult to operate individual valves or control local temperature.

On the other hand, in the fields of biochemistry, biology, and medicine where the microfluidic device is mainly used, the microfluidic device separates particles from biological samples, such as blood, saliva, and urine, in which fluid and particles are mixed. It is required to have In order to satisfy this, US Patent US 5,061,381 has been proposed. However, it is still required to perform the function of separating fluid and particles in a smaller area within the disk-like platform, and furthermore to have a function of quantitatively dispensing the separated fluid without going through a metering step using a separate unit. Required.

The present invention provides a centrifugal force-based microfluidic device and a microfluidic system including the same, which can separate fluids and particles from a sample containing fluids and particles in a disk-shaped platform by using centrifugal force, and quantitatively distribute the separated fluids. The purpose is to provide.

Centrifugal force-based microfluidic device according to an embodiment of the present invention, the rotatable disk-like platform; A sample inlet disposed on one side of the platform; One end is connected to the sample inlet, and extends to the outside of the disk-shaped platform, a space for centrifuging the sample containing particles injected through the sample inlet with particles and fluid by the rotation of the disk-shaped platform Providing a fluid separator; And at least one outlet connected to the fluid separator, each driven separately, and disposed at a position capable of discharging a predetermined volume of fluid among the separated fluids in the fluid separator by rotation of the disk-like platform. It includes a valve.

The microfluidic device according to another embodiment of the present invention is arranged to be connected to the radially outer end of the fluid separation part, and is connected to the fluid separation part to expand the space to collect particles separated by centrifugation. It may further comprise a particle separator to provide. In this case, the particle separation unit may be formed so that the depth is deeper than the fluid separation unit, the step is present at the boundary with the fluid separation unit. In addition, the depth of the fluid separation unit may be constant, or may be to gradually deepen the depth toward the outside of the disk-like platform.

The microfluidic device according to another embodiment of the present invention further includes a sample storage unit disposed to be connected to the radially inner end of the fluid separation unit and connected to the sample inlet to receive a sample injected through the sample inlet. can do. In this case, the microfluidic device may further include a surplus fluid collection unit connected to a radially inner portion of the fluid separation unit to receive surplus fluid exceeding a capacity of the fluid separation unit. The excess fluid collection portion may be provided with a valve connected to the fluid separation portion through a channel and passively or actively opening to the channel. The microfluidic device may further include the above-described particle separation unit at the same time as having the above-mentioned excess fluid collection unit. Even in this case, the fluid separation unit may have a constant depth, or may be gradually deepened toward the outside of the disk-like platform.

According to another embodiment of the present invention, the fluid separation portion may be arranged such that the axis connecting the inner portion and the outer portion has a predetermined slope with respect to the radial direction.

In the microfluidic device according to the various embodiments described above, the at least one outlet valve is initially arranged such that the valve plug closes the outlet of the fluid separation part, and the valve plug is melted by heat, and thus the initial position of the valve plug. It may be a phase-transfer-type opening valve which moves to the drain chamber provided adjacent to and opens the passage. The valve plug may include a valve material in which exothermic particles are dispersed in a phase change material having a solid phase at room temperature, and the valve material may be melted by heat due to electromagnetic waves radiated from an external energy source.

Here, the phase change material may be at least one selected from the group consisting of wax, gel, and thermoplastic resin, and the exothermic particles may have a diameter of 1 nm to 100 μm. In addition, the heating particles may be composed of a core that absorbs electromagnetic waves from the outside and converts them into thermal energy, and a shell surrounding the core. The exothermic particles may be at least one selected from the group consisting of polymer beads, quantum dots, gold nanoparticles, silver nanoparticles, metal compound beads, carbon particles, and magnetic beads.

A centrifugal force-based microfluidic system including a microfluidic device according to the present invention includes a centrifugal force-based microfluidic device of any one of the above-described embodiments; A rotation drive unit for supporting and controlling the microfluidic device and controlling the microfluidic device; And a valve drive unit for individually driving the selected valve in the microfluidic device.

