KR20170068356A - Device for storing reagents and apparatus for bio-reaction having the same - Google Patents

Abstract

The present invention relates to a reaction liquid storage device and a bioreactor having the same, the reaction liquid storage device being connected to a biochip and supplying reaction liquids into the biochip, the reaction liquid storage device having one end opened, And a plurality of diaphragms provided in the storage container and installed so as to be in close contact with an inner wall of the storage container, wherein the diaphragms are arranged in a direction And each of the diaphragms includes a through hole passing through the inside of the diaphragm.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a device for storing a reaction liquid and a bio-

The present invention relates to a reaction liquid storage device and a bioreactor having the same, and more particularly, to a reaction liquid storage device capable of storing a plurality of reaction liquids and a bioreactor having the same.

Development of a biochip for the quick and easy diagnosis and analysis of biological samples is being carried out. These biochips include a method of injecting only biological samples and a method of sequentially injecting various reaction solutions. Although the former is advantageous in its simplicity, it is not applicable to diagnostic analysis requiring complex biochemical reactions. The latter has the advantage of being able to apply various analysis protocols because complex reaction is possible, but it has a disadvantage that a complicated driving device for storing and supplying the reaction solution is additionally required.

Recent development trends of biochips are demanding the development of high-performance biochips with high sensitivity, quantification, reproducibility, and simultaneous analysis. In addition, development of a lab-on-a-chip type biochip that performs sample preprocessing, analysis and measurement sequentially on a single chip is underway. As described above, in order to develop a biochip in the form of a high-function lab-on-a-chip, a complex reaction protocol must be implemented in a reproducible manner, which can be achieved by sequential, quantitative and automated reaction liquid supply.

Up to now, most of the lab-on-a-chip has used the method of storing the required reaction solution externally and supplying it to the lab-on-a-chip by an external pumping device. Such a method of storing and supplying the reaction solution has a problem that the external device is complicated and large. On the other hand, a micro pump is installed on the lab-on-a-chip to remove the external pumping device. However, a complicated process for installing the micro pump on the chip and an additional cost are required. And there is still a problem that it is impossible to store the reaction solution.

To overcome this, several techniques have been proposed in the past to store the reaction solution on a lab-on-a-chip. One is a method in which a chamber for storing a reaction solution is provided on a chip, and a reaction solution is injected thereinto and sealed. In this case, not only the reaction liquid inlet but also the microchannel connected to the storage chamber is required to be sealed, which is mainly realized by a microvalve or a phase change material. However, there is a disadvantage in that the process and control operation for opening and closing the micro channel are somewhat complicated. In another method, there is a method of attaching a reaction liquid reservoir in the form of a pouch on a chip. In this case, the pouch is squeezed by a manual or mechanical device, and the reproducibility of the flow rate during the supply of the reaction liquid may be lowered, and further mechanical control is required.

Thus, in order to store the reaction solution, it is required to maintain the stock solution at a low temperature, to provide a low-cost solution, to provide a reaction solution having simple operation, reproducibility, and the like. However, the prior art has a limitation in satisfying the above requirement.

Disclosure of Invention Technical Problem [8] The present invention provides a reaction solution storage device capable of maintaining a homeostasis of a reaction solution, capable of realizing a low cost, and capable of supplying a replenishing reaction solution by simple operation, and a bioreaction device having the same.

According to an aspect of the present invention, there is provided a reaction solution storage device connected to a biochip, the reaction solution storage device for supplying reaction solutions into the biochip, the reaction solution storage device having one end opened, A storage container having a closed tubular shape at the opposite end thereof; And a plurality of diaphragms provided in the storage container and installed so as to be in close contact with an inner wall of the storage container, wherein the diaphragms are spaced apart from each other along a direction in which the one end and the other end are opposite to each other, Each includes a through hole penetrating its interior.

According to one embodiment, the storage container includes a plurality of storage spaces separated by the diaphragms, the reaction liquids are respectively stored in the plurality of storage spaces, and at least a part of the reaction liquids are different from each other Type reaction liquid.

According to one embodiment, the diaphragms include a first diaphragm and a second diaphragm spaced apart from the inlet in the one direction, and the reaction liquids include a first reaction between the first diaphragm and the second diaphragm And a second reaction liquid which is separated from the first reaction solution with the second diaphragm interposed therebetween, wherein the first diaphragm is configured to move toward the second diaphragm by an external force applied thereto, 1 While the diaphragm is moving, the first reaction liquid may be configured to be discharged to the outside of the storage container through the through-hole of the first diaphragm.

According to one embodiment, while the first reaction liquid is being discharged, the second diaphragm may be configured to be in a stopped state.

According to one embodiment, the through hole may completely penetrate the corresponding diaphragm along the one direction, and the ratio of the diameter of the through hole to the length of the through hole may be 0.02 to 0.2.

