KR102424845B1 - Microfluidic apparatus - Google Patents

Abstract

In one embodiment of the present invention, a body unit rotatable about a rotation axis, a plurality of arm units radially disposed on the body unit about the rotation axis, and one end of each of the plurality of arm units are detachably coupled to each other, , It provides a microfluidic device comprising a plurality of division units including a microfluidic structure for separating at least a first material from the introduced sample.

Description

Microfluidic apparatus

The present invention relates to microfluidic devices.

A device that transports a fluid within a microfluidic structure is called a microfluidic device. Such a microfluidic device is being used as a clinical diagnostic analysis device designed so that anyone can easily and inexpensively detect a small amount of a target substance in a fluid. In order to transport the fluid in the microfluidic device, a driving pressure is required. As the driving pressure, capillary pressure is sometimes used, or a pressure by a separate pump is used.

Recently, as such a microfluidic device, a microfluidic device that uses centrifugal force by placing a microfluidic structure on a circular disk-shaped rotatable platform, that is, a lab-on-a disk or Lab CD, has been developed. is being proposed

Lab-on-a-Disc, meaning 'laboratory on disc', is a variety of experimental procedures performed in the laboratory, for example, sample separation, purification, mixing, labeling, It implements analysis and cleaning on a small-sized chip, and it is a device that integrates various laboratory equipment necessary for the analysis of biological molecules into a CD-shaped device.

When a biological sample, such as blood, is injected into the microfluidic structure provided on the disk, there is an advantage in that fluids such as samples and reagents can be moved using only centrifugal force without a separate driving system such as driving pressure to transport the fluid. However, in order to provide sufficient centrifugal force to the microfluidic structure, the size of the disk must be increased. If the size of the disk increases, manufacturing becomes very difficult. There is a problem with increased risk.

KR 10-2008-0022029 A (2008.03.10)

An object of the present invention is to provide a microfluidic device capable of transmitting high centrifugal force to a microfluidic structure.

However, these problems are exemplary, and the scope of the present invention is not limited thereto.

In one embodiment of the present invention, a body unit rotatable about a rotation axis, a plurality of arm units radially disposed on the body unit about the rotation axis, and one end of each of the plurality of arm units are detachably coupled to each other, , It provides a microfluidic device comprising a plurality of division units including a microfluidic structure for separating at least a first material from the introduced sample.

In one embodiment of the present invention, the microfluidic structure may include a separation chamber for separating at least the first material from the sample by centrifugal force.

In an embodiment of the present invention, the microfluidic structure includes an input chamber to which the sample is input, a separation chamber connected to the input chamber, and a separation chamber for separating n materials having different densities from the sample by centrifugal force, each of the It is connected to the separation chamber and may include m storage chambers for storing the n separated substances.

In an embodiment of the present invention, the m storage chambers may cross each other and be connected to the separation chamber.

In an embodiment of the present invention, the m storage chambers may be alternately arranged left and right with respect to the separation chamber.

In one embodiment of the present invention, the m number of valves installed in each channel connecting the m storage chamber and the separation chamber may be further included.

In one embodiment of the present invention, the microfluidic device separates n materials having different densities from the sample by centrifugal force, and then sequentially opens the m valves from the inner valve adjacent to the rotation shaft to the outer valve. The n materials may be transferred to the m storage chambers.

In one embodiment of the present invention, it may further include a heating unit having a heating member disposed at a position corresponding to the valve.

In one embodiment of the present invention, it may further include a battery for supplying power to the heating member.

In one embodiment of the present invention, the battery may be disposed on the center of the heating unit.

In one embodiment of the present invention, a plurality of the batteries are provided on the heating unit, and the plurality of batteries may be symmetrically disposed.

In one embodiment of the present invention, it may further include a heat transfer member provided between the valve and the heating member.

In one embodiment of the present invention, the heat transfer member includes at least one of diamond, silver, aluminum oxide, boron nitride, zinc oxide and aluminum nitride in a combination containing at least one of epoxy, silicone, urethane, and acrylate. It may be made of the included material.

In one embodiment of the present invention, the heating member is made of a heating element, the heating element is made of an electronic component, and may further include a control unit for controlling a current or voltage applied to the electronic component.