Here, the valve drive unit is an external energy source for emitting electromagnetic waves that can induce heat generation of the heat generating particles in the valve; And an external energy source adjusting means for adjusting the position or direction of the external energy source so that the electromagnetic waves radiated from the external energy source intensively reach a region corresponding to the selected valve. At this time, the external energy source adjusting means may include a linear moving means for moving the external energy source installed toward the platform of the microfluidic device in the radial direction of the rotating body, or toward the platform of the microfluidic device. It may include a planar moving means for moving the external support installed in two directions on a plane parallel to the platform in accordance with a rectangular coordinate.

 Hereinafter, various embodiments of the present invention will be described in detail with reference to the accompanying drawings. Like reference numerals in the accompanying drawings indicate like elements. Structures such as chambers and channels shown are simplified in shape, and ratios of the sizes may be enlarged or reduced in reality. On the other hand, the sample here refers to a substance containing a fluid and particles having a higher density than the fluid, including biological samples such as blood, saliva, urine.

1 is a plan view showing an embodiment of a microfluidic device according to the present invention. According to the present embodiment, the centrifugal force-based microfluidic device 100 includes a disk-shaped platform 21 and structures 30 that provide a space in which fluid can be accommodated or a flow path that can flow therein. 40,49,82,811,822, etc.).

The disk-like platform 21 is easy to mold, the surface thereof may be made of a plastic material such as acrylic, PDMS, biologically inert. However, the present invention is not limited thereto, and a material having chemical, biological stability, optical transparency, and mechanical processability is sufficient. The disk-shaped platform 21 may be made of several layers of plates. A space and a passage may be provided inside the platform 21 by making an intaglio structure corresponding to a chamber or a channel on the surface where the plate and the plate abut each other and bonding them. Joining of the plate and the plate may be made by various methods such as adhesive using an adhesive or double-sided adhesive tape, ultrasonic welding, laser welding.

The microfluidic device 100 includes a fluid separator 40 capable of centrifuging a sample containing particles by fluid and particles by rotation of the platform 21. The fluid separation part 40 shown in FIG. 1 has a channel shape, but the shape is not limited. However, it is preferable to arrange | position so that the longitudinal direction relatively large among the longitudinal direction and the width direction may be laid out from the inside (close side to the center) of the platform 21 to the outside (far side from the center). There is no limitation on the size of the fluid separation unit 40. The size may be determined according to the size and thickness of the platform 21 and the size of the particles mixed with the amount of the sample to be centrifuged and dispensed.

A sample inlet 31 for injecting a sample from the outside is provided at the inner end of the fluid separation unit 40. Meanwhile, the sample is connected to the sample inlet 31 and the fluid separator 40, and receives the sample injected through the sample inlet 31, and separates the sample when the platform 21 rotates. It may further include a sample storage unit 30 to supply to the unit (31). The sample storage unit 30 may have a chamber shape as shown. An outer end portion of the fluid separator 40 is connected to an exhaust channel 49 for exhausting the sample to be transported from the sample inlet 31. The exhaust port 491 of the exhaust channel 49 is disposed closer to the center of the platform 21 than the inner end of the fluid separation part 40 to prevent fluid leakage during centrifugation of the sample by centrifugal force. do.

At least one outlet valve is disposed in a middle portion (between the inner end portion and the outer end portion) of the fluid separation portion 40. The microfluidic device 100 according to the embodiment of FIG. 1 includes two outlet valves 231 and 232. When there are two or more outlet valves 231 and 232, the outlet valves 231 and 232 may be driven individually, respectively, and may be driven from those arranged near the center of the platform 21. When the two outlet valves are referred to as the first outlet valve 231 and the second outlet valve 232, respectively, the first outlet valve 231 is opened in the microfluidic body 100 and the platform 21 is rotated. In this case, the fluid V1 inside the fluid separation part 40 than the first outlet valve 231 is discharged through the first distribution channel 811, and the second outlet valve 232 is opened. When the platform 21 is rotated, the fluid V2 between the first outlet valve 231 and the second outlet valve 232 in the fluid separation part 40 becomes the second distribution channel 821. Is discharged through and transferred to the test unit 82. Through such a configuration, the microfluidic device 100 according to the present invention may centrifuge a sample containing particles into a fluid and particles, and divide and separate the separated fluid into a predetermined constant volume.

