KR101720609B1

KR101720609B1 - MIP(Magnetic Iron Particles) Discrimination Device Using Magnetic Force Flow

Info

Publication number: KR101720609B1
Application number: KR1020150101986A
Authority: KR
Inventors: 이재구; 박성훈; 이훈석
Original assignee: 주식회사 지노바이오
Priority date: 2015-07-17
Filing date: 2015-07-17
Publication date: 2017-03-28
Also published as: KR20170009649A

Abstract

The present invention relates to a MIP (Magnetic Iron Particles) separator using a magnetic force flow so as to effectively separate magnetic beads present in a mixed solution.

Description

(Magnetic Iron Particles) MIP (Magnetic Iron Particles) Discrimination Device Using Magnetic Force Flow [

The present invention relates to a MIP separator for separating MIPs of blood or mixed solution using magnetic force flow.

Blood circulates in the blood vessels of people or animals, carries the oxygen that is received in the lungs to the tissue cells, and transports the carbon dioxide out of the tissues to the lungs.

In addition, blood transports nutrients absorbed from the digestive tract to organs or tissue cells, transports unnecessary substances to the living body, which is a decomposition product of tissue, into the kidneys, discharges them out of the body, and delivers hormones secreted from the endocrine glands to the organs and tissues .

On the other hand, blood cancer cells are cancer cells that are present in the peripheral blood of cancer patients and are cancer cells that have been eliminated from the primary lesion or metastatic lesion.

Such blood cancer cells are expected to be a promising biomarker in the diagnosis of cancer, the analysis of prognosis of treatment, and the analysis of micro-metastasis.

In addition, blood cancer cell analysis is a non-invasive method as compared with existing cancer diagnosis methods, and thus it is very promising as a cancer diagnosis method in the future.

However, blood cancer cells are very difficult to analyze accurately and require very sophisticated analysis methods because the distribution ratio of blood cells is very low in the blood distribution level of one cancer cell per one billion cells or one cancer cell per 10 ⁶ to 10 ⁷ white blood cells.

Currently, the most important issue in cell sorting methods used in cancer diagnosis and blood cell analysis is productivity and efficiency.

That is, fast separation rate and high separation efficiency are required.

Conventional technologies have used a method of filtering cells mainly through mechanical structures to meet productivity issues.

On the other hand, a method of separating cells using an electric field, density, etc. has been disclosed, but there has been a limit that can not satisfy most productivity issues.

In addition, when a mechanical structure is used, there arises a problem that it is difficult to attach the cells to the structure or to extract the separated cells again.

Therefore, although the cell separation rate is high, there is an additional problem that separation efficiency is low.

To solve the problems of the cell separation method using such a mechanical structure, a cell separation method using magnetism has been disclosed.

First, a mixed solution containing magnetic nanoparticles is prepared by mixing magnetic nanoparticles (referred to as magnetic beads) having an antibody that reacts specifically with cancer cells and a blood to be examined.

A conventional technique of flowing a mixed solution and a buffer solution (buffer, for example, distilled water) into a channel on which a channel is formed to control each flow according to the viscosity of the fluid and driving the magnet to separate blood cancer cells from the blood, same.

(1) Prior Art 1 is a method of inducing cancer cells to which magnetic nanoparticles are bound by providing one or more magnets outside the channel of the chip.

The prior art 1 has a disadvantage in that the separation efficiency of the magnetic beads is low.

(2) Prior Art 2 is a method of separating magnetic beads by a plurality of magnets arranged at regular intervals outside a channel of a chip.

That is, in the prior art 2, the magnetic beads are separated from each magnet disposed at regular intervals while the mixed solution flows through the channel of the chip.

Prior Art 2 also has a disadvantage in that the separation efficiency of magnetic beads is low.

(3) Prior Art 3 is a method of disposing magnets at regular intervals on the upper or side wall of a channel of a chip.

That is, in the prior art 3, the initial separation efficiency is higher than the prior art 1 or the prior art 2 in such a manner that magnetic beads are directly attached to the magnets to separate them.

However, there is a disadvantage that the separation efficiency decreases as the magnetic beads stick to the magnet.

The prior arts 1 to 3 are magnet or electromagnetically induced separation systems.

(4) The prior art 4 has a merit that the separation efficiency is higher than that of the prior art 1 to 3 in the magnetic induction type.

The magnetic beads in the mixed solution flowing into both sides through the wire pattern formed on the chip are separated at the center of the ferromagnetic wire pattern by the magnetic induction method.

Compared with the prior arts 1 to 3, the separation efficiency is high, but the following problems occur.

1) In the case of the chip used in the prior art 4, since the wire pattern to which the semiconductor technology is applied is basically used, the manufacturing cost of the chip is very high.

2) In the process of washing for chip recycling, there is a problem of wire pattern damage and the presence of residue after cleaning.

3) The air that may remain inside the chip during the chip cleaning process acts as an obstacle in the separation of magnetic beads.