In one embodiment of the present invention, the control unit may control the current or voltage applied to the electronic component according to the type of material constituting the valve or the rotational speed of the body unit and the heating unit.

In one embodiment of the present invention, the first distance from the rotation shaft to the end of the arm unit and the second distance from the end of the arm unit to the end of the dividing unit may have a ratio of 2:1 to 20:1. have.

In one embodiment of the present invention, the second radius from the rotation shaft to the end of the division unit may be twice or greater than the first radius from the rotation shaft to the outer edge of the body unit.

Other aspects, features, and advantages other than those described above will become apparent from the following detailed description, claims and drawings for carrying out the invention.

According to an embodiment of the present invention made as described above, the microfluidic device includes a plurality of arm units coupled to the body unit and a division unit detachably provided at one end of the plurality of arm units, thereby reducing the disk size. It is possible not only to provide a large centrifugal force, but also to apply a large centrifugal force to the dividing unit even in the same centrifugal force.

Of course, the scope of the present invention is not limited by these effects.

1 is a block diagram of a microfluidic device according to an embodiment of the present invention.
FIG. 2 is a diagram illustrating a part of the microfluidic device of FIG. 1 .
FIG. 3 is a diagram illustrating the division unit of FIG. 2 .
4 is a view for explaining a method of separating n materials using a dividing unit according to an embodiment of the present invention.

Hereinafter, various embodiments of the present disclosure are described in connection with the accompanying drawings. Various embodiments of the present disclosure are capable of various changes and may have various embodiments, and specific embodiments are illustrated in the drawings and the related detailed description is described. However, this is not intended to limit the various embodiments of the present disclosure to specific embodiments, and it should be understood to include all modifications and/or equivalents or substitutes included in the spirit and scope of the various embodiments of the present disclosure. In connection with the description of the drawings, like reference numerals have been used for like components.

Expressions such as “comprises” or “may include” that may be used in various embodiments of the present disclosure indicate the existence of the disclosed corresponding function, operation or component, and may include one or more additional functions, operations, or components, etc. are not limited. Also, in various embodiments of the present disclosure, terms such as “comprise” or “have” are intended to designate that a feature, number, step, action, component, part, or combination thereof described in the specification is present, It should be understood that it does not preclude the possibility of addition or existence of one or more other features or numbers, steps, operations, components, parts, or combinations thereof.

In various embodiments of the present disclosure, expressions such as “or” include any and all combinations of the words listed together. For example, "A or B" may include A, may include B, or may include both A and B.

Expressions such as “first”, “second”, “first”, or “second” used in various embodiments of the present disclosure may modify various components of various embodiments, but do not limit the components. does not For example, the above expressions do not limit the order and/or importance of corresponding components. The above expressions may be used to distinguish one component from another. For example, both the first user device and the second user device are user devices, and represent different user devices. For example, without departing from the scope of the various embodiments of the present disclosure, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component.

When a component is referred to as being “connected” or “connected” to another component, the component may be directly connected to or connected to the other component, but the component and It should be understood that other new components may exist between the other components. On the other hand, when an element is referred to as being "directly connected" or "directly connected" to another element, it will be understood that no new element exists between the element and the other element. should be able to

The terminology used in various embodiments of the present disclosure is only used to describe one specific embodiment, and is not intended to limit the various embodiments of the present disclosure. The singular expression includes the plural expression unless the context clearly dictates otherwise.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which various embodiments of the present disclosure pertain.

Terms such as those defined in a commonly used dictionary should be interpreted as having a meaning consistent with the meaning in the context of the related art, and unless explicitly defined in various embodiments of the present disclosure, ideal or excessively formal terms not interpreted as meaning

1 is a block diagram of a microfluidic device according to an embodiment of the present invention, FIG. 2 is a view showing a part of the microfluidic device of FIG. 1 , and FIG. 3 is a view showing the division unit of FIG. 2 .

1 to 3 , the microfluidic device 10 according to an embodiment of the present invention may include a body unit 100 , a plurality of arm units 110 , and a division unit 120 .

