KR101853602B1 - Single layer biomolecular preconcentrating device and fabrication method thereof - Google Patents

Abstract

The present invention relates to a biomolecule concentration apparatus having a single layer structure, and a biomolecule concentration apparatus according to an embodiment of the present disclosure includes a base, at least one buffer member formed to be surrounded by a hydrophobic substance bonded to the base, A sample reservoir formed to be surrounded by the hydrophobic material and in which the target material contained in the sample accommodated in the at least one buffer is concentrated and accommodated; At least one microchannel formed between the at least one buffer and the sample reservoir, the at least one microchannel being formed at a predetermined position of each of the at least one microchannel, And a selective ion permeable membrane for filtering the target material to be selectively transferred to the sample reservoir among the samples that are received through the microchannel. When a potential difference is generated across the microchannel, a specific target substance Can be concentrated.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biomolecule concentration apparatus having a single layer structure,

TECHNICAL FIELD The present invention relates to a biomolecule concentration apparatus and a method of manufacturing the same, and more particularly, to a biomolecule concentration apparatus having a single-layer structure and a manufacturing method thereof.

Modern medicine aims not only to extend life span, but also to prolong the healthy lifetime. Therefore, future medicine is not centered on therapeutic medicine, but paradigm is changing by implementing 3P of Preventive Medicine, Predictive Medicine, and Personalized Medicine. Early identification and early treatment of diseases are becoming very important means to achieve this specifically, and biomarkers have been actively studied as a means to achieve this.

A biomarker is a marker that can distinguish between normal or pathological conditions, or can be predicted and objectively measured.

Biomarkers include nucleic acid DNA, RNA (genes), proteins, lipids, metabolites, and their pattern changes. In other words, biomarkers such as BCR-ABL gene fusion of chronic myelogenous leukemia, which is a therapeutic target of Gleevec from the simple substance such as blood glucose for diagnosis of diabetes, are biomarkers practically used in clinical practice.

DNA (Deoxyribonucleic Acid) is a genetic material that exists in the nucleus, and a gene is a place where chemical information that determines the kind of protein that an organism produces is stored. The information constituting the human body can be grasped by analyzing the DNA, and various DNA analysis techniques are being researched and utilized for the prevention and treatment of diseases. To analyze disease using DNA, gene amplification technology called PCR (Polymerase Chain Reaction) is used. PCR is a method of repeating heating and cooling with a thermostable DNA polymerase to use a single strand produced by sequential separation of a double strand of DNA as an original to make a new double strand. First, heat the DNA and divide it into two chains . Add a short DNA called "primer" to this and cool it so that the primer binds to the DNA. When an enzyme called DNA polymerase is added to this, the primer part becomes the starting point and the DNA is replicated. The DNA is doubled in one cycle called "heating and cooling". Repeating this dozens of times will cause DNA to multiply in billions of times in about an hour.

Protein is a complex molecule made up of relatively simple molecules called amino acids, and is generally very large in molecular weight. There are about 20 kinds of amino acids that make proteins. These amino acids are connected to each other through chemical bonds to form polypeptides. In this case, the binding of amino acids is referred to as a peptide bond, and the peptide bond is referred to as a polypeptide. Proteins in a broad sense can also be called polypeptides. In general, a polypeptide having a relatively small molecular weight is referred to as a polypeptide, and a protein having a very large molecular weight is referred to as a protein. Such a protein is a representative molecule constituting the body of an organism, and is a substance that acts as a catalyst for various chemical reactions in cells and immunity (immunity). Proteins are very important organisms that constitute living organisms and participate in in vivo reactions and energy metabolism.

By analyzing the DNA or protein as described above, it is possible to grasp the fuming and progress of the cancer or disease. In particular, for the early diagnosis and treatment of intractable diseases such as cancer, a blood fingerprint analysis technique is known in which an indicator protein showing minute changes in the initial stage of normal cells in the blood is developed into cancer cells.

Blood fingerprint analysis is a comprehensive analysis of the metabolism data of metabolites present in the blood of cancer patients, taking into account that metabolites of the human body can change depending on the presence or absence of cancer. .

However, the present technology and devices for protein analysis are difficult to fabricate devices by using nanotechnology, and are relatively expensive and difficult to be popularized. In addition, there is a disadvantage in that a high sensitivity sensor is required for a protein analyzer or it is difficult to perform accurate analysis with a small sample.