4) Since the top plate of the chip is made of soft material, the dimension can be changed, and firm fixation is not guaranteed when buffer solution or mixed solution injection port is fixed.

Korean Patent Laid-Open Publication No. 2013-0103282 Korean Patent Laid-Open Publication No. 2013-0095485 Korean Patent No. 1212030 Korea Patent No. 1211862

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and an object of the present invention is to provide a MIP (Magnetic Iron Particles) separator using an economical magnetic force flow.

According to an aspect of the present invention, there is provided an apparatus for separating Magnetic Iron Particles (MIP) using magnetic force flow, comprising: a chip including a channel; And a magnet for applying a magnetic force to the chip, wherein the magnet and the chip are moved relative to each other, a mixing solution inlet and a buffer solution inlet are formed on one side of the chip, and a magnetic bead outlet And another particle outlet is formed.

A MIP (Magnetic Iron Particles) separator using magnetic force flow according to the present invention is characterized in that a plate is formed under the chip, the magnet is formed on the plate, and the plate rotates.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, a plurality of magnets are formed on the plate, the magnets are arranged along the circumference or the radial direction of the plate, And there is a difference in magnetic force between the magnets.

The Magnetic Particles (MIP) separator using the magnetic force flow according to the present invention is characterized in that the difference in magnetic force is caused by a height difference between one magnet and adjacent magnets or a magnitude difference between magnets adjacent to one magnet do.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, the plate is a disk, and the magnet disposed on the plate includes a first magnet portion; And a second magnet portion that is disposed to intersect with the first magnet portion.

A Magnetic Iron Particles (MIP) separator using a magnetic force flow according to the present invention includes a third magnet portion disposed between the first magnet portion and the second magnet portion, And a magnet portion.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, the magnets are regularly or irregularly arranged on the plate.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, the plate is eccentrically rotated about the center of the plate.

A MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention comprises: a belt positioned under the chip; And the magnet is disposed on the belt.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, the belt further includes a first pulley and a second pulley, and the driving unit drives the first pulley or the second pulley .

A MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention is characterized in that the belt comprises a first belt positioned below the chip; And a second belt spaced apart from the first belt by a predetermined distance and positioned at a lower portion of the chip.

A MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention comprises: a first driving unit for driving the first belt; And a second driving unit for driving the second belt.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, a plurality of the magnets are arranged on the belt, a horizontal separation distance between one magnet and an adjacent magnet is a, and a vertical separation distance is b .

A MIP (Magnetic Iron Particles) separator using a magnetic force flow according to the present invention is characterized in that a plurality of magnets in a diagonal direction are arranged in a line in a row, and one magnet disposed in a row and a magnet A magnet portion;

And a sixth magnet portion disposed parallel to the fifth magnet portion,

And the fifth magnet portion and the sixth magnet portion are repeatedly arranged.

The MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention is characterized in that the magnets are arranged irregularly on the belt.

The MIP (Magnetic Iron Particles) separating apparatus using magnetic force flow according to the present invention is characterized in that the magnet is formed by combining a plurality of magnets.

The MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention is characterized in that the channel is formed with an inclination.

The MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention is characterized in that a step is formed in the channel.

The MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention is characterized in that the channel is formed with a slope and a step.

The MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention is characterized in that the chip includes an upper plate and a lower plate coupled to the upper plate, the channel being formed on an upper plate of the chip, The height of the channel is constant with respect to the longitudinal direction of the chip.

A MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention is characterized in that the chip is disposed obliquely with respect to the magnet.

The MIP (Magnetic Iron Particles) separator using the magnetic force flow according to the present invention has the following advantages.

(1) As the magnet moves, a magnetic force is constantly applied to the magnetic beads inside the chip, so that the magnetic bead separation efficiency is remarkably improved.

(2) By forming a height difference in the radial direction of the arrangement of the magnets on the rotary plate, the flow of magnetic beads between adjacent magnets can be smooth.

(3) It is possible to prevent the phenomenon that the magnetic bead is pushed backward by forming the height difference in the circumferential direction of the arrangement of the magnets on the rotary plate.

(4) It is economical because a general material (for example, plastic) is used in chip manufacturing.

(5) Since the disposable chip is used, a recycling process such as washing is unnecessary.

(6) The magnetic bead separation efficiency does not deteriorate even if air is left inside the chip.

(7) When the chip size is long, the separation efficiency is improved by increasing the magnetic bead separation speed.

