US20080096285A1 - Method for Automatic Determination of Sample - Google Patents

Method for Automatic Determination of Sample Download PDF

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Publication number
US20080096285A1
US20080096285A1 US11/572,749 US57274905A US2008096285A1 US 20080096285 A1 US20080096285 A1 US 20080096285A1 US 57274905 A US57274905 A US 57274905A US 2008096285 A1 US2008096285 A1 US 2008096285A1
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Prior art keywords
sample
tip
plasma
analyzing
light
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US11/572,749
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English (en)
Inventor
Atsushi Koyata
Hiroyuki Yokoi
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LSI Medience Corp
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Mitsubishi Kagaku Iatron Inc
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Assigned to MITSUBISHI KAGAKU IATRON, INC. reassignment MITSUBISHI KAGAKU IATRON, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: KOYATA, ATSUSHI, YOKOI, HIROYUKI
Publication of US20080096285A1 publication Critical patent/US20080096285A1/en
Assigned to MITSUBISHI CHEMICAL MEDIENCE CORPORATION reassignment MITSUBISHI CHEMICAL MEDIENCE CORPORATION MERGER (SEE DOCUMENT FOR DETAILS). Assignors: MITSUBISHI KAGAKU IATRON, INC.
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    • 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
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/59—Transmissivity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00594—Quality control, including calibration or testing of components of the analyser
    • G01N35/00603—Reinspection of samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G01N2035/1062—General features of the devices using the transfer device for another function for testing the liquid while it is in the transfer device

Definitions

  • the present invention relates to a method for an automatic determination of a sample type, in a method for analyzing the sample, i.e., a method for analyzing a specific component contained in the sample such as body fluids, particularly blood.
  • a serum or plasma is commonly used as a blood sample and, in this case, a serum or plasma is generally separated from whole blood as rapidly as possible to avoid hemolysis.
  • a serum or plasma is generally separated from whole blood as rapidly as possible to avoid hemolysis.
  • Japanese Unexamined Patent Publication (Kokai) No. 10-48214 discloses a method for using completely hemolyzed whole blood by sonicating whole blood or mixing whole blood with a hypotonic solution.
  • 6-265554 discloses a method of analyzing a biochemical component of blood, comprising the steps of determining whether or not a sample contains blood cells; when the result that the sample contains blood cells is obtained, determining whether or not only one or more measurable items which can be analyzed by using a sample containing blood cells are selected; and when the result that only measurable item(s) which can be analyzed by using a sample containing blood cells are selected is obtained, stirring the sample and measuring the stirred sample.
  • the method for completely hemolyzing whole blood disclosed in the above patent reference 1 has several problems, for example, various states of hemolysis. Further, interferences which flow from the inside of blood cells to a reaction system, such as hemoglobin or substances derived from the cell nucleus, sometimes seriously affect the measurement by causing a nonspecific reaction or, particularly in an immunological assay, an interfering of immunoreaction.
  • a method of determining the kind of the sample i.e., whether or not the sample contains blood cells
  • the patent reference 2 only discloses that a means for determining the kind of a sample, such as a transmission optical sensor, may be located over cuvettes encapsulating a reagent, a sample, a diluent, or the like. Further, a concrete procedure and criterion for the determination are not disclosed in the patent reference 2, except for the disclosure that, when a sample contains blood cells, a hematocrit compensation should be carried out by stirring the sample.
  • a method of determining a kind of a sample preferably the presence or absence of a sample in a supplying means and/or a kind of a sample
  • a method for analyzing a substance by the steps of supplying the sample suspected of containing the substance to be analyzed to a reaction system by a supplying means comprising a transparent region composed of a transparent material, reacting a reagent for detecting the substance with the sample in the reaction system, and analyzing a signal derived from a product obtained by the reaction, characterized by irradiating the transparent region with light in the supplying step, and analyzing an optical intensity of the light.
