KR20060018474A - Method and apparatus for particle separation using centrifugal force and microfluidic channel - Google Patents

Abstract

The present invention relates to a method for separating microparticles using centrifugal force and microfluidic channel, and to shorten the separation time by using microfluidic channel in separating using the density difference between microparticles and fluid by centrifugal force, respectively. The fine particles and the fluid can be easily separated. Specifically, the present invention comprises a reservoir formed on a disk and a fine channel connected to the reservoir, and the fluid and particles are quickly separated by centrifugal force by rotating the disk or applying pressure to the fluid. The present invention is useful as a sample pretreatment device capable of analyzing by separating plasma from blood of a subject in a short time in a medical diagnostic device.

Centrifugal force, separation, microparticle, microchannel

Description

METHOD AND APPARATUS FOR PARTICLE SEPARATION USING CENTRIFUGAL FORCE AND MICROFLUIDIC CHANNEL}

1 is a plan view showing a fine particle separation apparatus according to a first embodiment of the present invention.

2 is a partially enlarged view of FIG. 1;

3 is a plan view showing a fine particle separation apparatus according to a second embodiment of the present invention.

4 is an enlarged partial view of FIG.

5 is an enlarged partial view of FIG. 4.

6 is an object freedom modeling the motion of the fine particles.

7a and 7b are graphs showing the movement distance of the microparticles according to the speed and initial radial position of the centrifugation.

*** Description of the protection of the main parts of the drawing ***

10: Disc 11: Storage

12: Microfluidic channel 13: Auxiliary microchannel

14: storage 21: storage

22: spiral microfluidic channel

24: separate storage

 The present invention relates to a method and apparatus for separating fine particles using centrifugal force and microfluidic channel. Specifically, it relates to an apparatus and a method for separating microparticles using a centrifugal force and a microchannel for a small amount of fluid.

When plasma or serum is to be separated from blood, conventionally, centrifugal force is applied to a large amount of blood for 30 minutes with a force of about 1200 g to separate plasma. Conventional centrifuges are widely used to separate microparticles from a large amount of sample, but it takes a lot of separation time and is not suitable for a microfluidic system that wants to obtain a lot of analysis information from a small amount of sample in a short time.

 In an emergency situation, in order to make a rapid diagnosis, the blood treatment time and the diagnosis time should be minimized so that the patient can receive appropriate treatment. To this end, a technique used in the on-site diagnostics is widely used to separate a porous membrane, but it is not easy to apply to a diagnostic apparatus using a microfluid because the throughput is small and the collected fluid is not easy to collect in the chamber. In addition, there is a method of collecting microparticles using ultrasonic waves and separating them using microfluidic channels, but there is a disadvantage in that ultrasonic waves must be generated externally.

Accordingly, it is an object of the present invention to provide a method and apparatus capable of separating a fluid containing fine particles in a simple manner within a short time.

Another object of the present invention is to provide a new type of separation device that is easy to apply with other diagnostic devices.

Other objects and features of the present invention will be more specifically set forth in the following detailed description.

In order to achieve the above object, according to a first aspect of the present invention, a disk; and on the disk, a reservoir which is installed at a predetermined distance in the radial direction from the center of the disk, and stores a fluid containing fine particles; and the A microfluidic channel formed on the disk and extending from one side of the reservoir, and formed on the disk, connected to the reservoir by the microfluidic channel, and the microparticles and the fluid by centrifugal force due to the rotation of the disk. Is separated storage is moved and stored in a state separated from each other; And an auxiliary microchannel extending from one side of the separation reservoir, into which the separated fluid is moved, and the microparticle separation apparatus using the centrifugal force and the microfluidic channel.

According to a second aspect of the present invention, there is provided a disk, comprising: a reservoir on the disk, which is installed at a predetermined distance in a radial direction from the center of the disk, and stores a fluid containing fine particles; A microfluidic channel formed on the disk and extending from one side of the reservoir to form a spiral; A centrifugal force formed on the disc; two separate reservoirs each having microparticles and fluids moved through the microfluidic channel and separated from each other by a centrifugal force due to the rotation of the disc. Provided is a microparticle separation device using a microfluidic channel.

On the other hand, the present invention is installed on a disk, the centrifugal force is applied to a plurality of reservoirs in which a fluid containing fine particles are stored; Conveying the microparticles and the fluid to the microfluidic channel extending from the reservoir by centrifugal force; By centrifugal force, there is provided a method for separating microparticles using a centrifugal force and a microfluidic channel comprising separating the microparticles and the fluid conveying the microfluidic channel.

The present invention shortens the centrifugation time by reducing the distance that the microparticles are moved by centrifugal force, and uses the laminar flow phenomenon in the microchannels to classify the separated microparticles and fluid into different chambers in real time to achieve separation efficiency. It is intended to increase.

Hereinafter, with reference to the drawings will be described in more detail the technical configuration and operation of the present invention.

