KR20190089807A - Immunodiagnostic device and syringe dispenser employed therein - Google Patents

Abstract

Disclosed is an immunodiagnostic device capable of supplying fluid for a reagent, such as various kinds of samples and cleaning solutions, to a reaction chamber member and recovering the fluid for a reagent from the reaction chamber member. The immunodiagnostic device comprises: a first syringe dispenser; a second syringe dispenser; a third syringe dispenser; a reaction chamber member coupled to the first syringe dispenser through a branched first microtube, coupled to the second syringe dispenser through a branched second microtube, coupled to the third syringe dispenser through a branched third microtube, and having an inner surface to which location-based materials combined with an antigen or an antibody are attached in a dot shape where the materials are arranged in uniform columns and rows; a fluorescent sensor disposed on the bottom surface of the reaction chamber member to measure a chemical light emitting signal generated by an immune reaction at each antibody spot for each pixel, and photographs a flat image for image analysis which analyzes a fine signal as a meaningful value; a first waste outlet coupled to a fourth microtube branched from the reaction chamber member and discharging an output completed with bio-reaction to the outside; a second waste outlet coupled to a fifth microtube branched from the reaction chamber member and discharging an output completed with bio-reaction to the outside; and a third waste outlet coupled to a sixth microtube branched from the reaction chamber member and discharging an output completed with bio-reaction to the outside.

Description

[0001] IMMUNODIAGNOSTIC DEVICE AND SYRINGE DISPENSER EMPLOYED THEREIN [0002]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an immunoassay diagnostic apparatus and a syringe dispenser employed therein, and more particularly, to an immunoassay diagnostic apparatus and a syringe dispenser employing the same, To an immunoassay diagnostic apparatus capable of supplying a reagent fluid to the reaction chamber member and capable of recovering a reagent fluid in the reaction chamber member, and a syringe dispenser employed therein.

An apparatus for examining or examining the presence of a single or multiple substances in a liquid sample, for example a urine or blood sample, is referred to as a diagnostic kit. Specifically, the modern diagnostic business field is integrated into one of the Point-Of-Care Testing (POCT). POCT is a test that is performed outside a centralized laboratory, and refers to equipment that can be used by the general public without expert knowledge. Currently, diagnostic fields are expanding from hospitals to field and individual.

For example, in a hospital, a patient may be required to take a large amount of antibiotics to fight infections and then take a small amount of blood to investigate whether an adequate amount of antibiotic is present in the blood, In the case of an overdose patient who is injured or unable to communicate, it is possible to quickly investigate the type of medication taken in the human body to ensure proper treatment. In particular, rapid diagnostic tests, such as immunochromatographic assays, are used to identify diseases or detect changes in the healthcare field, and to quantitatively and quantitatively analyze trace amounts of analytes in a variety of fields, It is being developed in a simple way. In the field of health care, applications are being extended to pregnancy, ovulation, infectious diseases, drug abuse, acute myocardial infarction, and cancer.

Korean Registered Patent No. 10-1148308 (2012. 05. 11.) (Microorganism meter inspection apparatus) Korean Patent Publication No. 2010-0104395 (2010. 09. 29.) (Immunoassay kit and diagnostic method using the same)

SUMMARY OF THE INVENTION Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and it is an object of the present invention to provide a reagent fluid, such as various kinds of samples or cleaning liquids, Which is capable of supplying the reagent fluid to the reaction chamber member, and capable of recovering the reagent fluid from the reaction chamber member.

It is another object of the present invention to provide a syringe dispenser employed in the above immunoassay diagnostic apparatus.

In order to achieve the object of the present invention, the immunoassay diagnostic apparatus according to an embodiment of the present invention includes: a first scanning type dispenser; A second scanning die dispenser; A third scanning die dispenser; Is connected to the first syringe dispenser through a branched first microtubule, is fastened to the second syringe dispenser through a branched second microtubule, and is connected to the third syringe dispenser through a branched third microtubule, A reaction chamber member attached to the inner surface of the reaction chamber in the form of a dot in which a position-based substance that binds to the antigen or antibody is arranged in a predetermined row and row; A fluorescence sensor arranged on the back surface of the reaction chamber member for photographing a chemiluminescence signal caused by an immune reaction in each antibody spot on a pixel-by-pixel basis to image the image in a planar manner for image analysis for analyzing a microscopic signal into a meaningful value; A first waste outlet coupled to a fourth microtubule branching from the reaction chamber member and discharging the bioreacted product to the outside; A second waste outlet coupled to a fifth microtubule branching from the reaction chamber member and discharging the bioreacted product to the outside; And a third waste outlet, which is fastened to a sixth microtubule branching from the reaction chamber member and discharges the bioreacted product to the outside.

