WO2015072718A1 - Multi-well cuvette provided with integrated reaction and detection means - Google Patents

Multi-well cuvette provided with integrated reaction and detection means Download PDF

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Publication number
WO2015072718A1
WO2015072718A1 PCT/KR2014/010784 KR2014010784W WO2015072718A1 WO 2015072718 A1 WO2015072718 A1 WO 2015072718A1 KR 2014010784 W KR2014010784 W KR 2014010784W WO 2015072718 A1 WO2015072718 A1 WO 2015072718A1
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WIPO (PCT)
Prior art keywords
sample
chamber
reagent
reaction
cuvette
Prior art date
Application number
PCT/KR2014/010784
Other languages
French (fr)
Korean (ko)
Inventor
김병철
문봉석
이원희
전찬영
Original Assignee
바디텍메드 주식회사
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by 바디텍메드 주식회사 filed Critical 바디텍메드 주식회사
Priority to US15/035,436 priority Critical patent/US10393738B2/en
Priority to ES14862520T priority patent/ES2716909T3/en
Priority to CN201480072072.5A priority patent/CN105874053A/en
Priority to JP2016529971A priority patent/JP6261736B2/en
Priority to EP14862520.5A priority patent/EP3070156B1/en
Priority claimed from KR1020140155885A external-priority patent/KR101661098B1/en
Publication of WO2015072718A1 publication Critical patent/WO2015072718A1/en

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5023Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/16Reagents, handling or storing thereof
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0825Test strips

Definitions

  • the present invention relates to multiwell cuvettes used for the detection and analysis of certain components in a sample, such as a biological sample.
  • the sample and the reagents used for the inspection of the sample are not influenced by external factors, and using the correct amount each time is very important for obtaining accurate and reproducible results.
  • the samples and reagents may be exposed to the outside, so it is necessary to effectively prevent exposure of such samples and reagents and to use the correct amount to ensure the accuracy of the inspection.
  • the detection means for detecting the reaction of the reagent and the sample for each test item and the reaction result thereafter are performed in separate apparatuses, thereby causing frequent misuse such as incorporation between reagents and use of the wrong amount. There was a problem.
  • the test for the detection of the reaction result is carried out in a single apparatus to reduce the test cost, the accuracy of the test as well as the steps included in the test and the cost to be added need.
  • Patent Document 1 Republic of Korea Patent Application 10-2007-7031051
  • the present invention has been made to solve the above-described problems, and it is an object of the present invention to provide a test apparatus capable of performing reaction and detection of a sample and a reagent in one apparatus.
  • the present application provides a multi-well cuvette having an integrated reaction and detection means, the multi-well cuvette according to the present invention, in the multi-well cuvette to examine the reaction between the sample and the reagent, A reaction chamber portion in which a sample and a reagent are placed; And a detector configured to detect a reaction between the sample and the reagent, wherein the reaction chamber includes: a sampling member waiting chamber in which a member for dispensing or dispensing a sample stands by; One or more sample filling chambers; And one or more reagent filling chambers in which a reagent is filled and a reaction with a sample is performed, wherein the detection unit includes a chromatographic analysis means for a reaction product between the sample and the reagent and a detection chamber accommodating the same.
  • the multiwell cuvette includes the collecting member atmospheric chamber, the reagent filling chamber and the detection chamber included therein in order to have at least one row.
  • the chromatographic analysis means includes, but is not limited to, lateral flow analysis means, the lateral flow analysis means is a lateral flow analysis cartridge, the cartridge is a base member; And a cover member engaged with the base member, wherein the base member includes a strip receiving portion for receiving a strip used for the lateral flow analysis and a reaction result well formed at a position extending from one end of the strip receiving portion
  • the cover member may include a measuring window formed in a portion corresponding to the strip receiving portion and an inlet formed in a portion corresponding to the reaction result well when the cover member is filled with the base member, or the base member or the cover member, or
  • the base member and the cover member include a capillary structure for delivering the reaction product to the strip, wherein the capillary structure formed on the cover member is formed on a lower surface adjacent to the inlet of the cover member, The formed capillary structure is formed in the sample well. It will, may further comprise a strip that is accommodated in the strip accommodation portion for analysis.
  • the multiwell cuvette of the present application further comprises a separation unit located at the bottom of the reaction product well of the means for lateral flow analysis.
  • the separating part is used to separate impurities contained in the reaction product, for example, including a magnet part.
  • the magnet part is composed of a magnet holder and a space in which the magnet is inserted, and is used to remove impurities contained in the sample to be analyzed.
  • the collecting member atmospheric chamber and the reagent filling chamber included in the multi-well cuvette of the present application includes an open portion formed at an upper portion thereof so that inspection equipment having a predetermined tip may be introduced.
  • two or more sample filling chambers and / or reagent filling chambers of the multiwellcuvet herein may be formed, and when two or more are filled, each chamber contains the same or different samples and reagents. can do.
  • the multi-well cuvette of the present application may further comprise a first cover covering the top surface of the reagent filling chamber.
  • the first cover has a thin film structure such that inspection equipment having a predetermined tip penetrates through at least a portion thereof.
  • the multi-well cuvette of the present invention may include a second cover that covers all or part of the upper surface of the multi-cube, and in one embodiment, the cover is used with the cover mounted.
  • Meltiwell cuvettes according to the present disclosure further comprise a barcode in any position of the second cover in one embodiment.
  • the inspection can be made with only a quick and simple operation as well as accuracy. That is, a sample filled in the sample filling chamber is collected by using a collecting member in the collecting member chamber by using a predetermined test equipment, and then reacted with the reagent filled in the reagent filling chamber. Then, specific components included in the reaction product are quantitatively and / or qualitatively analyzed by chromatographic methods.
  • All of these inspections are carried out on one multiwell cuvette including the configuration formed integrally and sequentially arranged in one direction, and when used with the inspection equipment, the inspection is carried out by displacing the cuvette on a straight line. Can be done.
  • the collecting member atmospheric chamber, the reagent filling chamber, and the detection chamber are sequentially disposed, the sampling, the mixing of the reagent and the sample, the reaction between the reagent and the sample, and the detection of the reaction result may be sequentially performed.
  • the positional change of the inspection equipment may be simply made in one direction.
  • the structure of the inspection equipment is simple and the inspection through this can also be made easily and quickly.
  • the multiwell cuvette according to the present invention has a structure in which the collecting member atmospheric chamber, the reagent filling chamber, and the detection chamber are integrally formed and arranged in one direction so that the structure of the manufacturing apparatus used for manufacturing is simple. It can be simplified and the manufacturing cost can be reduced.
  • the reagent chamber and the detection chamber are integrated, and in the case of the conventional chromatography test, the reagent and the detection cartridge are separately supplied for each test item. This overcomes the disadvantages of frequent misuse, such as mixing between reagents or using the wrong amount.
  • FIG. 1 is a perspective view schematically showing a multiwell cuvette according to an embodiment of the present invention.
  • FIG. 2 is an exploded perspective view schematically showing a multiwell cuvette according to an embodiment of the present invention.
  • FIG. 3 is a diagram illustrating a process of performing a test using a multiwell cuvette according to an embodiment of the present invention.
  • Figure 4 is an exploded perspective view schematically showing a cartridge for lateral flow analysis included in the multi-well cuvette according to an embodiment of the present invention.
  • 5A is a perspective view schematically illustrating a multiwell cuvette including a second cover according to an embodiment of the present invention.
  • FIG. 5B is a perspective view schematically illustrating a multiwell cuvette with the second cover of FIG. 5A partially removed.
  • FIG. 6 is a cross-sectional view taken along line AA ′ of FIG. 5A.
  • each member is exaggerated, omitted, or schematically illustrated for convenience and clarity of description.
  • the size and area of each component does not necessarily reflect the actual size or area.
  • FIG. 1 is a perspective view of an integrated multiwell cuvette 1 according to one embodiment of the invention
  • FIG. 2 is an exploded perspective view of an integrated multiwell cuvette 1 of the present invention.
  • Cuvettes according to the invention are used for the detection and / or analysis of analytes contained in a sample.
  • sample refers to an analyte or composition that includes an analyte
  • a sample that may be used in the present invention is a liquid phase or liquid like material.
  • the sample is a biological sample, and may be a body-derived body component such as whole blood, plasma, serum, urine, saliva, manure and cell extracts.
  • analyte is a compound of interest in a sample, also referred to as a target, that includes proteins and nucleic acids. Proteins herein include polypeptides and peptides.
  • nucleic acid herein also includes chemical synthetic DNA and RNA, including genome DNA, cDNA and oligonucleotides. In addition, the nucleic acid includes single- or double-stranded, genome DNA, cDNA and oligonucleotides and RNA can be prepared or synthesized according to methods known in the art.
  • a protein in a sample for example, high sensitivity C-reactive protein (hsCRP), MicroCRP, HbA1c (glycosylated hemoglobin), microalbumin, PSA (prostate specific antigen), AFP (Alpha-fetoprotein), cTnI (Cardiac) Used to detect Troponin I).
  • hsCRP high sensitivity C-reactive protein
  • MicroCRP MicroCRP
  • HbA1c glycoslated hemoglobin
  • microalbumin for example, high sensitivity C-reactive protein (hsCRP), MicroCRP, HbA1c (glycosylated hemoglobin), microalbumin, PSA (prostate specific antigen), AFP (Alpha-fetoprotein), cTnI (Cardiac) Used to detect Troponin I).
  • PSA prostate specific antigen
  • AFP Alpha-fetoprotein
  • cTnI Cardiac
  • Reagents herein are materials suitable for the detection and analysis of the analytes described above, depending on the specific analyte, for example, the reagents may be any antibody or the like that reacts with various substances in the body component, eg, antigens, and the like. It is not limited to this.
  • the reaction chamber unit 100 for receiving a sample and a reagent; And a detection unit 200 for detecting a reaction between the sample and the reagent
  • the chamber unit 100 includes: a collecting member waiting chamber 110 in which a member for dispensing or dispensing the sample stands by; A sample filling chamber 120 and a reagent filling chamber, and a reagent filling chamber 130 in which a reaction between the sample and the reagent is performed, wherein the detection unit is chromatographic analysis of the reaction product between the sample and the reagent.
  • Means for detection and detection chamber 210 containing the same.
  • the reaction chamber part 100 included in the multiwell cuvette 1 according to the present invention is configured to have a plurality of chambers for accommodating various samples used for the test and predetermined reagents reacting with the samples. Accordingly, the chamber part 100 may have a structure having a barrier for preventing unnecessary mixing between reagents and samples by separating the plurality of wells and the wells. That is, the reaction chamber part 100 may have a predetermined multi-well structure.
  • the chamber formed in the reaction chamber unit 100 may be a plurality, the number is not limited.
  • the reaction chamber unit 100 includes a collecting member atmospheric chamber 110 for dispensing or dispensing a sample, a sample filling chamber 120 for receiving a sample, and a reagent filling chamber 130 for filling a reagent.
  • a collecting member atmospheric chamber 110 for dispensing or dispensing a sample a sample filling chamber 120 for receiving a sample
  • a reagent filling chamber 130 for filling a reagent can be configured.
  • the sampling member atmospheric chamber 110 and the sample filling chamber 120 and the reagent filling chamber 130 in which the sample is filled are configured in a well structure separated by a predetermined barrier, respectively, so that the collecting member atmospheric chamber is formed.
  • the reagent filling chamber 120 and the reagent filling chamber 130 may have a structure that prevents unnecessary mixing of the reagent and the sample.