1 is a perspective view of a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention;
FIG. 2 is a diagram showing a magnetic arrangement of a plate on a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention.
FIG. 3 is a view showing a magnetic arrangement of plates on a plate in a MIP (Magnetic Iron Particles) separating apparatus using magnetic force flow according to the present invention
FIG. 4 is a view showing a magnetic separator according to an embodiment of the present invention. FIG.
FIG. 5 is a view illustrating a magnetic separator according to an embodiment of the present invention. FIG.
6 is a schematic view of a magnet disposed in a radial direction on a plate in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention
7 is a schematic view of a magnet disposed in a circumferential direction on a plate in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention
Fig. 8 is a perspective view of another preferred embodiment (belt drive system)
Fig. 9 is a perspective view of another embodiment (independent belt drive system)
Fig. 10 is a diagram showing a magnet layout on a belt in another embodiment (belt drive system)
FIG. 11 is a schematic view of a Magnetic Iron Particles (MIP) separator using a magnetic force flow according to the present invention,
12 is a perspective view of a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention.
13 is a bottom plan view of a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention
14 is a perspective view of a top plate of a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention.
15 is a perspective view of a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention
16 is a plan view of a bottom plate of a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention.
17 is a top plan view of a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention.
18 is a sectional view of a step formed inside a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention
19 is a sectional view of a channel formed in a chip in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention
20 is a diagram showing a layout of a chip and a magnet in a MIP (Magnetic Iron Particles) separating apparatus using a magnetic force flow according to the present invention

Hereinafter, a MIP (Magnetic Iron Particles) separating apparatus 10 using a magnetic force flow according to the present invention will be described in detail with reference to the drawings.

In the description of the MIP (Magnetic Iron Particles) separating apparatus 10 using the magnetic force flow according to the present invention, when it is said to be "above ", this means that it is in direct contact with the member, It can be done.

First, Magnetic Iron Particles (MIP) consist of magnetite (Fe3O4), maghemite (gamma Fe2O3), cobalt ferrite and manganese ferrite. Specific examples are magnetic beads, magnetic iron particle beads, magnetic iron nanoparticle beads, superparamagnetic agarose beads.

In the following description, the magnetic bead is an example of MIP.

First, the mixed solution flowing into the channel (CH) of the chip (200) is prepared by mixing magnetic nanoparticles coupled with antibodies specifically reacting with cancer cells and blood to be examined.

The blood may include normal cells (first substance species, PU) such as white blood cells, different kinds of cancer cells A (second substance species, PS1), and cancer cells B (third substance species, PS2).

When the types of cancer cells (PS2, PS3) are different, the number of markers (for example, antigens) expressed in cancer cells is different.

In the case of EpCAM (epithelial cellular adhesion molecule) markers, the number of EpCAM expression per cell of breast cancer cell SKBr-3 is about 500,000, the number of EpCAM expression per cell of prostate cancer cell PC3-9 is about 50,000, The number of EpCAM expression is approximately 2,000, and the number of markers expressed per cancer cell varies greatly depending on the carcinoma.

Therefore, when an antibody reacting specifically with EpCAM is bound to magnetic nanoparticles and the magnetic nanoparticles are mixed with the blood of cancer patients, a large difference occurs in the number of magnetic nanoparticles bound to cancer cells depending on the type of cancer cells.

Thus, the number of magnetic nanoparticles bound per cell is used to separate carcinomas using magnetic force.

On the other hand, a buffer solution such as distilled water flows into the buffer solution inlet 220b of the chip.

The buffer solution separately injected through the buffer solution inlet 220b of the chip and the mixed solution injected into the mixing solution inlet 220a flow at the channel CH of the chip 200 at their respective speeds and do not seem to invade their respective fluidized beds It shows the flow.

However, the magnetic beads are attracted to the buffer solution by the magnetic force of the magnet 150.

As described above, the magnetic nanoparticles or the magnetic iron particles are referred to as magnetic beads.

A magnetic force is applied to the lower portion of the chip 200.

Any material having magnetic properties can be used as the magnetic force, and Ni, Co, Fe, or compounds thereof can be used typically.

The magnetic force pulls magnetic particles out of the fluid and interrupts the flow of the particles.

A MIP (Magnetic Iron Particles) separator 10 using a magnetic force flow according to the present invention includes a chip 200 including a channel CH and a magnet 150 for applying a magnetic force to the chip.

First, the MIP (Magnetic Iron Particles) separating apparatus 10 using magnetic force flow includes a base 20.

A turntable 60, a driving unit (not shown), and a Z-axis and angle adjuster 70 are formed on the base 20.

The controller 20 further includes a controller 30 and a drive 40 for controlling the driving unit. The power supply unit SMPS 35 is further included in the upper portion of the base 20.

The chip holder 50 is coupled to the upper portion of the Z-axis and angle adjusting device 70.

The chip holder 50 is protruded toward the center of the plate 100 from the Z axis and angle regulating device 70 coupled to the upper side thereof, and has a cantilever support structure.

One end of the chip holder 50 engages with the Z-axis and the upper portion of the angle regulating device 70.

The Z axis and angle adjusting device 70 serve to adjust the distance and angle between the chip holder 50 and the plate 100 to be described later.

The chip 200 is placed in the chip holder 50.

The magnet 150 that imparts the magnetic force to the chip 200 moves with respect to the chip 200.