Here, the test unit 82 for receiving a quantitatively divided fluid may be provided in various ways according to the use of the microfluidic device 100. In FIG. 1, the test unit 82 is simply illustrated in a chamber shape, but any unit may be provided in the disc-shaped platform 21 by using a fluid dispensed and separated from the sample. It may correspond to (82).

FIG. 2A is a cross-sectional view illustrating a II-II 'cross section showing a fluid separator in FIG. 1. The disk-shaped platform 21 is composed of an upper plate 212 and the lower plate 211, the upper surface of the lower plate 211 is engraved to provide a space of the fluid separation unit 40. At this time, the fluid separation unit 40 may be a constant depth from the inner side to the outer side of the platform 21. That is, the bottom 411 of the fluid separation unit 40 may be formed flat throughout.

2B is a cross-sectional view illustrating a modified example of the bottom of the fluid separator shown in FIG. 2A. According to the modified example of FIG. 2B, the fluid separation part 40 may be deepened toward the outside thereof. That is, the bottom 412 of the fluid separation part 40 may be formed to have an inclination lowering toward the outside of the platform 21. When centrifuging the sample, relatively heavy particles are moved by gravity along with the centrifugal force to move outward along the bottom 412 of the fluid separator 40. At this time, the inclined bottom 412 may reduce the mutual interference between the particles gathered to the outside and the fluid moving inward to help the centrifugation in a shorter time.

3 is a plan view showing another embodiment of a microfluidic device according to the present invention. The centrifugal force-based microfluidic device 101 according to the present embodiment is centrifuged at the outer end of the fluid separation part 40 in comparison with the microfluidic device 100 according to the embodiment of FIG. 1. It is further provided with a particle separation unit 42 that can accommodate the particles collected by the. In this case, a step 421 may be present at the boundary between the fluid separation part 40 and the particle separation part 42, the depth of which is discontinuously changed. Particles once separated by the step 421 can be reduced to flow back toward the fluid separation portion 40 during fluid distribution.

FIG. 4A is a cross-sectional view illustrating a IV-IV 'cross section showing the fluid separator in FIG. 3, and FIG. 4B is a cross-sectional view showing a modified example of the bottom of the fluid separator shown in FIG. 4A. In the case of the microfluidic device 101 further including the particle separator 42, the depth of the fluid separator 40 may be constant or deeper toward the outside of the platform 21. have.

5 is a plan view showing another embodiment of a microfluidic device according to the present invention. According to the present embodiment, the centrifugal force-based microfluidic device 102 may further include a surplus fluid collecting unit 50 as compared to the microfluidic device 101 of FIG. 3. The excess fluid collection unit 50 is connected to the inner end of the fluid separation unit 40 through the channel 501, the channel 501 to block the flow of the normal fluid and to pass the fluid during operation ( normally closed) valve 233. The valve 233 may be a valve that is manually opened when a predetermined pressure or more is applied, such as a capillary valve or a hydrophobic valve, or may be a valve that is actively opened by receiving power or energy from the outside by an operation signal. It may be.

The case where the valve 233 is a manual valve will be described as a function of the surplus fluid collecting unit 50 as an example. When a sample exceeding the capacity of the fluid separation unit 40 is injected through the sample inlet 31, the valve may be caused by the pressure of the excess fluid acting on the portion to which the channel 501 is connected during the centrifugation operation. 233 is opened and excess fluid is collected in the excess fluid collection unit 50. It goes without saying that the excess fluid collection section 50 also has an exhaust channel 59 and an exhaust port 591 connected thereto. The microfluidic device 102 including the surplus fluid collection unit 50 may distribute the quantitative fluid even if some errors occur when initially injecting the sample by hand.

Here, the surplus fluid collecting unit 50 is added to the microfluidic device 101 according to the embodiment of FIGS. 3 to 5, but the microfluidic device 100 shown in FIGS. 1 to 3 or the following will be described below. Of course, the surplus fluid collecting unit 50 may be added to the microfluidic device 103 of FIG. 6A.