Recent developments in nanotechnology and MEMS technology have enabled it to rapidly separate and purify materials that require only a small amount of sample by patterning it into nanostructures in a single fluid device. These technologies are used in biotechnology and medical engineering Efforts to apply are actively being made. In addition, advanced MEMS / NEMS technology enables more precise patterning of nanostructures at desired locations with error tolerances of a few nanometers. This technology is combined with microfluidic channels to provide a micro total analysis system (μ- TAS) or lab-on-a-chip.

In particular, a method of implementing a concentration apparatus using glass or other heavy and expensive materials is known. This method forms a film so as to concentrate a specific substance at a predetermined position while diffusing analytes through a narrow tube or a thin plate. However, these methods are problematic in that it is difficult to manufacture a thickening apparatus, a large amount of money is put into the apparatus, a thickening apparatus is large and heavy, and handling is inconvenient.

Korean Patent Publication No. 1020120047269 (registered on May 11, 2012)

SUMMARY OF THE INVENTION The present invention has been made in order to solve the above problems, and it is an object of the present invention to provide a single-layer biomolecule concentration apparatus and a manufacturing method thereof.

In order to achieve the above object, a biomolecule concentration apparatus according to a first embodiment of the present invention comprises a base; At least one buffer surrounded by a hydrophobic material coupled to the base, the buffer being adapted to receive a sample; A sample reservoir formed so as to be surrounded by the hydrophobic material and in which the target material contained in the sample accommodated in the at least one buffer is concentrated and accommodated; At least one microchannel formed to be surrounded by the hydrophobic material and connecting each of the at least one buffer and the sample reservoir; And at least one microchannel pattern formed at a predetermined location of each of the at least one microchannel, the at least one microchannel being selectively delivered to the sample reservoir, Permeable film.

In addition, the biomolecule concentration apparatus according to the second embodiment of the present invention includes at least one buffer in which a sample is accommodated, a sample reservoir in which a target material contained in the sample accommodated in the at least one buffer is concentrated and accommodated, A single-layer base including at least one microchannel connecting each of the one buffer and the sample reservoir and transferring the sample stored in the buffer to the sample reservoir; And at least one microchannel, wherein the target material is selectively patterned in a predetermined position of the at least one microchannel to be received in the at least one buffer and transmitted through the microchannel, so that the target material is selectively transferred to the sample reservoir, And a selective iontophoretic film formed to open at least a portion of the microchannel to which it is delivered.

The method for manufacturing a biomolecule concentration apparatus according to the first embodiment includes at least one buffer in which a sample is received in a base, a sample reservoir in which a target material contained in the sample contained in the at least one buffer is concentrated and accommodated, Connecting each of the at least one buffer and the sample reservoir to adsorb the hydrophobic material to form a boundary of at least one hydrophilic microchannel that transfers the sample contained in the buffer to the sample reservoir; Permeating the hydrophobic material such that the adsorbed hydrophobic material is permeated into the base; And patterning a selective ion permeable membrane at a predetermined position of each of the at least one microchannel.

In addition, the method for producing a biomolecule concentration apparatus according to the second embodiment comprises at least one buffer in which a sample is accommodated, a sample reservoir in which a target material contained in the sample accommodated in the at least one buffer is concentrated and accommodated, Cutting the paper so as to form at least one microchannel connecting each of the buffers of the sample reservoir and the sample reservoir to transfer the sample housed in the buffer to the sample reservoir in the form of micrometer-sized lines; And forming a selective ion permeable film on a predetermined position of the microchannel of the cut paper by patterning.

In the present invention, the base is paper, PET or the like, and particularly preferably paper. The selective ion-permeable membrane may be formed of nafion, polystyrene sulfonate (PSS), polyallylamine hydrochloride (PAH), or the like.

According to the biomolecule concentration apparatus and method for producing a biomolecule according to the present invention, it is possible to manufacture a concentration apparatus for concentration of biomolecules in a very inexpensive and easy manner and to easily combine with other elements related to the sensor have.

1 is a plan view of a biomolecule concentration apparatus of a single layer structure according to the first embodiment of the present invention.
2 is a plan view of a biomolecule concentration apparatus of a single layer structure according to a second embodiment of the present invention.
FIG. 3 is a view showing that a single-layer biomolecule concentration apparatus according to an embodiment of the present invention is combined with another element.
4 is a plan view of a biomolecule concentration apparatus of a single layer structure according to the third embodiment of the present invention.
Figs. 5 and 6 show a method of forming a selective ion-permeable membrane on a microchannel of a biomolecule concentration apparatus of the single-layer structure of Fig.
7 is a plan view of a biomolecule concentration apparatus of a single layer structure according to a fourth embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted when it may make the subject matter of the present invention rather unclear.