1 is a plan view showing a fine particle separation apparatus according to a first embodiment of the present invention, Figure 2 is a partially enlarged view of FIG. A plurality of reservoirs 11 are formed on the plate-shaped circular disk 10. The reservoir 11 may be formed integrally with the disk 10 itself, or may be manufactured separately and coupled to the disk. The reservoir 11 stores a fluid including fine particles, and the position of the reservoir 11 is preferably located at a predetermined distance from the center near the center of the disk 10. The plurality of reservoirs 11 are preferably arranged on the circumference of each other.

A microfluidic channel (11 ′ in FIG. 2) extends from one side of the reservoir 11 and is connected to a separate reservoir 12. The separate storage 12 is preferably formed of a rod-shaped tube larger than the width. The microchannels 11 ′ and the separate reservoirs 12 are preferably in a straight line in the radial direction of the disk 10. However, it is not necessarily located in a straight line, and may be spaced apart from the reservoir 10 in the radial direction of the disk. The separation reservoir 12 stores a fluid including microparticles that have been moved through the microfluidic channel 11 ′. The microfluidic channel 11 ′ and the separate reservoir 12 may also be integrally formed on the disk 10, or may be separately manufactured and coupled to the disk 10.

The disk 10 may be provided with a rotating means (not shown). When the disk is rotated by the rotating means, centrifugal force is generated, and the fluid including the fine particles stored in the reservoir 11 is centrifugal force. Passed through the microfluidic channel (11 ') is stored in the separate storage (12). The microparticles and the fluid moved to the separating reservoir 12 are separated by the difference in density from each other. Usually, the microparticles are separated farther in the radial direction of the disk because of their high density.

Fluid or microparticles separated from the separating reservoir 12 may be separated through a separate auxiliary microchannel 13, respectively. 1 and 2 it can be seen that one end of the auxiliary microchannel 13 is connected to one side to discharge the fluid located in the front of the disk radial direction of the separate storage to the outside. A valve (not shown) may be connected to the auxiliary microchannel, and the other end of the auxiliary microchannel 13 is connected to the fluid storage reservoir 14.

As such, by forming a plurality of reservoirs 11 and the microfluidic channels 11 ′ and the separating reservoirs 12 connected to the reservoirs on the disc 10, a small amount of fluid is quickly separated from the fine particles therein. can do. In particular, it is possible to separate several kinds of fluids from each microparticle at once.

Figure 3 is a plan view showing a microparticle separation device according to a second embodiment of the present invention, Figure 4 is a partially enlarged view of FIG. A plurality of reservoirs 21 are formed on the plate-shaped circular disk 20. The reservoir 21 stores a fluid containing fine particles. The reservoir 21 may be formed integrally with the disk 20 itself, or may be manufactured separately and coupled to the disk.

It can be seen that the spiral microfluidic channel 22 extends from one side of the reservoir 21. The microfluidic channel 22 is preferably a very small thickness or diameter, for example, preferably formed in the range of tens to hundreds of micrometers. The fine channel is spirally formed on the disk, one end of which is connected to a separate reservoir 24.

The microfluidic channel 22 is divided into two channels near the end, and separate channels 24a and 24b are connected to each channel.

The disk 20 includes a rotating means (not shown) or a pressure applying means (not shown). The rotating means rotates the disk to generate centrifugal force radially from the center of the dask, and the pressure applying means applies pressure to the fluid stored in the reservoir 21 to move the fluid to the microfluidic channel 22. While moving the helical microfluidic channel 22, centrifugal force is received from the central direction of the microfluidic channel (center direction of the disk) to the outer surface (radial direction of the disk).

The fluid subjected to centrifugal force by the rotating means or the pressure applying means is separated from the fine particles by the centrifugal force while passing through the helical microfluidic channel 22. Since the microfluidic channel is very small in thickness or width, separation of the fluid and the microparticles passing through the inside is also very rapid. In general, since the fine particles are denser than the fluid, in the microfluidic channel, the fluid is separated from the central surface of the microfluidic channel (the disk direction) and the microparticles are separated from the outer surface (the radial direction of the disk). Will be moved.

The separated microparticles and the fluid pass through two separate channels formed at the ends of the microfluidic channel 22, respectively, and are stored in the separate reservoirs 24a and 24b. Referring to FIG. 5, which is an enlarged view of portion A of FIG. 4, the high-density microparticles are separated on the disk radial surface of the microfluidic channel and passed through the first separation channel 22a to be stored in the first separation storage 24a. The fluid is separated into the disk central direction surface of the microfluidic channel and passes through the second separation channel 22b to be stored in the second separation reservoir 24b.

6 is an object freedom diagram illustrating a principle in which fine particles are separated in the second embodiment. The fluid moving the microfluidic channel is moved by the pressures P1 and P2 at both ends of the channel, and the microparticles are accelerated by the centrifugal and frictional forces and finally move along one wall of the microfluidic channel by the force shown in the figure on the right. do. In the second embodiment of the present invention, the smaller the thickness or diameter of the microfluidic channel is, the shorter the movement path of the fine particles separated from the fluid can be.