According to one embodiment, the through holes of the diaphragms may be aligned along a straight line parallel to the one direction.

According to one embodiment, the diaphragms may be made of a material having elasticity.

According to one embodiment, the through-hole may be filled with air or oil.

According to an aspect of the present invention, there is provided a bio-reaction device comprising: a bio-chip for performing a bio-reaction; And a reaction liquid storage device connected to one end of the biochip, wherein the reaction liquid storage device comprises: a tubular storage container having an opened inlet; A plurality of diaphragms disposed in the storage vessel to be in close contact with an inner wall of the storage vessel and spaced apart from each other, each of the diaphragms including a through hole penetrating the interior thereof; And reaction liquids respectively stored in the storage spaces of the storage vessel separated by the diaphragms, wherein the reaction liquids are sequentially supplied into the biochip.

According to one embodiment, the diaphragm closest to the inlet of the diaphragms is a first diaphragm, and the biochip includes a tubular body portion and a reaction liquid transfer channel in the body portion, And is connected to the first diaphragm, and the reaction liquids can be transferred to the reaction liquid transfer channel.

According to one embodiment, the biochip further includes a reaction solution inlet provided at the one end of the body part and connected to the reaction solution transfer channel, wherein the reaction solution inlet is in communication with the through hole of the first diaphragm have.

According to an embodiment of the present invention, the apparatus further includes a connecting member disposed between the one end of the body and the first diaphragm, wherein the connecting member includes a connecting passage connecting the reaction solution inlet and the through hole of the first diaphragm can do.

According to an embodiment, the biochip further includes a driving member connected to the other end opposite to the one end of the biochip, wherein the driving member applies an external force to the first diaphragm through the biochip.

According to one embodiment, the diaphragm adjacent to the first diaphragm is the second diaphragm, and the reaction liquid between the first diaphragm and the second diaphragm among the reaction liquids is the first reaction liquid, The first diaphragm is configured to move linearly toward the second diaphragm by the applied external force, and the first reaction liquid can be transferred to the reaction liquid transfer channel while the first diaphragm is linearly moved.

According to one embodiment, while the first reaction liquid is being transferred to the reaction liquid transfer channel, the second diaphragm may be configured to be in a stopped state.

According to one embodiment, a target material for performing the bioreaction may be provided in the reaction liquid transport channel.

According to one embodiment, the body part is a first body part, the reaction solution transfer channel is a first reaction solution transfer channel, the bio chip is a second body part; A second reaction liquid transfer channel in the second body part; And a connection part connecting the first reaction solution transport channel and the second reaction solution transport channel.

According to one embodiment, the reaction liquids are transferred to the second reaction liquid transfer channel through the first reaction liquid transfer channel and the connection portion, and the second reaction liquid transfer channel is provided with a target substance Can be provided.

According to one embodiment, the through holes of the diaphragms may be aligned along a straight line parallel to the one direction.

According to one embodiment, the diaphragms may be made of a material having elasticity.

According to the embodiments of the present invention, a reaction liquid storage device capable of storing various reaction solutions can be realized by alternately injecting and installing reaction liquids and diaphragms in a tubular storage container having an opened inlet . Accordingly, it is possible to provide a reaction liquid storage device which can be manufactured at a low manufacturing cost and can maintain the homeostasis of reaction liquids.

According to the embodiments of the present invention, it is possible to sequentially move the diaphragms linearly by applying an external force to the diaphragms connected to the biochip using a simple driving member, and the reaction liquids pressurized by the linear movement of the diaphragms And may be sequentially supplied to the interior of the biochip through the formed through-holes. Accordingly, it is possible to provide a reaction liquid storage device capable of supplying a replenishing reaction liquid by a simple operation, and a bioreactor having the same.

1 is a view for explaining a reaction liquid storage device according to embodiments of the present invention.
FIG. 2 and FIG. 4 are exemplary perspective views of the reaction liquid storage device of FIG.
3A and 3B are cross-sectional views illustrating a diaphragm of a reaction liquid storage device according to embodiments of the present invention.
FIG. 5 is a view for explaining a method of storing reaction liquids in the storage container of FIG. 1;
6A and 6B are views for explaining a bioreactor having the reaction liquid storage device of FIG.
Figs. 7 and 8 are enlarged views corresponding to the portion A in Fig. 6A.
FIGS. 9A to 9E are views for explaining a method of operating the bioreactor of FIG. 6A.
FIGS. 10 and 11 are diagrams for explaining an example in which a bioreaction is performed using the bioreactor of FIG. 6A, wherein a part of the biochip is enlarged.
12 is a view for explaining a bio-reaction device according to embodiments of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS The advantages and features of the present invention, and how to accomplish them, will become apparent by reference to the embodiments described in detail below with reference to the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims. Like reference numerals refer to like elements throughout the specification.