Figure 6a is a plan view showing another embodiment of a microfluidic device according to the present invention. According to the present embodiment, the centrifugal force-based microfluidic device 103 may include a fluid separation part 44 arranged such that an axis connecting the inner portion and the outer portion thereof has a predetermined inclination θ with respect to the radial direction. Can be. Except for the arrangement of the fluid separator 44 in this embodiment, the other part is a combination of the features of any one or more of the embodiments (100, 101, 102) shown in Figs. It may be the same as the form.

As shown in FIG. 6A, the fluid separation unit 44 disposed to have an inclination θ with respect to the radial direction includes particles having relatively high density when the sample is centrifuged in the microfluidic device 103. By separating outward paths and relatively low density fluid inward paths, centrifugation speed is improved by reducing mutual interference of particles and fluids. The basic principle of improving the centrifugation speed by separating the moving paths of materials having different densities during centrifugation has been disclosed in US Pat. No. 5,588,946, referred to as “Boycott Effect”. The microfluidic device 103 according to the present embodiment improves the centrifugation speed by using the same principle even in the disk-shaped platform 21 instead of the test tube. Here, the inclination θ of the fluid separation unit 44 may be determined differently according to the size of the particles and the viscosity of the fluid contained in the sample to be centrifuged.

FIG. 6B is an experimental photograph showing the centrifugal velocity in the case where various angles of the fluid separator with respect to the radial direction are arranged in the embodiment of FIG. Of the three fluid splitters shown in the picture, the left side has its longitudinal center axis aligned with the radial direction of the disc platform, the center has a 15 degree inclination with respect to the radial direction, and the right side has a 30 degree with respect to the radial direction. It was arranged to have a slope. This experiment is to check the centrifugation speed according to the inclination of the fluid separator, so in the microfluidic device of the picture, there is no separate outlet valve connected to the fluid separator.

6B specifically shows 70 μl of a sample in which 1: 1 whole blood and PBS buffer are mixed through the above-described sample inlet, and centrifuged for about 80 seconds. Scales in centimeters (cm) were marked on each fluid separator to aid identification. Referring to FIG. 6B, the serum was separated only in the inside of the 0 scale from the fluid separation unit on the left side with a slope of 0 degrees. On the other hand, the serum was separated up to about 0.2 scale in the fluid separation unit with a slope of 15 degrees, and the serum was separated up to about 2.25 scale in the fluid separation unit at the right side with a slope of 30 degrees through a photograph. It can be seen that the inclination of the fluid separation unit contributes to the improvement of the centrifugation speed in the disk-like platform.

FIG. 7 is a plan view illustrating an opening valve employed in the microfluidic devices of FIGS. 1, 3, 5, and 6, and FIG. 8 is a cross-sectional view of the opening valve of FIG. An opening valve that can be employed as the first outlet valve 231 will be described as an example.

Opening valve 231 includes a valve plug 223 made of valve material that is solid at room temperature. The valve material may be a material in which exothermic particles are dispersed in a phase change material that is solid at room temperature. A pair of drain chambers 222L and 222R extending in width or depth upstream and downstream of the channels 221L and 221R adjacent to the initial position where the valve plug 223 in the solid state is disposed to provide a free space. ) Is placed. However, the shape shown in FIG. 7 represents a general shape in which the opening valve 231 is disposed in the middle of the channel, and as shown in FIGS. 1, 3, 5, and 6, the chamber structure or the other channel structure When applied as an outlet valve on the side, one of the pair of drain chambers 222L, 222R, for example, the drain chamber 222L on the left in FIG. 7, may be replaced by a portion of the chamber structure or other channel structure. Can be.

The valve plug 223 closes a predetermined portion of the channels 221L and 221R around the opening 223A at room temperature to block the flow of the fluid F flowing from the inlet I side. The valve plug 223 is melted at a high temperature and moved to the drain chambers 222L and 222R disposed adjacent to the upstream and downstream sides of the channels 221L and 221R, with the flow path of the fluid F open. Solidifies again. The opening 223A also serves as an inlet for injecting molten valve material to form a valve plug when the microfluidic device is manufactured.

