WO2013154213A1 - Cartouche de diagnostic - Google Patents

Cartouche de diagnostic Download PDF

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Publication number
WO2013154213A1
WO2013154213A1 PCT/KR2012/002722 KR2012002722W WO2013154213A1 WO 2013154213 A1 WO2013154213 A1 WO 2013154213A1 KR 2012002722 W KR2012002722 W KR 2012002722W WO 2013154213 A1 WO2013154213 A1 WO 2013154213A1
Authority
WO
WIPO (PCT)
Prior art keywords
micro flow
flow passage
flow passages
widths
reactant
Prior art date
Application number
PCT/KR2012/002722
Other languages
English (en)
Inventor
Kwangsuk YANG
Hyekyung JEON
Gueisam Lim
Jungsun Han
Original Assignee
Lg Electronics Inc.
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.)
Filing date
Publication date
Application filed by Lg Electronics Inc. filed Critical Lg Electronics Inc.
Priority to PCT/KR2012/002722 priority Critical patent/WO2013154213A1/fr
Publication of WO2013154213A1 publication Critical patent/WO2013154213A1/fr

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Classifications

    • 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
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40Static mixers
    • B01F25/42Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/433Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
    • B01F25/4331Mixers with bended, curved, coiled, wounded mixing tubes or comprising elements for bending the flow
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/40Static mixers
    • B01F25/42Static mixers in which the mixing is affected by moving the components jointly in changing directions, e.g. in tubes provided with baffles or obstructions
    • B01F25/43Mixing tubes, e.g. wherein the material is moved in a radial or partly reversed direction
    • B01F25/433Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
    • B01F25/4338Mixers with a succession of converging-diverging cross-sections, i.e. undulating cross-section
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01FMIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30Micromixers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • 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
    • B01L2200/06Fluid handling related problems
    • B01L2200/0684Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867Multiple inlets and one sample wells, e.g. mixing, dilution
    • 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
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087Multiple sequential chambers
    • 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
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0883Serpentine channels
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary forces