Or the chip 200 moves relative to the magnet 150.

As a result, the chip 200 and the magnet 150 move relative to each other.

Referring to FIG. 1, the following will be described.

One end (50a) of the chip holder is coupled to the upper portion of the Z-axis and angle adjusting device (70).

The chip holder 50 is positioned above the plate 100 from the middle 50b of the chip holder to the other end 50c of the chip holder.

The chip 200 is placed on the chip holder 50 positioned on the plate 100. Specifically, in order to apply a magnetic force to the chip 200, the chip 200 is moved from the middle 50b of the chip holder to the chip holder 50 And the other end 50c.

The plate 100 is positioned on a turntable 60 located below the plate 100 and the turntable 60 rotates the plate 100.

For reference, the method of driving the turntable 60 can be roughly classified into (1) indirect driving and (2) direct driving.

In the indirect drive system, the turntable (60) is driven by a belt, and the belt is connected to a pulley.

The pulley is driven by a motor.

In the direct drive type, the motor formed below the turntable 60 rotates the turntable 60 directly.

The chip 200 is placed on the chip holder 50 positioned on the upper side of the plate, and vice versa, the plate 100 is formed on the lower side of the chip 200.

On the other hand, a magnet 150 that applies a magnetic force to the chip 200 is formed on the plate 100.

If only one magnet is formed on the plate 100, only one magnetic force per rotation of the plate 100 is given to the chip 200. [

This configuration is disadvantageous in comparison with other embodiments of the present invention in terms of the separation speed of the magnetic beads in the mixed solution within the channel CH of the chip 200. [

Therefore, in order to increase the separation speed of the magnetic beads, it is preferable that the magnets 150 disposed on the plate 100 are arranged in a plurality and also have various magnet arrangements.

A plurality of magnets (150) are formed on the plate (100).

At this time, a magnet disposed along the circumferential direction of the plate 100 has a magnetic force difference between one magnet and an adjacent magnet, and the difference in magnetic force is realized by a height difference between the magnet 150 and the chip 200 .

That is, one magnet among the plurality of magnets arranged in the circumferential direction of the plate 100 is referred to as M1.

And a magnet behind the plate 100 in the circumferential direction of the plate 100 is referred to as M2.

When the plate 100 is rotated, a plurality of magnets 150 disposed along the circumferential direction of the plate 100 impart a magnetic force to the chip 200.

One magnetic bead moves in the direction of the magnetic bead outlet 220c in the channel CH of the chip by the magnetic force of the M1.

If the magnetic force of the magnet M2 at the rear of M1 is equal to M1, the magnetic beads induced by the magnetic force of M1 are moved back to the magnetic force of M2 again in the channel CH of the chip.

That is, when the magnetic bead is -

A backing effect is generated which moves in the direction of theta (theta).

Accordingly, in order to efficiently separate the magnetic beads, it is necessary to adjust the intensity of the magnetic force. This is because a plurality of magnets 150 arranged along the circumferential direction of the plate 100 are arranged so that the magnetic force of the adjacent magnets For example, by making the height difference between the magnet 150 and the chip 200 different from each other.

A magnet disposed along the radial direction of the plate 100 has a difference in magnetic force between one magnet and an adjacent magnet and the difference in magnetic force can be realized by a height difference between the magnet 150 and the chip 200 .

One magnet is referred to as M3 with respect to the radial direction of the plate 100, and a magnet closer to the center of the plate than M3 is referred to as M4.

It is assumed that one magnetic bead passes through M3 and moves in the direction of the magnetic bead outlet 220c in the channel CH of the chip by the magnetic force of M4.

If the magnetic force of M3 disposed farther from the center of the plate 100 than M4 is equal to M4, the magnetic beads which must pass through M3 and move toward the magnetic bead outlet 220c by the magnetic force of M4, .

That is, a backing effect occurs in which the magnetic beads move in the + R direction (the direction away from the center of the plate 100).

Accordingly, in order to smooth the flow of the magnetic bead, it is necessary to adjust the intensity of the magnetic force. This is because a plurality of magnets 150 arranged along the radial direction of the plate 100 are magnetized with respect to one magnet For example, by making the height difference between the magnet 150 and the chip 200 different.

It is preferable that the plate 100 positioned on the turntable 60 has a disc shape.

This is because when the plate 100 positioned on the turntable 60 is in the shape of a disk, the plate 100 is easily rotated and a plurality of magnets 150 disposed on the plate 100 are continuously magnetized Is easy to give.

However, the shape of the plate 100 is not limited to the disc shape. If the plate 100 is rotatable with the rotation of the turntable 60 on the turntable 60, The prize is possible.

Hereinafter, the arrangement of the magnets 150 disposed on the plate 100 will be described.

(1) A plurality of magnets 150 disposed on the plate 100 include a first magnet portion 150a.