Hereinafter, a configuration and a manufacturing method of a biomolecule concentration apparatus having a single layer structure according to an embodiment of the present invention will be described in detail with reference to the accompanying drawings.

1 is a plan view of a biomolecule concentration apparatus of a single layer structure according to the first embodiment of the present invention.

As shown in the drawing, the concentrating apparatus 100 according to the first embodiment of the present invention can be simply configured as a base 10 of a single-layer layer structure, not a multilayer layer structure. The first buffer 40 and the second buffer 50 formed on both ends of the microchannel 20 and the sample reservoir 60 and the selective ion permeable membrane 30 can be integrally formed.

First, a boundary of the hydrophilic microchannel 20 is formed in the shape of a micro-scale line on the quadrangular base 10. Referring to the plan view of FIG. 1, the quadrangular base 10 may be formed to have a size of about 2.5 cm and 2.5 cm. The size of the microchannel 20 may be several hundred micrometers or millimeters have.

In this embodiment, the base 10 includes a material having at least some fiber texture, and the hydrophobic material is additionally bonded to the base 10, and the space in which the microchannel 20 is formed is the hydrophobic material And the sample or the target material is moved through the space.

In this embodiment, the paper is used as the base 10, but the type of the base 10 is not limited to this, and PET (polyethylene terephthalate) is also possible. Particularly, it is preferable that the base 10 is made of a material having a structure capable of bonding with a hydrophobic substance or permeable to a hydrophobic substance.

A hydrophobic substance is bonded to the base 10 such that first and second buffers 40 and 50 and a sample reservoir 60 are formed at both ends and the center of the microchannel 20, respectively.

Herein, the meaning of the bonding means that the hydrophobic substance is immobilized on the base 10 to form the microchannel 20, the first and second buffers 40 and 50 and the sample reservoir 60 space by the combination of the hydrophobic substance and the base 10. [ Or may be bonded to, or adsorbed to, the substrate 10, or may be bonded thereto. However, the present invention is not limited to the specific method.

In the present embodiment, wax or the like may be used as a typical hydrophobic substance. The first and second buffers 40 and 50 are regions in which a sample containing a specific target substance to be extracted is accommodated. That is, the area where the sample to be analyzed is accommodated.

And a sample reservoir 60 is implemented on the microchannel 20 between the first and second buffers 40 and 50 and the sample contained in the first and second buffers 40 and 50 is introduced into the microchannel 20 20).

The first and second buffers 40 and 50 and the sample reservoir 60 described above are physical spaces formed by the hydrophobic material combined with the base 10 and in this embodiment, Discloses a method of coating a pattern of hydrophobic material (ex: wax pattern) on paper as a method of binding the materials. There is no particular limitation on the method of wax patterning, and it is possible to simply join the paper and the hydrophobic material, or to bond the paper with the hydrophobic material in a permeated state (permeated state), but preferably the hydrophobic material and the base 10 ) Is incomplete, there is a problem of leakage of the sample. In order to prevent this, it is preferable to bond the hydrophobic material to penetrate the paper.

The hydrophobic material to be bonded to the base 10 for forming the first and second buffers 40 and 50 and the sample reservoir 60 is not limited to only one of the wax components described above, Can be used as a different material.

Then, a selective ion-permeable membrane 30 is pattern-formed on a predetermined position of the microchannel 20.

In this embodiment, the selective ion-permeable membrane 30 for selecting and separating and concentrating the sample is a membrane made of nafion, polystyrene sulfonate (PSS) or polyallylamine hydrochloride (PAH) And may be embodied including at least one.

A protein sample to be analyzed can be accommodated in the buffers 40 and 50 formed at the both openings of the microchannel 20 and a wire (not shown) connected to the external power source is formed in each of the buffers 40 and 50 . A negative electrode, a positive electrode, or a ground is connected to the buffers 40 and 50 through the wire, and a potential difference is generated at both ends with respect to the channel 20. According to another embodiment of the present invention, the buffers 40 and 50 may be provided with thin-film electrodes to be connected to an external power source.