The body unit 100 may be rotatable about the rotation axis Ax1. The body unit 100 may be formed in the form of a disk having a predetermined height as shown. Although not shown, the body unit 100 may be rotated by a rotation driving unit such as a motor. The motor may be connected to the rotation shaft Ax1 of the body unit 100 , and the rotation speed of the body unit 100 may be controlled by a separate control unit for controlling the motor. The body unit 100 may be rotated by such a rotation driving unit, and centrifugal force may be provided to the division unit 120 connected to the body unit 100 .

The plurality of arm units 110 may be radially disposed on the body unit 100 with respect to the rotation axis Ax1 . As an embodiment, the plurality of arm units 110 may be formed in a form capable of being coupled to the body unit 100 . The length of the arm unit 110 extending in the radial direction may be longer than the first radius R1 of the body unit 100 . In this case, the arm unit 110 may include one end E1 coupled to the division unit 120 to be described later and the other end E2 coupled to the body unit 100 . The length of the other end E2 of the arm unit 110 may correspond to the first radius R1 of the body unit 100 , and the arm unit 110 is connected to the body unit 100 through the other end E2. ) can be stably bound to However, the present invention is not limited thereto, and it goes without saying that the plurality of arm units 110 may be integrally formed with the body unit 100 .

Meanwhile, the width of one end E1 of the arm unit 110 may be greater than the width of the other end E2 . In other words, in the arm unit 110 , the width of the other end E2 coupled to the body unit 100 is made small and the width of the one end E1 disposed far from the rotation axis Ax1 is made larger than this, so that the arm unit The center of gravity of 110 may be disposed radially outside the middle of the length. Through this, the centrifugal force caused by the rotation of the body unit 100 can be more effectively provided in the division unit 120 coupled to the one end E1. In addition, the thickness of the arm unit 110 may be the same from one end E1 to the other end E2, but by designing the thickness of the one end E1 to be thicker than the thickness of the other end E2, the arm unit The center of gravity of 110 may be disposed radially outside the middle of the length.

The plurality of arm units 110 may be radially disposed on the body unit 100 , and may be symmetrically disposed about the rotation axis Ax1 . Although the drawing shows a case in which the plurality of arm units 110 is composed of four, the present invention is not limited thereto, and it goes without saying that a smaller or larger number of arm units may be provided.

The division unit 120 is detachably coupled to one end E1 of each of the plurality of arm units 110 and may include a microfluidic structure for separating at least the first material from the introduced sample S. . Here, the sample S may be any biological sample including the first material to be separated. For example, the sample S may be selected from the group consisting of a biopsy sample, a tissue sample, a cell suspension in which isolated cells are suspended in a liquid medium, a cell culture, and combinations thereof. The sample S may be selected from the group consisting of blood, bone marrow fluid, saliva, tear fluid, urine, semen, mucosal fluid, and combinations thereof. The sample S may include a first material that is a target cell and a second material that is different from the first material. In this case, the first material or the second material may include microparticles, exosomes, extracellular vesicles, microvesicles, and the like.

The above-described embodiment including the first and second substances corresponds to one embodiment for separating a specific substance from the sample S, and as another embodiment, the sample S contains more n substances than this. may exist The division unit 120 may separate these n materials from the sample S, and the microfluidic structure for separating the n materials will be described later.

The division unit 120 is formed in a structure detachable from one end E1 of the plurality of arm units 110 , and may be replaced as necessary. Since the division unit 120 is formed to be replaceable, the amount of the sample S that can be inspected may be increased, and may be used as a residue of the sample S that may remain in the division unit 120 during the previous inspection. The effect of preventing contamination can be realized.

The division unit 120 may have a shape extending in the longitudinal direction of the plurality of arm units 110 . At this time, the first distance A from the rotation shaft Ax1 to the end of the arm unit 110 and the second distance B from the end of the arm unit 110 to the end of the dividing unit 120 are 2:1 to 20:1 ratio. When the ratio of the first distance (A) to the second distance (B) is less than 2:1, the magnitude of the centrifugal force applied to the dividing unit 120 becomes small, and the separation efficiency decreases, and the first distance (A) and the second distance (B) When the ratio of the two distances B is greater than 20:1, it may be difficult to secure a space for the microfluidic device 10 .

