KR20160081379A - Apparatus for separating and concentrating particle and method for using this - Google Patents

Abstract

The present invention provides a device to separate and concentrate particles which has a simple structure using an ion permeation layer and is able to easily separate particles; and method to separate, concentrate, and discharge particles. According to the present invention, the device to separate and concentrate particles comprises: a first channel; a second channel parallel with the first channel; the ion permeation layer installed between the first channel and the second channel, providing a transmission path of ions; a third channel connected to a side of the second channel; and a plurality of valves formed in at least a part of the second channel and the third channel, controlling a movement of a fluid passing through the second channel and the third channel. The device to separate and concentrate particles applies an electric field passing through the second channel, the ion permeation layer, and the first channel; thereby generating an ion concentration polarization (ICP) phenomenon at a part adjacent to the second channel and the ion permeation layer, and a particle separated from the fluid. Moreover, the particle is able to be moved by a plurality of valves.

Description

TECHNICAL FIELD The present invention relates to a particle separation and concentration apparatus and a method for concentrating and discharging particles using the same.

The present invention relates to a particle separation and concentration apparatus and a particle separation and concentration method using the same, and more particularly, to a particle separation and concentration apparatus for separating particles using a microchannel device having an ion- And a discharging method.

Particulate matter has a great influence on the human body and the global environment through various forms and paths. Its importance is also increasing with the development of related industries and the growing interest in the environment. Molecules that affect us, ranging from measuring various molecules that can acquire biometric information in living fluids to finding low concentrations of environmental substances in air, vary in size and concentration. Various sensors and reactors have been developed to efficiently measure and analyze these.

These sensors and reactors are designed to be driven in a state of being separated from other materials within a certain concentration range. The sensor and the reactors can be stably analyzed through a pretreatment process of separating and concentrating the particles and molecules to a desired level. The pretreatment process mainly includes a process of separating the substance according to the size, density and charge amount of the substance and concentrating the concentration of the substance to a measurable concentration range. The preprocessing process requires more advanced equipment and skilled manpower than a certain level.

In addition, the separation process is generally a temporary separation due to the difference in the mobility of the material. In order to maintain a high degree of separation, there is a minimum process time, minimizing dispersion and diffusion, and isolating the separated molecules. This is because dispersing and spreading proceeds with time according to the process. To compensate for this, methods for increasing the concentration before separation and maintaining the concentration more than necessary after separation are proposed.

However, the sensors and reactors are widely used for simply separating and concentrating particles larger than the separation particle size and concentrating them. In order to separate and concentrate particles of a specific size, various devices are connected to form a multi-stage configuration. There is a problem that the composition is complicated and the time for separating and concentrating the particles increases.

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 particle separation and concentration apparatus for separating particles easily and easily using an ion- The purpose is to provide. However, these problems are illustrative and do not limit the scope of the present invention.

According to one aspect of the present invention, a particle separation concentrating apparatus is provided. Said particle separation and concentration apparatus comprising: a first channel; A second channel disposed in parallel with the first channel; An ion-permeable membrane layer interposed between the first channel and the second channel to provide a path for transferring ions; A third channel connected to a side of the second channel; And a plurality of valves formed on at least a portion of the second channel and the third channel to control movement of fluid passing through the second channel and the third channel, An ion permeable membrane layer and an electric field passing through the first channel are applied to cause ion concentration polarization (ICP) phenomenon at a portion adjacent to the second channel and the ion permeable membrane layer, thereby separating particles from the fluid, The particles can be moved by the plurality of valves.

Wherein the plurality of valves includes a first valve, a second valve, a third valve, and a fourth valve, the first valve pressurizing a first region of the third channel such that the fluid within the second channel Wherein the second valve and the fourth valve prevent diffusion to the third channel during separation and concentration of the particles by ion concentration polarization, and the second valve and the fourth valve are located at the front end and the rear end of the second region in the extending direction of the second channel And the third valve presses the second region of the second channel to discharge the particles isolated through the third channel to the separation reservoir.

The first channel may be grounded to be electrically balanced.

And a bottleneck section in which the cross-sectional area is reduced and enlarged in the middle of the second channel and the third channel is repeatedly formed.

