WO2023219148A1 - 流体デバイス - Google Patents

流体デバイス Download PDF

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Publication number
WO2023219148A1
WO2023219148A1 PCT/JP2023/017822 JP2023017822W WO2023219148A1 WO 2023219148 A1 WO2023219148 A1 WO 2023219148A1 JP 2023017822 W JP2023017822 W JP 2023017822W WO 2023219148 A1 WO2023219148 A1 WO 2023219148A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluid
disc
shaped space
fluidic device
space
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2023/017822
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
雄弥 宮澤
陽子 熊谷
成史 伊藤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Provigate Inc
Original Assignee
Provigate 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 Provigate Inc filed Critical Provigate Inc
Priority to EP23803622.2A priority Critical patent/EP4524579A4/en
Priority to JP2024520492A priority patent/JPWO2023219148A1/ja
Priority to CN202380040261.3A priority patent/CN119137485A/zh
Priority to US18/864,638 priority patent/US20250303411A1/en
Publication of WO2023219148A1 publication Critical patent/WO2023219148A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/48707—Physical analysis of biological material of liquid biological material by electrical means
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502715—Containers 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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0645—Electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/088—Channel loops
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0409—Moving fluids with specific forces or mechanical means specific forces centrifugal forces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28—Electrolytic cell components
    • G01N27/30—Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
    • G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels

Definitions

  • the present disclosure relates to fluidic devices.
  • Microfluidic devices with small volumes have been developed to perform measurements of small volumes of liquid samples.
  • the target solution may be introduced into a relatively central portion of the volume due to the resistance of the wall surface, and the previous liquid may remain in the vicinity of the wall surface. This results in an unbalanced solution distribution within the fluidic device. As long as the volume of the fluidic device is large, these problems will have a small effect on the measurement results, and measurements can be performed in areas where problems do not occur. That is, these problems can be ignored.
  • microfluidic devices it is desired to improve the generation or persistence of voids and the efficiency of fluid exchange.
  • the present disclosure describes and provides microfluidic devices that suppress or avoid these and other problems.
  • a device body having a disc-shaped space that accommodates a fluid; a fluid inlet configured to introduce the fluid clockwise and tangentially at a zero o'clock position of a substantially circumferential portion of the disc-shaped space; and a fluid inlet configured to introduce the fluid in a clockwise and tangential direction; a fluid outlet configured to direct the fluid from the space at a 6 o'clock to 12 o'clock position;
  • a fluidic device is provided.
  • highly accurate measurements can be efficiently performed on a relatively small amount of sample.
  • FIG. 3 is a top view schematically showing a fluidic device according to a comparative example.
  • FIG. 3 is a top view schematically showing a fluidic device according to a comparative example.
  • 1 is a top view schematically illustrating a fluidic device according to some embodiments.
  • FIG. 1 is a top view schematically illustrating a fluidic device according to some embodiments.
  • FIG. FIG. 1 is a top view (A) and a perspective view (B) schematically showing a fluidic device according to an embodiment.
  • FIG. 1 is a top view (A) and a perspective view (B) schematically showing a fluidic device according to an embodiment.
  • FIG. 1 is a top view schematically showing a fluidic device according to an embodiment.
  • FIG. 1 is a top view schematically showing a fluidic device according to an embodiment.
  • FIG. 1 is an exploded perspective view of a fluidic device according to one embodiment.
  • FIG. 3 is a top view schematically showing a fluidic device according to a comparative example.
  • 2 is a graph showing output versus introduction amount in a fluid device according to an embodiment and a fluid device according to a comparative example.
  • 7 is a graph showing temporal changes in output at each height of a disc-shaped space according to an example. It is a graph which shows the relationship between the height of a disk-shaped space, and the maintenance time of the maximum output based on one Example.
  • a “disk-shaped space” as used herein generally refers to a cylindrical space.
  • the size of the cross section of the cylinder (size of major axis and/or minor axis, diameter or radius) is the same as or larger than the size in the central axis direction.
  • the cylinder of the "disk-shaped space” has a substantially perfect circular cross-section, and its diameter or radius is larger than its central axial size (height of the disc-shaped space).
  • a “fluid inlet” (referred to as “fluid inlet” or “inlet”) and/or a “fluid outlet” (referred to as “fluid outlet” or “outlet”) has a tubular space (flow path) inside. It may be detachably connected to the device main body, may be fixed to the device main body, or may be formed or manufactured integrally with the device main body. Inlet and/or outlet may refer to the flow path itself.
  • zero o'clock refers to the angular position of the disk space where the fluid flowing from the fluid inlet has substantially entered the disk space.
  • the direction from the center of the disk space toward the connection position of the fluid inlet to the disk space may be defined as 0 o'clock.
  • Zero o'clock may be defined as the radial direction perpendicular to the circumferential direction at the time of fluid introduction.
  • the introduced fluid, or at least a portion thereof flows circumferentially near the circumference of the disc-shaped space. This flow direction is defined herein as clockwise.
  • the inlets and/or outlets are arranged circumferentially, substantially circumferentially, or near the circumferentially.
  • circumferential portion refers to or near the circumference of a disk of a disk-shaped space of a fluidic device. This does not refer to a location on the geometric circumference, but rather to a location at least a distance away from the geometric circumference that is necessary for introducing fluid into or out of the disc-shaped space. Or point to a part.
  • the inlet and/or outlet may have a tubular structure with at least part or all of its diameter contained within the disk. In this case, the center of the inlet or outlet tube does not lie on the circumference of the disk.
  • the inlet and/or outlet may not be circumferentially circumferential or circumferentially circumferential due to manufacturing factors.
  • Disk-shaped space refers to a space that is formed in a cylindrical shape.
  • the cross section perpendicular to the central axis of the cylinder may be a perfect circle.
  • the cross section of the cylinder may be non-circular, for example elliptical.
  • the circumferential surface of the disc-shaped space may be formed as a substantially curved surface, preferably a continuous curved surface.
  • the fluid inlet may be configured to introduce fluid in a direction perpendicular to the central axis of the cylinder of the disc-shaped space, that is, in an in-plane direction of the disc. In some embodiments, it may be connected to the side of the disc from outside the disc-shaped space.
  • the fluid inlet may be configured to introduce fluid in a direction perpendicular to the central axis of the cylinder of the disc-shaped space, that is, in a direction inclined from the in-plane direction of the disc.