In order to apply heat to the valve plug 223, an external energy source (see 130L of FIG. 12 and 130P of FIG. 13) is disposed outside the microfluidic device, and the external energy source 130L is the valve plug 223. The electromagnetic wave is irradiated to the initial position of the region ie, the region including the opening 223A and its periphery. In this case, the external energy source 130L may be, for example, a laser light source for irradiating a laser beam, and in this case, may include at least one laser diode. The laser light source may emit a pulse laser having an energy of 1 mJ / pulse or more when irradiated with a pulsed laser, and a continuous wave laser having an output of 10 mW or more when irradiated with a continuous wave laser.

In the experiment described below with reference to FIGS. 9 to 11, a laser light source for irradiating a laser of 808 nm wavelength was used, but is not necessarily limited to irradiating a laser beam of this wavelength, and has a wavelength of 400 to 1300 nm. If it is a laser light source for irradiating a laser, it may be employed as an external energy source 130L of the microfluidic system.

The above-described channels 222L and 222R may be provided by a three-dimensional pattern formed on the inner surface of the upper plate 212 or the lower plate 211 constituting the disk-like platform 21. The upper plate 212 is made of an optically transparent material that transmits electromagnetic waves irradiated from an external energy source to be incident on the valve plug 223 and to observe the flow of the fluid F from the outside. It is desirable to be made. As an example, glass or transparent plastic material is advantageous in that it is excellent in optical transparency and low in manufacturing cost.

The exothermic particles dispersed in the valve plug 223 may have a diameter of 1 nm to 100 μm so as to be freely flowable in the channels 221L and 222R having a width of about several thousand micrometers (μm). The exothermic particles have a property of rapidly generating a temperature when the laser is irradiated by the radiant energy, and dissipates evenly in the wax. In order to have these properties, the exothermic particles may have a structure including a core including a metal component and a hydrophobic shell. For example, the exothermic particle may have a structure having a core made of Fe, a ferromagnetic material, and a shell made of a plurality of surfactants that are bonded to the Fe to surround Fe. Typically, the exothermic particles are stored dispersed in a carrier oil. The carrier oil is also preferably hydrophobic so that the exothermic particles having a hydrophobic surface structure can be evenly dispersed. The material of the valve plug 83 may be manufactured by pouring and mixing carrier oil in which the exothermic particles are dispersed in wax. The particle shape of the exothermic particles is not limited to the above-described examples, but may be polymer beads, quantum dots, gold nanoparticles, silver nanoparticles, or metal compound beads. metal composition, carbon particles, or magnetic beads. The carbon particles also include graphite particles.

The phase change material constituting the valve plug 223 may be wax. When the energy of the electromagnetic wave absorbed by the exothermic particles is transferred to the surroundings in the form of thermal energy, the wax melts to have fluidity, thereby causing the plug 223 to collapse and the flow path of the fluid F to be opened. The wax constituting the plug 223 preferably has a suitable melting point. If the melting point is too high, it takes a long time from the start of laser irradiation to melting, making it difficult to precisely control the opening point. On the contrary, if the melting point is too low, the fluid F leaks due to partial melting without the laser being irradiated. Because it may be. As the wax, for example, a paraffin wax, a microcrystalline wax, a synthetic wax, a natural wax, or the like can be employed.

The phase change material may be a gel or a thermoplastic resin. As the gel, polyacrylamide, polyacrylates, polymethacrylates, polyvinylamides, or the like may be employed. In addition, as the thermoplastic resin, COC, PMMA, PC, PS, POM, PFA, PVC, PP, PET, PEEK, PA, PSU, or PVDF may be employed.

9 is a series of high-speed photographs showing the operation of the opening valve of FIG. The results of the experiment measuring the reaction time of the aforementioned open valve are as follows. The pressure of the working fluid was maintained at 46 kPa in the test chip (microfluidic chip) for the experiment. A syringe pump (Havard PHD2000, USA) and a pressure sensor (MPX 5500DP, Freescale semiconductor Inc., AZ, USA) were used to maintain the pressure. As an external energy source for irradiating the electromagnetic wave to the valve, a laser light source having an emission wavelength of 808 nm and an output power of 1.5 W was used. Data on the reaction time of the valves were obtained through analysis of the results of the high speed imaging device (Fastcam-1024, Photron, CA, USA). The valve plug is a so-called magnetic fluid in which a ferrofluid and paraffin wax, in which magnetic beads having an average diameter of 10 nm, which are exothermic particles, are dispersed in a carrier oil, are mixed in a ratio of 1 to 1, that is, a volume ratio of magnetic fluid is 50%. Wax was used.