In order to confirm the microparticle separation ability of the microparticle separation apparatus according to the present invention, the following calculations were made. First, blood was loaded into a reservoir on the disc, and the rotational speed of the disc was rotated at about 1000 rpm for 1 minute to move blood through the microfluidic channel, and the filtered fluid and the separated fine particles were separated into separate separate reservoirs.

In the case where the particles initially have a radius of 10 mm on the disc, the position after 20 seconds of red blood cells (RBC), white blood cells (WBC), and platelets is shown in FIG. At this time, the specific gravity of red blood cells, white blood cells, and platelets is 1.09645, 1.075, 1.0645, respectively, and the density of the fluid is 1.0269. Since platelets move at about 1000 μm at about 500 μm after 20 seconds, separation can be seen in a few tens of seconds when the width of the channel is 200 to 300 μm. Therefore, the rotation speed can be separated within a few minutes by operating at 500 ~ 2000rpm.

The position of the particles after 20 seconds while fixing the rotational speed at 10000 rpm and changing the initial position is shown in FIG. 7B. It can be seen that even in the initial radial position within 10mm can be sufficiently separated.

When the rotational speed is 1000rpm and the initial radial position is 10mm from the above calculation results, when the width is 200㎛, the time taken for the fluid to move from the first reservoir to the separate reservoir takes about 40 seconds, and according to the present invention It can be seen that the helical microfluidic channel can simultaneously implement separation and fluid transfer of the microparticles.

As described above, when the microfluidic channels according to the present invention are arranged as shown in FIG. 1 or 3 on a disk, about 12 to 90 may be arranged, and after filtering the fluid, the microfluidic channels are connected to a diagnostic apparatus or an analyzer. Can be used immediately.

The present invention can shorten the separation time by using a microfluidic channel to shorten the path length that the microparticles must move by using a centrifugal force, and at the same time obtain a separated fluid in real time using laminar flow. Since the present invention uses centrifugal force, it is very easy to apply to a diagnoser using centrifugal force, and there is an advantage that the plasma can be separated continuously, and after separation, it is easy to apply to a diagnoser using microfluidics. It is useful as a small amount of blood separator. Therefore, the present invention can be used as a short time blood preprocessor that can be usefully used in a portable diagnostic device developed by many research institutes and diagnostic companies, or may be used as a filtering device for fluids containing microparticles.

Claims (13)

Disk; and A reservoir for storing a fluid including fine particles on the disc, the disc being installed at a predetermined distance in a radial direction from the center of the disc; and A microfluidic channel formed on the disk and extending from one side of the reservoir; and A separate reservoir formed on the disc, connected to the reservoir by the microfluidic channel, and stored in a state in which the microparticles and the fluid move and are separated from each other by centrifugal force due to the rotation of the disc; And A microparticle separation device using a centrifugal force and a microfluidic channel, comprising; an auxiliary microchannel extending from one side of the separation reservoir, the separated fluid is moved. The microparticle separation apparatus according to claim 1, further comprising a fluid storage reservoir for removing and storing the separated fluid from the separation reservoir through the auxiliary microchannel. According to claim 1, wherein the disk is a microparticle separation device using a centrifugal force and a microfluidic channel is connected to the rotating means. The apparatus of claim 1, wherein the reservoir, the microfluidic channel, and the separate reservoir are in a straight line in the radial direction of the disc. Disk; and A reservoir for storing a fluid including fine particles on the disc, the disc being installed at a predetermined distance in a radial direction from the center of the disc; and A microfluidic channel formed on the disk and spirally extending from one side of the reservoir; and Centrifugal force and fine formed on the disk, including two separate reservoirs each stored in a state in which the microparticles and the fluid moving through the microfluidic channel separated from each other by the centrifugal force according to the rotation of the disk; Fine particle separation device using a fluid channel. The apparatus of claim 5, wherein the microfluidic channels are separated into two at the end of the channel, and a separate reservoir is connected to each of the separated channels. 7. The apparatus of claim 5, wherein the disc has a centrifugal force and a microfluidic channel to which a rotating means is connected. The apparatus of claim 5, wherein the disk comprises pressure means for applying hydraulic pressure to the reservoir to pressurize a fluid including the microparticles to move through the microfluidic channel. A centrifugal force is applied to the disk, the centrifugal force being applied to a plurality of reservoirs in which fluid containing microparticles is stored; Conveying the microparticles and the fluid to the microfluidic channel extending from the reservoir by centrifugal force; By centrifugal force, comprising separating the fluid from the microparticles conveying the microfluidic channel Microparticle separation method using centrifugal force and microfluidic channel. 10. The method of claim 9, wherein the microparticles are separated through the microfluidic channel into the wall surface in the direction of the centrifugal force in the channel while being transported through the microfluidic channel. 10. The method of claim 9, wherein the centrifugal force is generated by rotating the disk. The centrifugal force and the microfluidic channel of claim 9, wherein the microfluidic channel is formed in a spiral shape, and the centrifugal force is generated by applying hydraulic pressure to the reservoir to move the microfluidic channel of the microparticles and the fluid. Fine particle separation method using. The method of claim 9, wherein the separated microparticles and the fluid are stored in separate reservoirs.

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