  • a fluid inlet may be connected to the bottom of the cylinder.
  • the fluid inlet may be connected to the bottom surface of the cylinder in a non-perpendicular or oblique direction. That is, the direction of the fluid inlet projected onto the bottom surface of the cylinder faces in the circumferential direction of the cylinder.
  • the angled inlet and outlet may be connected to the same bottom surface of the disc-shaped space. In some embodiments, the angled inlet may be connected to the first bottom surface (one bottom surface) and the outlet may be connected to the second bottom surface (the other bottom surface).
  • the two bottom surfaces may not necessarily be parallel.
  • the bottom surface may not be flat.
  • at least a portion thereof may be formed in a cone shape (convex or concave with respect to the disk space).
  • the bottom surface of one of the cylinders may be configured to diverge from the other bottom surface in the vicinity of the fluid inlet (convex cone). This allows, for example, air bubbles within the disc space to easily escape from the fluid outlet.
  • the bottom surface of one of the cylinders may be configured to approach the bottom surface of the other near the fluid inlet (concave cone).
  • the fluid introduced into the disk space easily passes around the circumference.
  • the water flow on the circumferential side which has a relatively low solution exchange rate, can be strengthened to increase the solution exchange rate.
  • the heights of the disk-shaped spaces are 10 ⁇ m, 15 ⁇ m, 20 ⁇ m, 25 ⁇ m, 30 ⁇ m, 40 ⁇ m, 50 ⁇ m, 60 ⁇ m, 70 ⁇ m, 80 ⁇ m, 90 ⁇ m, 100 ⁇ m, 150 ⁇ m, 200 ⁇ m, 300 ⁇ m, 400 ⁇ m, 500 ⁇ m, 600 ⁇ m, 700 ⁇ m, 800 ⁇ m, 900 ⁇ m. m, It may be a value such as 1000 ⁇ m or larger.
  • the heights of the disk-shaped spaces are 10 ⁇ m, 15 ⁇ m, 20 ⁇ m, 25 ⁇ m, 30 ⁇ m, 40 ⁇ m, 50 ⁇ m, 60 ⁇ m, 70 ⁇ m, 80 ⁇ m, 90 ⁇ m, 100 ⁇ m, 150 ⁇ m, 200 ⁇ m, 300 ⁇ m, 400 ⁇ m, 500 ⁇ m, 600 ⁇ m, 700 ⁇ m, 800 ⁇ m, 900 ⁇ m. m, It may be a value such as 1000 ⁇ m, 1.5 mm, 2 mm or a smaller value.
  • the feature quantity in the radius or surface direction of the disc-shaped space may be a value such as 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, or a larger value.
  • the feature amount in the radius or surface direction of the disk-shaped space is a value such as 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, etc. or more. It may be a small value.
  • the volumes of the disk-shaped spaces are 1 ⁇ L, 2 ⁇ L, 3 ⁇ L, 4 ⁇ L, 5 ⁇ L, 6 ⁇ L, 7 ⁇ L, 8 ⁇ L, 9 ⁇ L, 10 ⁇ L, 15 ⁇ L, 20 ⁇ L, 30 ⁇ L, 40 ⁇ L, 50 ⁇ L, 60 ⁇ L, 70 ⁇ L, 80 ⁇ L, 90 ⁇ L, 100 ⁇ L, 200 ⁇ L, 300 ⁇ L. , 400 ⁇ L, 500 ⁇ L, or a larger value.
  • the volume of the disc-shaped space is 5 ⁇ L, 6 ⁇ L, 7 ⁇ L, 8 ⁇ L, 9 ⁇ L, 10 ⁇ L, 15 ⁇ L, 20 ⁇ L, 30 ⁇ L, 40 ⁇ L, 50 ⁇ L, 60 ⁇ L, 70 ⁇ L, 80 ⁇ L, 90 ⁇ L, 100 ⁇ L, 200 ⁇ L, 300 ⁇ L, 400 ⁇ L, 500 ⁇ L, 1 mL, etc. or a smaller value.
  • the fluid inlet may have a volume of substantially 50% to 200% of the volume of the disc-shaped space.
  • the volume of the fluid inlet may be substantially 50%, 100%, 150%, or 200% of the volume of the disc-shaped space.
  • the sum of the volume of the disc-shaped space and the volume of the inlet is a value such as 2 ⁇ L, 3 ⁇ L, 4 ⁇ L, 5 ⁇ L, 6 ⁇ L, 7 ⁇ L, 8 ⁇ L, 9 ⁇ L, 10 ⁇ L, etc. It may be a larger value.
  • the total volume of the disc-shaped space and the volume of the inlet may be a value such as 10 ⁇ L, 15 ⁇ L, 20 ⁇ L, 30 ⁇ L, 40 ⁇ L, 50 ⁇ L, or a smaller value.
  • the fluidic device may have a sensor on the inner wall of the disc-shaped space.
  • the sensor may be located on the bottom inner wall of one or both of the disc-shaped spaces.
  • the subject may include or be a human.
  • the subject may include or be a non-human animal.
  • the subject may include or be a mammal.
  • the subject may be, for example and without limitation, a working animal, a domestic animal, a pet animal, or a wild animal.
  • the sample to be measured may be a solution.
  • the "solution" may be a body fluid, a solution derived from a body fluid, or a diluted body fluid.
  • the solution may be a solution that is not a body fluid (derived from a non-body fluid), or may be a body fluid or a mixture of a body fluid-derived solution and a non-body fluid-derived solution.
  • the solution may be a solution used for sample measurements or a solution used for calibration measurements.
  • the solution may be a standard solution or a calibration solution.
  • the solution may be a liquid that intentionally or intentionally does not contain the substance to be measured because it is used for calibration or the like.
  • the sample to be measured may be a specimen.
  • the solution may be a solution containing a chemical substance.
  • Body fluid may be lymph fluid, tissue fluid such as interstitial fluid, intercellular fluid, interstitial fluid, body cavity fluid, serosal fluid, pleural effusion, ascites fluid, pericardial fluid, cerebrospinal fluid ( It may be cerebrospinal fluid), joint fluid (synovial fluid), or aqueous humor (aqueous humor).