According to another embodiment of the present invention, the buffers 40 and 50 may be configured to be wetted with a conductive liquid. The conductive liquid includes a conductive component such as an electrically conductive ion or the like, and is effective in forming and controlling a potential difference when a conductive liquid is present in the buffer.

The microchannel 20 in which the selective ion-permeable membrane 30 is patterned serves as a kind of nanofilter that selectively transmits a proton.

For example, in the case where the selective ion-permeable membrane 30 is nafion or SO 3 - in the chemical structure of the ion, H + ions are selectively and rapidly permeated by the hopping and the vehicle mechanism do. Therefore, the microchannel 20 can act as a substantially nanochannel through a selective ion permeable material such as Nafion, and the protein substances to be analyzed can be efficiently concentrated in a specific region of the nanochannel in a very short period of time .

When power is connected to the buffers 40 and 50 at both ends of the microchannel 20 to generate a potential difference, the microchannel 20 accommodated in the first and second buffers 40 and 50, (60). At this time, the selective ion-permeable membrane 30 disposed in the microchannel 20 between each of the first and second buffers 40 and 50 and the sample reservoir 60 filters the sample, And concentrated in the burr 60.

In the sample reservoir 60 formed between the both selective ion-permeable membranes 30, a specific target substance is concentrated and a sensor (not shown) capable of detecting and sensing the target substance concentrated on the lower surface of the sample reservoir 60, etc. Time).

According to an embodiment of the present invention, a sensor forms an electrode pattern on a substrate, and a receptor for capturing a target substance is provided between the electrodes to react with a chemical or biological target material, And a transducer for converting the electrical signal into an electrical signal.

In the concentrating apparatus 100, the base 10 may be formed of paper, and the lower surface of the paper may be formed by attaching an adhesive tape having an adhesive force to one side or both sides of the paper, Since the paper can be easily attached (attached) to the sensing sensor or the like on the lower surface of the paper, the concentrating device can be easily combined with various functional layers in any form.

The biomolecule concentration apparatus of the single layer structure shown in Fig. 1 is manufactured as follows. First, a boundary of a hydrophilic microchannel 20 is formed on a base 10 such as paper in the form of micro-sized lines, and a first buffer 40 and a second buffer 30 are formed on both ends of the microchannel 20, (50) is formed.

At this time, the hydrophobic substance may be a wax, and adsorbed by printing wax on the base 10. Then, the hydrophobic material is infiltrated so that the adsorbed (printed) hydrophobic substance (wax) is bonded to the base 10. That is, the paper is heated so that the wax penetrates the base 10. Then, a selective ion permeable membrane 30 is formed by patterning Nichion or the like at a predetermined position of the microchannel 20.

In this embodiment, the hydrophobic substance is not limited to wax but may be selected from the group consisting of acrylic, olefins, amides, imides, styrenes, carbonates, vinyl acetals, dienes, vinyls, esters, Ketone, fluorocarbon, Teflon, PDMS, silane, and the like. In addition, as the components of the alkyl silane series Siliclad, n-octadecyltrichlorosilane, isobutyltrimethoxysilane, and fluoroalkylsilanes series, Heptadecafluorotetrahydrodecyltrichlorosilane, and the like. Examples of the silicone-based resin include 30% methylhydrogosiloxane-dimethyl (meth) acrylate, Siloxane copolymers such as Methylhydrosiloxane-Dimethylsiloxane Copolymer, Hydride terminated Polydimethylsiloxane, Trimethylsiloxy terminated Polydimethylsiloxane, Aquaphobe CM, Aquaphobe CF, Diacetoxy Til terminal and the like Ney suited polydimethylsiloxane (Diacetoxymethyl terminated Polydimethylsiloxane).

Generally, when a material becomes hydrophobic in a material, it may have hydrophobicity due to the influence of the structure of the surface contacting the water and the characteristics of the surface of the material itself. Particularly, in the case where the microchannel 20 is formed by coating the base paper 10, the latter corresponds to the latter. In the case of forming a channel by coating wax on paper, It is to make other parts hydrophobic. Such a hydrophobic property can be obtained by using a fiber material similar to paper to the base 10, so that it is also possible to use a fiber-based base 10 in addition to paper.

In the case of paper, it is easy to form a coating layer having a uniform thickness on paper in a form that is low in cost, good in elasticity and moldability, adsorbed and permeated with a hydrophobic substance, and has excellent bonding strength with a hydrophobic coating material. Such a coating layer is advantageous in that it is easy to store a sample and to form a microchannel 20 for moving a certain component.