In one embodiment, each of the first to third scanning type dispensers includes a cylinder-shaped cylinder outer cylinder including a closed end and an opened other end; A plurality of rubber packings spaced apart from each other by a predetermined distance in the cylinder outer cylinder; A reagent fluid contained in each of the compartments defined by rubber packs adjacent to each other; And a needle inserted into the closed end.

In order to achieve the above object, the syringe-type dispenser employed in the immunoassay diagnostic apparatus according to an embodiment of the present invention includes a cylinder-shaped cylinder outer cylinder including a closed end and an opened other end; A plurality of rubber packings spaced apart from each other by a predetermined distance in the cylinder outer cylinder; A reagent fluid contained in each of the compartments defined by rubber packs adjacent to each other; And a needle inserted into the closed end.

In one embodiment, the syringe-type dispenser employed in the immunoassay diagnostic apparatus may further include a plunger inserted into the cylinder outer cylinder at the other end of the cylinder outer cylinder and connected to the outermost rubber packing.

In one embodiment, the syringe-type dispenser employed in the immunoassay diagnostic apparatus has a length larger than the protruding length of the needle protruding from one end of the cylinder outer tube, and extends in the longitudinal direction of the cylinder outer cylinder from the cylinder outer cylinder And a peripheral member.

According to such an immunoassay diagnostic apparatus and a syringe dispenser employed therein, the reagent fluid receiving section constituted by the syringes is configured to contact the transfer channel member through the hole formed in the bottom plate, and the reaction chamber member is arranged below the transfer channel member And a fluorescence sensor is disposed under the reaction chamber member. As the plunger of the syringe is pushed, the reagent fluid is supplied to the reaction chamber member via the transfer channel member, and the reagent fluid on the transfer channel member is recovered as the plunger is pulled. In this way, reagent fluid such as various kinds of samples or cleaning liquid can be supplied to the reaction chamber member for immunodiagnostic operation through a fluorescence sensor disposed under one reaction chamber member, and reagent So that the fluid can be recovered.

1 is an exploded perspective view illustrating an immunoassay diagnostic apparatus according to an embodiment of the present invention.
Fig. 2 is a schematic diagram for explaining each of the components of the immunoassay diagnostic apparatus shown in Fig. 1. Fig.
3 is a perspective view schematically illustrating a syringe dispenser employed in an immunoassay diagnostic apparatus according to another embodiment of the present invention.
FIG. 4A is a front cross-sectional view of the syringe-type dispenser shown in FIG. 3, FIG. 4B is a sectional view after the pressurization of the syringe-type dispenser shown in FIG. 3, and FIG. 4C is an enlarged view of the area A shown in FIG. .
Fig. 5 is a schematic diagram for schematically explaining an immunoassay diagnostic apparatus employing the syringe dispenser shown in Fig. 3; Fig.
Fig. 6A is a plan view for schematically explaining the reaction chamber member shown in Fig. 5, Fig. 6B is a cross-sectional view cut along the line I-I 'of the reaction chamber member shown in Fig. 6A, Sectional view taken along a cutting line II-II 'of the reaction chamber member shown in FIG.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will now be described in more detail with reference to the accompanying drawings. The present invention is capable of various modifications and various forms, and specific embodiments are illustrated in the drawings and described in detail in the text. It should be understood, however, that the invention is not intended to be limited to the particular forms disclosed, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.

Like reference numerals are used for like elements in describing each drawing. In the accompanying drawings, the dimensions of the structures are enlarged to illustrate the present invention in order to clarify the present invention.

The terms first, second, etc. may be used to describe various components, but the components should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be referred to as a second component, and similarly, the second component may also be referred to as a first component. The singular expressions include plural expressions unless the context clearly dictates otherwise.

In this application, the terms "comprises", "having", and the like are used to specify that a feature, a number, a step, an operation, an element, a part or a combination thereof is described in the specification, But do not preclude the presence or addition of one or more other features, integers, steps, operations, components, parts, or combinations thereof.

Also, unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

1 is an exploded perspective view schematically illustrating an immunoassay diagnostic apparatus according to an embodiment of the present invention. Fig. 2 is a schematic diagram for explaining each of the components of the immunoassay diagnostic apparatus shown in Fig. 1. Fig.

1 and 2, the immunoassay diagnostic apparatus includes a fluorescence sensor 110, a reaction chamber member 120, a transfer channel member 130, a bottom plate 140, a top plate 150, (160).