  • the body fluid may be a digestive fluid such as saliva, gastric juice, bile, pancreatic juice, intestinal juice, etc., or may be sweat, tears, nasal mucus, urine, semen, vaginal fluid, amniotic fluid, or milk.
  • the body fluid may be an animal body fluid or a human body fluid.
  • a "body fluid” may be a solution.
  • the solution may contain a physiological buffer containing the substance to be measured, such as phosphate buffered saline (PBS) or N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer (TES). .
  • PBS phosphate buffered saline
  • TES N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer
  • the solution is not particularly limited as long as it contains the substance to be measured.
  • the solution may contain a substance to be measured.
  • the solution may have the possibility of containing the substance to be measured.
  • the substance to be measured may be a molecule, an ion, a polymer, a biomolecule, or the like.
  • the substance to be measured may include biomolecules.
  • the substance to be measured may be a protein, a glycated protein, or the like.
  • the solution may be tears, and the substance to be measured may be albumin, glycoalbumin, hemoglobin, or glycated hemoglobin contained in the tears.
  • the measurement target may be albumin, glycated albumin, hemoglobin, or glycated hemoglobin in blood, serum, or plasma, or albumin, glycated albumin, hemoglobin, or glycated hemoglobin in interstitial fluid, urine, or saliva.
  • Albumin may be oxidized albumin (HNA) or reduced albumin (HMA).
  • HNA oxidized albumin
  • HMA reduced albumin
  • the substance to be measured may be AGE (Advanced Glycation End Products).
  • the substance to be measured may be a glycated lipid.
  • the sensor may be a chemical sensor, a biosensor, an ion sensor, or the like (hereinafter sometimes referred to as a "sensor”, “biochemical sensor”, “chemical sensor”, or “electrochemical sensor”).
  • the sensor may include multiple sensors.
  • the sensor may include an electrode.
  • the electrode may be an amperometric type electrode.
  • the electrode may include a hydrogen peroxide electrode.
  • the electrode may include an oxygen electrode.
  • the electrode may be a potentiometric type electrode.
  • the electrode may be an electrode for ion detection (pH electrode, cyanide ion electrode, iodide ion electrode, etc.).
  • the senor may output an electrical signal. In some aspects, the sensor may output a current signal. The sensor may output a voltage signal or a charge. The sensor may be electrically connected to an ammeter, voltmeter, etc.
  • the senor may have an enzyme membrane over the electrode.
  • the enzyme membrane may include a protease.
  • protease is generally a general term for peptide bond hydrolases that hydrolyze and catabolize proteins and polypeptides. Proteases may be enzymes that break down proteins into peptide fragments. When a protein contains glycosylated amino acid residues, peptide fragments generated by the action of protease may include peptide fragments containing glycosylated amino acid residues and peptide fragments that are not glycosylated at all.
  • protease may be an animal-derived protease, a plant-derived protease, or a microbial-derived protease.
  • the protease may be an exopeptidase or an endopeptidase.
  • the protease may be an aspartic protease, a metalloprotease, a serine protease, or a thiol protease.
  • protease may include multiple types or types of proteases, or may include one type or type of protease.
  • protease may include either proteinase or peptidase, or both.
  • Degradation efficiency may be increased by mixing multiple proteases.
  • the protease may include a modified protease or a modified protease.
  • Proteases may be used with additives.
  • the additive may be, for example, a surfactant, urea. Additives can, for example and without limitation, destabilize or denature proteins.
  • modified proteases and additives for example and without limitation, protein degradation efficiency and substrate selectivity can be improved.
  • a “substrate” is a substance that catalyzes a chemical reaction by an enzyme.
  • a substrate is a substance that binds to an enzyme protein, thereby undergoing a reduction in the activation energy of a particular chemical reaction and, as a result, being converted to a particular product at an astonishing rate.
  • the enzyme membrane may include oxidase.
  • Oxidase is an enzyme that uses a molecular oxygen substrate as an electron acceptor.
  • oxidase is an enzyme that catalyzes a redox reaction that uses oxygen molecules as hydrogen or electron acceptors.
  • the oxidase may include a ketoamine oxidase.
  • the oxidase may include glucose oxidase. This can be used to measure the glucose concentration in a sample.
  • the substrate may include glucose.
  • the oxidase may include alcohol oxidase. In that case, the substrate may contain a primary alcohol. This can be used to measure the alcohol concentration in a sample.
  • Ketoamine oxidase generally recognizes the ketoamine structure of glycated amino acids or peptides or peptide fragments containing glycated amino acid residues, and oxidizes the glycated amino acids to produce amino acids, glucosone ( ⁇ -ketoaldehyde) and peroxidized Refers to an oxidase that produces hydrogen.
  • ketoamine oxidase produces a concentration of hydrogen peroxide that is proportional to or related to the concentration of the glycated amino acid or peptide or peptide fragment containing the glycated amino acid residue that it recognizes.
  • Ketoamine oxidase may be a dehydrogenase, a kinase, or an oxidase.
  • the ketoamine oxidase may be fructosyl amino acid oxidase (FAOD), fructosyl peptide oxidase, fructosylvalyl histidine oxidase, fructosyl amine oxidase, amadoriase, fructosyl amine deglycase, or modified forms thereof.
  • FOD fructosyl amino acid oxidase
  • FOD fructosyl peptide oxidase
  • fructosylvalyl histidine oxidase fructosyl amine oxidase
  • amadoriase fructosyl amine deglycase
  • the senor is capable of measuring glycated proteins.
  • a protease and a ketoamine oxidase may be placed on or near the electrode.
  • the enzyme membrane may include a protease and a ketoamine oxidase.
  • the general enzymatic method for measuring glycated proteins involves firstly decomposing the protein into amino acids using protease in the first step, and then peroxidizing only the glycated amino acids among those amino acids by using ketoamine oxidase in the second step. Hydrogen is generated and the hydrogen peroxide is measured optically or electrically in a third step.
  • the senor may include a detection unit.
  • the detection section may be a hydrogen peroxide detection section.
  • the "hydrogen peroxide detection section" (hydrogen peroxide sensor) may be an electrochemical electrode or a hydrogen peroxide electrode.
  • the hydrogen peroxide electrode may have a counter electrode, a reference electrode, and a working electrode.