In the case of paper, it is a hydrophilic material composed of a fiber type. In this case, a capillary is formed according to the fiber structure, and the liquid is moved by the capillary phenomenon when the liquid is dropped thereon. That is, by using such a capillary phenomenon, it is possible to move the liquid even if power is not externally supplied. If the drag force is used, the movement of the separated components can be facilitated for concentration of biomolecules . In addition to paper, other materials known as fiber-like hydrophilic materials can be used like paper. On the other hand, if the microchannel 20 is formed with a width of several tens of micrometers or less by using the wax coating technique, it is possible to reduce the capillary phenomenon to some extent. However, this is a rather special case. In general, a capillary phenomenon exists in the case of a fiber type material (especially a hydrophilic material such as paper), and the movement of a sample or a target component can be facilitated by using the capillary phenomenon.

Further, according to another embodiment of the present invention, when the concentration is progressed, the concentration plug can be gradually moved when it is concentrated to some extent. In this case, if the drag force can be reversed, it will be very helpful in improving the concentration ratio. This drag force is effective because the capillary phenomenon can be carried out without additional power.

2 is a plan view of a biomolecule concentration apparatus of a single layer structure according to a second embodiment of the present invention.

1, the channel 20 and the selective ion-permeable membrane 30 are integrally formed on the base 10. In this embodiment, However, unlike FIG. 1, it is possible to implement the device very simply by cutting the base 10 as it is according to the shape of the channel 20 and the buffers 40 and 50 without using a hydrophobic substance. However, when the sample sample contains a hydrophilic component, it is preferable to cut the base 10 coated with the hydrophobic material, rather than cut and use the base 10 made of pure paper.

The first and second buffers 40 and 50 formed at both ends of the microchannel 20 and the microchannel 20 and the first and second buffers 50 and 50 are formed in the base 10 in this embodiment. A sample reservoir 60 formed between the first buffer 40 and the sample reservoir 60 in the microchannel 20 and between the first buffer 40 and the sample reservoir 60 and between the first buffer 40 and the sample reservoir 60, And a selective ion-permeable membrane (30) formed between the ion-permeable membrane (30). At this time, the microchannel 20, the first buffer 40, the second buffer 50, and the sample reservoir 60 are formed by cutting a base (e.g., paper) of a single layer.

The selective ion permeable membrane 30 is formed on the channel 20 by patterning a selective ion permeable material such as nafion, polystyrene sulfonate (PSS), or polyallylamine hydrochloride (PAH).

In the above description, the first and second buffers 40 and 50 are formed at both ends of the sample reservoir 60. However, in order to concentrate a large amount of target material in the sample reservoir 60 A plurality of buffers (not shown) may be arranged radially around the sample reservoir 60. A plurality of buffers and a sample reservoir 60 are connected to the microchannel 20 and a selective ion permeable membrane 30 is formed in each of the microchannels 20 between the plurality of buffers and the sample reservoir 60 Filter. ≪ / RTI >

This is because when the target material is nanofiltered by the selective ion-permeable membrane 30 implemented on the microchannel 20, the amount of the target material concentrated in the sample reservoir 60 is small, to be. The target substance detector should be able to easily detect the target substance in order to perform the test on the target substance easily. However, if the amount of the target substance concentrated in the sample reservoir 60 is less than a preset reference amount in the detector, The substance detector can not detect the target substance. Thus, in order to increase the amount of target material concentrated in the sample reservoir 60, the plurality of buffers may be arranged radially in the center to increase the amount of target material concentrated in the sample reservoir 60.

FIG. 3 is a view showing that a single-layer biomolecule concentration apparatus according to an embodiment of the present invention is combined with another element.

An additional layer 300 having various functions may be additionally attached to the lower end of the biomolecule concentration apparatuses 100 and 200 having a single layer structure described with reference to FIGS. 1 and 2 to constitute a concentration function integrated sensor have.

The additional layer 300, which is additionally attached in this embodiment, is configured to (a) filter the target material that is concentrated in the sample reservoir 60, (b) react with the filtered target material to cause an absorption, , (c) detecting the concentration of the target substance.

 The structure described in this embodiment including FIG. 3 may be implemented by various types of biosensing tools for biosensing, for example, an ELISA method and a rapid kit.