On the other hand, the second radius (R2) from the axis of rotation (Ax1) to the end of the division unit 120 is twice the first radius (R1) from the axis of rotation (Ax1) to the outside of the body unit 100 or greater than this. have. As described above, in the unit configuration including the dividing unit 120 and the arm unit 110 , the centrifugal force can be more effectively provided to the dividing unit 120 by arranging the center of gravity outward with respect to the radial direction.

Hereinafter, the microfluidic structure of the dividing unit 120 will be described with reference to the drawings.

Referring back to FIG. 3 , the dividing unit 120 may include a body 121 and a microfluidic structure 123 provided in the body 121 .

The body portion 121 may be formed in a form capable of being coupled to one end E1 of the arm unit 110 . The body portion 121 is easy to mold and may be made of a plastic material such as acrylic or PDMS whose surface is biologically inactive. However, the present invention is not limited thereto, and any material having chemical and biological stability, optical transparency, and mechanical processability is sufficient. The body portion 121 may be formed of a plate of several layers. It is possible to provide a space for accommodating a fluid and a passage for a fluid by making an engraved structure corresponding to a chamber or a channel on the surface where the plate and the plate contact each other and bonding them.

The microfluidic structure 123 may include a separation chamber 1230 for separating at least the first material from the sample S by centrifugal force. More specifically, the microfluidic structure 123 may include an input chamber 122 , a separation chamber 1230 , and a storage chamber 1231 .

The input chamber 122 may be a chamber for introducing the sample S into the microfluidic structure 123 . In the input chamber 122, a separate material for separating the sample S, for example, a material such as magnetic beads may be added in a mixed state from the outside, and the sample S and a material separate from the input chamber ( 122) may be added and then mixed.

A separation chamber 1230 may be connected to the input chamber 122 . Here, the input chamber 122 may be connected to the separation chamber 1230 through a valve (V). The valve V may perform the same function as the valve 1232 connected between the separation chamber 1230 and the storage chamber 1231 to be described later. The separation chamber 1230 may be located farther from the rotation axis Ax1 than the input chamber 122 . The separation chamber 1230 may be formed to extend in a radial direction to separate n materials having different densities from the sample S by centrifugal force. As an embodiment, a density gradient medium (DGM) may be included in the sample S or the separation chamber 1230 to easily separate n materials. For example, when the sample S includes two first materials and a second material, the density gradient material DGM has a higher density than the first material and a lower density than the second material in the separation chamber 1230 . material may be included. In another embodiment, in order to separate three or more substances, the density gradient material (DGM) may include a first density material having a higher density than the first material and a lower density than the second material, a third material having a higher density than the second material and a third material. A second density material having a lower density may be included.

Each of the storage chambers 1231 is connected to the separation chamber 1230 and may be a chamber for storing n separated materials. A valve 1232 is installed in a channel connecting the m storage chambers 1231 and the separation chamber 1230 . As an embodiment, the valve 1232 may be a normally closed valve that closes a channel so that a fluid cannot flow until it is opened by receiving energy from the outside. For example, the valve 1232 may be a valve that can be opened and closed when heat is transferred to the outside, particularly, by a heat transfer unit disposed thereon.

A closed valve may comprise a valve material that is solid at room temperature. The valve material may block the channel by being present in the channel in a solidified state. The valve material melts at high temperatures and moves into the space within the channel, where it solidifies again with the channel open. The energy irradiated from the outside may be, for example, electromagnetic waves or high-temperature heat, and the energy source is a laser light source that irradiates a laser beam, a light emitting diode or a Xenon lamp that irradiates visible or infrared rays, or generates heat. may be small. In the case of a laser light source, at least one laser diode may be included. The external energy source may be selected according to the wavelength of electromagnetic wave that can be absorbed by the heating particles included in the valve material. The external energy source may be provided at a position corresponding to the valve, and the position may be fixed even during rotation of the microfluidic device. This allows the energy source to melt the valve material at the correct location, allowing precise control of the valve. In this specification, the external energy source may mean a heating unit having a heating member. The heating member may be formed of a heating element, and the heating element may be formed of an electrically controllable electronic component, for example, a resistor. Hereinafter, a case in which the heating element is formed of a resistor will be mainly described.