The reaction time from when the valve plug of the opening valve was irradiated with a laser beam until the valve plug was melted to open the channel was 0.012 seconds. It can be seen that the reaction time of the conventional wax valve was much faster than the reaction time was 2 to 10 seconds.

FIG. 10 is a graph showing a relationship between a volume ratio of a magnetic fluid included in a valve plug and a valve reaction time in the opening valve of FIG. 7. In general, the reaction time is shortened as the volume fraction of the magnetic fluid increases. However, apart from this, when the volume ratio of the magnetic fluid increases to 70% or more, the maximum hold-up pressure of the valve plug tends to be lowered. Thus, the volume ratio of the magnetic fluid to be included in the valve plug in the valve unit can be determined by a compromise between the demand for reaction time and the demand for maximum allowable pressure.

FIG. 11 is a graph showing a relation between a valve reaction time and a power of a laser light source used as an external energy source when the opening valve of FIG. 7 is driven. The higher the output, the shorter the reaction time. By the way, when the output of the laser light source approaches 1.5W, the change in the reaction time is gentle, and when it exceeds 1.5W (although not shown in the graph), it converges to a predetermined minimum response. This is because of the constraints of thermal conductivity through paraffin wax. In this experiment, a laser light source having a power of 1.5 W was used for this reason. However, the external energy source of the present invention is not limited thereto.

12 is a perspective view showing an embodiment of a microfluidic system including the microfluidic device of any one of FIGS. 1, 3, 5, and 6. Microfluidic system according to an embodiment of the present invention includes the microfluidic device (100 ~ 103) of the present invention described above. Here, the system including the microfluidic device 100 of FIG. 1 will be described as an example. The microfluidic system according to the present embodiment includes an external energy source 130L for supplying energy by irradiating predetermined electromagnetic waves to the outlet valves 231 and 232 of the individual driving method described above. The external energy source 130L may be a device capable of irradiating electromagnetic waves in a predetermined wavelength band selected from electromagnetic waves of various wavelengths, such as microwaves, infrared rays, visible rays, ultraviolet rays, and X-rays. Moreover, it is more preferable if it is the apparatus which can irradiate this electromagnetic wave intensively to a near target. The wavelength of the external energy source 130L is preferably in a range that is well absorbed by the heating particles contained in the valve material. Therefore, the device for generating electromagnetic waves in the external energy source 130L may be appropriately selected according to the material and surface conditions of the heating particles (M). The external energy source 130L may be, for example, a laser light source for irradiating a laser beam, and in this case, may include at least one laser diode. Details such as the wavelength and power of the laser beam may be determined according to the type of heating particles included in the phase change valve of the microfluidic device 100 as the main use target.

The microfluidic system adjusts the position or direction of the external energy source 130L, so that the electromagnetic waves irradiated therefrom are in a desired region of the microfluidic device 100, specifically, to the microfluidic device 100. External energy source adjusting means (not shown) for intensively reaching the area corresponding to any one selected from the at least one outlet valve (231,232) included. In the microfluidic system of FIG. 12, the external energy source adjusting means (not shown) moves the external energy source 130L installed toward the platform 21 of the microfluidic device 100 in the direction indicated by the arrow, that is, the platform 21. Can move in the radial direction. Mechanism for linearly moving the external energy source 130L may be provided in various ways, it will be apparent to those skilled in the art of the present invention, so the description thereof will be omitted.