  • the supplying means is a dispensing means in which a tip can be mounted (preferably, removably mounted) and liquid can be aspirated and poured out by means of the tip. That is, the present invention relates to a method of determining a kind of a sample (preferably the presence or absence of a sample in a tip and/or a kind of a sample, more preferably the mounting or detaching of a tip, the presence or absence of a sample in a tip, and/or a kind of a sample), in a method for analyzing a substance by the steps of supplying (preferably dispensing) the sample suspected of containing the substance to be analyzed to a reaction system by a dispensing means in which a tip is mounted and liquid can be aspirated and poured out by means of the tip, reacting a reagent for detecting the substance with the sample in the reaction system, and analyzing a signal derived from a product obtained by the reaction, characterized by
  • the supplying means is a tube or a channel. That is, the present invention relates to a method of determining a kind of a sample (preferably the presence or absence of a sample in a supplying means and/or a kind of a sample), in a method for analyzing a substance by the steps of supplying the sample suspected of containing the substance to be analyzed to a reaction system by a tube or a channel comprising a transparent region composed of a transparent material, reacting a reagent for detecting the substance with the sample in the reaction system, and analyzing a signal derived from a product obtained by the reaction, characterized by irradiating the transparent region with light in the supplying step (i.e., when the sample passes through the tube or the channel), and analyzing an optical intensity of the light.
  • a kind of a sample preferably the presence or absence of a sample in a supplying means and/or a kind of a sample
  • the sample is whole blood, a serum, or plasma.
  • the present invention relates to an apparatus for analyzing a substance by the steps of supplying a sample suspected of containing the substance to be analyzed to a reaction system by a supplying means, reacting a reagent for detecting the substance with the sample in the reaction system, and analyzing a signal derived from a product obtained by the reaction, characterized by comprising
  • a supplying means comprising a transparent region composed of a transparent material
  • an irradiating means capable of irradiating the transparent region with light in the supplying step
  • an optically analyzing means capable of analyzing a change in an optical intensity of the light
  • a means for determining a kind of the sample by the optical intensity
  • the determining means may comprise, for example,
  • a means for storing a threshold value obtained from a previously measured value a means for comparing a secondary measured value with the stored threshold value, a means for indicating a subsequent procedure (or a warning) according to the comparison result, and a means for outputting the comparison result (a warning means).
  • the supplying means is a dispensing means in which a tip can be mounted (preferably, removably mounted) and liquid can be aspirated and poured out by means of the tip.
  • the present invention relates to an apparatus for analyzing a substance by the steps of supplying (preferably dispensing) a sample suspected of containing the substance to be analyzed to a reaction system by a dispensing means in which a tip is mounted and liquid can be aspirated and poured out by means of the tip, reacting a reagent for detecting the substance with the sample in the reaction system, and analyzing a signal derived from a product obtained by the reaction, characterized by comprising
  • a dispensing means in which a tip can be mounted and liquid can be aspirated and poured out by means of the tip;
  • an irradiating means capable of irradiating a sample-holding portion of the tip with light in the supplying step (i.e., when the sample is aspirated into the tip);
  • an optically analyzing means capable of analyzing a change in an optical intensity of the light; and
  • a means for determining a kind of the sample preferably the presence or absence of a sample in a tip and/or a kind of a sample, more preferably the mounting or detaching of a tip, the presence or absence of a sample in a tip, and/or a kind of a sample by the optical intensity.
  • the supplying means is a tube or a channel. That is, the present invention relates to an apparatus for analyzing a substance by the steps of supplying a sample suspected of containing the substance to be analyzed to a reaction system by a tube or a channel comprising a transparent region composed of a transparent material, reacting a reagent for detecting the substance with the sample in the reaction system, and analyzing a signal derived from a product obtained by the reaction, characterized by comprising
  • a tube or a channel comprising a transparent region composed of a transparent material
  • an irradiating means capable of irradiating the transparent region with light in the supplying step
  • an optically analyzing means capable of analyzing a change in an optical intensity of the light
  • a means for determining a kind of the sample preferably the presence or absence of a sample in the tube or the channel and/or a kind of the sample
  • the sample is whole blood, a serum, or plasma.