  • the detection unit may detect oxygen. For example, the amount or concentration of oxygen reduced by an enzymatic reaction may be detected. Oxygen detection is relatively insensitive to molecules and ions that cause noise, and is considered to be resistant to interference. The amount of oxygen consumed may be measured by oxygen detection. Since the detection section is saturated with the atmosphere, it may be used for enzyme sensing.
  • the detection unit may be configured to be able to perform a plurality of detection methods selectively or in combination.
  • the fluidic device body may be configured to allow light to be directed into the interior of the disc-shaped space from the outside.
  • the fluidic device body may be at least partially transparent.
  • the fluidic device may include an optical device and may be configured to be connected to the optical device.
  • optical measurement generally refers to the use of optical elements or devices to determine optical properties of substances.
  • optical measurements of the substance of interest may be determined.
  • a substance bound to or associated with the target substance hereinafter referred to as a substance chemically, biologically, or physically bound to or associated with the target substance (e.g., a reagent), even if it is not the target substance itself) Properties may also be measured. Properties of the reagent may also be determined.
  • the reagent is sometimes referred to as a "target substance.”
  • optical measurements may include spectroscopic measurements.
  • the absorbance of the target substance may be measured.
  • a color-changing indicator depending on the substance of interest may be introduced. A color indicator may be detected or measured.
  • the fluidic device may include multiple disc-shaped spaces. Each disc may include an inlet and an outlet. Fluid may be provided to multiple inlets and disc-shaped spaces from a common flow path. Each of the plurality of inlets and disk-shaped spaces may be provided with fluid individually.
  • the plurality of disc-shaped spaces included in the fluidic device may have substantially the same volume or may have different volumes therebetween.
  • the fluidic device may be a stop-flow fluidic device. After the introduced fluid fills the disc-shaped space, the introduction of the fluid may be stopped. Thereafter, predetermined measurements or sensing may be performed on the fluid within the disc-shaped space.
  • predetermined measurements or sensing may be performed on the fluid in the disc-shaped space while the introduced fluid is flowing through the disc-shaped space.
  • FIG. 1A shows a schematic diagram of a fluidic device 100 as a comparative example.
  • the fluid device 100 has a main body 110 with a disk-shaped space 120 formed therein.
  • a fluid inlet 130 and a fluid outlet 140 are fluidly connected to this disc-shaped space 120 .
  • the fluid inlet 130 of FIG. 1A is arranged in a cross-sectional direction.
  • the fluid 151 (solid arrow) that has passed through the fluid inlet 130 is introduced into the disc-shaped space 120 perpendicularly to its 0 o'clock direction, that is, in the circumferential direction.
  • the fluid outlet 140 in FIG. 1A is located approximately at the center of the disc-shaped space 120 and directs the internal fluid to the outside of the disc-shaped space 120 from a bottom surface (not shown).
  • FIG. 1A shows a cross section of this disc-shaped space 120 perpendicular to the central axis.
  • the fluid outlet 140 is actually connected to the bottom surface of either disc-shaped space 120 and is not present in cross-section, but is shown in the same figure for illustrative purposes. The same applies to the following figures.
  • FIG. 1B shows the same fluidic device 100 as in FIG. 1A, and is used to explain an example of the flow of fluid 151 within disk-shaped space 120.
  • fluid 151 enters disc-shaped space 120 through fluid inlet 130, it flows around its circumference (see dashed line 152).
  • fluid outlet 140 is in the center of disc-shaped space 120. Therefore, the fluid 152 that has flowed through the circumferential portion leaves the circumferential portion, for example, from around 6 o'clock to 9 o'clock, without going around the circumferential portion.
  • the fluid 152 then flows in a drawn manner toward or into the fluid outlet 140 at the center of the disc-shaped space 120 . Therefore, a liquid level 153 is formed, and a space (sometimes called a bubble) 154 where no liquid exists is formed with this as a boundary.
  • a space sometimes called a bubble
  • FIG. 2A shows a schematic diagram of a fluidic device 200 as a comparative example.
  • the fluid device 200 has a main body 210 with a disk-shaped space 220 formed therein.
  • a fluid inlet 230 and a fluid outlet 240 are fluidly connected to this disc-shaped space 220 .
  • Fluid inlet 230 in FIG. 2A is arranged cross-sectionally.
  • the fluid 251 (solid arrow) that has passed through the fluid inlet 230 is introduced into the disc-shaped space 220 perpendicularly to its 0 o'clock direction, that is, in the circumferential direction.
  • the fluid outlet 240 in FIG. 2A is arranged near the circumference of the disc-shaped space 220 at the 3 o'clock position, and leads the internal fluid to the outside of the disc-shaped space 220 from the bottom surface (not shown).
  • FIG. 2B shows the same fluidic device 200 as FIG. 2A, and is used to explain an example of the flow of fluid 251 within disk-shaped space 220.
  • fluid 251 After fluid 251 enters disc-shaped space 220 through fluid inlet 230, it flows around its circumference (see dashed line 252).
  • Fluid outlet 240 is at the 3 o'clock position of disc-shaped space 220.
  • a part of the fluid 252 that has flowed around the circumference exits to the outside at the fluid outlet 240, but the rest flows further along the circumference.
  • the fluid 252 leaves the circumferential portion from around 6 o'clock to 9 o'clock, for example, without going around the circumference. Fluid 252 then flows in a manner that allows it to be pulled towards or into fluid outlet 240 .
  • a liquid level 253 is formed, and a space (sometimes called a bubble) 254 where no liquid exists is formed with this as a boundary.
  • a space sometimes called a bubble
  • the fluids 152, 252 (flows indicated by broken lines) inside the disk-shaped spaces 120, 220 shown in FIGS. 1 and 2 are merely examples, and should not be interpreted as being limited thereto. Other fluid flows are also possible. In some embodiments, the introduced fluid may completely fill the disc-shaped spaces 120, 220.
  • FIG. 3A-3D illustrate configurations of fluidic devices according to some embodiments.
  • FIG. 3A shows a fluidic device 300 in which a fluid outlet 340 is positioned near the circumference of the disc-shaped space 320 at the 6 o'clock position.
  • FIG. 3B shows fluidic device 400 with fluid outlet 440 positioned near the circumference of disc-shaped space 420 at about a 7:30 position.
  • FIG. 3C shows fluidic device 500 with fluid outlet 540 positioned near the circumference of disc-shaped space 520 at the 9 o'clock position.