The first magnet portion 150a is disposed on the plate 100 in the radial direction of the plate 100. [

The second magnet portion 150b is disposed to cross the first magnet portion 150a and the first magnet portion 150a and the second magnet portion 150b are disposed at an angle of 90 degrees with respect to each other.

In order to improve the separation efficiency of the magnetic beads, the magnet disposed on the plate 100 may further include a third magnet portion 150c and a fourth magnet portion 150d.

(2) The third magnet portion 150c is also arranged in the radial direction of the plate 100 on the plate 100. [

The fourth magnet portion 150d is disposed to intersect with the third magnet portion 150c and the third magnet portion 150c and the fourth magnet portion 150d are disposed at an angle of 90 degrees with respect to each other.

Meanwhile, since the third magnet portion 150c is disposed between the first magnet portion 150a and the second magnet portion 150b, the third magnet portion 150c is disposed between the third magnet portion 150c and the fourth magnet portion 150c, The magnet portion 150d is also disposed between the first magnet portion 150a and the second magnet portion 150b.

The first magnet portion 150a and the second magnet portion 150b are formed at an angle of 90 degrees and the third magnet portion 150c and the fourth magnet portion 150d are formed at an angle of 90 degrees with each other In another embodiment, when the chip 200 and the magnet 150 move relatively to each other while the magnetic bead flows smoothly, the plate 200 may be formed on the plate 100, It is also possible to dispose other additional magnet portions.

A plurality of magnets 150 may be irregularly arranged as long as the magnets are arranged as many as possible within the radial width range of the plate 100 in order to improve the separation efficiency of the magnetic beads.

The above description is based on the fact that the rotational motion of the plate 100 is made with respect to the center of the plate 100.

In another preferred embodiment of the present invention, the rotational movement of the plate 100 may be made eccentric with respect to the center of the plate 100.

That is, when the center of the plate 100 and the center of the driving unit 80 are positioned to be shifted from each other, the rotational movement of the driving unit 80 causes eccentric rotational movement of the plate 100.

The eccentric shaft 105 shown in FIG. 4 is formed eccentrically from the center of the plate 100.

The magnetic force applied to the chip 200 placed on the chip holder 50 when the plate 100 is eccentrically rotated with respect to the driving unit 80 exerts different forces as the plate 100 rotates eccentrically.

Therefore, it is possible to change the magnetic force given to the chip 200 without forming the difference in the magnetic force of the magnet 150 in the circumferential direction or the radial direction of the plate 100, for example, the height difference of the magnet 150 The separation efficiency of the magnetic bead can be improved.

As shown in Fig. 5, the plate 100 can be constructed by separating the inner ring 100b and the outer ring 100a.

The configuration in which the plate 100 is divided into the inner ring 100b and the outer ring 100a can make the rotational directions of the inner ring 100b and the outer ring 100a different from each other.

At this time, the driving unit 80 for driving the inner ring 100b and the outer ring 100a is preferably configured as an independent driving system.

When the inner ring 100b and the outer ring 100a are rotated in the same direction, the rotation speeds are different from each other, and the magnetic bead separation efficiency and separation speed can be improved.

In the following MIP (Magnetic Iron Particles) separating apparatus 10 using magnetic force flow according to the present invention, the magnetic beads are separated by the magnet 150 disposed on the belt 300.

That is, a belt 300 is disposed below the chip 200, and a magnet 150 is disposed on the belt 300.

It is advantageous to arrange a plurality of magnets 150 disposed on the belt 300 in terms of efficiency of separation of the magnetic beads.

The belt 300 may rotate clockwise or counterclockwise with respect to the drawing, and thus the belt 300 performs an endless track motion.

The first pulley 400 and the second pulley 500 are located inside the belt 300 so that the belt 300 performs endless orbital motion.

Thus, the belt 300 is disposed around the first pulley 400 and the second pulley 500.

The first pulley 400 or the second pulley 500 is driven so that the belt 300 disposed around the first pulley 400 and the second pulley 500 performs an endless track motion.

In a preferred embodiment of the present invention, the second pulley 500 is driven.

A drive unit (not shown) is coupled to the first pulley 400 or the second pulley 500, and a motor or the like is preferably used as the drive unit.

The Z-axis and angle adjuster 70 are further provided at one end 50a of the chip holder.

The Z axis and angle adjusting device 70 adjust the distance or angle between the chip 200 and the belt 300 to adjust the intensity of the magnetic force applied to the chip 200.

The belt 300 can be subjected to endless orbit motion by an independent driving method in order to more accurately control the intensity of the magnetic force applied to the chip 200 and further improve the induction efficiency of the magnetic beads.

That is, the first belt 300a and the second belt 300b located under the chip 200 are positioned.

The second belt 300b is spaced apart from the first belt 300a by a predetermined distance, but the belt 300 should be positioned below the chip 200. [

The first belt 300a is coupled to a first driving unit (not shown) for imparting driving force.

And the second belt 300b is coupled to a second driving unit (not shown) for applying driving force.