The body may have a shape of at least one of a linear oil pipe, a circular oil pipe, a triangular oil pipe and a rectangular oil pipe.

The plurality of valves may be connected to a pneumatic valve and a pressure pump as micro oil pipes having elasticity.

According to another aspect of the present invention, there is provided a particle separation and concentration method. Wherein the particle separation and concentration method comprises the steps of: supplying fluid to one end of the second channel of the particle separation and concentration apparatus described above; An ion depletion zone is formed by applying an electric field to the second channel and causing the ion concentration polarization (ICP) phenomenon to occur at a position adjacent to a branch point between the second channel and the ion permeable film layer Separating the particles from the fluid; Wherein the ion concentration polarization causes the particles to flow in the second region of the second channel and in the region adjacent to the second region while the first valve presses the first region of the third channel, ≪ / RTI > Closing the second valve and the fourth valve to isolate the first particles in the second region; And a third valve for pressurizing the second region of the second channel to open the first valve to discharge the first particles to the separation reservoir and the second particle to discharge the other end of the second channel And circulating in the particle separation and concentration apparatus.

According to an embodiment of the present invention as described above, since a fine channel device having an ion-permeable membrane layer is used, the structure is simple and the particles can be separately concentrated with low power, It is possible to realize a method of concentrating and using the particle separation used. Of course, the scope of the present invention is not limited by these effects.

FIG. 1 is a view schematically showing ion concentration polarization according to an embodiment of the present invention. FIG.
2 is a schematic view of a particle separation and concentration apparatus according to an embodiment of the present invention.
Fig. 3 is a view schematically showing a coupling structure of the particle separation and concentration apparatus shown in Fig. 2 (b).
Fig. 4 is a view schematically showing a cross section cut along C1-C2 shown in Fig. 2 (a).
FIG. 5 is a view schematically showing opening and closing of a valve according to an operation sequence of a particle separation and concentration apparatus according to an embodiment of the present invention. FIG.
6 is a schematic view illustrating various experimental examples of the body of the particle separation and concentration apparatus according to an embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. It should be understood, however, that the invention is not limited to the disclosed embodiments, but may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, Is provided to fully inform the user. Also, for convenience of explanation, the components may be exaggerated or reduced in size.

It is to be understood that throughout the specification, when an element such as a film, region or substrate is referred to as being "on", "connected to", "laminated" or "coupled to" another element, It is to be understood that elements may be directly "on", "connected", "laminated" or "coupled" to another element, or there may be other elements intervening therebetween. On the other hand, when one element is referred to as being "directly on", "directly connected", or "directly coupled" to another element, it is interpreted that there are no other components intervening therebetween do. Like numbers refer to like elements. As used herein, the term "and / or" includes any and all combinations of one or more of the listed items.

Although the terms first, second, etc. are used herein to describe various elements, components, regions, layers and / or portions, these members, components, regions, layers and / It is obvious that no. These terms are only used to distinguish one member, component, region, layer or section from another region, layer or section. Thus, a first member, component, region, layer or section described below may refer to a second member, component, region, layer or section without departing from the teachings of the present invention.

Also, relative terms such as "top" or "above" and "under" or "below" can be used herein to describe the relationship of certain elements to other elements as illustrated in the Figures. Relative terms are intended to include different orientations of the device in addition to those depicted in the Figures. For example, in the figures the elements are turned over so that the elements depicted as being on the top surface of the other elements are oriented on the bottom surface of the other elements. Thus, the example "top" may include both "under" and "top" directions depending on the particular orientation of the figure. If the elements are oriented in different directions (rotated 90 degrees with respect to the other direction), the relative descriptions used herein can be interpreted accordingly.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a," "an," and "the" include singular forms unless the context clearly dictates otherwise. Also, " comprise "and / or" comprising "when used herein should be interpreted as specifying the presence of stated shapes, numbers, steps, operations, elements, elements, and / And does not preclude the presence or addition of one or more other features, integers, operations, elements, elements, and / or groups.