  • the reagent filling chamber 130 may include a reagent suitable for detection and / or analysis thereof according to the type of analyte, and when a sample is introduced from the sample filling chamber 120, a reaction between the sample and the reagent introduced in the reagent filling chamber is performed. This is done.
  • the reagent filling chamber 130 may be formed in plural to be filled with the same or different types of samples and reagents, respectively, but in the case of a plurality of reagent filling chambers, not all of the reagent filling chambers should include reagents, only a part of them. Of course, it can also be used.
  • One embodiment according to the present invention includes, but is not limited to, the first reagent filling chamber 130 and the second reagent filling chamber 132.
  • the detection unit 200 includes a detection chamber 210 including chromatographic analysis means suitable for chromatographic analysis of the reaction product between the sample and the reagent performed in the reaction chamber unit 100.
  • the detection unit 200 may include a means suitable for chromatographic analysis of reactants, for example, lateral flow analysis.
  • the detection chamber 210 may comprise a cartridge, for example for a lateral flow assay.
  • Lateral flow analysis is a method of quantitatively or qualitatively examining a target analyte, eg, a particular nucleic acid or protein, contained in a sample, e.g., an oligonucleotide or a specific antibody and / or antigen that hybridizes to a nucleic acid of a constant sequence.
  • a chromatographic method comprising a nitrocellulose membrane (development medium) called strip 20 bound to a specific position is used to transfer the analyte in the reaction product to identify the sample in the sample through sequence specific hybridization or antigen antibody reactions. It is a method for detecting a nucleic acid or protein.
  • a target analyte eg, a particular nucleic acid or protein
  • a sample e.g., an oligonucleotide or a specific antibody and / or antigen that hybridizes to a nucleic acid of a constant sequence.
  • a chromatographic method comprising a nitrocellulose membrane (development medium
  • the detection chamber 210 comprises a cartridge suitable for lateral flow analysis, the cartridge comprising: a strip receiving portion for receiving a strip comprising a development medium; And a base member formed on one end side of the strip receiving portion in a position extending from the strip receiving portion, and formed with a well for receiving a reaction product of the reaction chamber portion, and a cover member engaged with the base member.
  • a cartridge suitable for lateral flow analysis the cartridge comprising: a strip receiving portion for receiving a strip comprising a development medium; And a base member formed on one end side of the strip receiving portion in a position extending from the strip receiving portion, and formed with a well for receiving a reaction product of the reaction chamber portion, and a cover member engaged with the base member.
  • the detection chamber according to the present application is a chromatographic analysis means of the reaction result, and includes a cartridge for lateral flow analysis as disclosed in, for example, Korean Patent Publication No. 2011-0046833 or FIG. 4.
  • the cartridge 220 is installed in the detection chamber 210 and includes a cover member 30 and a base member 10.
  • the reaction product is introduced into the well 12 through the inlet 32, and the triangular capillary structures 35 and 37 and the base member are formed on the lower surface of the cover member to transfer the reaction product from the well to the strip 20.
  • the corresponding structure is formed.
  • the lateral flow analysis cartridge included in the cuvette of the present application includes a base member 10; And a cover member 30 engaged with the base member, the base member having a strip receiving portion 18 for receiving a strip used for the lateral flow analysis, and a position extending from one end of the strip receiving portion.
  • a sample well 12 formed in the cover member wherein the cover member includes a measurement window 34 and a sample well for detecting a reaction result formed at a portion corresponding to the strip accommodating portion when the base member is filled with the base member.
  • a sample inlet 32 formed in a corresponding portion may be included, and if necessary, an air window 38 may be further included.
  • the base member or the cover member, or the base member and the cover member includes capillary structures 35 and 37, wherein the capillary structure formed on the cover member is formed on a lower surface adjacent to the sample inlet of the cover member, The capillary structure formed on the base member is formed in the sample well.
  • the sample inlet 32 is formed to be perpendicular to the well containing the reaction product. Covering the cover member 30 on the base member is interlocked with each other at its interface via a fastening means including a locking jaw and an uneven protrusion 16, thereby substantially waterproof and aerosol proof. ) It becomes a seal.
  • the strip receptacle also includes a guide for receiving a plurality of strips to prevent the mounted strip from shaking and to position the strip in a fixed position.
  • the reaction product introduced into the inlet 32 is moved to the strip 20 through various methods.
  • the lateral flow cartridge may have a predetermined microchannel structure formed between the well formed at a position perpendicular to the inlet and the strip receiving portion 18, and through the capillary phenomenon, the reaction product of the well is transferred to the strip.
  • lateral flow is disclosed, but not limited thereto.
  • one end of the strip is in direct contact with the well to absorb a liquid sample into the strip to initiate lateral flow, but is not limited thereto.
  • the multi-well cuvette according to the present invention may further include a magnet part 138 located at the bottom of the well containing the reaction product constituting the lateral flow cartridge.
  • the magnet part is composed of a magnet 140 and a well 142 for accommodating the magnet 140.
  • the magnet is for removing impurities contained in the reaction product to be analyzed.
  • the reagent filling chamber 130 includes a magnetic bead, and an antibody capable of specifically binding to impurities to be removed is bound to the magnetic bead.
  • impurities may include red blood cells contained in whole blood, and after reaction with samples and reagents, reaction products may include magnetic beads capable of reacting with a magnet and antibodies specific to impurities bound to the magnetic beads, such as red blood cells.
  • the cuvette 1 according to the present disclosure may further include a second cover 136.
  • the second cover 136 covers the upper end of the cuvette and covers all or part of the reaction chamber 100 and the detection unit 200 to identify and protect the surface of the product.
  • a first cover 134 covering the first reagent filling chamber and the second reagent filling chamber is located below the second cover.
  • the second cover is provided for dispensing or collecting the liquid sample provided in the equipment used with the cuvette according to the present application, for example, for entering or exiting the tip T or reading the detection result (in the case of a measuring window).
  • the sample filling chamber 120 corresponds to the sample inlet 32 and the measurement window 34 formed in the collecting member atmospheric chamber 110, the sample filling chamber 120, the first reagent filling chamber 132, the second reagent filling chamber 132, and the cartridge.
  • a hole of appropriate shape is formed in each of the corresponding parts.
  • the second cover can be peeled off if necessary as shown in FIG. 5B, but is normally used in a state in which the second cover is present.
  • the second cover may further include a barcode 400 at any position thereof.
  • Meltiwell cuvettes according to the present application are used in conjunction with certain inspection equipment as described below, such as automated equipment in which the dispensing of a sample, the reaction between a sample and a reagent, and the detection of a reaction result are performed automatically in one equipment.
  • the material or sample to be measured or analyzed by using a multi-well cuvette is made to match the ID chip inserted into the predetermined inspection equipment, and the ID chip contains information of the material to be measured and quantification thereof accordingly. Standard curve information, and information on error processing when the range is out of range are stored.
  • Cartridges mounted and used in the cuvette according to the present application may be manufactured in various sizes and shapes suitable for mounting and use in the detection chamber 210, may be manufactured in a rectangular shape and such a rectangle of the cuvette according to the present application It can be used in a variety of measuring equipment (readers) that can accommodate cartridges in the form, and can be made from chemically stable synthetic resins and combinations thereof.
  • readers measuring equipment
  • the multiwell cuvette 1 includes a collecting member atmospheric chamber 110, a sample filling chamber 120, a reagent filling chamber 130, 132, and a detection chamber 210. It is formed integrally on the multiwell cuvette 1, and are sequentially arranged in one direction to form heat.
  • a plurality of rows formed by the collecting member atmospheric chamber 110, the reagent filling chamber 130, and the detection chamber 210 may be plural, but is not limited thereto.
  • the multiwell cuvette 1 according to the invention having the structure as described above can be used with certain inspection equipment.
  • the test equipment may be an automated equipment in which a dispensing of a sample, a reaction between a sample and a reagent, and detection of a reaction result are automatically performed in one equipment.
  • the inspection when the inspection is performed using the multi-well cuvette 1 according to the present invention, the inspection can be made faster and simpler operation with only a linear displacement.
  • the reaction filling chamber including the reaction reagent is integrally structured in the detecting means, a separate reagent container is not required, thereby reducing the probability of erroneous inspection due to confusion of reagents during a plurality of different tests.
  • this feature allows the detection of various analytes without separate reagent replacement in one instrument.
  • the collecting member atmospheric chamber 110, the sample filling chamber 120, the reagent filling chamber 130, and the detection chamber 210 are integrally formed in one direction. Since the structure of the arrangement is simple, the structure of the manufacturing apparatus used for manufacturing is simplified and the manufacturing cost can be reduced.
  • the cuvettes according to the present application are used for single use and include the following disposable microtips (e.g. 2-1000 ⁇ l micropipette tips) used in practice and with means for dispensing reagents and dispensing, thus providing a separate reagent supply device and contamination. Can be used with equipment that does not have a means to clean the equipment, simplifying the operation of the equipment.
  • disposable microtips e.g. 2-1000 ⁇ l micropipette tips
  • the predetermined test equipment is an automated equipment in which the distribution of a sample and a reaction result and the detection of an analyte in the reaction result may be automated.
  • the automated equipment may include a means for distributing or dispensing a sample and a reaction result.
  • Dispensing or dispensing means included in the inspection equipment is the collecting member atmospheric chamber 110, the sample filling chamber 120, the reagent filling chamber 130 and the cartridge 230 of the detection unit 200 of the cuvette (1) according to the present application It is movable on the X axis along the inlet 32 formed in the inlet, and includes an arm equipped with a pump for suction and discharge of the liquid material for dispensing or dispensing a sample, a reagent, or a reaction product.
  • the end of the tip is formed.
  • the tip is inserted into a harvesting member, eg, 10 ⁇ l, 100 ⁇ l, 200 ⁇ l, or 500 ⁇ l volume microtip, located in the harvesting member atmospheric chamber 110, for use in dispensing and / or dispensing samples, reagents, and / or reaction products.
  • the collecting member standby chamber 110 is formed so that the upper portion is opened so that the inspection equipment having a predetermined tip is input as described above to collect a sample. That is, open portions 112 and 114 may be formed on the upper surfaces of the collecting member atmospheric chamber 110 and the sample filling chamber 120 to allow the tip to be introduced.
  • the microtips may be mounted through the openings 112 and 114 and a predetermined sample may be dispensed.
  • the multiwell cuvette 1 may include a cover covering the reagent filling chamber 130 and the upper surface of the detection chamber 210.
  • the cover covers at least a portion of the reagent filling chamber 130 and the detection chamber 210 and at least partially isolates the inner space covered by the cover to the outside. Accordingly, the reagent filled in the reagent filling chamber 130 and the mixture of the reagent and the sample placed in the detection chamber 210 may be prevented from being altered or inadvertently reacted by an external environment, thereby improving test reliability. Can be.
  • a first cover 134 is disposed on the reagent filling chamber 130, and the first cover 134 has a thin film structure so that inspection equipment having a predetermined tip penetrates at least a portion thereof. It can have That is, a first cover 134 having a thin thin film structure is disposed on the reagent filling chamber 130, and the first cover 134 is drilled by a tip equipped with a sampling member provided in the inspection equipment, and the collecting member is disposed. It may have a configuration that can be penetrated with a tip.
  • the first cover 134 may be a thin film made of a metal such as aluminum, or a thin film made of a synthetic resin such as plastic, but is not limited thereto.
  • connection jig 300 may be provided at one end.
  • the connecting jig 300 is disposed at one end of the multi-well cuvette 1 according to the present invention, and may be provided at one end in the longitudinal direction as shown in FIG. 1, but is not limited thereto. Can be placed in.