The fluorescence sensor 110 includes a plurality of pixels, and may be a charge-coupled device (CCD) or a complementary metal oxide semiconductor (CMOS) as a global shutter type image sensor. Each of the plurality of pixels includes a photo-diode, a storage diode, and a floating diffusion. Each of the plurality of pixels constituting the fluorescence sensor 110 further includes a first switch and a second switch for switching transmission and transmission interruption to the storage diode and the floating diffusion in association with the charge stored in each of the plurality of pixels . The photo-diodes of each of the plurality of pixels receive the exposure incident through the microlenses, convert them into electric signals, and accumulate the electric charges converted into electric signals. The storage diode of each of the plurality of pixels collectively stores charges accumulated in each of the photo-diodes.

The reaction chamber member 120 is disposed above the fluorescence sensor 110. The reaction chamber member 120 is provided with one or more inlets into which a reagent fluid flows, one or more chambers, one or more outlets through which a reagent fluid flows out, and chambers or chambers adjacent to each other, And a plurality of microchannels to be connected. A target antibody may be immobilized on each of the chambers. Alternatively, each of the chambers may be provided with a location-based material (dendron, hydrogel pad, etc.) that bonds with an antigen or an antibody.

The above-described position-based material may be arranged in a two-dimensional structure or in a three-dimensional structure in each of the chambers in the reaction chamber member 120. The two-dimensional structure is disposed on the inner bottom surface of the reaction chamber member 120, and the three-dimensional structure is a structure that connects the inner bottom surface and the inner ceiling surface of the reaction chamber member 120 to each other (E. G., In the form of a column).

When the position-based material is a hydrogel pad, the hydrogel of the hydrogel pad is a hydrophilic material which, when mixed with water, does not dissolve or dissolve and remains in a three-dimensional structure due to crosslinking of the polymer chains or polymer chains, ≪ / RTI > For example, the hydrogel may be selected from the group consisting of polyethylene diacrylate (PEGDA) hydrogel, PMA hydrogel, polydimethylamino acrylamide (PDGPA) hydrogel, polyethyloxazoline, silicone hydrogel, etc. Various types of hydrogels may be included. In this embodiment, the hydrogel pads may comprise a PEGDA hydrogel.

Each of the hydrogel pads is mixed with a plurality of different antibodies or antigens.

In the present embodiment, the term "antibody" may comprise a recombinant protein construct comprising an intact antibody molecule, an antibody fragment and the antigen binding domain of the antibody. The term "antibody" may also include intact antibody molecules, antibody fragments, and antibody constructs chemically modified by, for example, label introduction. The term "antibody" is used as a specific component for analyzing a biological material, and includes a primer, a probe, an antibody, an aptamer, a DNA as a component for quantitative or qualitative analysis of a specific biological substance, Or RNA polymerase, and it may mean a component necessary for performing a real-time PCR, a canonical enzyme reaction, or an LCR (Ligase Chain Reaction).

In this embodiment, the term "antigen" is well understood in the art and includes immunogenic substances, i.e., immunogens, and substances that induce immunological unresponsiveness or immune anergy, can do. When the antigen is a polypeptide, the antigen may be a transmembrane molecule (e. G., A receptor) or a ligand, e. G. A growth factor. Examples of antigens include molecules such as renin, growth hormone including human growth hormone and bovine growth hormone, growth hormone releasing factor, parathyroid hormone, thyroid stimulating hormone, lipoprotein, alpha-1-antitrypsin, insulin A-chain, insulin B Factors VIII, Factor IX, Tissue Factor (TF), and von Willebrands Factor, anti-coagulation factors, such as, for example, Such as, for example, protein C, atrial sodium excretion enhancer, pulmonary surfactant, plasminogen activator such as eukaryotic or human urine or tissue-type plasminogen activator (t-PA), bombesin, thrombin , Human macrophage inflammatory protein (MIP-1-alpha), serum albumin (MIP-1-alpha), tumor necrosis factor- alpha and beta, Encephalinase, RANTES , For example, human serum albumin, Muellerian-inhibiting substances, rilacsin A-chain, lilaxin B-chain, prolylaxin, mouse gonadotropin-related peptides, microbial proteins such as beta-lactamase (CTLA), such as CTLA-4, inhivin, actibin, vascular endothelial growth factor (VEGF), receptor for hormone or growth factor, protein A or D, Neurotrophic factor such as bone-induced neurotrophic factor (BDNF), neurotrophin-3, -4, -5 or -6 (NT-3, NT-4, NT- 6, or nerve growth factors such as NGF- ?, platelet-derived growth factor (PDGF), fibroblast growth factor such as aFGF and bFGF, epidermal growth factor (EGF) For example, TGF-alpha and TGF-beta (including TGF-? 1, TGF-? 2, TGF-? 3, TGF-? 4 or TGF-? 5), insulin- II), des (1-3) -IGF-I IGF-I), insulin-like growth factor binding proteins, CD proteins such as CD3, CD4, CD8, CD19 and CD20, erythropoietin, bone inducing factors, immunotoxins, For example IL-1 to IL-10, such as interferon-alpha, -beta and -gamma, colony stimulating factors (CSF) such as M-CSF, GM-CSF and G-CSF, interleukin , A superoxide dismutase, a T-cell receptor, a surface membrane protein, a decelerating factor, a viral antigen such as a part of an AIDS envelope, a transport protein, a homing receptor, an adenosine, a regulatory protein, Such as CD11a, CD11b, CD11c, CD18, ICAM, VLA-4 and VCAM, tumor associated antigens such as HER2, HER3 or HER4 receptors and fragments of any of the listed polypeptides.