  • the kind of a sample can be automatically determined, and a step in which a measurer inputs or sets the kind of the sample into an analyzer before the measurement can be skipped. Therefore, the present invention is useful, particularly, for a general operator not having a dedicated device such as a centrifuge or for an unrespited emergency test. Further, according to the present invention, a failure to apply a sample into the analyzer can be detected, as well as the determination of the type of the sample. Furthermore, according to the present invention, a failure to mount a dispensing tip can be simultaneously detected in an automatic analyzer in which dispensing tips are mounted.
  • FIG. 1 [ FIG. 1 ]
  • FIG. 1 is a front view (A) and a side view (B) which schematically illustrate an embodiment of an automatic analyzer to which the determining method of the present invention may be applied.
  • FIG. 2 [ FIG. 2 ]
  • FIG. 2 schematically illustrates procedures of an embodiment of an automatic analyzing method to which the determining method of the present invention may be applied.
  • FIG. 3 [ FIG. 3 ]
  • FIG. 3 schematically illustrates an embodiment of an optical analyzing system which may be used in the present invention.
  • FIG. 4 is an enlarged partial front view (A) and an enlarged partial side view (B) which schematically illustrate a state in which an embodiment of an optical analyzing system which may be used in the present invention is incorporated into an automatic analyzer.
  • the determining method of the present invention can be applied to a method for an automatic analysis of a sample, such as body fluids, particularly blood, so long as the automatic analyzing method comprises a step of supplying the sample to a reaction system.
  • the automatic analyzing method there may be mentioned, for example, an automatic analyzing method comprising a step of supplying (for example, dispensing) a sample to a reaction system by a dispensing means in which a tip can be mounted and liquid can be aspirated and poured out by means of the tip, or an automatic analyzing method comprising a step of supplying a sample to a reaction system by a transfer means (for example, a tube or a channel) capable of aspirating the sample from one end thereof and transferring the sample from the other end thereof.
  • a transfer means for example, a tube or a channel
  • the analyzing apparatus of the present invention can be applied to an automatic analyzer equipped with a means for supplying a sample to a reaction system.
  • an automatic analyzer there may be mentioned, for example, an analyzer equipped with a dispensing means in which a tip can be mounted and liquid can be aspirated and poured out by means of the tip, or an analyzer equipped with a transfer means (for example, a tube or a channel) capable of aspirating the sample from one end thereof and transferring the sample from the other end thereof.
  • FIGS. 1 and 2 An embodiment of an automatic analyzing method and an automatic analyzer to which the determining method of the present invention can be applied will be explained with reference to FIGS. 1 and 2 .
  • the automatic analyzer 1 shown in FIG. 1 comprises a measuring table 2 on which one or more cartridges 3 having plural wells for samples and/or reagents for detection can be placed.
  • a line of plural nozzles 5 in which tips 4 can be mounted and liquid can be aspirated and poured out by means of the tips 4 , are placed over the measuring table.
  • the nozzles 5 can be moved up and down in the vertical direction.
  • an aspiration of liquid from wells of the cartridge 3 pouring of liquid to wells thereof, mixing of liquid in the wells by continuously repeating aspiration and injection, or the like can be carried out.
  • wells of interest can be placed directly below the nozzles by moving the measuring table 2 in the horizontal direction.
  • one or more magnets capable of being brought into contact with the outer sidewalls of tips 4 may be positioned.
  • magnetic particles as a reagent for detection such as magnetic particles coated with an antibody specific to a compound to be analyzed, may be used together with the magnets to carry out a B/F separation in the tips.
  • an aspiration/injection means in which a tip portion is integrated with a nozzle portion, a transfer means capable of aspirating a sample from one end thereof and transferring the sample from the other end thereof, or the like may be used, instead of the nozzles in which tips can be mounted as shown in FIG. 1 .
  • the transfer means there may be mentioned, for example, a tube such as a flexible tube or a capillary tube, or a channel.