  • connection jig 300 As the connecting jig 300 is provided, replacement or disposal may be easily performed after the inspection is performed using the multi-well cuvette 1 according to the present invention. That is, an easy inspection can be performed by detachably connecting the multiwell cuvette 1 according to the present invention to the predetermined inspection apparatus using the connection jig 300.
  • FIG 3 is a view showing performing a predetermined test using the multi-well cuvette 1 according to the present invention.
  • the tip T provided in the predetermined inspection equipment S mounts the micro tip of the collecting member atmospheric chamber 110 through the open part 112, and then moves to the X axis, so that the sample as shown in (A). Take a sample filled in the filling chamber.
  • the inspection equipment (S) is moved as shown in (B) to dispense a sample into the reagent filling chamber 130 to react the reagent with the sample.
  • the collected sample is administered in the reagent filling chamber 130 to react.
  • the reaction product of the reactant and the sample is administered to the detection chamber 210 through an inlet.
  • the detection chamber 210 may be provided with a cartridge having a strip 20 for lateral flow as described above, the analysis result in the chromatography is detected through the reader of the equipment (S) through the measurement window .

Abstract

The present application discloses a multi-well cuvette for integrating the reaction between a sample and a reagent with the detection of a specific analyte included therein, and the multi-well cuvette comprises: a reaction chamber part having a sample and a reagent placed therein; and a detection part for detecting the reaction between the sample and the reagent, wherein the reaction chamber part comprises: an extraction member standby chamber in which a member for dividing or distributing the sample is on standby; a sample filling chamber; and a reagent filling chamber which is filled with the reagent, and in which the reaction with the sample is carried out, wherein the detection part comprises: a chromatography analysis means for a reactive product between the sample and the reagent; and a detection chamber for accommodating the same.

Description

일체화된 반응 및 검출 수단을 구비하는 멀티웰 큐베트Multiwell cuvettes with integrated reaction and detection means
본 발명은 생물학적 시료와 같은 시료 중 특정 성분의 검출 및 분석에 사용되는 멀티웰 큐베트에 관한 것이다.The present invention relates to multiwell cuvettes used for the detection and analysis of certain components in a sample, such as a biological sample.
의학 및 각종 관련 기술의 발전에 따라서, 혈액 등과 같은 소정의 생물학적 시료에 포함된 혈구, 핵산, 단백질 및 항원 등과 같은 물질의 검사가 이루어지고 있다. 상기와 같은 시료를 채취한 후, 채취된 시료를 소정의 시약과 반응시킨 후 일어나는 변화를 분석 관찰함으로써, 시료에 포함된 다양한 물질 존재 유무, 비율, 및 분량 등의 검사가 이루어질 수 있으며, 이에 따라서 질병의 유무, 질환의 상태 등에 관한 정보를 수득할 수 있다. With the development of medicine and various related technologies, the testing of substances such as blood cells, nucleic acids, proteins and antigens contained in certain biological samples such as blood and the like has been made. After taking the sample as described above, by analyzing and observing the change that occurs after reacting the sample with a predetermined reagent, the presence or absence of various substances contained in the sample, the ratio, and the amount can be examined, accordingly Information on the presence or absence of a disease, the condition of the disease, and the like can be obtained.
이러한 시료의 검사 과정에서는 상기 시료 및 시료의 검사에 사용되는 시약이 외부 요인에 영향을 받지 않으며, 매회 정확한 양을 사용하는 것이 재현성 있는 정확한 결과의 수득에 매우 중요하다. 검사 과정에서, 상기 시료 및 시약은 외부에 노출될 수 있으므로, 이러한 시료 및 시약의 노출을 효과적으로 방지하고, 정확한 양을 사용하여 검사의 정확도를 확보할 필요가 있다.In the inspection of such a sample, the sample and the reagents used for the inspection of the sample are not influenced by external factors, and using the correct amount each time is very important for obtaining accurate and reproducible results. In the course of inspection, the samples and reagents may be exposed to the outside, so it is necessary to effectively prevent exposure of such samples and reagents and to use the correct amount to ensure the accuracy of the inspection.
또한 종래 검사의 경우 검사항목별 시약과 시료의 반응 및 그 이후 반응 결과의 검출을 위한 검출용 수단이 각각 별개의 기구에서 수행되어, 이로 인한 시약 간에 혼입, 잘못된 양의 사용 등과 같은 빈번한 오사용의 문제점이 있었다. In addition, in the case of the conventional test, the detection means for detecting the reaction of the reagent and the sample for each test item and the reaction result thereafter are performed in separate apparatuses, thereby causing frequent misuse such as incorporation between reagents and use of the wrong amount. There was a problem.
따라서, 상기 시약과 시료의 반응 후, 반응 결과물의 검출을 위한 검사가 하나의 기구에서 이루어지도록 하여 검사 비용을 절감하여, 검사의 정확성은 물론 검사 전반에 포함되는 단계 및 투입되는 비용을 절감시키는 것도 필요하다.Therefore, after the reaction between the reagent and the sample, the test for the detection of the reaction result is carried out in a single apparatus to reduce the test cost, the accuracy of the test as well as the steps included in the test and the cost to be added need.
[선행기술문헌][Preceding technical literature]
[특허문헌][Patent Documents]
(특허문헌 1) 대한민국 특허출원 10-2007-7031051(Patent Document 1) Republic of Korea Patent Application 10-2007-7031051
본 발명은 전술한 문제점을 해결하기 위해 안출된 것으로서, 시료와 시약의 반응 및 검출이 하나의 기구에서 수행가능한 검사용 기구를 제공하고자 한다.SUMMARY OF THE INVENTION The present invention has been made to solve the above-described problems, and it is an object of the present invention to provide a test apparatus capable of performing reaction and detection of a sample and a reagent in one apparatus.
상술한 목적을 달성하기 위하여, 본원은 일체화된 반응 및 검출 수단을 구비하는 멀티웰 큐베트를 제공하며, 본원에 따른 멀티웰 큐베트는, 시료와 시약 간의 반응을 검사하는 멀티웰 큐베트에 있어서, 시료와 시약이 놓이는 반응 챔버부; 및 상기 시료와 시약 간의 반응이 검출되는 검출부;를 포함하되, 상기 반응 챔버부는,시료의 분주 또는 분배를 위한 부재가 대기하는 채취부재 대기 챔버; 하나 이상의 시료 충진 챔버; 및 시약이 충진되고, 시료와의 반응이 수행되는 하나 이상의 시약 충진 챔버;를 포함하고, 상기 검출부는, 상기 시료와 시약간의 반응 결과물에 대한 크로마토그래피 분석용 수단 및 이를 수용하는 검출 챔버를 포함한다. In order to achieve the above object, the present application provides a multi-well cuvette having an integrated reaction and detection means, the multi-well cuvette according to the present invention, in the multi-well cuvette to examine the reaction between the sample and the reagent, A reaction chamber portion in which a sample and a reagent are placed; And a detector configured to detect a reaction between the sample and the reagent, wherein the reaction chamber includes: a sampling member waiting chamber in which a member for dispensing or dispensing a sample stands by; One or more sample filling chambers; And one or more reagent filling chambers in which a reagent is filled and a reaction with a sample is performed, wherein the detection unit includes a chromatographic analysis means for a reaction product between the sample and the reagent and a detection chamber accommodating the same. .
본원에 따른 일 구현예에서 멀티웰 큐베트는 이에 포함된 상기 채취부재 대기 챔버, 시약 충진 챔버 및 검출 챔버는 일 방향으로 순차적으로 배치되어 적어도 하나의 열을 갖는다. In one embodiment according to the present invention, the multiwell cuvette includes the collecting member atmospheric chamber, the reagent filling chamber and the detection chamber included therein in order to have at least one row.
본원에 따른 일 구현예에서 상기 크로마토그래피 분석용 수단은 측방유동분석용 수단을 포함하나 이로 제한하는 것은 아니며, 상기 측방유동분석용 수단은 측방유동 분석용 카트리지로 상기 카트리지는 베이스 부재; 및 상기 베이스 부재와 채결되는 커버 부재를 포함하고, 상기 베이스 부재는, 상기 측방유동 분석에 사용되는 스트립을 수용하는 스트립 수용부 및 상기 스트립 수용부의 일 말단으로부터 연장되는 위치에 형성된 반응 결과물 웰을 포함하고, 상기 커버 부재는 상기 베이스 부재와 채결시, 상기 스트립 수용부와 대응되는 부분에 형성된 측정창 및 상기 반응 결과물 웰과 대응되는 부분에 형성된 투입구를 포함하고, 상기 베이스 부재 또는 상기 커버 부재, 또는 상기 베이스 부재 및 상기 커버 부재는 상기 반응 결과물을 상기 스트립으로의 전달을 위한 모세관 구조물을 포함하며, 상기 커버 부재에 형성된 모세관 구조물은 상기 커버 부재의 상기 투입구와 인접한 하면에 형성되고, 상기 베이스 부재에 형성된 모세관 구조물은 상기 시료용 웰에 형성되는 것이며, 분석을 위해 상기 스트립 수용부에 수용되는 스트립을 추가로 포함할 수 있다. In one embodiment according to the present invention, the chromatographic analysis means includes, but is not limited to, lateral flow analysis means, the lateral flow analysis means is a lateral flow analysis cartridge, the cartridge is a base member; And a cover member engaged with the base member, wherein the base member includes a strip receiving portion for receiving a strip used for the lateral flow analysis and a reaction result well formed at a position extending from one end of the strip receiving portion The cover member may include a measuring window formed in a portion corresponding to the strip receiving portion and an inlet formed in a portion corresponding to the reaction result well when the cover member is filled with the base member, or the base member or the cover member, or The base member and the cover member include a capillary structure for delivering the reaction product to the strip, wherein the capillary structure formed on the cover member is formed on a lower surface adjacent to the inlet of the cover member, The formed capillary structure is formed in the sample well. It will, may further comprise a strip that is accommodated in the strip accommodation portion for analysis.
본원에 따른 일 구현에서, 본원의 멀티웰 큐베트는 측방유동분석용 수단의 상기 반응결과물 웰의 하부에 위치하는 분리부를 추가로 포함한다. 분리부는 반응결과물 중에 포함된 불순물을 분리하기 위한 것으로 예를 들면 자석부를 포함하며, 자석부는 자석과 자석이 들어가는 공간이 자석홀더로 구성되며, 분석되는 시료에 포함된 불순물의 제거에 사용된다. In one embodiment according to the present application, the multiwell cuvette of the present application further comprises a separation unit located at the bottom of the reaction product well of the means for lateral flow analysis. The separating part is used to separate impurities contained in the reaction product, for example, including a magnet part. The magnet part is composed of a magnet holder and a space in which the magnet is inserted, and is used to remove impurities contained in the sample to be analyzed.
본원에 따른 일 구현예에서 본원의 멀티웰큐베트에 포함되는 채취부재 대기 챔버 및 상기 시약 충진 챔버는 소정의 팁을 갖는 검사 장비가 투입될 수 있도록 상부에 형성된 오픈부를 포함한다. In one embodiment according to the present application, the collecting member atmospheric chamber and the reagent filling chamber included in the multi-well cuvette of the present application includes an open portion formed at an upper portion thereof so that inspection equipment having a predetermined tip may be introduced.
본원에 따른 일 구현예에서 본원의 멀티웰큐베트의 시료 충진 챔버 및/또는 시약 충진 챔버는 두 개 이상 형성될 수 있으며, 두 개 이상 충진되는 경우, 각각의 챔버는 동일 또는 상이한 시료 및 시약을 포함할 수 있다. In one embodiment according to the present application, two or more sample filling chambers and / or reagent filling chambers of the multiwellcuvet herein may be formed, and when two or more are filled, each chamber contains the same or different samples and reagents. can do.