Hereinafter, embodiments of the present invention will be described with reference to the drawings schematically showing ideal embodiments of the present invention. In the figures, for example, variations in the shape shown may be expected, depending on manufacturing techniques and / or tolerances. Accordingly, the embodiments of the present invention should not be construed as limited to the particular shapes of the regions illustrated herein, but should include, for example, changes in shape resulting from manufacturing.

FIG. 1 is a view schematically showing ion concentration polarization according to an embodiment of the present invention. FIG.

Referring to FIG. 1, ion concentration polarization phenomenon according to an embodiment of the present invention is as follows. When a fluid is supplied into the microchannel 200a having the ion-permeable membrane layer 500 and an electric field is applied to both ends of the microchannel 200a, ion concentration polarization (ICP) A high electric field and a low electric field are locally distributed in the vicinity of the substrate 500.

That is, in the depletion zone near the ion-permeable membrane layer 500, a low ion concentration and a high electric field are distributed, while a relatively small electric field is distributed at the outer periphery. At this time, under the electric field, the molecules and charged particles receive both F _drag due to electroosmosis and F _EP due to electrophoresis.

The points of equilibrium of the forces are different depending on the particle size and the amount of charge. In the equilibrium regions (EP1 and EP2), all the particles in the microchannel 200a are concentrated. At this time, the equilibrium regions EP1 and EP2 may vary depending on the size of the molecules and the amount of charge.

Here, the ion concentration polarization phenomenon is one of electrochemical transfer phenomena observed around the structure having the nanofilm. The nanofibers can be understood as an ion-permeable membrane layer 500. Assuming that the thickness of the electric double layer is similar to that of the nanofilm, the electric double layer overlaps the inside of the nanofilm to show a single ion permeability. Ions having the same charge as the wall surface charge of the nanofiltration membrane can not pass through the nanofiltration membrane due to diffusion and drifting force, and ions having opposite charge to that of the wall surface telephone can pass through, so that depletion and excessive ionization appear.

A strong electrical repulsive force acts between the ions which have not passed through the nanofibers, so that both the positive ions and the negative ions are affected, and thus the ion concentration gradient occurs. At this time, charged particles, cells, and droplets are also affected by the electrical repulsive force of the ions at the interface of the ion concentration depletion layer and are pushed around the nanofibers.

In addition, most of the materials have a certain charge and potential on the surface of the material when they are in contact with the electrolyte. Thus, in the aqueous solution, a positive charge and a negative charge are distributed within the channel, Gathered. This phenomenon of surface electric charge and the resultant opposite polarity of ions moving in the electric field and creating fluid and particle flow is called electrohydraulic phenomenon. In this case, the force due to electroosmosis (F _drag ) is a force due to the flow of fluid inside the channel, and the force (F _EP ) due to electrophoresis is a force that varies according to the mobility of particles inside the channel.

That is, when an arbitrary charged solution is supplied into the microchannel 200a and a voltage is applied to both ends of the microchannel 200a, a force due to ion concentration polarization due to an ion concentration gradient causes a specific charge The material can be pushed away from the interface of the ICP Zone by ion concentration polarization. At this time, the material can be electrically balanced by a force (F _drag ) by electroosmosis and a force (F _EP ) by electrophoresis. The points of equilibrium may be different depending on the molecular weight of each substance and the amount of charge.

FIG. 2 is a schematic view of a particle separation and concentration apparatus according to an embodiment of the present invention, and FIG. 3 is a view schematically showing a coupling structure of the particle separation and concentration apparatus shown in FIG. 2 (b).

Referring to FIG. 2A, a particle separation apparatus 1000 according to an embodiment of the present invention includes a first channel 100, a second channel 100 disposed in parallel with the first channel 100, An ion transmission membrane layer 500 interposed between the first channel 100 and the second channel 200 to provide a path for ions to pass through and a third channel 300 connected to a side surface of the second channel 200, And a plurality of valves (410, 410) formed in at least a portion of the second channel (200) and the third channel (300) to control movement of fluid passing through the second channel (200) 420, 430, 440). The first channel 100 may be grounded to be electrically balanced. Here, the fluid can be understood as, for example, an arbitrary charged solution.