The terminology used herein is for the purpose of illustrating embodiments and is not intended to be limiting of the present invention. In the present specification, the singular form includes plural forms unless otherwise specified in the specification. As used herein, the terms 'comprises' and / or 'comprising' mean that the stated element, step, operation and / or element does not imply the presence of one or more other elements, steps, operations and / Or additions.

In addition, the embodiments described herein will be described with reference to cross-sectional views and / or plan views, which are ideal illustrations of the present invention. In the drawings, the thicknesses of the films and regions are exaggerated for an effective description of the technical content. Thus, the shape of the illustrations may be modified by manufacturing techniques and / or tolerances. Accordingly, the embodiments of the present invention are not limited to the specific forms shown, but also include changes in the shapes that are generated according to the manufacturing process. For example, the etched area shown at right angles may be rounded or may have a shape with a certain curvature. Thus, the regions illustrated in the figures have schematic attributes, and the shapes of the regions illustrated in the figures are intended to illustrate specific types of regions of the elements and are not intended to limit the scope of the invention.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

1 is a view for explaining a reaction liquid storage device according to embodiments of the present invention. FIG. 2 and FIG. 4 are exemplary perspective views of the reaction liquid storage device of FIG. 3A and 3B are cross-sectional views illustrating a diaphragm of a reaction liquid storage device according to embodiments of the present invention.

Referring to FIG. 1, a reaction liquid storage device 100 may include a plurality of diaphragms 120 provided in a storage container 110 and a storage container 110. The diaphragms 120 may separate the internal space of the storage container 110 into a plurality of storage spaces, and the reaction liquids 130 may be stored in each of the plurality of storage spaces.

In detail, the storage vessel 110 may have a tubular shape with an open inlet 112. In other words, the storage container 110 may have one end opened and the other end opposite to the one end closed. The diaphragms 120 may be provided through the open inlet 112 of the storage vessel 110 to be in intimate contact with the inner wall of the storage vessel 110. That is, the diaphragms 120 may have a shape that can be inserted into and closely contact with the inner wall of the storage container 110. And, each of the diaphragms 120 may have a through hole 122 penetrating the inside thereof. The through hole 122 may serve as a path through which the reaction liquids 130 are transferred. The storage container 110 may be made of glass or plastic. Preferably, the storage container 110 may be made of a transparent plastic material. However, the embodiments of the present invention are not limited thereto. The diaphragms 120 may be made of a material having elasticity. For example, diaphragms 120 may comprise rubber or PDMS (polydimethylsiloxane).

The reaction liquid storage device 100 according to embodiments of the present invention may be configured to be connected to the biochip 200 (see FIG. 6A) to sequentially supply the reaction liquids 130 into the biochip 200 have. The biochip 200 may be provided with a biomarker, that is, a target material contained in a biological sample (for example, blood, urine, or saliva), and the reaction liquids 130 may sequentially react with the target material And can be composed of various kinds of reaction liquids. The diaphragms 120 may be sequentially moved linearly to external forces to pressurize the reaction liquids 130 so that the reaction liquids 130 are supplied to the diaphragms 120 Through the through hole 122 formed in the storage container 110. The detailed operation of the reaction liquid storage device 100 will be described later. Hereinafter, the configuration of the reaction liquid storage device 100 will be described in more detail with reference to FIG.

Referring to Figures 1 and 2, the storage vessel 110 may have a cylindrical shape with an open inlet 112. Preferably, the storage container 110 may have an elongated shape having a major axis in a direction in which both ends thereof face each other. That is, the storage container 110 may have a length L and an inner diameter d1 in a direction in which both ends thereof face each other. The length L and / or the inner diameter d1 of the storage container 110 may be variously sized depending on the number of types of reaction liquids 130 required and / or the capacity of the reaction liquids 130 . For example, when the number of kinds of reaction liquids 130 necessary for the analysis of the target material is large, the number of the diaphragms 120 necessary for separate storage of the target substances increases, Can be longer. The length L of the storage container 110 and / or the inner diameter d1 of the storage container 110 can be increased when the required amount of the reaction liquids 130 is large. In the drawing, three diaphragms 120 are provided in the storage container 110, and three reaction liquids 130 are separately stored in the liquid storage container 110. However, it is to be understood that the embodiments of the present invention are not limited thereto But is not limited thereto. The three diaphragms 120 may be referred to as first to third diaphragms 120a, 120b, and 120c, respectively, from the inlet 112 of the storage vessel 110 along its longitudinal direction, The reaction solutions 130 may be referred to as first to third reaction solutions 130a, 130b, and 130c, respectively.