본원에 따른 일 구현예에서 본원의 멀티웰큐베트는 시약 충진 챔버의 상면를 덮는 제 1 커버를 더 포함할 수 있다. 일 구현예에서, 제 1 커버는, 소정의 팁을 갖는 검사 장비가 적어도 일부분을 뚫고 침투되도록 얇은 박막 구조를 갖는다. In one embodiment according to the present application the multi-well cuvette of the present application may further comprise a first cover covering the top surface of the reagent filling chamber. In one embodiment, the first cover has a thin film structure such that inspection equipment having a predetermined tip penetrates through at least a portion thereof.
나아가 본원에 따른 일 구현예에서 본원의 멀티웰큐베트는 멀티상기 큐베트는 그 상면의 전부 또는 일부를 커버하는 제 2 커버를 포함할 수 있으며 일 구현예에서는 커버가 장착된 상태로 사용된다.Furthermore, in one embodiment according to the present application, the multi-well cuvette of the present invention may include a second cover that covers all or part of the upper surface of the multi-cube, and in one embodiment, the cover is used with the cover mounted.
본원에 따른 멜티웰 큐베트는 일구현에서 제2 커버의 임의의 위치에 바코드를 추가로 포함한다. Meltiwell cuvettes according to the present disclosure further comprise a barcode in any position of the second cover in one embodiment.
본 발명에 따른 멀티웰 큐베트를 이용하여 시료 중에 포함된 특정 성분의 검출 및 분석을 수행하는 경우, 정확성은 물론 보다 신속하고 간단한 동작만으로 검사가 이루어질 수 있다. 즉, 소정의 검사 장비를 이용하여 채취부재 챔버 내의 채취부재를 이용하여, 시료 충진 챔버에 충진된 시료를 채취한 후 이를 시약 충진 챔버 내에 충진된 시약과 반응시킨 후 검출 챔버에 상기 반응 결과물을 분주하여, 상기 반응 결과물에 포함된 특정 성분을 크로마토그래피 방법으로 정량 및/또는 정성 분석한다. When performing the detection and analysis of the specific components contained in the sample using the multi-well cuvette according to the present invention, the inspection can be made with only a quick and simple operation as well as accuracy. That is, a sample filled in the sample filling chamber is collected by using a collecting member in the collecting member chamber by using a predetermined test equipment, and then reacted with the reagent filled in the reagent filling chamber. Then, specific components included in the reaction product are quantitatively and / or qualitatively analyzed by chromatographic methods.
이러한 검사의 모든 과정은 일체로 형성되고 일 방향으로 순차적으로 배치된 상기 구성을 포함하는 하나의 멀티웰 큐베트 상에 수행되며, 검사 장비와 함께 사용되는 경우, 큐베트를 직선상에서 변위시킴으로써 검사가 이루어질 수 있다. All of these inspections are carried out on one multiwell cuvette including the configuration formed integrally and sequentially arranged in one direction, and when used with the inspection equipment, the inspection is carried out by displacing the cuvette on a straight line. Can be done.
아울러, 채취부재 대기 챔버와 시약 충진 챔버 및 검출 챔버는 순차적으로 배치됨에 따라서, 시료의 채취, 시약과 시료의 혼합, 시약과 시료 사이의 반응 미 및 반응 결과물의 검출이 순차적으로 이루어질 수 있으므로, 검사 과정에서 검사 장비의 위치 변화가 단순히 일 방향으로 이루어질 수 있다. In addition, as the collecting member atmospheric chamber, the reagent filling chamber, and the detection chamber are sequentially disposed, the sampling, the mixing of the reagent and the sample, the reaction between the reagent and the sample, and the detection of the reaction result may be sequentially performed. In the process, the positional change of the inspection equipment may be simply made in one direction.
따라서 본 발명에 따른 멀티웰 큐베트를 이용하여 검사를 수행할 경우, 검사 장비의 구조가 간단해지고 아울러 이를 통한 검사 또한 간편하고 신속하게 이루어질 수 있다.Therefore, when performing the inspection using the multi-well cuvette according to the present invention, the structure of the inspection equipment is simple and the inspection through this can also be made easily and quickly.
아울러, 본 발명에 따른 멀티웰 큐베트는 채취부재 대기 챔버와 시약 충진 챔버 및 검출 챔버가 일체로 형성되되 일 방향 일렬로 배치된 구조를 가지므로 그 구조가 간단하여 제조에 사용되는 제조 장치의 구조가 간단해지며 제조 단가가 절감될 수 있다.In addition, the multiwell cuvette according to the present invention has a structure in which the collecting member atmospheric chamber, the reagent filling chamber, and the detection chamber are integrally formed and arranged in one direction so that the structure of the manufacturing apparatus used for manufacturing is simple. It can be simplified and the manufacturing cost can be reduced.
또한 본 발명에 따른 멀티웰 큐베트를 이용하여 검사를 수행하는 경우 시약용 챔버와 검출 챔버가 일체화되어 있어, 종래의 크로마토그래피 검사의 경우 검사항목 마다 시약과 검출용 카트리지가 각각 분리되어 공급되어, 이로 인해 시약 간에 혼입 사용되거나 잘못된 양을 사용하는 등의 빈번한 오사용 단점을 극복할 수 있다.In addition, when the test is performed using the multi-well cuvette according to the present invention, the reagent chamber and the detection chamber are integrated, and in the case of the conventional chromatography test, the reagent and the detection cartridge are separately supplied for each test item. This overcomes the disadvantages of frequent misuse, such as mixing between reagents or using the wrong amount.
도 1 은 본 발명의 일 구현예에 따른 멀티웰 큐베트를 개략적으로 나타낸 사시도이다. 1 is a perspective view schematically showing a multiwell cuvette according to an embodiment of the present invention.
도 2 는 본 발명의 일 구현예에 따른 멀티웰 큐베트를 개략적으로 나타낸 분해 사시도이다. 2 is an exploded perspective view schematically showing a multiwell cuvette according to an embodiment of the present invention.
도 3 은 본 발명의 일 구현예에 따른 멀티웰 큐베트를 사용하여 검사를 수행하는 과정을 도식적으로 나타낸 것이다.3 is a diagram illustrating a process of performing a test using a multiwell cuvette according to an embodiment of the present invention.
도 4는 본 발명의 일 구현예에 따른 멀티웰 큐베트에 포함되는 측방유동 분석용 카트리지를 개략적으로 나타낸 분해사시도이다.Figure 4 is an exploded perspective view schematically showing a cartridge for lateral flow analysis included in the multi-well cuvette according to an embodiment of the present invention.
도 5a는 본 발명의 일 구현예에 따른 제 2 커버를 포함하는 멀티웰 큐베트를 개략적으로 나타낸 사시도이다. 5A is a perspective view schematically illustrating a multiwell cuvette including a second cover according to an embodiment of the present invention.
도 5b는 도 5a의 제 2 커버가 일부 탈착된 상태의 멀티웰 큐베트를 개략적으로 나타낸 사시도이다. FIG. 5B is a perspective view schematically illustrating a multiwell cuvette with the second cover of FIG. 5A partially removed.
도 6은 도 5a의 A-A' 에 따른 단면도이다.6 is a cross-sectional view taken along line AA ′ of FIG. 5A.
이하, 첨부된 도면을 참조하여, 본 발명에 따른 바람직한 실시예에 대하여 설명한다. 본 실시예는 예시적인 것으로 어떤 식으로든 본 발명을 제한하는 것은 아니다. Hereinafter, exemplary embodiments of the present invention will be described with reference to the accompanying drawings. This example is illustrative and does not limit the invention in any way.
공간적으로 상대적인 용어인 "아래", "후면", "위", "상부" 등은 도면에 도시되어 있는 바와 같이 하나의 부재 또는 구성 요소들과 다른 소자 또는 구성 요소들과의 상관관계를 용이하게 기술하기 위해 사용될 수 있다. 공간적으로 상대적인 용어는 도면에 도시되어 있는 방향에 더하여 사용 시 또는 동작 시 소자의 서로 다른 방향을 포함하는 용어로 이해되어야 한다. 예를 들면, 도면에 도시되어 있는 부재를 뒤집을 경우, 다른 부재의 "아래(below)"또는 "아래"로 기술된 부재는 다른 부재의 "위"에 놓여질 수 있다. 따라서, 예시적인 용어인 "아래"는 아래와 위의 방향을 모두 포함할 수 있다. 부재는 다른 방향으로도 배향될 수 있고, 이에 따라 공간적으로 상대적인 용어들은 배향에 따라 해석될 수 있다. 예컨대 “가로 방향” 은 “상하 방향” 으로도 해석될 수 있으며 이에 한정하지 아니한다.The spatially relative terms "bottom", "back", "top", "top", etc., as shown in the figures, facilitate the correlation of one element or component with another element or components. Can be used to describe. Spatially relative terms are to be understood as terms that include different directions of the device in use or operation in addition to the directions shown in the figures. For example, when flipping the member shown in the figure, the member described as "below" or "below" of the other member may be placed "above" of the other member. Thus, the exemplary term "below" can encompass both an orientation of above and below. The member can also be oriented in other directions, so that spatially relative terms can be interpreted according to the orientation. For example, "horizontal direction" may also be interpreted as "up and down direction", but is not limited thereto.
도면에서 각 부재의 두께나 크기는 설명의 편의 및 명확성을 위하여 과장되거나 생략되거나 또는 개략적으로 도시되었다. 또한 각 구성요소의 크기와 면적은 실제크기나 면적을 전적으로 반영하는 것은 아니다. In the drawings, the thickness or size of each member is exaggerated, omitted, or schematically illustrated for convenience and clarity of description. In addition, the size and area of each component does not necessarily reflect the actual size or area.
또한, 실시예에서 본 발명의 구조를 설명하는 과정에서 언급하는 각도와 방향은 도면에 기재된 것을 기준으로 한다. 명세서에서 본 발명을 이루는 구조에 대한 설명에서, 각도에 대한 기준점과 위치관계를 명확히 언급하지 않은 경우, 관련 도면을 참조하도록 한다.In addition, the angle and direction mentioned in the process of demonstrating the structure of this invention in the Example are based on what was described in drawing. In the description of the structure constituting the present invention in the specification, if the reference point and the positional relationship with respect to the angle is not clearly mentioned, reference is made to related drawings.
도 1 은 본 발명의 일 구현예에 따른 일체형 멀티웰 큐베트(1)의 사시도이며, 도 2 는 본 발명의 일체형 멀티웰 큐베트(1)의 분해 사시도이다. 1 is a perspective view of an integrated multiwell cuvette 1 according to one embodiment of the invention, and FIG. 2 is an exploded perspective view of an integrated multiwell cuvette 1 of the present invention.
본원에 따른 큐베트는 시료 중에 포함된 분석물의 검출 및/또는 분석에 사용된다. 본원에서 사용된 용어 "시료"는 분석물을 포함하는 분석대상 화합물 또는 조성물을 가리키며, 본 발명에서 사용될 수 있는 시료는 액체상 또는 액체와 유사한 유동성 있는 물질이다. 본원에 따른 일 구현예에서 시료는 생물학적 시료로, 전혈, 혈장, 혈청, 뇨, 타액, 분뇨 및 세포 추출물과 같은 생체 유래 체성분일 수 있다. Cuvettes according to the invention are used for the detection and / or analysis of analytes contained in a sample. As used herein, the term “sample” refers to an analyte or composition that includes an analyte, and a sample that may be used in the present invention is a liquid phase or liquid like material. In one embodiment according to the present application, the sample is a biological sample, and may be a body-derived body component such as whole blood, plasma, serum, urine, saliva, manure and cell extracts.