In this case, the microfluidic device may further include a battery for supplying power to the heating member. A battery (not shown) may be centrally disposed on the heating unit. As another embodiment, a plurality of batteries (not shown) may be provided on the heating unit, and the plurality of batteries (not shown) may be symmetrically disposed. In addition, the microfluidic device may further include a controller for controlling the current or voltage applied to the resistor. The controller may control the current or voltage applied to the resistor according to the type of material constituting the valve or the rotational speed of the body unit and the heating unit.

As the valve material, a phase change material that is in a solid state at room temperature may be employed. The phase change material may be wax. Wax melts when heated, turns into a liquid state, and expands in volume. As the wax, for example, paraffin wax, microcrystalline wax, synthetic wax, or natural wax may be employed. The phase change material may be a gel or a thermoplastic resin.

Meanwhile, the microfluidic device may control the on/off power source and the energy source in consideration of the type of the valve material and the rotation speed of the microfluidic device so that the energy source completely melts the valve material. In addition, the microfluidic device can balance the centrifugal force acting on the front surface of the body while the microfluidic device rotates by symmetrically disposing the battery and other components for supplying power to the external energy source, and the centrifugal force It is possible to prevent noise and damage to the microfluidic device.

In addition, the microfluidic device may further include a heat transfer member between the valve and the energy source, that is, the heating element, to effectively transfer heat, which is energy generated by the energy source, to the valve. Through this, the microfluidic device can effectively control the fluid even when the dividing unit 120 is separated from the center of the body 100 by a predetermined distance or more. The heat transfer member may be made of a material including at least one of diamond, silver, aluminum oxide, boron nitride, zinc oxide, and aluminum nitride in a combination including at least one of epoxy, silicone, urethane, and acrylate.

Meanwhile, the m storage chambers 1231 may cross each other and be connected to the separation chamber 1230 . More specifically, the m storage chambers 1231 may be alternately arranged left and right based on the separation chamber 1230 . The separation chamber 1230 may extend in length in a radial direction, and the m storage chambers 1231 may be alternately disposed left and right along the longitudinal direction of the separation chamber 1230, and may be sequentially connected to the separation chamber 1230. .

Hereinafter, a method of separating n materials in the dividing unit 120 will be described with reference to the drawings.

4 is a view for explaining a method of separating n materials by using the dividing unit 120 according to an embodiment of the present invention.

Referring to FIG. 4A , the sample S may be first introduced into the input chamber 122 of the division unit 120 . In this case, the dividing unit 120 may be coupled to one end E1 of the arm unit 110 .

Next, referring to FIG. 4B , when the body unit 100 of the microfluidic device 10 rotates, centrifugal force acts on the arm unit 110 and the division unit 120 connected to the body unit 100 . do. When a centrifugal force is applied in the dividing unit 120 , n materials (a to g) having different densities may be sequentially separated in the separation chamber 1230 due to the difference in density. Here, the n substances may be various biological particles, such as proteins, nucleic acids, exosomes, microvesicles, and extracellular vesicles, included in the biological sample (S). The microfluidic device 10 according to an embodiment may directly separate the n materials from the biological sample S, but in another embodiment, it is also possible to separate the biological particles by binding a separate binding material. . For example, since exosomes are very small in size, they can be aggregated with a binding material called lectin, which is larger than exosomes, and then separated using the microfluidic device 10 . The exosome-lectin aggregate separated by the above method is stored in the storage chamber 1231 and then the lectin is separated through a post-treatment process, thereby extracting the exosome.

As an embodiment, the microfluidic device 10 may use a rate-zonal centrifugation principle. In this case, when the sample (S) is put into the input chamber 122 and centrifugal force is applied, the sedimentation rate is changed according to the size of the cells and the density of the particles, and the materials can be separated for each layer according to the size and density of the particles at a specific time. have. In other words, the heaviest material g in the sample may be located in the space farthest from the rotation axis Ax1 in the separation chamber 1230, and the lightest material a in the separation chamber 1230 is located in the space closest to the rotation axis Ax1 in the separation chamber 1230. can be located In particular, each of the n materials a to f may be more effectively separated by the sample S or the density gradient material DGM included in the separation chamber 1230 .