The diaphragms 120 may have a hollow cylindrical shape corresponding to the shape of the storage container 110. Each of the diaphragms 120 has a thickness (or length, H) in the direction in which the outer diameter d2, the inner diameter (i.e., the diameter of the through hole 122, d3) . The thickness H of each of the diaphragms 120 may correspond to the length of the through-hole 122. The diaphragms 120 in a state in which the diaphragms 120 are not formed in the storage container 110 are made of materials having elasticity so that the diaphragms 120 can be stretched more than the inner diameter d1 of the storage container 110 And may have a large outer diameter d2. In this case, the diaphragms 120 are compressed and provided into the storage container 110, and can be strongly adhered to the inner wall of the storage container 110 by its restoring force.

The through holes 122 are formed in such a manner that the reaction liquids 130 separated through the diaphragm 120 are separated from the through holes 122 in the state where no external force is applied to the diaphragms 120 in the storage container 110 So that diffusion and mixing with each other can be minimized. According to the embodiments, the ratio of the diameter d3 of the through hole 122 to the length H of the through hole 122 (in other words, the inner diameter d3 of the diaphragm 120 to the diaphragm 120 of the diaphragm 120) Thickness (H)) may be 0.02 to 0.2. When the diameter d3 of the through hole 122 is large, the length H of the through hole 122 is relatively large in order to prevent diffusion and mixing between the adjacent reaction liquids 130 with the diaphragm 120 therebetween. It can be implemented long. On the other hand, when the size of the through hole 122 is small, the flow resistance of the reaction liquid 130 passing through the through hole 122 becomes large and the external force applied to the diaphragm 120 for transferring the reaction liquid 130 becomes large . For example, the diameter of the through hole 122 may be 0.1 to 1 mm. The through holes 122 may be filled with an inert liquid material such as air or oil to minimize diffusion between the reaction liquids 130.

In this example, although the cross-sectional shape of the through hole 122 is shown as being circular, the embodiments of the present invention are not limited thereto. In another example, the cross-sectional shape of the through-hole 122 may be square as shown in Fig. 3A. In this case, the through hole 122 may have a width d3. For example, the width d3 of the through hole 122 may be 0.1 to 1 mm. In another example, the cross-sectional shape of the through-hole 122 may be rectangular, as shown in Fig. 3B. In this case, the through hole 122 may have a first width d3a in the major axis direction and a second width d3b in the minor axis direction. For example, the first width d3a may be less than 1 mm, and the second width d3b may be greater than 0.1 mm.

The diaphragms 120 may be installed in the storage container 110 such that the through holes 122 are aligned along a straight line parallel to the longitudinal direction of the storage container 110. [ For example, the through holes 122 may be formed in the center portion of the diaphragms 120, in terms of one cross section. In this case, it may be easy to align the through holes 122 of the diaphragms 120 installed in the storage container 110 along a straight line. However, the embodiments of the present invention are not limited thereto.

Alternatively, according to another embodiment, the storage container 110 may have a rectangular (e.g., square) tubular shape with an open inlet 112, as shown in FIG. The storage container 110 may have a length L and an inner width d1 in a direction in which both ends thereof face each other. Further, the diaphragms 120 may have a shape corresponding to the shape of the storage container 110, that is, a rectangular square column shape. Each of the diaphragms 120 may have an outer width d2, an inner diameter d3, and a length (or thickness, H). The contents (d1, L) of the storage container 110 and the sizes (d2, d3, H) of the diaphragms 120 are the same as those described with reference to Fig.

According to another embodiment, although not shown, the storage container 110 may have a triangular, hexagonal, or octagonal tubular shape (i.e., a polygonal tubular shape) with an open inlet 112. The diaphragms 120 may have the shape of a hollow triangular, hexagonal, or octagonal column corresponding to the shape of the storage container 110.

FIG. 5 is a view for explaining a method of storing reaction liquids in the storage container of FIG. 1;

Referring to FIG. 5, a plurality of reaction liquids 130a, 130b, and 130c and diaphragms 120a, 120b, and 120c are connected to an inlet (not shown) with the open inlet 112 of the storage container 110 facing upward 112 into the storage container 110 alternately. For example, the third reaction solution 130c may be injected into the storage container 110, and then the third partition 120c may be installed in the storage container 110 so as to be in close contact with the inner wall of the storage container 110. [ The third diaphragm 120c may be disposed in contact with the third reaction solution 130c, but is not limited thereto. If necessary, an inert liquid such as oil may be filled in the through hole 122 of the third diaphragm 120c. Subsequently, the second reaction solution 130b and the second diaphragm 120b are sequentially introduced into the storage container 110. Similarly, the first reaction solution 130a and the first diaphragm 120a are sequentially introduced into the storage container 110 110 < / RTI > If necessary, the through hole 122 of the second diaphragm 120b and the through hole 122 of the first diaphragm 120a may be filled with an inert liquid such as oil. The first to third diaphragms 120a, 120b, and 120c may be disposed in the storage container 110 along the longitudinal direction of the storage container 110. The diaphragms 120 The first to third reaction solutions 130a, 130b, and 130c may be stored in the storage spaces of the separate storage container 110, respectively.