The additional layer 300 can be used to enrich red blood cells when concentrating a particular target material in a bulk sample, such as a whole blood containing whole blood components such as red blood cells, white blood cells, plasma, platelets, Can serve as a functional part that can accurately detect the target substance by extracting only the pure target substance by separating the target substance from the target substance.

In addition, it can function as a functional part for visually confirming the detection of the target substance even when a separate electrical means is not provided by allowing the target substance to react with the target substance to be discolored or react with the luminescent or fluorescent material.

The additional layer 300, on the other hand, serves to backing the overall concentrator. However, according to one embodiment of the present invention, a cross electrode portion is formed on the upper surface of the additional layer 300, in which two electrodes (not shown) form a slit and are pattern-formed on the substrate so as to be spaced apart from each other by a predetermined distance. The target material concentrated in the reservoir 60 can be captured in the slit formed by the two electrodes.

That is, the additional layer 300 can perform the function of a detector for detecting the concentration of a target material, and the sensor can form an electrode pattern on the substrate and a receptor for capturing the target material between the electrodes And a transducer for allowing the receptor to react with a chemical or biological target substance and detecting the change of the receptor and converting it into an electrical signal.

4 is a plan view of a biomolecule concentration apparatus according to a third embodiment of the present invention.

1 and 2, the selective ion-permeable membrane 30 of the biomolecule concentration apparatus is configured to completely block the microchannel 20 between the first and second buffers 40 and 50 and the sample reservoir 60 Whereas in FIG. 4, the selective ion-permeable membrane 31 does not completely block the microchannel 20, but is partially opened.

1 and 2, since the selective ion-permeable membrane 30 is completely isolated from the microchannel 20, the filtering performance of the nanofilter realized by the selective ion-permeable membrane 30 is high. However, the capillary force of the base 10 is weakened as the selective ion-permeable membrane 30 implemented with nafion completely blocks the microchannel 20, and as a result, The drag force by which the base 10 transfers the sample accommodated in the first and second buffers 40 and 50 to the sample reservoir 60 is weakened. Therefore, the absolute amount of the target substance concentrated in the sample reservoir 60 is very small. In some cases, the target substance may not be concentrated in the sample reservoir 60 when the target substance has a large molecular structure. In the above description, a plurality of buffers are disposed in a radial fashion to increase the amount of target material concentrated in the sample reservoir 60. However, There is a problem that it is difficult to manufacture because the film 30 has to be formed.

On the other hand, in the biomolecule thickening apparatus 400 shown in FIG. 4, a part of the selective ion-permeable membrane 31 formed on the microchannel 20 is formed to be opened so that the capillary force of the base 10 force can be maintained. The sample accommodated in the first and second buffers 40 and 50 can be easily transferred to the sample reservoir 60 through the selective ion permeable membrane 31 by the pulling force of the base 10, It is possible to greatly increase the absolute amount of the target substance concentrated in the reaction chamber 60.

Here, the concentration ratio of the target substance concentrated in the sample reservoir 60 can be adjusted through the size ratio of the open region of the selective ion-permeable membrane 31. That is, the filtering performance of the nanofilter realized by the ion-permeable membrane 31 shown in FIG. 4 is reduced by the open region, and the concentration ratio is reduced. However, the absolute amount of the target substance concentrated in the sample reservoir 60 is greatly increased So that the target material detector can more easily detect the target material, thereby improving the performance.

The biomolecule concentration apparatus of FIG. 4 can increase the absolute amount of the target substance concentrated in the sample reservoir 60 through the open selective ion-permeable membrane 31, so that unlike FIGS. 1 and 2, the sample reservoir It is not necessary to increase the number of buffers 40 and 50 in order to increase the amount of the target material to be concentrated in the buffers 60 and 60. However, the biomolecule concentration apparatus of FIG. 4 may also include a plurality of buffers and microchannels 20 and a selective ion-permeable membrane 31 arranged radially around the sample reservoir 60.

Figs. 5 and 6 show a method of forming the selective ion-permeable membrane 30 on the microchannel 20 of the biomolecule concentration apparatus of Fig.

5, in the method of forming the selective ion-permeable film 31 of FIG. 4 in which a part of the area is opened, the microchannel 20 and the first and second buffers 40 and 50 and the sample The method of forming the reservoir 60 is the same as the conventional method. 1 and 2, the method of forming the microchannel 20, the first and second buffers 40 and 50, and the sample reservoir 60 is the same.