In addition, in the conventional array method, the immune diagnosis speed is slow because the dielectric substance is disposed only on the surface. However, the hydrogel pads disclosed in this embodiment have a high immunodiagnosis rate due to the antigen-antibody reaction not only on the surface but also inside the hydrogel pads due to the three-dimensional structure of the polymer chains. Therefore, it is possible to perform real-time immunodiagnosis according to position by forming an array with hydrogel pads. In addition, since the fluorescence is emitted only from the hydrogel pad, the intensity of the detected signal is increased due to an increase in the amount of light, and more sensitive experiments are possible.

That is, since the hydrogel has a porous property, the blood or the reactant can freely move, and the probability of antigen-antibody reaction with the antibody can be increased. In this embodiment, a variety of antibodies or antigens mixed in the hydrogel of the hydrogel pad may be attached in a matrix form to define an antibody or antigen microarray.

In this embodiment, the reaction chamber member 120 is fitted in a hole formed in the transfer channel member 130, and a fluorescence sensor 110 is disposed at a lower portion thereof. Reagent fluid is introduced into the inlet of the reaction chamber member 120 via the transfer channel member 130 and the introduced reagent fluid is filled into the chambers of the reaction chamber member 120, The reagent fluid is discharged via the outlet and the transfer channel member 130. That is, the flow path of reagent and sample fluid is defined through the reagent fluid receiving portion 160, the transfer channel member 130 and the reaction chamber member 120, and the reaction chamber member 120, the transfer channel member 130 ) And the reagent fluid receiving portion 160 define the discharge path of the reagent and the sample fluid. The flow of the inflow path and the flow of the discharge path described above can be performed by the reagent fluid receiving portion 160.

The transfer channel member 130 includes a first hole exposing the reaction chamber member 120 and is disposed above the reaction chamber member 120. The reaction chamber member 120 disposed above the fluorescence sensor 110 is arranged to be exposed by the first hole.

The bottom plate 140 includes a second hole exposing the reaction chamber member 120 exposed by the transfer channel member 130 and is disposed on the transfer channel member 130. The bottom plate 140 has an opening that transmits light of a specific wavelength to the reaction site.

The top plate 150 is spaced apart from the bottom plate 140 and disposed on the bottom plate 140. The top plate 150 and the bottom plate 140 are arranged in parallel. Between the top plate 150 and the bottom plate 140, support rods (not shown) may be disposed to maintain a constant interval between the top plate 150 and the bottom plate 140. The support bars may be fastened to the edge regions of the top plate 150 and the edge regions of the bottom plate 140.

The reagent fluid receiving portion 160 penetrates the hole formed in the top plate 150 and the hole formed in the bottom plate 140 and contacts the transfer channel member 130, The reagent fluid supplied to the reaction chamber member 120 via the member 130 or the reagent fluid for which reaction has been completed in the reaction chamber member 120 is provided via the transfer channel member 130 and is stored. In this embodiment, the reagent fluid receiving portion 160 is composed of six syringes. For example, a first syringe 161 is used for sample delivery. The second syringe 162 and the third syringe 163 are used to store washing buffer. The fourth syringe 164, the fifth syringe 165, and the sixth syringe 166 are used for waste storage. A function of supplying the fluid contained in the reaction chamber member 120 by pressing the plunger of each of the six syringes in a downward direction and performing a function of withdrawing the fluid of the reaction chamber member in such a manner that the plunger is pulled upward .

Although not separately shown, each of the syringes 161, 162, 163, 164, 165, 166 may include a check valve to prevent the reagent from moving in an undesired direction.