According to the embodiments of the present invention, a reaction liquid storage device capable of storing various reaction solutions can be realized by alternately injecting and installing reaction liquids and diaphragms in a tubular storage container having an opened inlet . Accordingly, it is possible to provide a reaction liquid storage device which can be manufactured at a low manufacturing cost and can maintain the homeostasis of reaction liquids.

6A and 6B are views for explaining a bioreactor having the reaction liquid storage device of FIG. Figs. 7 and 8 are enlarged views corresponding to the portion A in Fig. 6A. The bioreactor 500 of FIG. 6A and the bioreactor 500 of FIG. 6B may be identical to each other only at different locations where the driving member 300 is connected. In order to simplify the following description, the bioreactor 500 of FIG. 6A will be used as a reference.

Referring to FIG. 6A, the bioreactor 500 may include a reaction liquid storage device 100, a biochip 200, and a driving member 300.

The reaction liquid storage device 100 includes a storage container 110, a storage container 110 separated by the diaphragms 120 and the diaphragms 120 in the storage container 110 as described above with reference to the drawings, And a plurality of reaction liquids 130, which are respectively stored in the storage spaces of the reaction chambers. The reaction liquid storage device 100 may be connected to the biochip 200 to sequentially supply the reaction liquids 130 into the biochip 200.

The biochip 200 may perform a bioreaction (or a biochemical reaction) using the reaction solutions 130 sequentially supplied from the reaction solution storage device 100. For example, the biochip 200 may be a biochip 200 in the form of a lab-on-a-chip. According to one embodiment, the biochip 200 may be fabricated in the form of a capillary tube, inserted into the storage vessel 110 and connected to the diaphragm 120 of the reaction liquid storage device 100.

In detail, the biochip 200 may include a body part 210 and a reaction liquid transfer channel 220 formed in the body part 210. The body portion 210 may have a tubular shape and may have an outer diameter or outer width that is less than the inner diameter d1 (see FIG. 2) of the storage container 110 for insertion into the storage container 110. The body portion 210 may be made of, for example, silicon, glass, plastic polymer, or a combination thereof. One end of the reaction solution transfer channel 220 may be provided with a reaction solution inlet 230 through which the reaction solutions 130 of the reaction solution storage device 100 are injected. One end of the body 210 having the reaction solution inlet 230 may be inserted into the storage vessel 110 and directly connected to the diaphragm 120 installed adjacent to the inlet 112 of the storage vessel 110. That is, as shown in FIG. 7, one end of the body 210 may be directly connected to the first diaphragm 120a. At this time, the reaction solution inlet 230 of the biochip 200 can be aligned with the through holes 122 of the first diaphragm 120a and communicate with each other.

In another embodiment, the biochip 200 may be connected to the first diaphragm 120a using a connecting member 240. [ One end of the body 210 may be coupled to the connecting member 240 and the connecting member 240 may be coupled to the storage container 110 through the inlet 112 of the storage container 110, May be inserted into the first diaphragm 110 and connected to the first diaphragm 120a. The connection member 240 may have a connection passage 242 therein and the connection passage 242 may be formed in the reaction solution inlet 230 of the biochip 200 and the through hole 122 of the first diaphragm 120a Can be connected. The connecting member 240 may be in close contact with the inner wall of the storage container 110. For example, the connecting member 240 may be made of the same material as the diaphragms 120, but the embodiments of the present invention are not limited thereto. As a result, one end of the biochip 200 may be inserted into the storage container 110 and directly or indirectly connected to the diaphragm 120 of the reaction liquid storage device 100.

The body 210 may include an outlet port (not shown) for discharging reaction liquids 130 transferred into the reaction liquid transfer channel 220 and / or an inlet port (not shown) for injecting the biological sample into the reaction liquid transfer channel 220. And may further include a biological sample injection port (not shown).

In this embodiment, the reaction liquid transfer channel 220 may be provided with a target material. The target substance may be, for example, a protein, a cell, a virus, a nucleic acid, an organic molecule, or an inorganic molecule contained in a biological sample (for example, blood, urine, saliva or the like) to be analyzed. In the case of a protein, any biomaterial such as an antigen, an antibody, a substrate protein, an enzyme, and a coenzyme can be used. And in the case of nucleic acids, DNA, RNA, PNA, LNA or their hybrid.

According to one embodiment, the driving member 300 may be connected to the bio chip 200 to provide a driving force to the bio chip 200. The driving force of the driving member 300 allows the biochip 200 to move linearly so as to press the diaphragm 120 connected thereto. 6A, the driving member 300 may be directly or indirectly connected to the other end of the body portion 210, and the body portion 210 may be connected to the other end of the body portion 210 by a driving force of the driving member 300, The first diaphragm 120a connected to one end thereof can be pressed. Meanwhile, the driving member 300 may be connected to the side of the body 210.