On the other hand, the microfluidic system includes a rotation drive unit 140 for driving the platform 21. The rotation driver 140 shown in the drawing is a part for seating the platform 21 and transmitting the rotational force, and although not shown in the drawing, the rotation driver 140 may rotate the platform 21 at a desired speed or a desired angle. Which may include a motor and related parts thereof. Like the external energy source adjusting means (not shown), an example of a specific configuration of the rotation driving unit 140 will be omitted herein. In the microfluidic system of FIG. 12, the external energy source 130L concentrates electromagnetic waves in a selected region of the microfluidic device 100 with the help of the external energy source adjusting means (not shown) and the rotation driving unit 140. Can be investigated.

On the other hand, the microfluidic system according to the present invention can optically observe the results of centrifugation using the microfluidic device 100 and the results of various experiments using other functional units included in the microfluidic device 100. The light detector 150 may be further provided. For example, the photodetector 150 may include reagents previously injected into the serum and the test unit 82 when the centrifuged and quantitative serum is transferred to the test unit (see FIG. 1) 82. For example, it may be to enable optical detection of a reaction with a reagent) that indicates whether or not a specific antibody or antigen is present in serum.

FIG. 13 is a perspective view illustrating another embodiment of the microfluidic system including the microfluidic device of any one of FIGS. 1, 3, 5, and 6. In the microfluidic system according to the present embodiment, the matters related to the microfluidic device 100, the rotation driving unit 140, and the external energy source 130P itself are the same as those of the embodiment of FIG. 16 described above. However, in the case of the microfluidic system according to the present embodiment, the external energy source adjusting means (not shown) orthogonally intersects the external energy source 130P installed toward the platform 21 on a plane parallel to the platform 21. It may include a plane moving means for moving the electromagnetic wave to reach the target point on the platform 21 by moving in two directions (for example, x-axis and y-axis direction, see arrows).

In addition, although not shown in the drawing, the external energy adjusting means may be configured to change the direction of the external energy source whose position is fixed at a point above the platform 21 so that the emitted electromagnetic waves reach the target point. have.

14A to 14B are photographs showing an experimental example of separating and quantitatively distributing plasma from blood using the microfluidic device shown in FIG. 5. 14A shows a state in which blood is injected as a sample into the fluid separation unit, that is, a state before centrifugation. Fig. 14B shows a state in which blood is separated into serum (fluid portion in the fluid separation portion) and particles such as blood cells (opaque portion in the particle separation portion connected to the end of the fluid separation portion), which are fluids, by centrifugation. FIG. 14C shows the opening of the first outlet valve connected to the fluid separator and discharge of 10 μL of serum between the first outlet valve and the excess sample collection connecting channel within the fluid separator. FIG. 14D finally shows the opening of the second outlet valve and discharging 10 μl of serum that was between the second outlet valve and the first outlet valve in the fluid separation unit.

Although the preferred embodiment according to the present invention has been described above, this is merely exemplary, and it will be understood by those skilled in the art that various modifications and equivalent other embodiments are possible. Therefore, the protection scope of the present invention should be defined by the appended claims.

The centrifugal force-based microfluidic device and the microfluidic system including the same require a separate operation for separating the fluid and the particles from the sample containing the fluid and the particles using the centrifugal force in the disk-shaped platform and metering. The separated fluid can be quantitatively dispensed without.

Claims (21)