The plurality of valves 410, 420, 430 and 440 may include a first valve 410, a second valve 420, a third valve 430 and a fourth valve 440. The first valve 410 separates and concentrates the particles within the second channel 200 with ion concentration polarization while pressurizing the first region of the third channel 300, And the fourth valve 440 are arranged and isolated at the front end and the rear end of the second region in the extension direction of the second channel 200 and the third valve 430 isolates and isolates the second And the third channel 300 can be discharged to the separation and storage tank. Here, the second region refers to a region where the second channel 200 and the third channel 300 are connected to each other. The first region is located in the third channel 300, and the region adjacent to the second region 300 It means. Here, a detailed description of the plurality of valves 410, 420, 430, and 440 will be described later with reference to FIG.

In addition, the body 250 may include a bottleneck section in which a bottleneck section is repeatedly formed in the middle of the second channel 200 and the third channel 300. The body 250 may have various shapes of bottlenecks. The various shapes of the body 250 may have a shape of at least one of a linear oil pipe, a circular oil pipe, a triangular oil pipe, and a rectangular oil pipe when viewed from the upper surface, for example. A detailed description of the body 250 having the bottleneck section will be given later with reference to FIG.

On the other hand, referring to FIG. 2 (b) and FIGS. 3 (a) to 3 (c), a particle separation and concentration apparatus 1000 can be manufactured. The particle separation and concentration apparatus 1000 may include an upper layer portion 1000a and a lower layer portion 1000b. First, the upper layer portion 1000a may include a plurality of valves having a structure capable of selectively closing the oil holes in the lower layer portion 1000b by applying pressure. And the discharge of concentrated and isolated particles of the oil canals can be achieved by the plurality of valves.

In the lower layer portion 1000b, an electrode for applying an electric field is located at both ends of the second channel 200, and a fluid is contained in the second channel 200. The first channel 100 is disposed in parallel with the second channel 200 and the ion permeable film layer 500 is formed as a nano structure between the first channel 100 and the second channel 200, The first channel 100 and the second channel 200 may be connected. The first channel 100 is grounded so that current can flow through the ion-permeable membrane layer 500. The first channel (100) may be filled with a buffer solution of a different concentration than the fluid provided in the second channel (200). This allows the electric field to be adjusted.

In addition, although the second channel 200 has a repeating rectangular structure, it can be designed in various shapes depending on the kind of the conductive liquid, the concentration concentration of separation, and the like. And a discharge port through which the third channel 300 is connected to the middle of the second channel 200 to discharge the sample in which the conductive liquid is separated and concentrated.

Fig. 4 is a view schematically showing a cross section cut along C1-C2 shown in Fig. 2 (a).

4A and 4B, although not shown in the drawings, the plurality of valves 410, 420, 430, and 440 may be connected to a pneumatic valve and a pressure pump as microchannels having elasticity. Depending on size and charge, the separated and concentrated materials can be isolated and analyzed in the microchannel through the pneumatic valve to be injected and analyzed through the outlet with minimal diffusion and dispersion.

For example, the first valve 410 shown in Fig. 4 (a) may be placed on the substrate 10 with a liquid sample 20 thereon. At this time, polydimethylsiloxane (PDMS 30) constituting a microchannel is a transparent material having stretchability, and has a characteristic capable of stably simulating a small structure.

4 (b), when the first valve 410 is operated, that is, when the pneumatic valve (first valve) 410 is operated, as the pressure AP changes, the PDMS The microchannel 30 can pressurize the sample 20 to isolate the microchannel.

That is, the pneumatic valve 410 can function to shut off the external air so that the ion concentration polarization phenomenon can occur stably. Secondly, it is possible to effectively isolate a high-concentration sample from diffusion and dispersion in a microchannel in which no electric field is applied. Finally, it is possible to perform the function of applying pressure so that the isolated sample can be discharged to the outside.

Hereinafter, an experimental example to which the technical idea described above is applied will be described in order to facilitate understanding of the present invention. It should be understood, however, that the following examples are for the purpose of promoting understanding of the present invention and are not intended to limit the scope of the present invention.