According to another embodiment, the driving member 300 may be connected to the reaction liquid storage device 100 to provide a driving force to the reaction liquid storage device 100. For example, the driving member 300 may be directly or indirectly connected to the other end of the storage container 110, as shown in FIG. 6B. And can be moved forward in the direction toward one end opened at the other end of the storage container 110 by the driving force of the driving member 300. At this time, the biochip 200 is fixed, and as a result, the biochip 200 can press the diaphragm 120 connected thereto.

The driving member 300 may include a driving unit for generating driving force, a power transmitting unit for transmitting the rotational force generated from the driving unit to the body unit 210, and a controller for controlling the driving unit. The driving portion may include, for example, a motor, and the power transmitting portion may include, for example, a gear. The controller may control the driving unit to adjust the driving force transmitted to the diaphragm 120 through the body 210. By controlling the driving force, the feeding speed of the reaction liquids 130 discharged from the storage container 110 can be controlled.

When the reaction liquids 130 are supplied from the reaction liquid storage device 100 to the reaction liquid transport channels 220, the bioreaction can be performed in the reaction liquid transport channels 220. Biological signals due to bio-reactions can be measured using various physicochemical detection methods. For example, the biochip 200 may be configured to be removably attached to the reaction liquid storage device 100, and the biochip 200 detached from the reaction liquid storage device 100 after performing the bio-reaction may measure the bio- And the like. As another example, the bio-reaction device 500 may be equipped with measurement means (e.g., a light source and a photodetector) for detecting the result of the bio-signal to detect the bio- Can be configured.

FIGS. 9A to 9E are views for explaining a method of operating the bioreactor of FIG. 6A. That is, FIGS. 9A to 9E are views for explaining a method of supplying the reaction liquids from the reaction liquid storage device into the biochip.

Referring to FIGS. 6A and 9A, a bioreactor 500 in which no external force is applied to the first diaphragm 120a is provided. That is, the biochip 200 having the reaction liquid storage device 100 having the first to third reaction solutions 130a, 130b and 130c and the body 210 connected to the first diaphragm 120a is provided . The reaction solution inlet 230 provided in the body 210 is aligned with the through holes 122 of the first diaphragm 120a and communicated with each other.

Referring to FIGS. 6A and 9B, an external force may be applied to the first diaphragm 120a by linearly moving the body 210 along the longitudinal direction thereof by the driving member 300. The first diaphragm 120a to which the external force is applied may be linearly moved in the longitudinal direction of the storage container 110 (i.e., the direction from one end of the storage container 110 to the other end). The first reaction solution 130a can be compressed and the compressed first reaction solution 130a can be discharged to the reaction solution inlet 230 through the through hole 122 of the first diaphragm 120a have. Meanwhile, the second diaphragm 120b may be in a stopped state while the first reaction liquid 130a is being conveyed. This is because the diaphragms 120 are made of a material having elasticity and are installed in intimate contact with the inner wall of the storage container 110 so that the second diaphragm 120b and the second diaphragm 120b are less in flow resistance than the first reaction liquid 130a, It may be because the shear resistance is larger due to the close contact of the storage container 110. Accordingly, mixing of the first reaction solution 130a and the second reaction solution 130b while the first reaction solution 130a is being transferred can be prevented. The driving member 300 may control an external force transmitted to the first diaphragm 120a through the body 210 to adjust the feeding speed of the first reaction liquid 130a.

Referring to FIGS. 6A and 9C, the first diaphragm 120a may be linearly moved along the longitudinal direction of the storage container 110 until the first diaphragm 120a contacts the second diaphragm 120b. The first reaction solution 130a may be completely transferred to the reaction solution transfer channel 220 of the biochip 200 while the first diaphragm 120a moves linearly until it contacts the second diaphragm 120b. Meanwhile, as the first diaphragm 120a and the second diaphragm 120b are physically connected, the external force applied to the first diaphragm 120a can be transmitted to the second diaphragm 120b. Accordingly, the second diaphragm 120b can be moved along with the first diaphragm 120a in the longitudinal direction of the storage container 110. [

Referring to FIGS. 6A and 9D, the second diaphragm 120b may be linearly moved along the longitudinal direction of the storage container 110 until the second diaphragm 120b contacts the third diaphragm 120c. The second reaction liquid 130b may be entirely transferred to the reaction liquid transfer channel 220 of the biochip 200 while the second diaphragm 120b moves linearly until it contacts the third diaphragm 120c. At this time, the transferred first reaction solution 130a may be discharged through an outlet (not shown). As the second diaphragm 120b and the third diaphragm 120c are physically connected to each other, the external force applied to the first diaphragm 120a is transmitted to the third diaphragm 120c through the second diaphragm 120b . Accordingly, the third diaphragm 120c can be moved in the longitudinal direction of the storage container 110 together with the first and second diaphragms 120a and 120b.