Definitions

  • the present invention relates to a diagnostic cartridge having a structure wherein air bubbles are removed and mixing is accelerated, and more particularly, to a diagnostic cartridge that is provided with a micro flow passage through which air bubbles can be removed and the mixing of samples can be accelerated.
  • micro fluid control technology controlling the flow, flow rate, or flowing direction of a micro fluid
  • the specific components contained in a biological fluid like blood are detected quantitatively or qualitatively. Therefore, the technology is recognized as one of main technology in the fields of a biochip or lab-on-a-chip (LOC).
  • a diagnostic cartridge should not have any air bubbles while fluids are being moved. Except that the generation of the air bubbles is intendedly needed, the diagnostic cartridge possibly suppresses the generation of air bubbles to permit the flow of the fluids to be constantly adjusted.
  • commercial diagnostic cartridges should conduct a biochemical reaction using a small quantity of biological sample and a mixing process for accelerating the biochemical reaction. So as to perform the unit operation in a single cartridge, air bubbles are unavoidably formed while the samples are being moved.
  • the formation of the air bubbles causes the residual pressure in the interiors of microfluidic channels during the samples are moved or mixed and further interferes with a gentle reaction between an object substance in the sample and an electrode, the antibody on the electrode, or the antibody fixed on a surface.
  • the present invention has been made in view of the above-mentioned problems occurring in the prior art, and it is an object of the present invention to provide a diagnostic cartridge that can remove the air bubbles generated in a microfluidic system and accelerate the gentle mixing of fluids like samples, thereby enhancing the reliability of the measured signal and obtaining reproducible measured results.
  • a diagnostic cartridge including: an injection part adapted to inject a biological sample and a reactant thereinto; a micro flow passage adapted to move the injected biological sample and reactant from the injection part therealong; and a detector adapted to detect the reaction result of the biological sample and reactant moved along the micro flow passage, wherein the micro flow passage is formed in such a manner where a plurality of micro flow passages having small widths and a plurality of micro flow passages having large widths are connected to each other in an alternating manner.
  • the micro flow passage is bent at the portions where the plurality of micro flow passages having large widths are connected to the plurality of micro flow passages having small widths.
  • the plurality of micro flow passages having small widths connected to the bent plurality of micro flow passages having large widths are disposed in parallel to each other.
  • the diagnostic cartridge further includes a moving part adapted to move the injected biological sample and reactant.
  • the moving part pushes or sucks the air in the micro flow passage to move the injected biological sample and reactant.
  • the plurality of micro flow passages having large widths are rounded on the outside thereof.
  • the plurality of micro flow passages having large widths catch the air bubbles generated while the injected biological sample and reactant are being moved.
  • the plurality of micro flow passages having large widths make the moving speeds of the injected biological sample and reactant different from each other, thereby raising their mixing ratio.
  • the diagnostic cartridge can remove the air bubbles generated in a microfluidic system and accelerate the gentle mixing of the fluids like samples, thereby enhancing the reliability of the measured signal and obtaining reproducible measured results.
  • FIG.1 is a view showing a configuration of a diagnostic cartridge according to a preferred embodiment of the present invention.
  • FIG.2 is a view showing an effect of the micro flow passage in the diagnostic cartridge according to the preferred embodiment of the present invention.
  • FIGS.3 and 4 are views showing other effects of the micro flow passage in the diagnostic cartridge according to the preferred embodiment of the present invention.
  • FIGS.5 to 7 are views showing configurations of diagnostic cartridges according to various embodiments of the present invention.
  • FIG.1 is a view showing a configuration of a diagnostic cartridge according to a preferred embodiment of the present invention.
  • the portion shown in FIG.1 shows the configuration of a fluid channel, that is, a micro flow passage in the diagnostic cartridge, through which a fluid is passed to move.
  • the diagnostic cartridge according to the present invention includes an injection part (not shown) into which a biological sample and a reactant are injected.
  • the biological sample and the reactant are at the same time injected into one injection part (not shown), and alternatively, they are injected respectively into two different injection parts (not shown).
  • a micro flow passage 100 is formed by connecting micro flow passages having different widths to each other in an alternating manner. That is, as shown in FIG.1, micro flow passages 110-1, 110-2, 110-3, 110-4, and 110-5 having small widths and micro flow passages 120-1, 120-2, 120-3, and 120-4 having large widths are connected alternately to each other.
  • the injected substances are first moved in the order of the micro flow passage 110-1 having small width, the micro flow passage 120-1 having large width, the micro flow passage 110-2 having small width, the micro flow passage 120-2 having large width, and the like. At this time, the micro flow passages 120-1, 120-2, 120-3, and 120-4 having large widths are bent to make the moving directions changed. Also, the micro flow passages 110-1, 110-2, 110-3, 110-4, and 110-5 having small widths are disposed in parallel to each other.
  • the diagnostic cartridge according to the present invention further includes a detector (not shown) adapted to detect the reaction result of at least one of the biological sample and reactant moved along the micro flow passage 100. If an optical method is applied, the detector is composed of an LED (Light Emitting Diode) or PD (Photo Detector), and if a method of physical chemistry is applied, it is composed of an electrode.
  • a detector not shown
  • FIG.2 is a view showing an effect of the micro flow passage in the diagnostic cartridge according to the preferred embodiment of the present invention.
  • FIG.2 is an enlarged view of FIG.1, wherein the micro flow passage 110-1 having small width is connected to the micro flow passage 120-1 having large width and air bubbles 10 generated from the injection of liquid (fluid) are shown by circles.
  • the air bubbles 10 are caught by the plurality of micro flow passages having large widths. That is, if the air bubbles 10 are generated, they are moved along the micro flow passage 110-1 having small width, but when they reach the micro flow passage 120-1 having large width, it is difficult to be moved to the micro flow passage 110-2 having small width.
  • the micro flow passages 110-1, 110-2,... having small widths desirably have smaller widths than the diameters of the air bubbles 10, but even when they have larger widths than the diameters of the air bubbles 10, the air bubbles 10 are effectively removed through a plurality of steps, so that no air bubbles are contained in the liquid (fluid) discharged finally.
  • the detector serves to analyze the liquid (fluid) from which the air bubbles 10 are removed, thereby providing more precise results.
  • FIGS.3 and 4 are views showing other effects of the micro flow passage in the diagnostic cartridge according to the preferred embodiment of the present invention.
  • the configuration of the micro flow passage 100 of FIG.3 is basically the same as in FIG.1, and FIG.4 is an enlarged view of the micro flow passage having large width in the whole configuration of the micro flow passage 100 of FIG.3.
  • the arrows of FIGS.3 and 4 indicate the routes along which a first solution 20 and a second solution 30 flow.
  • the first solution 20 is moved along the outside of the micro flow passage with large width and the second solution is moved to the inside thereof.
  • FIG.4 shows the movements of the two solutions in a clear manner.
  • the length of the outside of the micro flow passage having large width is longer than that of the inside thereof.
  • the inside length thereof is 3mm
  • the outside length thereof is 6.7mm because it is turned along the curved line thereof. Therefore, the ratio of the outside length to the inside length is 1:2.3, which makes the outside length longer by about 2.3 times than the inside length.
  • the mixing of the two solutions is accelerated through the difference of the moving distances thereof.
  • the first solution 20 and the second solution 30, which exist before and after the moving distance of about 2.3 times, become close to each other up to a distance of 100um, that is, the width of the micro flow passage having small width, thereby minimizing the distance required for their diffusion. That is, when the two solutions are moved along the micro flow passage having small width and then enter the micro flow passage having large width again, if the width of the micro flow passage having small width is only about 100um, the two solutions are diffused within a relatively narrow range to reduce the distance required for their diffusion.
  • the structure of the micro flow passage 100 of the diagnostic cartridge allows the mixing and diffusion of the solutions to be easily conducted.
  • the widths of the micro flow passage 100 are adjusted large and small to optimize the mixing effect of the solutions, thereby advantageously enhancing the reaction speed of different liquids (fluids).
  • the numeric values as mentioned above are used just to describe the preferred embodiment of the present invention, but they may be varied, without any limitation thereto.
  • the micro flow passages having large widths may have the widths in a range between 0.1mm and 10mm, and in the same manner as above, the micro flow passages having small widths may have the widths in a range between 10um and 500um. That is, only if there is a difference between the widths of the micro flow passages having large widths and the widths of the micro flow passages having small widths, all of numeric values do not matter.
  • FIGS.5 to 7 are views showing configurations of diagnostic cartridges according to various embodiments of the present invention.
  • FIG.5 shows another embodiment of the present invention wherein the micro flow passages having small widths are short in length and the micro flow passages having large widths have more rounded shapes than those in FIG.1.
  • the mixing effect can be more optimized.
  • FIG.6 shows still another embodiment of the present invention, which is similar to FIG.5, wherein the micro flow passages having small widths are more bent than those in FIG.5.
  • the mixing effect can be more optimized like FIG.5.
  • FIG.7 shows yet another embodiment of the present invention wherein the micro flow passages having small widths scarcely exist in shape and the micro flow passages having large widths mainly exist.
  • the effect of removing air bubbles can be best optimized.
  • the diagnostic cartridge according to the preferred embodiments of the present invention can remove the air bubbles generated in the microfluidic system and accelerate the gentle mixing of the solutions like samples, thereby enhancing the reliability of the measured signal and obtaining reproducible measured results.
  • the effect of removing the air bubbles which is mentioned in FIG.2
  • the effect of accelerating the mixing and reacting speeds which is mentioned in FIGS.3 and 4 are all provided to obtain more precise measurement results.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Analytical Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