As described above, according to the present invention, the reagent fluid receiving portion 160 composed of the syringes is configured to contact the transfer channel member 130 through the second hole formed in the bottom plate 140, The reaction chamber member 120 is disposed below the channel member 130 and the fluorescence sensor 110 is disposed below the reaction chamber member 120. [ As the pusher of the syringe is pushed, the reagent fluid contained in the syringe is supplied to the reaction chamber member 120 via the transfer channel member 130, and the reagent fluid on the transfer channel member 120 Is recovered. Accordingly, reagent fluid such as various kinds of samples or cleaning liquid can be supplied to the reaction chamber member 120 for immunodiagnostic operation through the fluorescence sensor 110 disposed under one reaction chamber member 120 And the reagent fluid can be recovered in the reaction chamber member 120.

Each of the syringes shown in Figs. 1 and 2 can receive a single kind of reagent fluid. Accordingly, for immunodiagnosis, it is necessary to store analytical samples, washing buffer, etc. in each of the plurality of syringes and to discharge different analytical samples and washing buffer at different times.

Hereinafter, a syringe type dispenser capable of sequentially injecting analytical samples or washing buffer in a manner of storing different reagent fluids, for example, analytical samples, washing buffer, and the like, in a single syringe in a sequential manner Explain.

3 is a perspective view schematically illustrating a syringe dispenser employed in an immunoassay diagnostic apparatus according to another embodiment of the present invention. FIG. 4A is a front cross-sectional view of the syringe-type dispenser shown in FIG. 3, FIG. 4B is a cross-sectional view after the pressurization of the syringe-type dispenser shown in FIG. 3, and FIG. 4C is an enlarged view of the area A shown in FIG. .

3 to 4C, the syringe dispenser 10 includes an outer cylinder 11, a plurality of rubber packings 12, a reagent fluid 13, and a needle 14.

The cylinder outer cylinder 11 has a cylinder shape. The cylinder-shaped cylinder outer cylinder 11 includes a closed end and an opened other end. The needle 14 can be inserted into the closed end.

The rubber packings 12 are disposed in the cylinder outer cylinder 11 at a predetermined distance. The rubber packing 12 may comprise a rubber packing. A hole may be formed in the center of the rubber packing in order to facilitate the penetration of the needle 14 in correspondence with the needle 14. Before the penetration of the needle 14, the hole is maintained in a contracted state to block the outflow of the reagent fluid 13, and the needle 14 is extended as it is inserted into the hole, Allow. Accordingly, the reagent fluid 13 can flow out through the needle 14 to the outside.

The reagent fluid 13 is contained in each of the compartments defined by the rubber packings 12 adjacent to each other. In this embodiment, three compartments can be defined by four rubber packings 12.

The needle 14 is inserted into the cylinder outer cylinder 11 from the one end of the cylinder outer tube 11 toward the rubber packing 12 and passes through the corresponding rubber packing 12 as the rubber packing 12 approaches, The reagent fluid 13 is discharged to the outside. In this embodiment, the reagent fluid 13 may include a first cleaning liquid 13a, a reactant 13b including a fluorescent substance, and a second cleaning liquid 13c. Accordingly, the needle 14 can sequentially discharge the first cleaning liquid 13a, the reactant 13b, and the second cleaning liquid 13c to the outside in response to external pressure.

In the present embodiment, the syringe-like dispenser 10 may further include a plunger 15. The plunger 15 is inserted into the cylinder outer cylinder 11 at the other end of the cylinder outer cylinder 11 and connected to the outermost rubber packing.

In this embodiment, the syringe-like dispenser 10 may further include a perimeter member 16. The circumferential member 16 has a length larger than the protruding length of the needle 14 protruding from one end of the cylinder outer cylinder 11 and extends in the longitudinal direction of the cylinder outer cylinder 11 from the cylinder outer cylinder 11. [

Fig. 5 is a schematic diagram for schematically explaining an immunoassay diagnostic apparatus employing the syringe dispenser shown in Fig. 3; Fig.

5, the immunoassay diagnostic apparatus includes a first scanning type dispenser 210, a second scanning type dispenser 220, a third scanning type dispenser 230, a reaction chamber member 250, a fluorescence sensor 260, A first waste outlet 271, a second waste outlet 272, and a third waste outlet 273. In this embodiment, each of the first spiral dispenser 210, the second spiral dispenser 220, and the third spiral dispenser 230 is the scanning type dispenser described in Figs. 3 to 4C. In this embodiment, the first spout dispenser 210, the second spout dispenser 220, the third spout dispenser 230, the reaction chamber member 250, the fluorescence sensor 260, the first waste outlet 271, the second waste outlet 272, and the third waste outlet 273 may be disposed in one cartridge.