When the first belt 300a and the second belt 300b which are spaced apart from each other by a predetermined distance are coupled to the independent driving portions, the endless motion of the first belt 300a and the second belt 300b, Can be adjusted differently.

If the infinite orbital movement speeds of the first belt 300a and the second belt 300b can be controlled independently of each other, the magnetic beads in the chip channel CH can be more accurately induced and separated.

That is, the magnetic bead has an infinite orbital movement speed near the magnetic bead outlet 220c formed on the chip 200, and the infinite orbital movement speed of the belt, which is located near the magnetic bead outlet 220c, By making it slower than the moving speed, the magnetic bead can be more accurately guided and separated toward the magnetic bead outlet 220c side.

The first belt 300a and the second belt 300b have the same infinite orbital movement speed and the first and second belts 300a and 300b have different arrangements of the magnets 150 on the second belt 300b, Can be more accurately guided and separated toward the magnetic bead outlet 220c side.

A plurality of magnets 150 may be disposed on the belt 300.

When the horizontal distance between one magnet and the adjacent magnet is a, the vertical distance between one magnet and the adjacent magnet is b.

In this case, a and b can be the same, and the magnets 150 disposed on the belt 300 can be arranged in various ways by making a and b different from each other, such as a <b or a> b.

On the belt 300, a plurality of magnets are arranged in a row in a diagonal direction, and a fifth magnet portion 150e having the same distance from one magnet disposed adjacent to the other magnets in a row is formed.

Thus, a dead zone having no magnetic force in the channel CH of the chip 200 can be eliminated.

And a sixth magnet portion 150f is disposed parallel to the fifth magnet portion 150e.

Since the fifth magnet portion 150e and the sixth magnet portion 150f are arranged in parallel to each other, the sixth magnet portion 150f is also arranged in a line in parallel with the plurality of magnets, The distances from the other magnets are the same.

The fifth magnet portion 150e and the sixth magnet portion 150f are repeatedly arranged on the belt.

If the chip 200 and the magnet 150 move smoothly while flowing the magnetic bead smoothly, a plurality of magnets 150 are irregularly arranged on the belt 300 for improving the efficiency of separation of the magnetic beads It is possible.

In the above description, the magnet 150 disposed on the plate 100 or on the belt 200 may be formed by combining a plurality of magnets (see FIG. 11).

In other words, when describing a rod-like magnet, an N pole is formed at one end of the magnet and an S pole is formed at the other end of the magnet.

The magnitude of the magnetic force in the bar magnet is highest in the N and S poles, while the midpoint between the N and S poles has little or no magnetic force.

If a plurality of magnets are combined to form a single magnet as shown in the drawing, the magnitude of the magnetic force at an intermediate point where the N pole and the S pole meet can be increased without increasing the installation space of the magnet disposed on the plate or the belt .

That is, although the magnetic force is small at the point where the N pole and the S pole meet, a plurality of magnets are superimposed on each other, so that the magnetic force can be increased at an intermediate point where the N pole and the S pole meet.

When a plurality of magnets are combined to form a single magnet, the magnetic bead induction and separation efficiency can be improved by eliminating the non-uniformity of the magnetic force while increasing the intensity of the magnetic force at the midpoint where the N pole and the S pole meet There are advantages.

The shape of the chip 200 in the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow is as follows.

The chip 200 includes an upper plate 210 and a lower plate 220 having a substantially rectangular plate shape.

The upper plate 210 of the chip and the lower plate 220 of the chip are combined to form a channel CH.

First, the lower plate 220 of the chip is formed with a recess 225 and a plurality of holes 220a to 220d which are hollowed inside.

The plurality of holes 220a to 220d include a mixed solution inlet 220a into which a mixed solution is injected and a buffer solution inlet 220a into which a buffer solution such as saline is injected.

On one side 200a of the chip, a mixed solution inlet 220a through which a mixed solution is injected, and a buffer solution inlet 220a into which a buffer solution such as saline is injected is formed.

The plurality of holes 220a to 220d include a magnetic bead outlet 220c through which magnetic beads are discharged and other particle discharging ports 220d through which other particles are discharged.

The other side 200b of the chip is provided with a magnetic bead outlet 220c and another particle outlet 220d through which other particles are discharged.

The lower plate 220 of the chip engages with the upper plate 210 of the chip.

Through this coupling, a channel CH and a plurality of passages 225a to 225d are formed between the depressed portion 225 formed in the lower plate 220 of the chip and the inner surface of the upper plate 210 of the chip.

The plurality of passages 225a to 225d includes a mixed solution passage 225a for connecting the mixed solution inlet 220a and the channel CH, a buffer solution passage 225b for connecting the buffer solution inlet 220b and the channel CH, .

The plurality of passages 225a to 225d also include a magnetic particle passage 225c for connecting the magnetic bead outlet 220c and the channel CH and another particle passage 225d for connecting the channel CH to the other particle outlet 220d. ).