[Experimental Example]

In order to confirm the operation according to various shapes of the body 250 of the particle separation and concentration apparatus 1000 described above with reference to FIG. 2 (b), two different polymers, Sulforhodamine B (SRB) dye and The Alexa 488 dye was exposed under an electric field. In the particle separation and concentration apparatus 1000, the blue region is a region where the separation and concentration of the particles occurs, and the red region is a region of the pneumatic valve that serves to isolate the concentrated particles and to discharge the particles.

FIG. 5 is a view schematically showing opening and closing of a valve according to an operation sequence of a particle separation and concentration apparatus according to an embodiment of the present invention. FIG.

Referring to FIG. 5, a method of concentrating particles according to an embodiment of the present invention includes the steps of (a) and (b) And applying an electric field to both ends of the second channel 200 to apply ion concentration polarization (ICP) to a portion adjacent to the bifurcation between the second channel 200 and the ion-permeable membrane layer 500, ) Phenomenon may occur to form an ion depletion zone (ICP Zone shown in FIG. 1) to separate the particles.

5 (a), 5 (b) and 5 (c) are photographs in the order in which the valves of the particle separation and concentration apparatus are opened and closed, This is an analysis of the phenomenon in which ink is separated from each channel of the concentrating apparatus. 5 (a), 5 (b), and 5 (c), the areas of the ink shown in FIGS. 5 (d) And the body 250 where the fourth valve 440 is located is omitted in the figure.

5 (a) and 5 (d), a first valve 410 presses a first region of a third channel 300 so that the particles flow into a second region of the second channel 200, And separating the first and second particles in the region adjacent to the first and second regions.

5 (b) and 5 (e), the second valve 420 and the fourth valve 440 are closed to isolate the first particles in the second region, The second region of the second channel 200 may be pressurized and the first valve 410 may be opened to discharge the first particles to the separation reservoir.

5 (c) and 5 (f), the second particle is discharged to the outside through the other end of the second channel 200 or circulated in the particle separation and concentration apparatus 1000 .

Figure 6 is a schematic illustration of various embodiments of the body of the particle separation and concentration apparatus according to one embodiment of the present invention.

Referring to FIG. 6, in various embodiments of the body 250 of the particle separation and concentration apparatus according to an embodiment of the present invention, FIG. 6 (a) is a separation concentrate in a body 250 formed as a straight tube, 6 (b) is a plan view of the body 250 formed with a rectangular oil pipe, and FIG. 6 (c) is a cross- . Sulfur Rhodamine B is free to separate and concentrate the dyes and Alexa dyes, so that the ratio of the electric field can be efficiently controlled. In addition, it can be confirmed that the ions are separated after ion polarization polarization in various oil pipes. At this time, it was confirmed that the shape of the oil pipe was separately concentrated in a linear shape, a circular shape, a triangle shape, and a square shape.

In other words, according to Bernoulli's principle, the quadrangular structure of a large area is sharply slower than that of a linear one, and the concentrated effect of the electric field in the structure of rapidly expanding or shrinking rapidly causes the undesired outflow Can be minimized, so that the position of the concentrated particles by ion concentration polarization can be determined in advance. In addition, since it can block the fluidized bed according to the structure of the pneumatic valve layer, it can efficiently separate and concentrate and isolate through the repeated rectangular structure.

As described above, conventionally, there has been a possibility that concentration is lowered by separating a sample having a high concentration, or heat or time is required at the time of concentration to affect the reactivity of the molecule.

Further, in the prior art, a gel which functions as a matrix is required in the separation process, or a buffer having a different concentration is required in the concentration process. However, this method does not require any additional substance, Separation and concentration occur simultaneously by using ion concentration and electric field distribution as a result of ion separation phenomenon in aqueous solution. Therefore, a process of separating and extracting from a matrix such as gel is unnecessary.

In addition, the thus-separated polymer of a specific size having a specific charge amount can be selectively discharged outside the apparatus through the valve. Depending on the structure, the polymer may be post-treated in the apparatus or utilized and analyzed in connection with the used apparatus can do.

Conventionally, the concentrator using the ion concentration polarization phenomenon performs the concentration function but does not perform the separation function. Although some separation phenomena were observed, there was no function to stably generate and extract them. Concentration methods that do not rely on ion concentration polarization and other structures have the disadvantage that when the electric field or other driving principle is removed, the concentration is lowered because of the large diffusion and dispersion due to the high concentration gradient.