  • the closer the fluid outlet is to the fluid inlet the less likely air bubbles will remain in the disc-shaped space.
  • FIG. 3D shows fluidic device 600 with fluid outlet 640 positioned near the circumference of disc-shaped space 620 at about the 10 o'clock position.
  • Outlet 640 in FIG. 3D is positioned as close to fluid inlet 630 as possible without interfering with fluid inlet 630.
  • the fluid introduced from the fluid inlet 630 and the fluid flowing along the circumference of the disc-shaped space 620 meet, and turbulence is likely to occur. Therefore, air (space or bubbles where no liquid exists) tends to remain.
  • the fluid outlet 640 can efficiently exhaust the air bubbles seen in FIGS. 1B and 2B to the outside.
  • the cross section of the disc-shaped space may be circular.
  • the cross section of the disc-shaped space may not be a circle, but may be another curved line, or may be composed of a plurality of curved surfaces.
  • the cross-section of the disc-shaped space may be elliptical.
  • FIGS. 4A and 4B show fluidic devices 700, 800 having an oval disc-shaped space.
  • the fluidic device 700 shown in FIG. 4A has an elliptical long axis in the 0 o'clock-6 o'clock direction of the disk-shaped space 720.
  • Fluid 751 is introduced into disc-shaped space 720 circumferentially by fluid inlet 730 at the zero o'clock position, which is one end of the longitudinal axis.
  • the fluidic device 800 shown in FIG. 4B has an elliptical long axis in the 3 o'clock-9 o'clock direction of the disc-shaped space 820.
  • Fluid 851 is introduced into disc-shaped space 820 circumferentially by fluid inlet 830 at the zero o'clock position, which is one end of the minor axis.
  • the fluid outlet 740, 840 is located at about 10 o'clock or a position close to the fluid inlet 730, 830 so as not to interfere with it.
  • the fluid inlet may be arranged in the in-plane direction of the cross-section of the disc-shaped space. In some embodiments, the fluid inlet may be positioned at an angle to the cross-section of the disc-shaped space.
  • FIG. 5 shows a fluidic device 900 according to one embodiment in which the fluid inlet is arranged in the in-plane direction of the cross-section of the disc-shaped space.
  • FIG. 5A shows a cross section parallel to the bottom surface, or top view, of fluidic device 900.
  • FIG. 5B is a perspective view of fluidic device 900, with main body 910 omitted.
  • the fluidic device 900 has a fluid inlet 930 arranged in an in-plane direction parallel to the bottom surface of the disc-shaped space 920.
  • the fluid inlet 930 introduces the fluid 951 in the in-plane direction of the disk-shaped space 920 at the 0 o'clock position (actually from near 11 o'clock to the 0 o'clock (12 o'clock) position).
  • the fluid (dashed line 952) flows primarily circumferentially within the disc-shaped space 920 and fills the disc-shaped space 920.
  • Fluid 952 finally exits through a fluid outlet 940 oriented generally vertically from the bottom of one of disc-shaped spaces 920 .
  • FIG. 6 shows an embodiment of a fluidic device 1000 in which the fluid inlet is arranged at an angle to the cross-section of the disc-shaped space.
  • FIG. 6A shows a cross section parallel to the bottom surface, or top view, of fluidic device 1000.
  • FIG. 6B is a perspective view of fluidic device 1000, with main body 1010 omitted.
  • the fluidic device 1000 has a fluid inlet 1030 oriented at an angle ⁇ with respect to the bottom surface of the disc-shaped space 1020.
  • the fluid inlet 1030 introduces the fluid 1051 into the disc-shaped space 1020 from the direction of the angle ⁇ at the 0 o'clock position of the disc-shaped space 1020 (actually from near 11 o'clock to the 0 o'clock (12 o'clock) position). .
  • the fluid (dashed line 1052) flows primarily circumferentially within the disc-shaped space 1020 and fills the disc-shaped space 1020.
  • Fluid 1052 finally exits through a fluid outlet 1040 oriented generally vertically from the bottom of one of disc-shaped spaces 920 .
  • the fluidic device may include a sensor within its disc-shaped space.
  • the sensor can sense the fluid introduced into the disc-shaped space or the substance contained in the fluid.
  • FIG. 7 shows a top view of a fluidic device 1100 according to one embodiment.
  • the solid lines and dashed lines are not to be interpreted as corresponding to whether or not they are visible from the top surface, but merely schematically illustrate the configuration of internal components of fluidic device 1100.
  • the fluid device 1100 has a disk-shaped space 1120 inside the main body 1110.
  • a fluid inlet 1130 and a fluid outlet 1140 are formed in the disc-shaped space 1120.
  • the fluid inlet 1130 is arranged obliquely with respect to the bottom surface of the disc-shaped space 1120, and the fluid outlet 1140 is arranged perpendicularly to the bottom surface of the disc-shaped space 1120.
  • the fluid introduction port 1131 is formed perpendicular to the plane of the main body 1110 or the disc-shaped space 1120, and introduces fluid introduced from the outside into the fluid introduction port 1131.
  • the fluid then enters the fluid inlet 1130 and is introduced into the disc-shaped space 1120 from an oblique direction.
  • the fluid outlet 1140 is formed at right angles to the plane of the body 1110 or disc-shaped space 1120. Fluid is directed from disc-shaped space 1120 to the outside via fluid outlet 1140.
  • Sensing electrodes 1121, 1122, and 1123 are arranged in the disk-shaped space 1120.
  • the sensing electrode is an electrochemical measurement electrode having three electrodes.
  • the sensing electrode has a working electrode 1121, a counter electrode 1122, and a reference electrode 1123. These electrodes are connected to corresponding connection terminals 1161, 1162, and 1163 via lead wires.
  • the connection terminal is exposed on the outer surface of the main body 1110 and can form an electrical connection from the outside.
  • FIG. 8 shows an exploded perspective view of a fluidic device 2000 according to one embodiment.
  • the fluidic device 2000 includes, from top to bottom, a pipette port 2100, a top seal 2200, a channel cell 2300, an adhesive film 2400, a sensor chip 2500, a sensor chip support 2600, an O-ring 2700, and a waste liquid tank 2800, which are arranged in the vertical direction. It is composed of a combination of.