Although the depression 225 is formed on the bottom plate 220 of the chip, the depression may be formed on the top plate 210 of the chip.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, a slope is formed in the channel CH.

By forming a downward slope in the channel CH in the direction of the magnetic bead outlet 220c, the magnetic bead separation speed and efficiency are improved.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, a step 250 is formed in the channel CH in the direction of the magnetic bead outlet 220c.

As shown in FIG. 19, when the chip 200 is viewed from the side, a step 250 is formed in the longitudinal direction of the chip 200, specifically in the direction of the channel CH to the magnetic bead outlet 220c.

A magnetic bead flowing inside the channel CH of the chip is guided by one magnet M1 disposed on the plate 100 or on the belt 300 and then by the magnetic force of the magnet M2 located behind the M1 It can flow back again.

A step 250 as shown in FIG. 16 is formed on the channel CH to prevent the rearward movement of the magnetic beads.

It is possible to prevent the phenomenon that the magnetic beads move backward (backing effect) by the step 250 formed in the channel CH.

In the MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention, the inclination and the step 250 can be combined with the channel CH of the chip 200.

When the inclination and the step 250 are combined with each other in the channel CH, the magnetic bead separation speed and efficiency can be improved in the flow of the magnetic bead, and the phenomenon that the magnetic bead moves backward Effect, backing effect) can be prevented.

The channel CH is formed by a depression 225 formed in the upper plate 210 of the chip or the lower plate 220 of the chip.

As described above, the dimples 225 can be formed on the upper plate 210 of the chip or the lower plate 220 of the chip.

If the height of the channel CH is kept constant with respect to the longitudinal direction of the chip 200, the change in the flow rate inside the channel CH can be reduced.

It is obvious that the separation efficiency of the magnetic beads is improved when the change of the flow rate in the channel CH is reduced.

In the MIP (Magnetic Iron Particles) separating apparatus 10 using the magnetic force flow according to the present invention, the chip 200 includes an upper plate 210 and a lower plate 220 coupled to the upper plate 210.

The channel CH further includes a step 250 formed in the upper plate 21 of the chip or the lower plate 220 of the chip.

The height of the channel CH is made constant with respect to the longitudinal direction of the chip 200.

In order to keep the height of the channel CH constant with respect to the longitudinal direction of the chip when the top plate 210 of the chip or the step 250 formed on the bottom plate 220 of the chip is included in the channel CH, A step 250 corresponding to the step 250 formed on the chip 220 must be formed on the top plate 210 of the chip.

The chip 200 may be disposed tilted relative to the magnet 150.

The chip 200 is positioned in the chip holder 50 located on the plate 100 or the belt 300 and the chip 200 is placed on the plate 100 or on the belt 300, (150) are positioned parallel to each other.

However, the magnetic beads may not flow smoothly in the channel CH due to magnetic interference between the plurality of magnets 150 disposed on the plate 100 or the belt 300.

That is, when the magnetic beads have the same magnetic force in the course of inducing the magnetic beads in a desired direction in the mixed solution, the flow in the channel CH is not smooth.

Therefore, it is necessary that the magnetic force acting on the chip 200 in the longitudinal direction, more specifically, the magnetic bead outlet 220c, is larger than the magnetic force acting on the mixed solution passage 225a.

The chip 200 can be inclined downward with respect to the magnet 150 so that the magnetic force acting on the magnetic bead outlet 220c can be made larger than the magnetic force acting on the mixed solution passage 225a.

When the chip 200 is disposed with a downward inclination relative to the magnet 150, the magnetic force acting on the magnetic bead outlet 220c can be made larger than the magnetic force acting on the mixed solution passage 225a.

Therefore, the magnetic bead can be guided to the magnetic bead outlet 220c at a high speed.

The magnetic force acting on the magnetic bead outlet 220c can be made smaller than the magnetic force acting on the mixed solution passage 225a when the chip 200 is disposed with an upward inclination relative to the magnet 150. [

In this arrangement, the magnetic bead can be more accurately guided by the magnetic bead outlet 220c.

As shown in FIG. 20, since the chip 200 is placed on the chip holder 50, the tilting of the chip holder 50 is the same as when the chip 200 is tilted.

It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

In addition, various embodiments disclosed in the present invention can be implemented in various combinations.

The MIP (Magnetic Iron Particles) separating apparatus using the magnetic force flow according to the present invention is not only high in magnetic bead separating efficiency but also economical because the manufacturing cost of the chip is low.