As shown in (a), the boundary line wgl of the region to be opened at the position where the selective ion-permeable membrane 31 is to be formed in the microchannel 20 to form the selective ion-permeable membrane 31 is immersed in a hydrophobic substance And then adsorbed. Here, the hydrophobic substance may be a wax, and the base 10 may be printed or heated to bind the wax.

The distance A, A 'from the boundary of the microchannel 20 to the boundary of the area to be opened can be adjusted to control the concentration ratio of the target substance concentrated in the sample reservoir 60. The concentration ratio can be controlled by using the ratio of the sum (A + A ') of distances from the boundary of the microchannel 20 to the boundary of the area to be opened to the distance (B) of the open area.

When the boundaries of the regions to be opened are formed by hydrophobic materials, selective ion permeable materials such as nafion, polystyrene sulfonate (PSS), or polyallylamine hydrochloride (PAH) are patterned as shown in FIG. The selective ion-permeable membrane 31 can be formed.

Here, there is no particular limitation on the method of patterning the selective ion-permeable material. However, as a method for increasing the concentration efficiency of the target material in the microchannel and controlling the concentration ratio, the conventional printing techniques (e.g., inkjet printing) To form a selective ion permeable material.

In addition, the discontinuous point of the selective ion permeable material, that is, the boundary line, can be formed by penetrating the hydrophobic material or by using a separate material for boundary formation (guideline function) to induce the movement of the sample component.

6, a hydrophobic substance such as wax is used to form a selective ion-permeable material, such as a direct ion-permeable material, without forming a boundary line to the open region of the selective ion-permeable membrane 31, Ion-permeable film 31 is formed. Since the method of FIG. 6 does not form a boundary, it is possible to form the selective ion-permeable film 31 having a partially open region compared with FIG. 5, but since the selective ion-permeable film 31 is formed only by patterning, It is difficult to precisely control the concentration ratio of the target substance concentrated in the reservoir 60.

7 is a plan view of a biomolecule concentration apparatus according to a fourth embodiment of the present invention.

The biomolecule concentration apparatus in which two or more buffers 40 and 50 are disposed around the sample reservoir 60 has been described. This is a method for increasing the amount of target substance that is filtered by the selective ion-permeable membrane 30 formed in the microchannel 20, as described above, to be concentrated in the sample reservoir 60.

However, by using the selective ion-permeable film 31 having a partially open area as shown in FIG. 4, the absolute amount of the target material concentrated in the sample reservoir 60 can be greatly increased. That is, even if only one buffer is provided, a sufficient amount of target material can be concentrated in the sample reservoir. 7 shows one buffer 41 disposed on one side of the sample reservoir 61. The sample reservoir 61 and the buffer 41 are connected to each other through a microchannel 20, ) Shows a biomolecule concentration apparatus 500 in which a selective ion-permeable membrane 31 having a partially open area is formed.

Since the biomolecule concentration apparatus 500 shown in FIG. 7 has only one buffer 41, the resultant sample can be concentrated in a sufficient amount to the sample reservoir 61 while having the simplest structure.

The embodiments disclosed in the specification of the present invention do not limit the present invention. The scope of the present invention should be construed according to the following claims, and all the techniques within the scope of equivalents should be construed as being included in the scope of the present invention.

100, 200, 400, 500: Concentration device
10: Base
20: channel
30, 31: selective ion permeable membrane
40, 41: first buffer
50: second buffer
60, 61: Sample reservoir
300: additional layer

Claims (19)