The particle separation and concentration apparatus according to an embodiment of the present invention can stabilize the flow of the sample through a repetitive quadrangular structure instead of the straight pipe and isolate the high concentration sample through the pneumatic valve while suppressing diffusion or dispersion . In addition, it is possible to integrally perform the function of discharging the separated molecules and particles so that they can undergo sufficiently additional processing.

Meanwhile, the particle separation and concentration apparatus according to one embodiment of the present invention is a technique of separating and concentrating DNA of a mother and DNA of a fetus by pre-processing step of analysis using cell-free fetal DNA or the like Available. It is possible to diagnose the fetal genetic condition early in pregnancy.

In addition, the particle separation and concentration apparatus according to an embodiment of the present invention can be utilized as a new method of electrophoresis (free solution electrophoresis). The technology to separate existing DNA by length has a big market of about $ 1.5 billion, but the fundamental way of excluding the gel and the device optimization did not change much. However, the present method can be performed more quickly and with high efficiency because separation and concentration are simultaneously performed.

Accordingly, when the concentration is performed through the particle separation and concentration apparatus according to one embodiment of the present invention, the concentrations of various environmental substances that can be measured at the ppm or ppb level can be reduced to several hundreds to several thousand times.

While the present invention has been described with reference to exemplary embodiments, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. Accordingly, the true scope of the present invention should be determined by the technical idea of the appended claims.

100: 1st channel
200: Second channel
250: Body
300: Third channel
410: first valve
420: second valve
430: third valve
440: fourth valve
500: ion-permeable membrane layer
1000a: Upper layer
1000b:
1000: particle separation and concentration apparatus

Claims (7)

A first channel;
A second channel disposed in parallel with the first channel;
An ion-permeable membrane layer interposed between the first channel and the second channel to provide a path for transferring ions;
A third channel connected to a side of the second channel; And
A plurality of valves formed in at least a portion of the second channel and the third channel to control movement of fluid passing through the second channel and the third channel;
Lt; / RTI >
An ion permeable film layer and an electric field passing through the first channel are applied to generate ion concentration polarization (ICP) phenomenon in a portion adjacent to the second channel and the ion permeable film layer, And the particles can be moved by the plurality of valves,
Particle separation concentrator. The method according to claim 1,
Wherein the plurality of valves includes a first valve, a second valve, a third valve, and a fourth valve,
Wherein the first valve presses a first region of the third channel to prevent diffusion of the fluid within the second channel to the third channel while the particles separate and concentrate by the ion concentration polarization phenomenon, The second valve and the fourth valve are disposed at the front end and the rear end of the second region in the extending direction of the second channel to isolate the separated and enriched particles, 2 region is pressed to discharge the particles isolated through the third channel to the separation and storage tank. The method according to claim 1,
Wherein the first channel is grounded to be electrically balanced. The method according to claim 1,
And a bottleneck section in which the cross-sectional area is reduced and enlarged in the middle of the second channel and the third channel is repeatedly formed. 5. The method of claim 4,
Wherein the body has a shape of at least one of a linear oil pipe, a circular oil pipe, a triangular oil pipe, and a rectangular oil pipe. The method according to claim 1,
Wherein the plurality of valves are connected to a pneumatic valve and a pressure pump as microtubules having elasticity. Supplying the fluid to one end of the second channel of the particle separation and concentration apparatus according to any one of claims 1 to 6;
An ion depletion zone is formed by applying an electric field to the second channel and causing the ion concentration polarization (ICP) phenomenon to occur at a position adjacent to a branch point between the second channel and the ion permeable film layer Separating the particles from the fluid;
Wherein the ion concentration polarization causes the particles to flow in the second region of the second channel and in the region adjacent to the second region while the first valve presses the first region of the third channel, ≪ / RTI >
Closing the second valve and the fourth valve to isolate the first particles in the second region; And
The second valve is opened by the third valve to discharge the first particle to the separation reservoir by opening the first valve and the second particle is discharged through the other end of the second channel Circulating in the particle separation and concentration apparatus;
/ RTI >
Particle separation and concentration method.

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