Rotatable disc platforms; A sample inlet disposed on one side of the platform; One end is connected to the sample inlet, and extends to the outside of the disk-shaped platform, a space for centrifuging the sample containing particles injected through the sample inlet with particles and fluid by the rotation of the disk-shaped platform Providing a fluid separator; And At least one outlet valve connected to the fluid separator, each individually driven, and disposed at a position capable of discharging a predetermined volume of fluid among the separated fluids in the fluid separator by rotation of the disk-like platform Centrifugal force-based microfluidic device comprising a. The method of claim 1, And a particle separator disposed to be connected to the radially outer end of the fluid separator, the particle separator being connected to the fluid separator to provide an expanded space for collecting particles separated by centrifugation. Centrifugal force based microfluidic device. The method of claim 2, The particle separator is deeper than the fluid separator, the centrifugal force-based microfluidic device, characterized in that the step is formed so as to exist in the boundary with the fluid separator. The method according to claim 1 or 3, The fluid separation unit is a centrifugal force-based microfluidic device, characterized in that the deeper gradually toward the outside of the disk-like platform. The method of claim 1, A centrifugal force-based microfluidic device, further comprising a sample storage unit disposed to be connected to the radially inner end of the fluid separation unit and connected to the sample inlet to receive a sample injected through the sample inlet. The method according to claim 1 or 5, Centrifugal force-based microfluidic device further comprises a surplus fluid collecting unit connected to the radially inner portion of the fluid separation unit for receiving surplus fluid exceeding a capacity of the fluid separation unit. The method of claim 6, The surplus fluid collecting part is connected to the fluid separating part through a channel, the centrifugal force-based microfluidic device characterized in that it has a valve that is passively or actively open to the channel. The method of claim 6, And a particle separator disposed to be connected to the radially outer end of the fluid separator, the particle separator being connected to the fluid separator to provide an expanded space for collecting particles separated by centrifugation. Centrifugal force based microfluidic device. The method of claim 8, The particle separator is deeper than the fluid separator, the centrifugal force-based microfluidic device, characterized in that the step is formed so as to exist in the boundary with the fluid separator. The method of claim 8, The fluid separation unit is a centrifugal force-based microfluidic device, characterized in that the deeper gradually toward the outside of the disk-like platform. The method of claim 1, The fluid separation unit is a centrifugal force-based microfluidic device, characterized in that the axis connecting the inner portion and the outer portion is arranged to have a predetermined slope with respect to the radial direction. The method of claim 1, The at least one outlet valve is initially arranged such that a valve plug closes the outlet of the fluid separation unit, and the valve plug is melted by heat to move to a drain chamber provided adjacent to the initial position of the valve plug to open the passage. Centrifugal force-based microfluidic device characterized in that the phase-transition opening valve. The method of claim 12, The valve plug includes a valve material in which exothermic particles are dispersed in a phase change material having a solid phase at room temperature, and the valve material is melted by heat due to electromagnetic waves irradiated from an external energy source. Flow device. The method of claim 13, The phase change material is a centrifugal force-based microfluidic device, characterized in that at least one selected from the group consisting of wax, gel, thermoplastic resin. The method of claim 13, The exothermic particles are centrifugal force-based microfluidic device, characterized in that the diameter of 1 nm to 100 ㎛. The method of claim 13, The heating particle is a centrifugal force-based microfluidic device, characterized in that consisting of a core (core) for absorbing electromagnetic waves from the outside to convert into thermal energy and a shell surrounding the core (shell). The method of claim 13, The exothermic particles are at least one selected from the group consisting of polymer beads, quantum dots, gold nanoparticles, silver nanoparticles, metal compound beads, carbon particles, and magnetic beads. . A sample including a rotatable disk-shaped platform, a sample inlet disposed on one side of the platform, one end of which is connected to the sample inlet, and extends outwardly of the disk-shaped platform, and includes particles injected through the sample inlet; A predetermined volume of fluid of the separated fluids in the fluid separator that is connected to the fluid separator and the fluid separator that provides a space for centrifuging the particles and the fluid by the rotation of the disk-like platform, is driven separately. A centrifugal force-based microfluidic device including at least one outlet valve disposed at a position capable of being discharged by rotation of the disc-shaped platform; A rotation driver for supporting and controlling the microfluidic device and rotationally controlling the microfluidic device; Centrifugal force-based microfluidic system comprising a valve drive unit for individually driving the selected valve in the microfluidic device. The method of claim 18, The valve drive unit, An external energy source emitting electromagnetic waves capable of inducing heat generation of the heat generating particles in the valve; And A centrifugal force-based microfluidic system comprising an external energy source adjusting means for adjusting the position or direction of the external energy source so that the electromagnetic waves irradiated from the external energy source intensively reach a region corresponding to the selected valve. . The method of claim 19, The external energy source adjusting means is a centrifugal force-based microfluidic system comprising a linear movement means for moving the external energy source installed toward the platform of the microfluidic device in the radial direction of the rotating body. The method of claim 19, The external energy source adjusting means includes a centrifugal force-based moving means for moving the external energy source installed toward the platform of the microfluidic device in two directions along a rectangular coordinate on a plane parallel to the platform. Microfluidic system.

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