Each of the first, second, and third spraying type dispensers 210, 220, and 230 may include a sample such as blood or urine, a first washing liquid, a reactant (fluorescent material) And the second cleaning liquid are received separately from each other. In addition, the blood or urine contained in each of the first, second, and third injecting dispensers 210, 220 and 230 may be samples taken from different people.

The first spiral dispenser 210 is fastened to the first microtubule 261 branched from the reaction chamber member 250. As the first spiral dispenser 210 is pushed by the finger or the mechanical pressing device of the operator, the sample, such as blood or urine, the first washing liquid, the reactant (fluorescent substance), and the sample 2 cleaning liquid is sequentially supplied to the reaction chamber member 250. In this embodiment, the first rinsing liquid or the second rinsing liquid is, for example, BRIJ, TRITON, TWEEN, THESIT, LUBROL, GENAPOL, Nonionic cleaning liquids or surfactant classes known under the trade designation PLURONIC, TETRONIC, and SPAN.

On the inner surface of the reaction chamber member 250, a position-based substance (dendron, hydrogel pad, etc.) that bonds with an antigen or an antibody is attached in a dot-like arrangement in a predetermined row and row arrangement.

FIG. 6A is a plan view for schematically explaining the reaction chamber member 250 shown in FIG. 5, FIG. 6B is a sectional view taken along the line I-I 'of the reaction chamber member 250 shown in FIG. 6A, 6C is a cross-sectional view of the reaction chamber member 250 shown in FIG. 6A cut along the cutting line II-II '.

6A and 6B, the reaction chamber member 250 includes a bottom member 310, a middle member 320 disposed on the bottom member 310 and defining one or more reaction channels 303, And a top member 330 disposed to face the member 310 and sealing the reaction channel except for both ends of each of the reaction channels.

The bottom member 310 may be formed of various materials, but preferably includes polydimethylsiloxane (PDMS), cycle olefin copolymer (COC), polymethylmethacrylate (PMMA) A material selected from the group consisting of polycarbonate (PC), polypropylene carbonate (PPC), polyether sulfone (PES), and polyethylene terephthalate (PET) Lt; / RTI >

In addition, the top surface of the bottom member 310 can be treated with a hydrophilic material (not shown), which allows the immunodiagnostic function to be performed smoothly. A single layer containing a hydrophilic material may be formed on the bottom member 310 by the treatment of the hydrophilic material. The hydrophilic material may be a variety of materials but is preferably selected from the group consisting of a carboxyl group (-COOH), an amine group (-NH2), a hydroxyl group (-OH), and a sulfone group (-SH) The treatment of the hydrophilic material can be carried out according to methods known in the art.

The middle member 320 is disposed on the bottom member 310 to define one or more reaction channels 303. A syringe-type dispenser is connected to one end of the one or more reaction channels 303. Therefore, a sample such as blood or urine, a first washing liquid, a reactant (fluorescent substance), and a second washing liquid are sequentially introduced into at least one reaction channel 303 to proceed with the immunodiagnostic reaction.

The middle member 320 may be made of a variety of materials and is preferably made of polymethylmethacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC), poly Polyamide (PA), polyethylene (PE), polypropylene (PP), polyphenylene ether (PPE), polystyrene (PS), polyoxymethylene Polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutyleneterephthalate (PBT) ), Fluorinated ethylenepropylene (FEP), perfluoralkoxyalkane (PFA), and combinations thereof. Which may be a thermoplastic resin or a thermosetting resin material.

The inner wall of the middle member 320 may be coated with a material such as silane series or bovine serum albumin (BSA) to prevent adsorption of DNA and protein, The treatment can be carried out according to methods known in the art.

The top member 330 is disposed on the middle member 320 to seal the reaction channels except for both ends of each of the reaction channels.

Thus, the top member 330 covers one or more reaction channels 303 formed in the middle member 320.

The top member 330 may be made of a variety of materials, but is preferably made of polydimethylsiloxane (PDMS), cycle olefin copolymer (COC), polymethylmethacrylate (PMMA) ), Polycarbonate (PC), polypropylene carbonate (PPC), polyether sulfone (PES), and polyethylene terephthalate (PET), and combinations thereof. Or the like.

The one or more reaction channels 303 may be formed by a processing method selected from the group consisting of injection molding, hot-embossing, casting, and laser ablation.

In addition, the hydrophilic material on the surface of the bottom member 310 may be treated by a method selected from the group consisting of oxygen and argon plasma treatment, corona discharge treatment, and surfactant application and may be performed according to methods known in the art have.