10: Separation device
20: Base 30: Controller
40: driver 50: chip holder
60: turntable 70: Z axis and angle adjusting device
100: Plate 150: Magnet
150a: first magnet part 150b: second magnet part
150c: third magnet section 150d: fourth magnet section
150e: fifth magnet section 150f: sixth magnet section
200: chip 210: chip top plate
220: lower plate of chip 220a: mixed solution inlet
220b Buffer solution inlet 220c: Magnetic bead outlet
220d: Other particle outlet 250: Step
300: Belt 400: First pulley
500: second pulley

Claims

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A chip including a channel;
And a magnet for applying a magnetic force to the chip,
Wherein the magnet is disposed on the plate, the plate rotates, the magnet and the chip move relative to each other, and the magnet formed on the plate has a plurality of Wherein the magnets are disposed along the circumference or radial direction of the plate,
A magnetic bead discharge port and a particle discharge port are formed on the other side of the chip, and the magnetic bead discharge port and the other particle discharge port are formed on one side of the chip. Magnetic Iron Particles (MIP) separator using magnetic force flow

The method of claim 3,
Wherein the difference in magnetic force is caused by a height difference between one magnet and a neighboring magnet or a difference in magnitude between adjacent ones of the magnets, and a magnetic iron particle (MIP)

The method of claim 3,
The plate is a disc,
The magnet disposed on the plate includes a first magnet portion;
And a second magnet portion disposed to intersect with the first magnet portion. The Magnetic Iron Particles (MIP)

The method of claim 5,
And a third magnet portion disposed between the first magnet portion and the second magnet portion,
And a fourth magnet portion disposed to intersect with the third magnet portion. The Magnetic Iron Particles Separator (MIP)

The method of claim 3,
Characterized in that the magnets are irregularly arranged on the plate. The Magnetic Iron Particles (MIP)

The method of claim 3,
Characterized in that the plate is eccentrically rotated with respect to the center of the plate, characterized in that a magnetic iron particle (MIP)

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A chip including a channel;
A belt positioned below the chip;
And a magnet disposed on the belt and imparting a magnetic force to the chip,
The magnet and the chip making relative movement with respect to each other, the belt being located at the bottom of the chip;
And a second belt spaced a predetermined distance from the first belt and positioned at a lower portion of the chip, wherein a mixing solution inlet and a buffer solution inlet are formed on one side of the chip, A bead discharge port and other particle discharge ports are formed.

The method of claim 11,
A first driving unit for driving the first belt;
And a second driving unit for driving the second belt. The Magnetic Iron Particles Separator (MIP)

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A chip including a channel;
A belt positioned below the chip;
And a magnet disposed on the belt and imparting a magnetic force to the chip,
The magnet and the chip are moved relative to each other, a plurality of magnets arranged in a row in a diagonal direction, a fifth magnet having a same distance from one magnet disposed adjacent to the other magnet in a row;
And a sixth magnet portion disposed in parallel with the fifth magnet portion, wherein the fifth magnet portion and the sixth magnet portion are repeatedly arranged, wherein a mixing solution inlet and a buffer solution inlet are formed on one side of the chip, And a magnetic bead outlet and another particle outlet are formed on the other side of the chip. The MIP (Magnetic Iron Particles) separator

A chip including a channel;
A belt positioned below the chip;
And a magnet disposed on the belt and imparting a magnetic force to the chip,
Wherein the magnet and the chip make relative movement with respect to each other,
The belt comprising: a first belt positioned below the chip;
And a second belt spaced a predetermined distance from the first belt and positioned at a lower portion of the chip, wherein a plurality of magnets are arranged in a line in a diagonal direction, A fifth magnet portion having a distance to another adjacent magnet; And a sixth magnet portion disposed in parallel with the fifth magnet portion, wherein the fifth magnet portion and the sixth magnet portion are repeatedly arranged, wherein a mixing solution inlet and a buffer solution inlet are formed on one side of the chip, And a magnetic bead outlet and another particle outlet are formed on the other side of the chip. The MIP (Magnetic Iron Particles) separator

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A chip including a channel;
And a magnet for applying a magnetic force to the chip,
The magnet and the chip move relative to each other, a step is formed in the channel, a mixing solution inlet and a buffer solution inlet are formed on one side of the chip, a magnetic bead outlet and another particle outlet are formed on the other side of the chip A magnetic iron particle (MIP) separator using a magnetic force flow

A chip including a channel;
And a magnet for applying a magnetic force to the chip,
The magnet and the chip are moved relative to each other,
Wherein a magnetic bead outlet and another particle outlet are formed on the other side of the chip, wherein the magnetic bead outlet and the other particle outlet are formed on one side of the chip, the mixing solution inlet and the buffer solution inlet are formed on the channel, (Magnetic Iron Particles) Separator

A chip including a channel;
And a magnet for applying a magnetic force to the chip,
The magnet and the chip are moved relative to each other,
The chip includes an upper plate and a lower plate coupled with the upper plate,
The channel further includes a step formed on an upper plate of the chip or a lower plate of the chip, the height of the channel being constant with respect to a longitudinal direction of the chip, a mixing solution inlet and a buffer solution inlet are formed on one side of the chip , And a magnetic bead outlet and another particle outlet are formed on the other side of the chip. The MIP (Magnetic Iron Particles) separator

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