  • the sensor chip support 2600 has a sensor chip receiving part 2680, and the sensor chip 2500 is installed therein.
  • a channel cell 2300 is tightly attached onto this via an adhesive film 2400.
  • the channel cell 2300 has a disk-shaped depression 2320 on its lower surface.
  • This disk-shaped depression 2320, the opposing surface of the electrode portion 2520 on the upper surface of the sensor chip 2500, and the through-hole 2320 of the adhesive film 2400 sandwiched therebetween define a disk-shaped space.
  • the top seal 2200 adheres to and seals the top surface of the channel cell 2300. Above this, a pipette port 2100 is placed.
  • the pipette port 2100 has a fluid inlet channel 2130 at the center and a pipette receiving portion 2131 that receives the pipette tip and continues to the fluid inlet channel 2130.
  • Top seal 2200 has a flow path inlet hole 2230 leading from pipette port 2100 to flow path cell 2300 .
  • the sensor chip support 2600 is pressed against the waste liquid tank 2800 via the O-ring 2700.
  • the channel cell 2300 above it has a mating pawl 2380 that mates with the pawl receiver 2880 of the waste liquid tank 2800 .
  • the pipette port 2100, top seal 2200, channel cell 2300, adhesive film 2400, sensor chip 2500, and sensor chip support 2600 assembled by adhesive are brought into close contact with the waste liquid tank 2800.
  • the fluid inlet channel 2130 of the pipette port 2100, the channel inlet hole 2230 of the top seal 2200, and the top opening of the fluid inlet 2330 of the channel cell 2300 are aligned. Accordingly, the fluid introduced from the pipette (not shown) passes through the fluid inlet channel 2130 of the pipette port 2100, the channel inlet hole 2230 of the top seal 2200, and the fluid inlet 2330 of the channel cell 2300, and passes through the disc-shaped space. 2320.
  • the contact opening 2260 of the top seal 2200, the contact through hole 2360 of the channel cell 2300, and the contact opening 2460 of the adhesive film 2400 are aligned so as to be placed above the contact terminal 2560 of the sensor chip 2500.
  • the connection pins (not shown) can approach and electrically connect to the contact terminals 2560 of the sensor chip 2500 from outside the fluidic device 2000 through these openings and through holes. In this manner, surface electrochemical measurements can be performed on the introduced liquid via the electrode section 2520 of the sensor chip 2500, and electrical signals can be acquired.
  • the fluid (waste liquid) coming out of the disk-shaped space 2320 of the channel cell 2300 goes up through the fluid outlet 2340 of the channel cell 2300 and is sealed by the groove 2341 formed on the top surface of the channel cell 2300 and the top seal 2200.
  • the second fluid outlet 2342 is guided downward through the passage 2341 formed by the second fluid outlet 2342 .
  • the waste liquid then passes through the through hole 2440 of the adhesive film and the through hole 2640 of the sensor chip support 2600, falls into the waste liquid storage space 2840 of the waste liquid tank 2800, and is collected therein in a sealed manner.
  • the air opening 2270 of the top seal 2200, the air through hole 2370 of the flow path cell 2300, the air opening 2470 of the adhesive film 2400, and the air through hole 2670 of the sensor chip support 2600 are aligned. That is, the waste liquid storage space 2840 of the waste liquid tank 2800 and the outside of the fluid device 2000 are fluidly connected to form an air vent. Thereby, as the waste liquid is introduced into the waste liquid storage space 2840, the air that was inside the waste liquid storage space 2840 sealed by the O-ring 2700 can escape to the outside. In other words, the waste liquid can flow into the receiving space 2840 within the waste liquid tank 2800.
  • FIG. 9 shows a top view of a fluid device 1200 having a straight channel as a comparative example.
  • the solid lines and dashed lines are not to be interpreted as corresponding to whether or not they are visible from the top, but merely schematically illustrate the configuration of the internal components of fluidic device 1200.
  • the fluid device 1200 has a straight space 1220 inside the main body 1210.
  • a fluid inlet 1230 and a fluid outlet 1240 are formed near the ends of the straight space 1220.
  • the fluid inlet 1230 and the fluid outlet 1240 are formed perpendicular to the plane of the main body 1210 or the straight space 1220.
  • the fluid is introduced into the straight space 1220 from the fluid inlet 1230, flows in the straight space 1220 in its longitudinal direction, fills the straight space 1220, and is led out from the fluid outlet 1240.
  • Sensing electrodes 1221, 1222, and 1223 extending in the longitudinal direction of the straight space 1220 are arranged.
  • the sensing electrode is an electrochemical measurement electrode having three electrodes.
  • the sensing electrode has a working electrode 1221, a reference electrode 1222, and a counter electrode 1223. These electrodes are connected to corresponding connection terminals 1261, 1262, and 1263 via lead wires.
  • the connection terminal is exposed on the outer surface of the main body 1210 and can form an electrical connection from the outside.
  • ⁇ Comparison between disc type and straight type> In a sensing device that generally uses a stop-flow method, it is recognized that sensing performance deteriorates when the volume of the measurement liquid is low.
  • One of the reasons for this is that in the stop-flow method, compared to the flow method in which the measurement liquid is constantly supplied, it is difficult to completely replace the measurement space filled with the preceding liquid with the measurement liquid, and it is difficult to eliminate air bubbles that have entered the system. It is assumed that this is the case. Therefore, in this experimental example, the sensing performance of a disk-shaped channel and a straight channel was compared in terms of the amount of liquid introduced, especially at low volumes.
  • the configuration of the device used is as follows.
  • the disc-shaped channel had a configuration similar to that shown in FIG.
  • Three electrodes having a configuration substantially similar to that shown in FIG. 7 were arranged on the bottom surface inside this space.
  • Three electrodes having a configuration substantially similar to that shown in FIG. 9 were arranged on the bottom surface inside this space.
  • FOD fructosyl amino acid oxidase
  • HEPES solution (10mM HEPES, 150mM NaCl, trace amount of preservative, pH 8.0) was prepared.
  • Each channel was filled with HEPES solution to prepare the enzyme membrane for measurement.
  • a plurality of amounts (50 to 1000 ⁇ L) of the measurement liquid were introduced into each channel device by pipetting, and at that time, changes over time in the current output from the electrodes were measured.