The lower surface of the top member 330 and the upper surface of the middle member 320 and the lower surface of the middle member 320 and the upper surface of the bottom member 310 are bonded by thermal bonding, And can be carried out according to methods known in the art.

A double-sided adhesive or a thermoplastic resin or a thermosetting resin (not shown) may be treated between the top member 330 and the middle member 320 and between the middle member 320 and the bottom member 310. [

An antibody (AB) or an antigen is disposed in the reaction channel 303 formed in the reaction chamber member 250. The antibody (AB) or antigen is attached to the inner bottom surface of the reaction chamber member (250) so as to be close to the fluorescence sensor (260). Accordingly, the sensor of the fluorescence sensor 260 and the reactant can be positioned closely to each other, thereby enabling sensitive fluorescence detection.

5, the reaction chamber member 250 is fastened to the first screw-type dispenser 210 through the end of the first microtubule 261 and the second microtubule 262 through the end of the second microtubule 262, And is fastened to the spraying type dispenser 220. In addition, the reaction chamber member 250 is fastened to the third screw-type dispenser 230 through the end of the third microtubule 263.

The reaction chamber member 250 is disposed to measure or analyze the analytical signal by bonding or reacting with the analyte present in the sample. When the sample flows into the reaction chamber member 250, the analyte present in the sample is subjected to an enzyme reaction, an immunoreaction, a chemical reaction, a hybridization reaction of DNA or RNA, aggregation and agglutination reactions occur and generate a detection signal by the analyte. The analytical signals can be analyzed by spectroscopic methods such as coloration, luminescence, fluorescence, refractive index change, FRET (fluorescence resonance energy transfer), electrochemical method through oxidation / reduction, a quartz crystal microbalance method or a microcantilever method can be used. The reaction chamber member 250 may further include an enzyme, an antigen, an antibody, a DNA, an RNA, an apatmer, a ligand, a receptor, a receptor, a binding probe, an enzyme substrate, and the like. Since the sample introduced into the reaction chamber member 250 is required to accurately determine the volume of the reaction chamber member 250 as required, various types of electrodes may be introduced into the reaction chamber member 250 to improve the conductivity between the electrodes due to the influx of the sample. The change in the resistance or the resistance is measured electrochemically to quantify the volume of the sample introduced into the reaction chamber member 250 or the reaction chamber member 250 is analyzed spectroscopically when the reaction chamber member 250 is transparent, It is possible to quantify the volume of the sample that has flowed into the apparatus.

The fluorescence sensor 260 disposed on the PCB substrate is disposed on the back surface of the reaction chamber member 250 to measure the chemiluminescence signal generated by the immune reaction in each antibody spot on a pixel-by-pixel basis, The image is taken in a plane for analysis. BACKGROUND OF THE INVENTION Fluorescence lifetime imaging (FLIM) techniques are commonly used to exponentially decay the fluorescence emitted from a fluorescent material. The time constant, which is a characteristic of the material, depends on the surrounding environment of the fluorescent material It is a technique to visualize the change of the time constant measured by using the fact that it is different. At this time, a minute amount of fluorescence can be detected without using an emission filter by applying a method of measuring a time constant.

In general, a fluorescent material generates fluorescence in a longer wavelength band when light of a specific wavelength band according to its intrinsic property is received. At this time, the intensity (n (t)) of the emitted light is characterized by an initial value of n (0) and a time constant exponentially decreasing by τ.

The time constant of the curve, which exponentially decreases with respect to the fluorescence quantities n (T1) and n (T2) measured at different times T1 and T2 after fluorescence is expressed, can be obtained as follows.

The fluorescence emitted as a result of the bioreaction is a fluorescent light with a wavelength longer than that of the excitation light. If you need to detect fluorescence, you need an emission filter that removes the excitation light and passes the fluorescence. On the other hand, if the excitation light does not exist when fluorescence is detected, the emission filter may be omitted.

The first waste outlet 271 is fastened to the fourth microtubule 264 branched from the reaction chamber member 250 and discharges the bioreacted product to the outside.

The second waste outlet 272 is fastened to the fifth microtubule 265 branched from the reaction chamber member 250 and discharges the bioreacted product to the outside.

The third waste outlet 273 is fastened to the sixth microtubule 266 branched from the reaction chamber member 250 and discharges the bioreacted product to the outside.

Meanwhile, the syringe dispenser according to the present invention may be employed in a PCR apparatus for performing PCR (Multiplex Polymerase Chain Reaction) for amplifying various nucleic acids having a specific base sequence.