Base;
At least one buffer surrounded by a hydrophobic material coupled to the base, the buffer being adapted to receive a sample;
A sample reservoir formed so as to be surrounded by the hydrophobic material and in which the target material contained in the sample accommodated in the at least one buffer is concentrated and accommodated;
At least one microchannel formed to be surrounded by the hydrophobic material and connecting each of the at least one buffer and the sample reservoir; And
A pattern formed at a predetermined position of each of the at least one microchannel, the width of the formed pattern being adjusted corresponding to a concentration ratio of the target material to be concentrated in the sample reservoir, And a selective ion-permeable membrane for filtering the target material, which is delivered through the channel, to be selectively transferred to the sample reservoir,
The selective ion-permeable membrane is formed at both side ends of each of the at least one microchannel to have a predetermined size smaller than the width of the microchannel so that the sample is filtered and transferred to the sample reservoir Wherein the biomolecule concentration is in the range of 1 to 10. The method according to claim 1,
Wherein the base includes a material having at least a part of a fiber structure, the hydrophobic material is additionally bonded to the base, the space in which the microchannel is formed includes at least a space in which the hydrophobic substance is not present, Wherein the sample or the target material moves through the space in which the sample is formed. The method according to claim 1,
The base is at least one of paper or PET (polyethylene terephthalate)
Wherein the selective ion-permeable membrane is at least one of nafion, polystyrene sulfonate (PSS), or polyallylamine hydrochloride (PAH). The method according to claim 1,
Wherein the hydrophobic substance is a wax. The method according to claim 1,
Wherein each of the at least one buffer is wetted with a conductive liquid. The method according to claim 1,
Wherein when the at least one buffer is provided in plurality, the sample reservoir is radially arranged at the same distance around the sample reservoir. The method according to claim 1,
Wherein the base is paper and the hydrophobic material is at least partially bonded to the base in an adsorbed or infiltrated state,
Wherein the selective ion-permeable membrane is formed on the movement path of the sample formed by the at least one microchannel, and the target substance is patterned in consideration of the width of the microchannel so that the target substance is filtered and transferred through the movement path. A biomolecule concentration device. delete The method according to claim 1,
Wherein the selective ion-permeable membrane is formed by ink-jet printing. At least one buffer in which a sample is received in a base, a sample reservoir in which a target material contained in the sample contained in the at least one buffer is concentrated and accommodated, Adsorbing a hydrophobic substance such that a boundary of at least one hydrophilic microchannel that transfers the sample contained in the buffer to the sample reservoir is formed;
Permeating the hydrophobic material such that the adsorbed hydrophobic material is permeated into the base; And
Patterning a selective ion-permeable membrane having a predetermined pattern width corresponding to a concentration ratio of the target material to be concentrated in the sample reservoir at a predetermined position of each of the at least one microchannel; Lt; / RTI >
The selective ion-permeable membrane is formed at both side ends of each of the at least one microchannel to have a predetermined size smaller than the width of the microchannel so that the sample is filtered and transferred to the sample reservoir ≪ / RTI > 11. The method of claim 10,
Wherein the base includes a material having at least a part of a fiber structure, the hydrophobic material is penetrated and bonded to the base, and the space in which the microchannel is formed includes at least a space in which the hydrophobic substance is not present, Wherein the sample or the target substance moves. 11. The method of claim 10,
The base is at least one of paper or PET (polyethylene terephthalate)
Wherein the selective ion-permeable membrane is at least one of nafion, polystyrene sulfonate (PSS), or polyallylamine hydrochloride (PAH). 11. The method of claim 10,
Wherein the hydrophobic substance is a wax. 11. The method of claim 10,
Wherein when the at least one buffer is a plurality of buffers, the plurality of buffers are radially arranged at the same distance around the sample reservoir. 14. The method of claim 13,
Wherein the step of adsorbing the hydrophobic material comprises printing the wax on the base,
Wherein the step of infiltrating the hydrophobic substance comprises heating the base on which the wax is printed to melt the wax into the base. At least one buffer in which a sample is received, a sample reservoir in which a target material contained in the sample contained in the at least one buffer is concentrated and accommodated, and a sample reservoir connected to each of the at least one buffer and the sample reservoir, A single-layered base including at least one microchannel for transferring the sample to the sample reservoir; And
Wherein the target material is selectively patterned in a predetermined position of each of the at least one microchannel and is accommodated in the at least one buffer and transferred through the microchannel to selectively transfer the target material to the sample reservoir, And a selective ion permeable membrane formed to open at least a portion of the transferred microchannel. 17. The method of claim 16,
The base comprising a material having at least some fiber texture,
Characterized in that a hydrophobic substance is added to the base and the space in which the microchannel is formed contains at least a space in which the hydrophobic substance is not present and the sample or the target substance moves through the space. Device. 17. The method of claim 16,
The single-layer base is one of paper or PET (polyethylene terephthalate)
Wherein the selective ion-permeable membrane is at least one of nafion, polystyrene sulfonate (PSS), or polyallylamine hydrochloride (PAH). 17. The method of claim 16,
The selective ion-permeable membrane is formed at both side ends of each of the at least one microchannel to have a predetermined size smaller than the width of the microchannel so that the sample is filtered and transferred to the sample reservoir Wherein the biomolecule concentration is in the range of 1 to 10.

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