Referring to FIGS. 6A and 9E, the third diaphragm 120c may be linearly moved along the longitudinal direction of the storage container 110 until the third diaphragm 120c contacts the other end of the storage container 110. The third reaction liquid 130c may be entirely transferred to the reaction liquid transfer channel 220 of the biochip 200 while the third diaphragm 120c moves linearly until it contacts the other end of the storage container 110 . At this time, the transferred second reaction liquid 130b may be discharged through an outlet (not shown).

According to the embodiments of the present invention, it is possible to sequentially move the diaphragms linearly by applying an external force to the diaphragms connected to the biochip using a simple driving member, and the reaction liquids pressurized by the linear movement of the diaphragms And may be sequentially supplied to the interior of the biochip through the formed through-holes. Accordingly, it is possible to provide a reaction liquid storage device capable of supplying a replenishing reaction liquid by a simple operation, and a bioreactor having the same.

Hereinafter, an example in which the bioreaction is performed using the bioreactor of FIG. 6A will be described. FIGS. 10 and 11 are diagrams for explaining an example in which a bioreaction is performed using the bioreactor of FIG. 6A, wherein a part of the biochip is enlarged.

Referring first to FIGS. 6A and 10, in this example, the biochip 200 may be a biochip for an immune reaction. In this case, the primary antibody 212 for immune reaction can be immobilized on the inner wall of the reaction solution transport channel 220. For the performance of the immune response, a biological sample such as blood containing the antigen may first be injected into the reaction solution transfer channel 220. The biological sample may be injected through a biological sample inlet (not shown) separately formed in the body 210. Thereby, an immune response of the primary antibody 212 and the antigen can occur. Thereafter, according to the method described with reference to FIGS. 9A to 9E, the plurality of reaction liquids 130 can be sequentially supplied to the reaction liquid transfer channel 220 of the biochip 200. In this example, the plurality of reaction solutions 130 may be composed of a washing solution, a labeled secondary antibody, and a substrate. Thus, an immune reaction can be performed in the biochip 200.

The immune response signal generated by the immune response can be measured using a color reaction method, a chemiluminescence method, a fluorescence method, a staining signal amplification method, or the like. For example, in the case of measuring an immune response signal using an optical method, light is injected into the reaction solution transport channel 220 before and after the immunity reaction using an optical signal generator, and then, By measuring the change, the presence and amount of the target substance (i.e., biomarker) can be measured.

Referring to FIGS. 6A and 11, in this example, the biochip 200 may be a biochip for gene preprocessing. In this case, a solid substrate 214 may be provided in the reaction liquid transfer channel 220. For gene pretreatment, a biological sample such as blood may be injected into the reaction solution transfer channel 220 first. The biological sample may be injected through a biological sample inlet (not shown) separately formed in the body 210. Thereafter, according to the method described with reference to FIGS. 9A to 9E, the plurality of reaction liquids 130 can be sequentially transferred to the reaction liquid transfer channel 220 of the biochip 200. In this example, the plurality of reaction solutions 130 may be composed of a cell lysis buffer, a washing buffer, and an elution buffer. The cell lysate may be first supplied to the reaction liquid transport channel 220 to break down the cells and the intracellular gene may be bound to the solid substrate 214. Thereafter, the washing solution and the elution solution are sequentially supplied to the reaction solution transfer channel 220, whereby the adhesive gene can be eluted.

12 is a view for explaining a bio-reaction device according to embodiments of the present invention. The bioreactor 500A of FIG. 12 may be substantially the same as the bioreactor 500 of FIG. 6A except that the bio-chip 200 is configured differently. For the sake of simplicity of description, a duplicate description of the configuration is omitted.

Referring to FIG. 12, the biochip 200 may include a first body 210, a second body 250, and a connection 245. The first body part 210 may include a first reaction solution inlet 230, a first reaction solution transfer channel 220, and a first reaction solution outlet 222. The second body part 250 may include a second reaction solution inlet 252 and a second reaction solution 130b transfer channel 260. The connection portion 245 may include a transfer passage for connecting the first reaction liquid outlet 222 and the second reaction liquid inlet 252.

One end of the first body part 210 may be connected to the diaphragm 120 of the reaction liquid storage device 100 and the second body part 250 may be connected to the first body part 210 through the connection part 245 . The reaction liquids 130 supplied from the reaction liquid storage device 100 are supplied to the first reaction liquid inlet 230, the first reaction liquid transfer channel 220, the first reaction liquid outlet 222, (252) to the second reaction liquid transfer channel (260). In this embodiment, the target material may be provided in the second reaction liquid transport channel 260, and thus the bioreaction may be performed in the second reaction liquid transport channel 260. The second body part 250 may include a discharge port (not shown) and / or a second reaction liquid transfer channel 260 for discharging the reaction liquids 130 transferred into the second reaction liquid transfer channel 260 And a biological sample injection port (not shown) for injecting the biological sample.