본원에서 사용된 용어 "분석물"은 시료 중의 분석 대상 화합물로, 표적자라고도 하며 단백질 및 핵산을 포함하는 것이다. 본원에서 단백질은 폴리펩타이드 및 펩타이드를 포함한다. 또한 본원에서 용어 "핵산"은 지놈 DNA, cDNA 및 올리고뉴클레오타이드를 포함하는 화학합성 DNA 및 RNA를 포함한다. 또한 상기 핵산은 단일가닥 또는 이중가닥을 포함하며, 지놈 DNA, cDNA 및 올리고뉴클레오타이드 및 RNA는 당업계의 공지된 방법에 따라 제조 또는 합성할 수 있다. As used herein, the term “analyte” is a compound of interest in a sample, also referred to as a target, that includes proteins and nucleic acids. Proteins herein include polypeptides and peptides. The term “nucleic acid” herein also includes chemical synthetic DNA and RNA, including genome DNA, cDNA and oligonucleotides. In addition, the nucleic acid includes single- or double-stranded, genome DNA, cDNA and oligonucleotides and RNA can be prepared or synthesized according to methods known in the art.
본원에 따른 일 구현예에서는 시료 중의 단백질 예를 들면 hsCRP(high sensitivity C-reactive protein), MicroCRP, HbA1c (당화혈색소), microalbumin, PSA(prostate specific antigen), AFP(Alpha-fetoprotein), cTnI (Cardiac Troponin I)의 검출에 사용된다. In one embodiment according to the present invention, a protein in a sample, for example, high sensitivity C-reactive protein (hsCRP), MicroCRP, HbA1c (glycosylated hemoglobin), microalbumin, PSA (prostate specific antigen), AFP (Alpha-fetoprotein), cTnI (Cardiac) Used to detect Troponin I).
본원에서 시약은 상술한 분석물의 검출 및 분석에 적합한 물질로, 구체적 분석물에 따라 상이하며, 예를 들면, 상기 시약은 상기 체성분 내의 다양한 물질 예를 들면 항원 등과 반응을 일으키는 소정의 항체 등일 수 있고, 이에 한정하지 않는다. Reagents herein are materials suitable for the detection and analysis of the analytes described above, depending on the specific analyte, for example, the reagents may be any antibody or the like that reacts with various substances in the body component, eg, antigens, and the like. It is not limited to this.
본 발명에 따른 멀티웰 큐베트(1)는, 시료와 시약을 수용하는 반응 챔버부 (100); 상기 시료와 시약 간의 반응이 검출되는 검출부(200)를 포함하며, 상기 챔버부(100)는, 상기 시료의 분배 또는 분주를 위한 부재가 대기하는 채취부재 대기 챔버(110); 시료가 충진되는 시료 충진 챔버(120) 및 시약이 충진되고, 상기 시료 및 시약 간의 반응이 수행되는 시약 충진 챔버(130)를 포함하고, 상기 검출부는 상기 시료와 시약간의 반응 결과물에 대한 크로마토그래피 분석용 수단 및 이를 수용하는 검출 챔버(210)를 포함한다. Multi-well cuvette 1 according to the present invention, the reaction chamber unit 100 for receiving a sample and a reagent; And a detection unit 200 for detecting a reaction between the sample and the reagent, wherein the chamber unit 100 includes: a collecting member waiting chamber 110 in which a member for dispensing or dispensing the sample stands by; A sample filling chamber 120 and a reagent filling chamber, and a reagent filling chamber 130 in which a reaction between the sample and the reagent is performed, wherein the detection unit is chromatographic analysis of the reaction product between the sample and the reagent. Means for detection and detection chamber 210 containing the same.
본 발명에 따른 멀티웰 큐베트(1)에 포함되는 반응 챔버부(100)는 검사에 사용되는 각종 시료와, 상기 시료와 반응하는 소정의 시약을 수용할 수 있도록 복수개의 챔버를 갖도록 구성된다. 이에 따라서, 상기 챔버부(100)는 다수의 웰(well)과 상기 웰 사이를 구분하여 시약과 시료들 사이의 불필요한 섞임을 방지하는 장벽이 구비된 구조를 가질 수 있다. 즉, 상기 반응 챔버부(100)는 소정의 멀티-웰(Multi-well)구조를 가질 수 있다. 한편, 상기 반응 챔버부(100)에 형성되는 챔버는 복수일 수 있으며, 그 수는 한정하지 아니한다. The reaction chamber part 100 included in the multiwell cuvette 1 according to the present invention is configured to have a plurality of chambers for accommodating various samples used for the test and predetermined reagents reacting with the samples. Accordingly, the chamber part 100 may have a structure having a barrier for preventing unnecessary mixing between reagents and samples by separating the plurality of wells and the wells. That is, the reaction chamber part 100 may have a predetermined multi-well structure. On the other hand, the chamber formed in the reaction chamber unit 100 may be a plurality, the number is not limited.
본원에 따른 상기 반응 챔버부(100)는 시료의 분주 또는 분배를 위한 채취부재 대기 챔버(110), 시료를 수용하는 시료 충진 챔버(120) 및 시약이 충진되는 시약 충진 챔버(130)를 포함하여 구성될 수 있다. 상술한 바와 같이, 상기 채취부재 대기 챔버(110)와 시료가 충진되는 시료 충진 챔버(120) 및 시약 충진 챔버(130)는 각각 소정의 장벽에 의해서 구분된 웰 구조로 구성되어 상기 채취부재 대기 챔버(110), 시약 충진 챔버(120) 및 시약 충진 챔버(130) 내에 충진된 시료와 시약이 불필요하게 섞이는 것이 방지되는 구조를 가질 수 있다. 시약 충진 챔버(130)에는 분석물의 종류에 따라 이의 검출 및/또는 분석에 적합한 시약을 포함할 수 있으며, 시료 충진 챔버(120)로부터 시료가 투입되는 경우, 시약 충진 챔버에서 투입된 시료 및 시약간의 반응이 수행된다. 아울러, 상기 시약 충진 챔버(130)는 각각 동일 또는 상이한 종류의 시료와 시약이 충진되도록 복수개로 형성될 수 있으나, 복수개인 경우, 반드시 모든 시약 충진 챔버가 시약을 포함해야 하는 것은 아니고, 이중 일부만이 사용될 수도 있음은 물론이다. 본원에 따른 일 구현예에서는 제 1 시약 충진 챔버(130) 및 제 2 시약 충진 챔버(132)를 포함하나, 이에 한정하지 않는다. The reaction chamber unit 100 according to the present invention includes a collecting member atmospheric chamber 110 for dispensing or dispensing a sample, a sample filling chamber 120 for receiving a sample, and a reagent filling chamber 130 for filling a reagent. Can be configured. As described above, the sampling member atmospheric chamber 110 and the sample filling chamber 120 and the reagent filling chamber 130 in which the sample is filled are configured in a well structure separated by a predetermined barrier, respectively, so that the collecting member atmospheric chamber is formed. 110, the reagent filling chamber 120 and the reagent filling chamber 130 may have a structure that prevents unnecessary mixing of the reagent and the sample. The reagent filling chamber 130 may include a reagent suitable for detection and / or analysis thereof according to the type of analyte, and when a sample is introduced from the sample filling chamber 120, a reaction between the sample and the reagent introduced in the reagent filling chamber is performed. This is done. In addition, the reagent filling chamber 130 may be formed in plural to be filled with the same or different types of samples and reagents, respectively, but in the case of a plurality of reagent filling chambers, not all of the reagent filling chambers should include reagents, only a part of them. Of course, it can also be used. One embodiment according to the present invention includes, but is not limited to, the first reagent filling chamber 130 and the second reagent filling chamber 132.
본원에 따른 검출부(200)는 상기 반응 챔버부(100)에서 수행된 상기 시료와 시약간의 반응 결과물을 크로마토그래피 방식으로 분석하기에 적합한 크로마토그래피 분석 수단을 포함하는 검출 챔버(210)를 포함한다. 이에 따라서, 상기 검출부(200)는 반응물의 크로마토그래피 분석 예를 들면 측방유동 분석에 적합한 수단을 포함할 수 있다. 바람직하게는, 상기 검출 챔버(210)는 예를 들면 측방유동 분석(lateral flow assay)을 위한 카트리지를 포함할 수 있다. The detection unit 200 according to the present invention includes a detection chamber 210 including chromatographic analysis means suitable for chromatographic analysis of the reaction product between the sample and the reagent performed in the reaction chamber unit 100. Accordingly, the detection unit 200 may include a means suitable for chromatographic analysis of reactants, for example, lateral flow analysis. Preferably, the detection chamber 210 may comprise a cartridge, for example for a lateral flow assay.
측방유동 분석은 시료에 포함된 목표 분석물, 예를 들면 특정 핵산 또는 단백질을 정량 또는 정성적으로 검사하는 방법으로, 예를 들면 일정한 서열의 핵산에 교잡하는 올리고뉴클레오타이드 또는 특정 항체 및/또는 항원이 특정 위치에 결합되어 있는 스트립(20)이라고 불리는 나이트로셀룰로스 막(전개용 매질)을 포함하는 크로마토그래피 방법으로 반응 결과물 중의 분석물을 이동시켜 서열 특이적 교잡반응 또는 항원 항체 반응을 통해 시료 중의 특정 핵산 또는 단백질을 검출하는 방법이다. 예를 들면 대한민국 공개 특허공보 제2003-0065341호, 제2011-0007699호, 제2011-0127386호, 및 등록공보 제1149357호 등에 기재된 것을 참조할 수 있다. Lateral flow analysis is a method of quantitatively or qualitatively examining a target analyte, eg, a particular nucleic acid or protein, contained in a sample, e.g., an oligonucleotide or a specific antibody and / or antigen that hybridizes to a nucleic acid of a constant sequence. A chromatographic method comprising a nitrocellulose membrane (development medium) called strip 20 bound to a specific position is used to transfer the analyte in the reaction product to identify the sample in the sample through sequence specific hybridization or antigen antibody reactions. It is a method for detecting a nucleic acid or protein. For example, reference may be made to those disclosed in Korean Unexamined Patent Publication Nos. 2003-0065341, 2011-0007699, 2011-0127386, and Registration No. 1149357.
따라서, 도 2를 참조하면 본원에 따른 일 구현예에서 검출 챔버(210)는 측방유동 분석에 적합한 카트리지를 포함하며, 상기 카트리지는, 전개용 매질을 포함하는 스트립을 수용하는 스트립 수용부; 및 상기 스트립 수용부와 연장되는 위치의 상기 스트립 수용부의 일 말단 측에 형성되어, 반응 챔버부의 반응 결과물을 수용하는 웰이 형성된, 베이스 부재 및 상기 베이스 부재와 채결되는 커버부재를 포함하도록 구성된다. 예를 들면 대한민국 공개 특허공보 제2003-0065341호, 제2011-0007699호, 제2011-0127386호, 및 등록공보 제1149357호 등에 기재된 것을 참조할 수 있다. Thus, referring to FIG. 2, in one embodiment according to the present disclosure, the detection chamber 210 comprises a cartridge suitable for lateral flow analysis, the cartridge comprising: a strip receiving portion for receiving a strip comprising a development medium; And a base member formed on one end side of the strip receiving portion in a position extending from the strip receiving portion, and formed with a well for receiving a reaction product of the reaction chamber portion, and a cover member engaged with the base member. For example, reference may be made to those disclosed in Korean Unexamined Patent Publication Nos. 2003-0065341, 2011-0007699, 2011-0127386, and Registration No. 1149357.