  • the current value after a predetermined time approximately 120 seconds
  • FIG. 10 shows the current value (vertical axis) obtained with respect to the amount of solution (horizontal axis) for each device.
  • the current value is normalized with the value at 1000 ⁇ L (1 mL) as 100%.
  • the output decreased significantly, especially at 400 ⁇ L or less. That is, at low capacities, a decrease in output was recognized.
  • the disk-shaped channel a decrease in output was observed at 200 ⁇ L or less, but even at 50 ⁇ L, the decrease in output was about 7%.
  • the disk-shaped flow path did not experience the significant power reduction problems at low volumes seen with the straight-type flow path. Thus, it was found that the disk-shaped channel has high sensing performance even for a low volume of introduced solution.
  • the introduced measurement liquid flows most fluidly at the center of the channel (the center in the width direction). That is, when a sufficient amount of solution is introduced (for example, 1000 ⁇ L), it is considered that the entire volume of the HEPES solution in the channel has been replaced by the measurement solution. However, if a sufficient amount of solution was not introduced (for example, 400 ⁇ L or less), it is considered that the entire volume of the HEPES solution in the channel was not replaced by the measurement solution. Therefore, the measurement liquid came into contact with only a portion of the total area of the electrode. This is thought to have led to a decrease in the measured current. This situation is thought to worsen as the amount introduced becomes smaller, and this agrees with the trend of the experimental results shown in FIG. In other words, the straight channel has a low solution conversion efficiency, whereas the disc-shaped channel has a high conversion efficiency.
  • low solution conversion efficiency means that the previous solution remains. Since this is a phenomenon in which two different fluids come into contact with each other, it can cause variations in the conversion efficiency of the solution, that is, the sensing output. In fact, the inventors have observed such variations in straight flow channels. On the other hand, the disk-shaped channel has high conversion efficiency, allows some amount of the previous solution to remain, and is less likely to cause variations in output.
  • the disc-shaped flow path has a high solution conversion efficiency for a low volume of introduced measurement solution and enables measurement with high sensitivity and/or high stability.
  • the enzyme membrane having fructosyl amino acid oxidase (FAOD) immobilized by crosslinking with bovine serum albumin (BSA) was formed on this electrode.
  • the enzyme membrane had a thickness of about 25 ⁇ m, which was smaller than the height accuracy of the internal space.
  • the four types of channel devices had the same bottom shape and area, the same enzyme membrane, and different internal space heights.
  • a HEPES solution was prepared in the same manner as the experiment shown in FIG.
  • Each channel was filled with HEPES solution to prepare the enzyme membrane for measurement. Thereafter, 100 ⁇ L of the substrate solution was introduced into each channel device by pipetting, and at that time, changes over time in the current output from the electrodes were measured.
  • a plurality of channel devices were prepared and measured at each height, and one example is shown in FIG. 11.
  • the 0.1 mm height device had the highest maximum output (about 28 nA) and the fastest time to reach maximum output (about 58 seconds), but the maximum output was maintained for only a short time.
  • the 0.28 mm height device had a lower maximum output (approximately 24 nA) and a slower time to reach maximum output (approximately 120 seconds), but the maximum output was maintained for a significantly longer time. .
  • FIG. 12 shows the relationship between the height of the disc-shaped space and the maximum output maintenance time.
  • the 0.6 mm height device shown in FIG. 11 showed a slightly lower maximum output current compared to the 1.0 mm height device. However, no substantial difference was observed between the two. That is, it is estimated that there is almost no change in the characteristics at a height of 0.6 mm or more (see FIG. 12). Of course, if the height becomes extremely large, the trends in these properties can change. For example, the height may be 1 mm or less. The measurement volume can be kept small. Furthermore, inclusion of air bubbles can be suppressed.
  • the 0.1 mm height device that showed the highest maximum output current would have the highest measurement sensitivity.
  • the maximum output current exhibited by the 0.6 mm height device and the 1.0 mm height device provides sufficient measurement sensitivity for the disclosed device.
  • the time of maximum output current varies depending on variations in the timing of introduction of the substrate liquid into the channel device, the liquid feeding speed, etc. That is, a longer period of time during which the maximum output current is maintained is advantageous for the stability of measurement results.
  • the introduction of the substrate liquid into the channel device can be the starting point for calculating the measurement time.
  • a current value a certain period of time after the measurement time when the substrate liquid was introduced into the channel device may be adopted as the measured value.
  • the device with a height of 0.6 mm and the device with a height of 1.0 mm gave a maximum output maintenance time of approximately 100 seconds. In reality, the maximum output current is stable, so the error in this calculated sustain time is large. Furthermore, as mentioned above, in this example, although there was some difference between the device with a height of 0.6 mm and the device with a height of 1.0 mm, it was found that they exhibited the same characteristics overall. There is. Therefore, as mentioned above, it is estimated that there is almost no change in the maximum output maintenance time at a height of 0.6 mm or more (FIG. 12).
  • the maximum output maintenance time monotonically increased almost linearly (FIG. 12). For example, if this time is 1 minute (60 seconds), stable measurement can be performed. Since a height of 0.28 mm indicates a maximum output maintenance time of approximately 60 seconds, this is considered to be substantially sufficient. Accordingly, in some embodiments, the height of the interior space may be 0.28 mm or more. Also, a height of 0.3 mm can provide a maximum output maintenance time of approximately 60 seconds. Accordingly, in some embodiments, the height of the interior space may be 0.3 mm or more. The height of the interior space may be a value such as 0.4 mm, 0.5 mm, or greater.
  • the thickness of the enzyme membrane was approximately 25 ⁇ m as described above, but the inventors confirmed a similar tendency with a thickness of 10 ⁇ m to 35 ⁇ m (not shown). ⁇ When the thickness of the enzyme membrane was less than 10 ⁇ m, the output current value changed rapidly and its stability was low. On the other hand, when the thickness of the enzyme membrane was 40 ⁇ m, the diffusion of the substrate within the enzyme membrane was slow, making current measurement inefficient.
  • a short maximum output time often means that the current value drops rapidly after the time of maximum output current. Variations in the properties of enzyme membranes occur to some extent due to the manufacturing process. A configuration that causes a sudden change in current can be a factor that reduces reproducibility in measurement. Therefore, having a certain maximum output current maintenance time is meaningful, at least for high reproducibility.