While the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, It will be understood. It is therefore to be understood that the above-described embodiments are illustrative and not restrictive in every respect.

Claims (20)

A reaction liquid storage device connected to a biochip and supplying reaction liquids into the biochip,
A storage container having an open end and a closed end opposite to the one end; And
A plurality of diaphragms provided in the storage container and installed so as to be in close contact with an inner wall of the storage container,
Wherein the diaphragms are spaced apart from each other along one direction which is a direction in which the one end and the other end are opposite to each other,
Wherein each of the diaphragms includes a through hole penetrating the inside thereof. The method according to claim 1,
The storage vessel comprising a plurality of storage spaces separated by the diaphragms,
The reaction solutions are stored in the plurality of storage spaces, respectively,
Wherein at least a part of the reaction liquids are different kinds of reaction liquid. 3. The method of claim 2,
Wherein the diaphragms include a first diaphragm and a second diaphragm spaced apart from the inlet in the one direction,
The reaction liquids include a first reaction liquid between the first diaphragm and the second diaphragm and a second reaction liquid separated from the first reaction liquid through the second diaphragm,
Wherein the first diaphragm is configured to move toward the second diaphragm by an external force applied thereto,
Wherein the first reaction liquid is discharged to the outside of the storage container through the through hole of the first diaphragm while the first diaphragm moves. The method of claim 3,
And the second diaphragm is in a stopped state while the first reaction liquid is being discharged. The method according to claim 1,
Wherein the through-hole penetrates the corresponding diaphragm all along the one direction,
And the ratio of the diameter of the through-hole to the length of the through-hole is 0.02 to 0.2. The method according to claim 1,
Wherein the through holes of the diaphragms are aligned along a straight line parallel to the one direction. The method according to claim 1,
Wherein the diaphragms are made of a material having elasticity. The method according to claim 1,
Wherein the through hole is filled with air or oil. A biochip for carrying out a bioreaction; And
And a reaction liquid storage device connected to one end of the biochip,
The reaction solution storage device comprises:
A tubular storage vessel having an open inlet;
A plurality of diaphragms disposed in the storage vessel to be in close contact with an inner wall of the storage vessel and spaced apart from each other, each of the diaphragms including a through hole penetrating the interior thereof; And
And reaction liquids respectively stored in the storage spaces of the storage vessel separated by the diaphragms,
Wherein the reaction liquids are sequentially supplied into the biochip. 10. The method of claim 9,
Wherein the diaphragm closest to the inlet of the diaphragms is a first diaphragm,
The biochip includes a tubular body portion and a reaction liquid transfer channel in the body portion,
Wherein one end of the body is connected to the first diaphragm, and the reaction liquids are transferred to the reaction liquid transfer channel. 11. The method of claim 10,
The biochip further includes a reaction solution inlet provided at the one end of the body and connected to the reaction solution transfer channel,
Wherein the reaction solution inlet is in communication with the through hole of the first diaphragm. 12. The method of claim 11,
And a connecting member disposed between the one end of the body portion and the first diaphragm,
Wherein the connection member includes a connection passage for connecting the reaction solution inlet and the through-hole of the first diaphragm. 11. The method of claim 10,
And a driving member connected to the other end opposite to one end of the biochip,
Wherein the driving member applies an external force to the first diaphragm through the biochip. 14. The method of claim 13,
Wherein the diaphragm adjacent to the first diaphragm is a second diaphragm,
The reaction liquid between the first diaphragm and the second diaphragm among the reaction liquids becomes the first reaction liquid,
Wherein the first diaphragm is linearly moved toward the second diaphragm by the applied external force,
Wherein the first reaction liquid is transferred to the reaction liquid transfer channel while the first diaphragm is linearly moved. 15. The method of claim 14,
And the second diaphragm is in a stationary state while the first reaction liquid is transferred to the reaction liquid transfer channel. 11. The method of claim 10,
Wherein a target material for performing the bioreaction is provided in the reaction solution transfer channel. 11. The method of claim 10,
Wherein the body portion is a first body portion, the reaction liquid transport channel is a first reaction liquid transport channel,
The biochip comprises:
A second body portion;
A second reaction liquid transfer channel in the second body part; And
And a connection portion connecting the first reaction solution transfer channel and the second reaction solution transfer channel. 18. The method of claim 17,
The reaction liquids are transferred to the second reaction liquid transfer channel through the first reaction liquid transfer channel and the connection portion,
Wherein the second reaction solution transport channel is provided with a target material for performing the bioreaction. 10. The method of claim 9,
Wherein the through holes of the diaphragms are aligned along a straight line parallel to the one direction. 10. The method of claim 9,
Wherein the diaphragms are made of a material having elasticity.

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