La présente invention concerne une cartouche de diagnostic qui comprend : une partie d'injection conçue pour injecter un échantillon biologique et un réactif à l'intérieur; un passage à petit débit conçu pour déplacer l'échantillon biologique et le réactif injectés depuis la partie d'injection sur sa longueur; et un détecteur conçu pour détecter le résultat de réaction de l'échantillon biologique et du réactif déplacés le long du passage à petit débit, le passage à petit débit étant formé de telle manière qu'une pluralité de passages à petit débit ayant une faible largeur et une pluralité de passages à petit débit ayant une grande largeur sont reliés les uns aux autres d'une manière alternée, de sorte que les bulles d'air générées dans un système microfluidique puissent être éliminées et que le mélange délicat des fluides, comme les échantillons, puisse être accéléré, ce qui améliore la fiabilité du signal mesuré et permet d'obtenir des résultats mesurés reproductibles.
PCT/KR2012/002722 2012-04-10 2012-04-10 Cartouche de diagnostic WO2013154213A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/KR2012/002722 WO2013154213A1 (fr) 2012-04-10 2012-04-10 Cartouche de diagnostic

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2012/002722 WO2013154213A1 (fr) 2012-04-10 2012-04-10 Cartouche de diagnostic

Publications (1)

Publication Number Publication Date
WO2013154213A1 true WO2013154213A1 (fr) 2013-10-17

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Application Number Title Priority Date Filing Date
PCT/KR2012/002722 WO2013154213A1 (fr) 2012-04-10 2012-04-10 Cartouche de diagnostic

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110836859A (zh) * 2019-12-13 2020-02-25 循证医疗科技(杭州)有限公司 一种血样检测流道结构

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6326211B1 (en) * 1995-06-29 2001-12-04 Affymetrix, Inc. Method of manipulating a gas bubble in a microfluidic device
US20060171864A1 (en) * 2005-01-07 2006-08-03 Philippe Caze High performance microreaction device
US20070125434A1 (en) * 2005-12-02 2007-06-07 Enplas Corporation Microfluidic device
US20070280856A1 (en) * 2006-06-02 2007-12-06 Applera Corporation Devices and Methods for Controlling Bubble Formation in Microfluidic Devices
US20100078086A1 (en) * 2008-09-29 2010-04-01 Roland Guidat Multiple flow path microreactor design

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6326211B1 (en) * 1995-06-29 2001-12-04 Affymetrix, Inc. Method of manipulating a gas bubble in a microfluidic device
US20060171864A1 (en) * 2005-01-07 2006-08-03 Philippe Caze High performance microreaction device
US20070125434A1 (en) * 2005-12-02 2007-06-07 Enplas Corporation Microfluidic device
US20070280856A1 (en) * 2006-06-02 2007-12-06 Applera Corporation Devices and Methods for Controlling Bubble Formation in Microfluidic Devices
US20100078086A1 (en) * 2008-09-29 2010-04-01 Roland Guidat Multiple flow path microreactor design

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110836859A (zh) * 2019-12-13 2020-02-25 循证医疗科技(杭州)有限公司 一种血样检测流道结构

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