Specifically, in order to amplify deoxyribonucleic acid (DNA) having a specific nucleotide sequence, a PCR apparatus is constructed by heating a sample solution containing double-stranded DNA at a specific temperature, for example, about 95 ° C, A denaturing step of separating the DNA into DNA of the present invention and an oligonucleotide primer having a sequence complementary to the specific nucleotide sequence to be amplified in the sample solution, Annealing step of annealing the sample solution at an appropriate temperature, for example, 72 DEG C, after the annealing step; cooling the sample solution to 55 DEG C to bond the primer to a specific base sequence of single stranded DNA to form a partial DNA- (DNA polymerase) to form double-stranded DNA on the basis of a primer of a partial DNA-primer complex DNA having a specific nucleotide sequence can be exponentially amplified by performing an extension step and repeating the step 3, for example, 20 to 40 times. In some cases, the PCR apparatus can simultaneously perform the annealing step and the extension (or amplification) step. In this case, the PCR apparatus performs two steps consisting of an extension step and an annealing and extension (or amplification) 1 cycle may be completed. Therefore, the PCR apparatus refers to an apparatus including modules for performing the steps, and it is assumed that the detailed modules not described herein are included in the scope of the prior art for performing the PCR in the range disclosed and obvious .

In addition, the PCR apparatus can perform PCR and simultaneously measure the presence or absence of the PCR product and measure the degree of the occurrence of the PCR product. A fluorescent substance as well as a reagent necessary for the PCR reaction are added to the PCR chip and the fluorescent substance is emitted by the light of the specific wavelength according to the generation of the PCR product to cause the optical signal which can be measured and analyzed.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the invention as defined in the appended claims. You will understand.

110: Fluorescent sensor 120, 250: Reaction chamber member
130: transmission channel member 140: bottom plate
150: top plate 160: fluid reservoir for reagent
10: syringe type dispenser 11: cylinder outer cylinder
12: Rubber packing 13: Reagent fluid
14: Needle 210: First Screwdriver Dispenser
220: second spouting dispenser 230: third spouting dispenser
260: Fluorescence sensor 271: First waste outlet
272: Second Waste Outlet 273: Third Waste Outlet
310: bottom member 320: middle member
330: Top member 261: First microtubule
262: 2nd US Customs House 263: Third US Customs House

Claims (5)

A first scanning die dispenser;
A second scanning die dispenser;
A third scanning die dispenser;
Is connected to the first syringe dispenser through a branched first microtubule, is fastened to the second syringe dispenser through a branched second microtubule, and is connected to the third syringe dispenser through a branched third microtubule, A reaction chamber member attached to the inner surface of the reaction chamber in the form of a dot in which a position-based substance that binds to the antigen or antibody is arranged in a predetermined row and row;
A fluorescence sensor arranged on the back surface of the reaction chamber member for photographing a chemiluminescence signal caused by an immune reaction in each antibody spot on a pixel-by-pixel basis to image a microscopic image into a meaningful value for image analysis in plan view;
A first waste outlet coupled to a fourth microtubule branching from the reaction chamber member and discharging the bioreacted product to the outside;
A second waste outlet coupled to a fifth microtubule branching from the reaction chamber member and discharging the bioreacted product to the outside; And
And a third waste outlet coupled to a sixth microtubule branching from the reaction chamber member and discharging the bioreacted result to the outside. 2. The apparatus of claim 1, wherein each of the first to third scanning type dispensers comprises:
A cylinder-shaped cylinder outer cylinder including a closed end and an opened other end;
A plurality of rubber packings spaced apart from each other by a predetermined distance in the cylinder outer cylinder;
A reagent fluid contained in each of the compartments defined by rubber packs adjacent to each other; And
And a needle inserted into the closed one end portion. A cylinder-shaped cylinder outer cylinder including a closed end and an opened other end;
A plurality of rubber packings spaced apart from each other by a predetermined distance in the cylinder outer cylinder;
A reagent fluid contained in each of the compartments defined by rubber packs adjacent to each other; And
And a needle inserted into the closed one end portion of the syringe dispenser. 4. The syringe dispenser according to claim 3, further comprising a plunger inserted into the cylinder outer cylinder at the other end of the cylinder outer cylinder and connected to the outermost rubber packing. 4. The apparatus according to claim 3, further comprising a circumferential member having a length larger than a protruding length of the needle protruding from one end of the cylinder outer cylinder and extending along the longitudinal direction of the cylinder outer cylinder in the cylinder outer cylinder Syringe dispenser used in analytical diagnostic devices.

Images