일예로 본원에 따른 검출 챔버는 반응 결과물의 크로마토그래피 분석 수단으로, 예를 들면 대한민국 공개 특허공보 제2011-0046833호 또는 도 4에 개시된 바와 같은 측방유동 분석용 카트리지를 포함한다. For example, the detection chamber according to the present application is a chromatographic analysis means of the reaction result, and includes a cartridge for lateral flow analysis as disclosed in, for example, Korean Patent Publication No. 2011-0046833 or FIG. 4.
도 4를 참조하면 상기 카트리지(220)는 검출 챔버(210)내에 설치되며, 커버부재(30) 및 베이스부재(10)를 포함한다. 반응 결과물은 투입구(32)를 통하여 웰 (12)로 유입되고, 웰로부터 스트립(20)으로의 반응 결과물의 전달을 위해 커버부재의 하면에는 삼각형 형상의 모세관 구조물(35, 37) 및 베이스부재에는 이에 대응되는 구조가 형성되어 있다. 구체적으로 본원의 큐베트에 포함되는 측방유동 분석용 카트리지는 베이스 부재(10); 및 상기 베이스 부재와 채결되는 커버 부재(30)를 포함하고, 상기 베이스 부재는, 상기 측방유동 분석에 사용되는 스트립을 수용하는 스트립 수용부(18), 및 상기 스트립 수용부의 일 말단으로부터 연장되는 위치에 형성된 시료용 웰(12)을 포함하고, 상기 커버 부재는 상기 베이스 부재와 채결시, 상기 스트립 수용부와 대응되는 부분에 형성된 반응 결과의 검출을 위한 측정창(34) 및 상기 시료용 웰과 대응되는 부분에 형성된 시료 투입구(32)를 포함하고, 필요한 경우 공기창(38)을 추가로 포함할 수 있다. 상기 베이스 부재 또는 상기 커버 부재, 또는 상기 베이스 부재 및 상기 커버 부재는 모세관 구조물(35, 37)을 포함하며, 상기 커버 부재에 형성된 모세관 구조물은 상기 커버 부재의 상기 시료투입구와 인접한 하면에 형성되고, 상기 베이스 부재에 형성된 모세관 구조물은 상기 시료용 웰에 형성된다. Referring to FIG. 4, the cartridge 220 is installed in the detection chamber 210 and includes a cover member 30 and a base member 10. The reaction product is introduced into the well 12 through the inlet 32, and the triangular capillary structures 35 and 37 and the base member are formed on the lower surface of the cover member to transfer the reaction product from the well to the strip 20. The corresponding structure is formed. Specifically, the lateral flow analysis cartridge included in the cuvette of the present application includes a base member 10; And a cover member 30 engaged with the base member, the base member having a strip receiving portion 18 for receiving a strip used for the lateral flow analysis, and a position extending from one end of the strip receiving portion. And a sample well 12 formed in the cover member, wherein the cover member includes a measurement window 34 and a sample well for detecting a reaction result formed at a portion corresponding to the strip accommodating portion when the base member is filled with the base member. A sample inlet 32 formed in a corresponding portion may be included, and if necessary, an air window 38 may be further included. The base member or the cover member, or the base member and the cover member includes capillary structures 35 and 37, wherein the capillary structure formed on the cover member is formed on a lower surface adjacent to the sample inlet of the cover member, The capillary structure formed on the base member is formed in the sample well.
시료 투입구(32)는 상기 반응 결과물을 수용하는 웰과 연직하도록 형성된다. 베이스 부재에 커버부재(30)를 덮으면 걸림턱, 요철형상 돌기(16)을 포함하는 체결수단을 통해 그 경계면에서 서로 맞물려 닫히게 되어(interlocking), 실질적으로 워터프루프(waterproof), 에어로솔프루프(aerosol proof) 실(seal)이 된다. 또한 스트립 수용부는 여러 개의 스트립 수용을 위한 가이드를 포함하여 장착된 스트립이 흔들림을 방지함은 물론 일정한 위치에 스트립을 위치하도록 한다. The sample inlet 32 is formed to be perpendicular to the well containing the reaction product. Covering the cover member 30 on the base member is interlocked with each other at its interface via a fastening means including a locking jaw and an uneven protrusion 16, thereby substantially waterproof and aerosol proof. ) It becomes a seal. The strip receptacle also includes a guide for receiving a plurality of strips to prevent the mounted strip from shaking and to position the strip in a fixed position.
상기 투입구(32)로 투입된 반응 결과물은 다양한 방식을 통해 스트립(20)으로 이동하게 된다. 일예로 상기 측방유동 카트리지는 상기 투입구와 연직하는 위치에 형성된 웰과 스트립 수용부(18)사이에 형성된 소정의 미세 채널구조가 형성될 수 있으며, 이를 통한 모세관 현상으로 웰의 반응 결과물이 스트립으로 전달되고 측방유동이 개시되나, 이에 한정하지 않는다. 다른 예로는 상기 스트립의 일 말단이 상기 웰과 직접 접촉하여 액상 시료가 스트립으로 흡수되어 측방유동이 개시되나, 이에 한정하지 아니한다.The reaction product introduced into the inlet 32 is moved to the strip 20 through various methods. For example, the lateral flow cartridge may have a predetermined microchannel structure formed between the well formed at a position perpendicular to the inlet and the strip receiving portion 18, and through the capillary phenomenon, the reaction product of the well is transferred to the strip. And lateral flow is disclosed, but not limited thereto. In another example, one end of the strip is in direct contact with the well to absorb a liquid sample into the strip to initiate lateral flow, but is not limited thereto.
본원에 따른 멀티웰 큐베트는 상기 측방유동 카트리지를 구성하는 상기 반응결과물을 수용하는 웰의 하부에 위치하는 자석부(138)를 추가로 포함할 수 있다. 자석부는 자석(140) 및 이를 수용하는 웰(142)로 구성된다. 자석은 분석되는 반응 결과물에 포함된 불순물을 제거하기 위한 것이다. 이를 위해 시약 충진 챔버(130)는 자석비드를 포함하고 있으며 자석비드에는 제거하고자 하는 불순물에 특이적으로 결합할 수 있는 항체가 결합되어 있다. 불순물은 예를 들면 전혈에 포함된 적혈구를 예로 들수 있으며, 시료와 시약과 반응 후 반응 결과물에는 자석에 반응할 수 있는 자석비드와 자석비드에 결합된 불순물에 특이적인 항체, 예를 들면 적혈구의 제거를 위해서는 적혈구 항체가 결합되어 있다. 이 후 반응 결과물 중의 적혈구는 항체를 통해 자석비드에 결합되어 있고, 반응결과물을 수용하는 웰의 하부에 위치한 자석비드는 자석(140)과 접촉시 바닥으로 침강되어, 스트립으로 이동되지 않아 결과적으로 분석되지 않는다. The multi-well cuvette according to the present invention may further include a magnet part 138 located at the bottom of the well containing the reaction product constituting the lateral flow cartridge. The magnet part is composed of a magnet 140 and a well 142 for accommodating the magnet 140. The magnet is for removing impurities contained in the reaction product to be analyzed. To this end, the reagent filling chamber 130 includes a magnetic bead, and an antibody capable of specifically binding to impurities to be removed is bound to the magnetic bead. For example, impurities may include red blood cells contained in whole blood, and after reaction with samples and reagents, reaction products may include magnetic beads capable of reacting with a magnet and antibodies specific to impurities bound to the magnetic beads, such as red blood cells. For erythrocyte antibodies are bound. Thereafter, the red blood cells in the reaction product are bound to the magnetic beads through the antibody, and the magnetic beads located in the lower part of the well containing the reaction product settle to the bottom when contacted with the magnet 140 and do not move to the strip, resulting in analysis. It doesn't work.
도 5a 및 도 5b를 참조하면 본원에 따른 큐베트(1)는 제 2 커버(136)를 추가로 포함할 수 있다. 상기 제 2 커버(136)는 큐베트의 상단을 덮는 것으로, 반응 챔버부(100) 및 검출부(200)의 전부 또는 일부를 커버하는 것으로 제품의 식별과 표면 보호를 위한 것이다. 이런 경우, 도 5b에 도시된 바와 같이 제 1 시약 충진 챔버 및 제 2 시약 충진 챔버를 커버하는 제 1 커버(134)는 제 2 커버의 아래에 위치한다. 후술하는 바와 같이 본원에 따른 큐베트와 함께 사용되는 장비에 구비된 액상 시료의 분배 또는 채취 수단 예를 들면 팁(T)의 입출 또는 검출 결과의 판독 (측정창의 경우)을 위해, 제 2 커버에는 채취부재 대기 챔버(110), 시료 충진 챔버 (120), 제 1 시약 충진 챔버(132), 제 2 시약 충진 챔버(132) 및 카트리지에 형성된 시료 투입구(32) 및 측정창(34)에 해당하는 부분이 노출될 수 있도록, 상기 각 해당부분에 적절한 형태의 홀이 형성되어 있다. 또한 제 2 커버는 도 5b에 도시된 바와 같이 필요한 경우 벗겨낼 수 있으나, 통상 사용시에는 제 2 커버가 있는 상태에서 사용된다. 5A and 5B, the cuvette 1 according to the present disclosure may further include a second cover 136. The second cover 136 covers the upper end of the cuvette and covers all or part of the reaction chamber 100 and the detection unit 200 to identify and protect the surface of the product. In this case, as shown in FIG. 5B, a first cover 134 covering the first reagent filling chamber and the second reagent filling chamber is located below the second cover. As described below, the second cover is provided for dispensing or collecting the liquid sample provided in the equipment used with the cuvette according to the present application, for example, for entering or exiting the tip T or reading the detection result (in the case of a measuring window). Corresponding to the sample inlet 32 and the measurement window 34 formed in the collecting member atmospheric chamber 110, the sample filling chamber 120, the first reagent filling chamber 132, the second reagent filling chamber 132, and the cartridge. In order to expose the parts, a hole of appropriate shape is formed in each of the corresponding parts. In addition, the second cover can be peeled off if necessary as shown in FIG. 5B, but is normally used in a state in which the second cover is present.
본원에 따른 일 구현예에서 상기 제 2 커버는 그 임의의 위치에 바코드(400)을 추가로 포함할 수 있다. 본원에 따른 멜티웰 큐베트는 후술하는 바와 같은 소정의 검사 장비, 예를 들면 시료의 분주, 시료와 시약간의 반응 및 반응 결과물의 검출이 하나의 장비에서 자동으로 수행되는 자동화 장비와 함께 사용된다. 이 경우, 멀티웰 큐베트를 이용하여 측정 또는 분석하고자 하는 물질 또는 시료가 상기 소정의 검사 장비에 삽입되는 ID 칩과 일치하도록 하는 것으로, 상기 ID 칩에는 측정하고자 하는 물질의 정보 및 이에 따라 이의 정량을 위한 스탠다드 커브 정보, 그리고 상기 범위를 벋어난 경우의 에러처리에 대한 정보 등이 저장되어 있다. In one embodiment according to the present application, the second cover may further include a barcode 400 at any position thereof. Meltiwell cuvettes according to the present application are used in conjunction with certain inspection equipment as described below, such as automated equipment in which the dispensing of a sample, the reaction between a sample and a reagent, and the detection of a reaction result are performed automatically in one equipment. In this case, the material or sample to be measured or analyzed by using a multi-well cuvette is made to match the ID chip inserted into the predetermined inspection equipment, and the ID chip contains information of the material to be measured and quantification thereof accordingly. Standard curve information, and information on error processing when the range is out of range are stored.