  • a longer maximum output time means a longer time for the diffusion/supply rate of the substrate to the enzyme membrane or the concentration gradient of the substrate within the enzyme membrane to be constant. Therefore, high reproducibility can be obtained. Furthermore, the accuracy of the measured value of the GA value obtained based on the output current curve also increases.
  • the current value at a predetermined time from the time when the substrate liquid is introduced into the device space may be acquired.
  • multiple current values on the current curve may be selected or obtained.
  • statistical values may be obtained from the current curve.
  • a certain statistical value may be obtained from current values at a plurality of times.
  • a GA value may be calculated based on one or more statistical values.
  • the GA value may be determined based on the maximum output current value and the current values 10 seconds before and after the maximum output current value.
  • the GA value may be determined based on the area given by the output current curve.
  • the present disclosure includes the following embodiments: A001 a device body having a disc-shaped space that accommodates a fluid; a fluid inlet configured to introduce the fluid in a tangential direction at a substantially circumferential 0 o'clock position of the disc-shaped space; a fluid outlet configured to direct the fluid from the space at the 12 o'clock position; A fluidic device comprising: A011
  • A012 The fluidic device according to embodiment A011, comprising: the fluid outlet is configured to direct the fluid from the space at a substantially circumferential 9 o'clock to 12 o'clock position of the disc-shaped space; Fluid device.
  • A013 The fluidic device according to any one of embodiments A001 to A012, comprising: The fluid outlet is disposed in the disc-shaped space at a position counterclockwise from the inlet (upstream side of the fluid flow). Fluid device.
  • A021 The fluidic device according to any one of embodiments A001 to A013, comprising: The volume of the disc-shaped space is 1 ⁇ L to 100 ⁇ L, Fluid device.
  • A022 The fluidic device according to embodiment A021, comprising: The volume of the disc-shaped space is 3 to 20 ⁇ L, Fluid device.
  • A023 The fluidic device according to embodiment A021, comprising: The height of the disc-shaped space is one or more of 0.28 mm, 0.3 mm, 0.4 mm, 0.5 mm, and 0.6 mm, Fluid device.
  • A025 The fluidic device according to any one of embodiments A001 to A023, comprising: The total volume of the disc-shaped space and the volume of the fluid inlet is 2 ⁇ L to 200 ⁇ L, Fluid device.
  • A026 The fluidic device according to embodiment A025, comprising: The total volume of the disc-shaped space and the volume of the fluid inlet is 6 ⁇ L to 40 ⁇ L, Fluid device.
  • A027 The fluidic device according to any one of embodiments A001 to A026, comprising: The volume of the fluid inlet is substantially 50%, 100%, 150%, or 200% of the volume of the disc-shaped space. Fluid device.
  • A031 The fluidic device according to any one of embodiments A001 to A027, The fluid device further includes a sensor on an inner wall of the disc-shaped space.
  • A032 The fluidic device according to embodiment A031, comprising: the sensor is a biosensor; Fluid device.
  • A033 The fluidic device according to embodiment A031 or A032, comprising: The sensor has an electrode. Fluid device. A034 The fluidic device according to embodiment A033, comprising: the electrode has a hydrogen peroxide electrode; Fluid device. A035 The fluidic device according to embodiment A034, comprising: The sensor further includes an enzyme membrane on the hydrogen peroxide electrode. Fluid device. A036 The fluidic device according to embodiment A035, comprising: the enzyme membrane contains an oxidase; Fluid device. A037 The fluidic device according to embodiment A036, comprising: the oxidase is FAOD; Fluid device. A038 The fluidic device according to any one of embodiments A035 to A037, the enzyme membrane contains a protease; Fluid device.
  • A039 The fluidic device according to embodiment A036, comprising: the oxidase is glucose oxidase, Fluid device.
  • A041 The fluidic device according to any one of embodiments A031 to A039, the sensor is a protein sensor; Fluid device.
  • A042 The fluidic device according to embodiment A041, comprising: The sensor includes a glycoalbumin sensor and/or an albumin sensor. Fluid device.
  • A051 The fluidic device according to any one of embodiments A031 to A042, comprising: A fluidic device comprising an optical sensor outside the disc-shaped space or configured to be combined with an optical sensor outside the disc-shaped space.
  • A061 The fluidic device according to any one of embodiments A001 to A051, A fluidic device that is a stop-flow fluidic device.

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025137104A1 (en) * 2023-12-22 2025-06-26 Coopersurgical, Inc. Multi-chamber systems and methods for sorting sperm

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4522392B1 (en) * 1964-10-08 1970-07-28 Ceskoslovenska Akademie Ved A through-flow measuring cell for photometers
JPH10507837A (ja) * 1995-04-21 1998-07-28 ヘモク アクチボラゲット 毛管マイクロキュベット
JP2004219325A (ja) * 2003-01-16 2004-08-05 Ntt Advanced Technology Corp 電気化学オンライン型バイオセンサ及びその製造方法
WO2004074846A1 (ja) * 2003-02-19 2004-09-02 Japan Science And Technology Agency 血液分析装置及び血液分析方法
WO2006044841A2 (en) * 2004-10-18 2006-04-27 Applera Corporation Fluid processing device including size-changing barrier
JP2018524608A (ja) * 2015-05-28 2018-08-30 ピクセル メディカル テクノロジーズ リミテッドPixcell Medical Technologies Ltd 流体試料分析システム

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4522392B1 (en) * 1964-10-08 1970-07-28 Ceskoslovenska Akademie Ved A through-flow measuring cell for photometers
JPH10507837A (ja) * 1995-04-21 1998-07-28 ヘモク アクチボラゲット 毛管マイクロキュベット
JP2004219325A (ja) * 2003-01-16 2004-08-05 Ntt Advanced Technology Corp 電気化学オンライン型バイオセンサ及びその製造方法
WO2004074846A1 (ja) * 2003-02-19 2004-09-02 Japan Science And Technology Agency 血液分析装置及び血液分析方法
WO2006044841A2 (en) * 2004-10-18 2006-04-27 Applera Corporation Fluid processing device including size-changing barrier
JP2018524608A (ja) * 2015-05-28 2018-08-30 ピクセル メディカル テクノロジーズ リミテッドPixcell Medical Technologies Ltd 流体試料分析システム

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4524579A4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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