Next, as shown in FIG. 4C , the microfluidic device 10 separates n materials (a to g) having different densities from the sample S by centrifugal force, and then the inner valve adjacent to the rotation shaft Ax1 The m number of valves 1232 may be sequentially opened from the to the outer valve to transfer the n substances (a to g) to the m number of storage chambers (1 to 6). More specifically, when the microfluidic device 10 opens the inner valve adjacent to the rotation shaft Ax1 and rotates the division unit 120 , the material a may be introduced into the first storage chamber 1 and stored. Separated substances can be stored in each storage chamber 1 to 6 while sequentially repeating the opening and closing of the valve from the inside to the outside. Here, the m storage chambers 1 to 6 may have the same number as the n materials a to g, but as shown, the m storage chambers 1 to 6 may be smaller than the number of separated materials. have.

As described above, the microfluidic device according to embodiments of the present invention includes a plurality of arm units coupled to the body unit and a division unit detachably provided at one end of the plurality of arm units, thereby reducing the size of the disk. Not only is it possible, but it is also possible to impart a large centrifugal force to the dividing unit even in the same centrifugal force.

As such, the present invention has been described with reference to the embodiments shown in the drawings, which are merely exemplary, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible therefrom. . Therefore, the true technical protection scope of the present invention should be determined by the technical spirit of the appended claims.

10: microfluidic device
100: body unit
110: arm unit
120: division unit
121: body part
122: dosing chamber
123: microfluidic structure
1230: separation chamber
1231: storage chamber
1232: valve

Claims (17)

a body unit rotatable about a rotation axis;
a plurality of arm units radially disposed on the body unit with respect to the rotation axis; and
a plurality of division units detachably coupled to one end of each of the plurality of arm units and including a microfluidic structure for separating at least a first material from the introduced sample;
The first distance from the rotation shaft to the end of the arm unit and the second distance from the end of the arm unit to the end of the dividing unit have a ratio of 2:1 to 20:1,
The second radius from the axis of rotation to the end of the division unit is twice or greater than the first radius from the axis of rotation to the outer edge of the body unit,
The length of the other end of the arm unit coupled to the body unit corresponds to the first radius, microfluidic device. The method of claim 1,
wherein the microfluidic structure comprises a separation chamber for separating at least a first material from the sample by centrifugal force. The method of claim 1,
The microfluidic structure is
an input chamber into which the sample is introduced;
a separation chamber connected to the input chamber and configured to separate n materials having different densities from the sample by centrifugal force; A microfluidic device comprising a. 4. The method of claim 3,
The microfluidic structure is
Each of the separation chambers and connected to the m storage chambers for storing the separated n materials; further comprising,
and the m storage chambers intersect each other and are connected to the isolation chamber. 5. The method of claim 4,
The m storage chambers are alternately arranged left and right with respect to the separation chamber. 6. The method of claim 5,
The microfluidic device further comprising m valves installed in each channel connecting the m storage chambers and the separation chamber. 7. The method of claim 6,
The microfluidic device separates n materials having different densities from the sample by centrifugal force, and then sequentially opens the m valves from the inner valve adjacent to the rotation shaft to the outer valve to store the n materials. A microfluidic device, delivered into the chamber. 7. The method of claim 6,
The microfluidic device further comprising; a heating unit having a heating member disposed at a position corresponding to the valve. 9. The method of claim 8,
The microfluidic device further comprising a battery for supplying power to the heating member. 10. The method of claim 9,
The battery is disposed centrally on the heating unit, microfluidic device. 10. The method of claim 9,
A plurality of batteries are provided on the heating unit, and the plurality of batteries are symmetrically disposed. 9. The method of claim 8,
The microfluidic device further comprising a heat transfer member provided between the valve and the heating member. 13. The method of claim 12,
The heat transfer member is made of a material comprising at least one of diamond, silver, aluminum oxide, boron nitride, zinc oxide and aluminum nitride in a combination comprising at least one of epoxy, silicone, urethane and acrylate, microfluidic device . 9. The method of claim 8,
The heating member is made of a heating element,
The heating element is made of an electronic component,
The microfluidic device further comprising a controller for controlling the current or voltage applied to the electronic component. 15. The method of claim 14,
The control unit controls the current or voltage applied to the electronic component according to the type of material constituting the valve or the rotational speed of the body unit and the heating unit, microfluidic device. delete delete

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