본원에 따른 큐베트에 장착되어 사용되는 카트리지는 검출 챔버(210)에 장착되어 사용되기에 적합한 크기와 형태로 다양하게 제조될 수 있으며, 직사각형 형태로 제조될 수 있고 본원에 따른 큐베트의 이러한 직사각형 형태의 카트리지를 수용할 수 있는 다양한 측정 장비(판독기)에서 사용될 수 있으며, 화학적으로 안정한 합성수지 및 이들의 조합으로 만들어 질 수 있다. Cartridges mounted and used in the cuvette according to the present application may be manufactured in various sizes and shapes suitable for mounting and use in the detection chamber 210, may be manufactured in a rectangular shape and such a rectangle of the cuvette according to the present application It can be used in a variety of measuring equipment (readers) that can accommodate cartridges in the form, and can be made from chemically stable synthetic resins and combinations thereof.
도 1 에 도시된 바와 같이, 본원에 따른 멀티웰 큐베트(1)는 채취부재 대기 챔버(110), 시료 충진 챔버(120), 시약 충진 챔버(130, 132) 및 검출 챔버(210)가 하나의 멀티웰 큐베트(1) 상에 일체로 형성되며, 일 방향으로 순차적으로 배치되어 열을 형성한다. 이때, 도 1 에 도시되지는 아니하였으나, 상기 채취부재 대기 챔버(110)와 시약 충진 챔버(130) 및 검출 챔버(210)가 형성하는 열이 복수일 수 있고, 이에 한정하지 않는다.As shown in FIG. 1, the multiwell cuvette 1 according to the present invention includes a collecting member atmospheric chamber 110, a sample filling chamber 120, a reagent filling chamber 130, 132, and a detection chamber 210. It is formed integrally on the multiwell cuvette 1, and are sequentially arranged in one direction to form heat. In this case, although not shown in FIG. 1, a plurality of rows formed by the collecting member atmospheric chamber 110, the reagent filling chamber 130, and the detection chamber 210 may be plural, but is not limited thereto.
상술한 바와 같은 구조를 갖는 본원에 따른 멀티웰 큐베트(1)는 소정의 검사 장비와 함께 사용될 수 있다. 일예로 검사 장비는 시료의 분주, 시료와 시약간의 반응 및 반응 결과물의 검출이 하나의 장비에서 자동으로 수행되는 자동화 장비일 수 있다. The multiwell cuvette 1 according to the invention having the structure as described above can be used with certain inspection equipment. For example, the test equipment may be an automated equipment in which a dispensing of a sample, a reaction between a sample and a reagent, and detection of a reaction result are automatically performed in one equipment.
상술한 바와 같은 일렬 배치 구조를 가짐에 따라서, 본 발명에 따른 멀티웰 큐베트(1)를 이용하여 검사를 수행할 때, 직선상의 변위만으로 보다 신속하고 간단한 작동으로 검사가 이루어질 수 있다. 또한 반응 시약을 포함하는 반응 충진 챔버가 검출용 수단에 일체형으로 구조화되어 별도의 시약 구비 통이 필요치 않아, 서로 다른 복수개의 검사시 시약의 혼동에 의한 오검사를 확률을 줄 일수 있다. 또한 동일 또는 상이한 다수의 시약이 반응 충진 챔버에 포함되는 경우, 이러한 특징으로 인해 하나의 장비에 별도의 시약 교체 없이 다양한 분석물을 검출할 수 있다. With the arrangement arrangement as described above, when the inspection is performed using the multi-well cuvette 1 according to the present invention, the inspection can be made faster and simpler operation with only a linear displacement. In addition, since the reaction filling chamber including the reaction reagent is integrally structured in the detecting means, a separate reagent container is not required, thereby reducing the probability of erroneous inspection due to confusion of reagents during a plurality of different tests. In addition, when multiple reagents, which are the same or different, are included in the reaction filling chamber, this feature allows the detection of various analytes without separate reagent replacement in one instrument.
아울러, 본 발명에 따른 멀티웰 큐베트(1)는 채취부재 대기 챔버(110), 시료 충진 챔버(120), 시약 충진 챔버(130) 및 검출 챔버(210)가 일체로 형성되되 일 방향 일렬로 배치된 구조를 가지므로 그 구조가 간단하여 제조에 사용되는 제조 장치의 구조가 간단해지며 제조 단가가 절감될 수 있다.In addition, in the multi-well cuvette 1 according to the present invention, the collecting member atmospheric chamber 110, the sample filling chamber 120, the reagent filling chamber 130, and the detection chamber 210 are integrally formed in one direction. Since the structure of the arrangement is simple, the structure of the manufacturing apparatus used for manufacturing is simplified and the manufacturing cost can be reduced.
본원에 따른 큐베트는 일회용으로 사용되고, 실제 사용시 시약 및 분배 분주를 위한 수단과 사용되는 후술하는 일회용 마이크로팁(예를 들면 2-1000μl 용량의 마이크로파이펫팁)을 포함하고 있어, 별도의 시약공급 장치 및 오염을 세척하는 수단을 구비하지 않는 장비와 사용될 수 있어, 장비의 작동이 간소화 된다. The cuvettes according to the present application are used for single use and include the following disposable microtips (e.g. 2-1000μl micropipette tips) used in practice and with means for dispensing reagents and dispensing, thus providing a separate reagent supply device and contamination. Can be used with equipment that does not have a means to clean the equipment, simplifying the operation of the equipment.
일예로 소정의 검사 장비는 시료 및 반응 결과물의 분배 및 반응 결과물 중의 분석물의 검출이 자동화로 이루어질 수 있는 자동화 장비로, 상기 자동화 장비는 시료 및 반응 결과물의 분배 또는 분주를 위한 수단을 구비할 수 있다. 검사 장비에 포함되는 분배 또는 분주 수단은 본원에 따른 큐베트(1)의 채취부재 대기 챔버(110), 시료 충진 챔버(120), 시약 충진 챔버(130) 및 검출부(200)의 카트리지 (230)에 형성된 투입구(32) 상을 따라 X 축으로 이동이 가능한 것으로, 시료, 시약, 반응 결과물의 분배 또는 분주를 위해, 액상물질의 흡입 및 배출용 펌프가 구비된 암(arm)을 포함하며, 암의 말단은 팁이 형성되어 있다. 상기 팁은 채취부재 대기 챔버(110)에 위치한 채취부재 예를 들면 10μl, 100μl, 200μl, 또는 500μl 용량의 마이크로팁에 삽입되어 시료, 시약, 및/또는 반응 결과물의 분주 및/또는 분배에 사용된다. 상기 채취부재 대기 챔버(110)는 상기와 같이 소정의 팁을 갖는 검사 장비가 투입되어 시료를 채취할 수 있도록 상부가 오픈되게 형성된다. 즉, 상기 채취부재 대기 챔버(110) 및 시료 충진 챔버(120)의 상면에는 상기와 같은 팁이 투입될 수 있도록 하는 오픈부(112, 114)가 형성될 수 있다. 물론, 상기 오픈부(112, 114)를 통해 마이크로팁의 장착, 소정의 시료의 분배가 이루어질 수 있다. For example, the predetermined test equipment is an automated equipment in which the distribution of a sample and a reaction result and the detection of an analyte in the reaction result may be automated. The automated equipment may include a means for distributing or dispensing a sample and a reaction result. . Dispensing or dispensing means included in the inspection equipment is the collecting member atmospheric chamber 110, the sample filling chamber 120, the reagent filling chamber 130 and the cartridge 230 of the detection unit 200 of the cuvette (1) according to the present application It is movable on the X axis along the inlet 32 formed in the inlet, and includes an arm equipped with a pump for suction and discharge of the liquid material for dispensing or dispensing a sample, a reagent, or a reaction product. The end of the tip is formed. The tip is inserted into a harvesting member, eg, 10 µl, 100 µl, 200 µl, or 500 µl volume microtip, located in the harvesting member atmospheric chamber 110, for use in dispensing and / or dispensing samples, reagents, and / or reaction products. . The collecting member standby chamber 110 is formed so that the upper portion is opened so that the inspection equipment having a predetermined tip is input as described above to collect a sample. That is, open portions 112 and 114 may be formed on the upper surfaces of the collecting member atmospheric chamber 110 and the sample filling chamber 120 to allow the tip to be introduced. Of course, the microtips may be mounted through the openings 112 and 114 and a predetermined sample may be dispensed.
본원에 따른 일 구현예에서, 본 발명에 따른 멀티웰 큐베트(1)는 상기 시약 충진 챔버(130), 및 검출 챔버(210) 상면의 적어도 일부를 덮는 커버를 포함할 수 있다.In one embodiment according to the present invention, the multiwell cuvette 1 according to the present invention may include a cover covering the reagent filling chamber 130 and the upper surface of the detection chamber 210.
커버는 상기 시약 충진 챔버(130), 및 검출 챔버(210) 상면의 적어도 일부를 덮어 커버에 의해서 덮여진 내측 공간을 외부에 대해 적어도 일부분 격리한다. 이에 따라서, 상기 시약 충진 챔버(130)에 충진된 시약 및 상기 검출 챔버(210)에 놓인 시약과 시료의 혼합물이 외부 환경에 의해서 변질되거나 또는 의도하지 않게 반응하는 것이 방지되어 검사 신뢰성이 더욱 향상될 수 있다.The cover covers at least a portion of the reagent filling chamber 130 and the detection chamber 210 and at least partially isolates the inner space covered by the cover to the outside. Accordingly, the reagent filled in the reagent filling chamber 130 and the mixture of the reagent and the sample placed in the detection chamber 210 may be prevented from being altered or inadvertently reacted by an external environment, thereby improving test reliability. Can be.
이때, 바람직하게는, 상기 시약 충진 챔버(130) 상에는 제 1 커버(134)가 배치되며, 상기 제1 커버(134)는, 소정의 팁을 갖는 검사 장비가 적어도 일부분을 뚫고 침투되도록 얇은 박막 구조를 가질 수 있다. 즉, 상기 시약 충진 챔버(130) 상에는 얇은 박막 구조를 갖는 제1 커버(134)가 배치되며, 상기 제1 커버(134)는 검사 장비에 마련된 채취부재가 장착된 팁에 의해서 뚫어지고 상기 채취부재를 구비한 팁이 침투될 수 있는 구성을 가질 수 있다. 예컨대, 상기 제1 커버(134)는 알루미늄과 같은 금속으로 구성된 박막, 또는 플라스틱과 같은 합성수지로 구성된 박막일 수 있으며, 이에 한정하지 아니한다. In this case, preferably, a first cover 134 is disposed on the reagent filling chamber 130, and the first cover 134 has a thin film structure so that inspection equipment having a predetermined tip penetrates at least a portion thereof. It can have That is, a first cover 134 having a thin thin film structure is disposed on the reagent filling chamber 130, and the first cover 134 is drilled by a tip equipped with a sampling member provided in the inspection equipment, and the collecting member is disposed. It may have a configuration that can be penetrated with a tip. For example, the first cover 134 may be a thin film made of a metal such as aluminum, or a thin film made of a synthetic resin such as plastic, but is not limited thereto.
바람직하게는, 소정의 연결 지그(300)가 일 단에 구비될 수 있다. 상기 연결 지그(300)는 본 발명에 따른 멀티웰 큐베트(1)의 일 단에 배치되며, 도 1 에 도시된 바와 같이 길이 방향 일 단에 구비될 수 있으나, 이에 한정하지 않고, 임의의 위치에 배치될 수 있다.Preferably, a predetermined connection jig 300 may be provided at one end. The connecting jig 300 is disposed at one end of the multi-well cuvette 1 according to the present invention, and may be provided at one end in the longitudinal direction as shown in FIG. 1, but is not limited thereto. Can be placed in.
상기 연결 지그(300)가 구비됨에 따라서, 본 발명에 따른 멀티웰 큐베트(1)를 사용하여 검사를 수행한 후 교체 또는 폐기가 용이하게 이루어질 수 있다. 즉, 상기 연결 지그(300)를 이용하여 본 발명에 따른 멀티웰 큐베트(1)를 소정의 검사 장치에 탈착가능하게 연결함에 따라서 용이한 검사가 수행될 수 있다.As the connecting jig 300 is provided, replacement or disposal may be easily performed after the inspection is performed using the multi-well cuvette 1 according to the present invention. That is, an easy inspection can be performed by detachably connecting the multiwell cuvette 1 according to the present invention to the predetermined inspection apparatus using the connection jig 300.
도 3 은 본 발명에 따른 멀티웰 큐베트(1)를 사용하여 소정의 검사를 수행하는 것을 나타낸 도면이다.3 is a view showing performing a predetermined test using the multi-well cuvette 1 according to the present invention.
먼저 소정의 검사 장비(S) 에 구비된 팁(T)이 오픈부(112)를 통해 채취부재 대기 챔버(110)의 마이크로팁을 장착한 후, X 축으로 이동하여, (A)와 같이 시료 충진 챔버에 충진된 시료를 취한다. First, the tip T provided in the predetermined inspection equipment S mounts the micro tip of the collecting member atmospheric chamber 110 through the open part 112, and then moves to the X axis, so that the sample as shown in (A). Take a sample filled in the filling chamber.
다음으로, (B) 와 같이 상기 검사 장비(S)를 이동시켜 상기 시약 충진 챔버(130)에 시료를 분주하여 충진된 시약과 상기 시료를 반응시킨다. 이때, 상기 채취된 시료가 시약 충진 챔버(130) 내에 투여되어 반응이 어루어진다. Next, the inspection equipment (S) is moved as shown in (B) to dispense a sample into the reagent filling chamber 130 to react the reagent with the sample. In this case, the collected sample is administered in the reagent filling chamber 130 to react.
이어서, (C) 와 같이, 상기 반응이 이루어진 시약과 시료의 반응 결과물을 검출 챔버(210)에 투입구를 통하여 투여한다. 이때, 검출 챔버(210) 내에는 상기와 같이 측방유동을 위한 스트립(20)을 구비한 카트리지가 구비될 수 있으며, 크로마토그래피에 분석 결과는 측정창을 통해 장비 (S)의 판독기를 통하여 검출된다. Subsequently, as in (C), the reaction product of the reactant and the sample is administered to the detection chamber 210 through an inlet. At this time, the detection chamber 210 may be provided with a cartridge having a strip 20 for lateral flow as described above, the analysis result in the chromatography is detected through the reader of the equipment (S) through the measurement window .
이상에서는 바람직한 실시예에 대하여 도시하고 설명하였지만, 본 발명은 상술한 특정의 실시예에 한정되지 아니하며, 청구범위에서 청구하는 본 발명의 요지를 벗어남이 없이 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자에 의해 다양한 변형실시가 가능한 것은 물론이고, 이러한 변형실시들은 본 발명의 기술적 사상이나 전망으로부터 개별적으로 이해되어서는 안될 것이다.Although the preferred embodiments have been illustrated and described above, the invention is not limited to the specific embodiments described above, and does not depart from the gist of the invention as claimed in the claims. Various modifications may be made by the person having the above, and these modifications should not be individually understood from the technical spirit or the prospect of the present invention.
이상에서 본원의 예시적인 실시예에 대하여 상세하게 설명하였지만 본원의 권리범위는 이에 한정되는 것은 아니고 다음의 청구범위에서 정의하고 있는 본원의 기본 개념을 이용한 당업자의 여러 변형 및 개량 형태 또한 본원의 권리범위에 속하는 것이다.Although the exemplary embodiments of the present application have been described in detail above, the scope of the present application is not limited thereto, and various modifications and improvements of those skilled in the art using the basic concepts of the present invention defined in the following claims are also provided. It belongs to.
본 발명에서 사용되는 모든 기술용어는, 달리 정의되지 않는 이상, 본 발명의 관련 분야에서 통상의 당업자가 일반적으로 이해하는 바와 같은 의미로 사용된다. 본 명세서에 참고문헌으로 기재되는 모든 간행물의 내용은 본 발명에 도입된다.All technical terms used in the present invention, unless defined otherwise, are used in the meaning as commonly understood by those skilled in the art in the related field of the present invention. The contents of all publications described herein by reference are incorporated into the present invention.
[부호의 설명][Description of the code]
1: 큐베트1: cuvette
100: 반응 챔버부100: reaction chamber portion
110: 채취부재 대기 챔버 110: collecting member atmospheric chamber
112, 114: 오픈부 112, 114: open section
120: 시료 충진 챔버 120: sample filling chamber
130: 제 1 시약 충진 챔버130: first reagent filling chamber
132: 제 2 시약 충진 챔버132: second reagent filling chamber
134: 제1 커버134: first cover
136: 제2 커버136: second cover
138: 분리부 또는 자석부138: separator or magnet
140: 자석140: magnet
142: 자석 홀더142: magnet holder
200: 검출부200: detector
210: 검출 챔버 210: detection chamber
220: 카트리지220: cartridge
300: 연결 지그300: connecting jig
400: 바코드400: barcode

Claims (11)

  1. 일체화된 반응 및 검출 수단을 구비하는 멀티웰 큐베트로서, A multiwell cuvette having integrated reaction and detection means,
    시료와 시약이 놓이는 반응 챔버부; 및 A reaction chamber portion in which a sample and a reagent are placed; And
    상기 시료와 시약 간의 반응이 검출되는 검출부;를 포함하되, Including; detection unit for detecting a reaction between the sample and the reagent,
    상기 반응 챔버부는,The reaction chamber portion,
    시료의 분주 또는 분배를 위한 부재가 대기하는 채취부재 대기 챔버; 시료 충진 챔버; 및 시약이 충진되고, 상기 시료와의 반응이 수행되는 하나 이상의 시약 충진 챔버;를 포함하고,A collecting member waiting chamber in which a member for dispensing or dispensing a sample waits; A sample filling chamber; And at least one reagent filling chamber in which a reagent is filled and a reaction with the sample is performed.
    상기 검출부는,The detection unit,
    상기 시료와 시약간의 반응 결과물에 대한 크로마토그래피 분석용 수단 및 이를 수용하는 검출 챔버를 포함하는, 멀티웰 큐베트.And means for chromatographic analysis of the reaction product between the sample and the reagent and a detection chamber therein.
  2. 제 1 항에 있어서, The method of claim 1,
    상기 크로마토그래피 분석용 수단은 측방유동분석용 카트리지인, 멀티웰 큐베트.The means for chromatographic analysis is a cartridge for lateral flow analysis, multi-well cuvette.
  3. 제 2 항에 있어서, 상기 측방유동분석용 카트리지는 베이스 부재; 및 상기 베이스 부재와 채결되는 커버 부재를 포함하고, 3. The lateral flow analysis cartridge according to claim 2, further comprising: a base member; And a cover member engaged with the base member,
    상기 베이스 부재는, 상기 측방유동 분석에 사용되는 스트립을 수용하는 스트립 수용부 및 상기 스트립 수용부의 일 말단으로부터 연장되는 위치에 형성된 반응 결과물 웰을 포함하고, The base member includes a strip receiving portion containing a strip used for the lateral flow analysis and a reaction result well formed at a position extending from one end of the strip receiving portion,
    상기 커버 부재는 상기 베이스 부재와 채결시, 상기 스트립 수용부와 대응되는 부분에 형성된 측정창 및 상기 반응 결과물 웰과 대응되는 부분에 형성된 투입구를 포함하고, The cover member includes a measuring window formed at a portion corresponding to the strip receiving portion and an opening formed at a portion corresponding to the reaction result well when the base member is filled with the base member.
    상기 베이스 부재 또는 상기 커버 부재, 또는 상기 베이스 부재 및 상기 커버 부재는 상기 반응 결과물을 상기 스트립으로의 전달을 위한 모세관 구조물을 포함하며, 상기 커버 부재에 형성된 모세관 구조물은 상기 커버 부재의 상기 투입구와 인접한 하면에 형성되고, 상기 베이스 부재에 형성된 모세관 구조물은 상기 시료용 웰에 형성되는 것인, 멀티웰 큐베트.The base member or the cover member, or the base member and the cover member includes a capillary structure for delivering the reaction product to the strip, wherein the capillary structure formed on the cover member is adjacent to the inlet of the cover member. Is formed on the lower surface, the capillary structure formed in the base member is formed in the sample well, multi-well cuvette.
  4. 제 3 항에 있어서, 상기 멀티웰 큐베트는 상기 반응결과물 웰의 하부에 위치하는 자석부를 추가로 포함하는 것인, 멀테웰 큐베트. 4. The multi-well cuvette of claim 3, wherein the multiwell cuvette further comprises a magnet located under the reaction well.
  5. 제 1 항에 있어서, The method of claim 1,
    상기 채취부재 대기 챔버, 시약 충진 챔버 및 검출 챔버는 일 방향으로 순차적으로 배치되어 적어도 하나의 열을 갖게 배치된, 멀티웰 큐베트.The collection member atmospheric chamber, the reagent filling chamber and the detection chamber are arranged in sequence in one direction to have at least one row, multi-well cuvette.
  6. 제 1 항에 있어서, The method of claim 1,
    상기 채취부재 대기 챔버 및 상기 시약 충진 챔버는 소정의 팁을 갖는 검사 장비가 투입될 수 있도록 상부에 형성된 오픈부를 갖는, 멀티웰 큐베트.And the collecting member atmospheric chamber and the reagent filling chamber have an open portion formed at an upper portion thereof so that inspection equipment having a predetermined tip can be inserted therein.
  7. 제 1 항에 있어서, The method of claim 1,
    상기 시약 충진 챔버는 두 개 이상 형성되는 것인 멀티웰 큐베트.Wherein at least two reagent filling chambers are formed.
  8. 제 1 항에 있어서, The method of claim 1,
    상기 시약 충진 챔버의 상면를 덮는 제 1 커버를 더 포함하는, 멀티웰 큐베트.And a first cover covering a top surface of said reagent filling chamber.
  9. 제 1 항에 있어서, The method of claim 1,
    상기 제 1 커버는, 소정의 팁을 갖는 검사 장비가 적어도 일부분을 뚫고 침투되도록 얇은 박막 구조를 갖는, 멀티웰 큐베트.And the first cover has a thin film structure such that inspection equipment having a predetermined tip penetrates through at least a portion thereof.
  10. 제 1 항에 있어서, The method of claim 1,
    상기 큐베트는 그 상면의 전부 또는 일부를 커버하는 제 2 커버를 포함하는 것인, 멀티웰 큐베트.And the cuvette comprises a second cover covering all or part of its top surface.
  11. 제 10 항에 있어서, 상기 제 2 커버는 상기 멜티웰 큐베트를 이용하여 분석되는 시료의 종류를 식별하는 바코드를 추가로 포함하는 것인, 멀티웰 큐베트. The multiwell cuvette of claim 10, wherein the second cover further comprises a barcode that identifies the type of sample to be analyzed using the Meltiwell cuvette.
PCT/KR2014/010784 2013-11-12 2014-11-11 Multi-well cuvette provided with integrated reaction and detection means WO2015072718A1 (en)

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