  • the present invention will further explained with reference to embodiments equipped with the dispensing means in which a tip can be mounted and liquid can be aspirated and poured out by means of the tip, but is by no means limited to these embodiments.
  • FIG. 2 An embodiment of an automatic analyzing method using the automatic analyzer shown in FIG. 1 is shown in FIG. 2 .
  • magnetic particles coated with the first antibody, the second antibody labeled with an enzyme, and a luminescence substrate are used as reagent for detection, together with magnets capable of being brought into contact with the outer walls of tips, to carry out a B/F separation in the tips.
  • first reaction a predetermined amount of a sample is added, by means of a tip, to the first well to which a predetermined amount of antibody-coated magnetic particles is previously dispensed, the sample and the antibody-coated magnetic particles are properly mixed by pipetting, and the mixture is incubated.
  • the reaction liquid is aspirated into the tip, and the reaction liquid is poured out while capturing the magnetic particles on the inner wall of the tip with a magnet.
  • the tip is inserted in the second well to which a predetermined amount of a washing solution is previously dispensed, and the magnetic particles captured with the magnet are washed by pipetting of the washing solution.
  • the tip is inserted in the third well to which a predetermined amount of an enzyme-labeled antibody solution is previously dispensed, the magnetic particles and the solution are properly mixed by pipetting of the labeled antibody solution, and the mixture is incubated.
  • the reaction liquid is aspirated into the tip, and the reaction liquid is poured out while capturing the magnetic particles on the inner wall of the tip with the magnet.
  • the tip is inserted in the fourth well to which a predetermined amount of a washing solution is previously dispensed, and the magnetic particles captured with the magnet are washed by pipetting of the washing solution.
  • the tip is inserted in the fifth well to which a predetermined amount of a luminescence substrate solution is previously dispensed, and a luminescence reaction is carried out by pipetting of the substrate solution. After the reaction is carried out for a predetermined time, an amount of luminescence may be measured to determine an amount or concentration of a substance to be analyzed.
  • body fluids particularly blood, such as whole blood, a serum, or plasma.
  • a substance to be analyzed contained in the sample is not particularly limited, so long as a substance which specifically binds with the analyte to form a reaction product can be selected.
  • a combination of the analyte and a substance specific thereto there may be mentioned, for example, an antigen and an antibody, an antibody and an antigen, a protein and a ligand, or a sugar chain and a lectin, preferably an antigen and antibody, or an antibody and an antigen.
  • the term “to specifically bind” used herein means to form a reaction product by biochemically and specifically binding with a subject.
  • hepatitis B virus surface antigen HBV
  • HCV hepatitis C virus
  • HCV human immunodeficiency virus
  • HMV-1 human T-cell leukemia virus-1
  • TP Treponema pallidum
  • myocardial markers for example, creatine kinase MB (CKMB), myoglobin, or troponin
  • hormones, serum proteins, or the like may be used.
  • a reaction system for measuring a sample is not particularly limited.
  • an immunoassay based on an antigen-antibody reaction may be preferably used.
  • the determination in the present invention is based on an optical technique.
  • a sample is aspirated into a tip, and a portion in which the sample is held is irradiated with light.
  • the optical intensity may be analyzed to determine whether or not the tip is mounted, whether or not the sample exists in the tip, and/or the kind of the sample.
  • a portion in which the sample is held is irradiated with light, preferably before the aspiration and after the aspiration, and an optical change in, for example, transmission, reflection, or scattering may be detected with a well-known device such as a photodetector to determine whether or not the tip is mounted, whether or not the sample exists in the tip, and/or the kind of the sample.
  • a well-known device such as a photodetector to determine whether or not the tip is mounted, whether or not the sample exists in the tip, and/or the kind of the sample.
  • the transparent region is irradiated with light, and an optical intensity, which varies according to the presence or absence of the sample and/or the kind of the sample transferred in the tube or the channel, may be analyzed to determine the presence or absence of the sample and/or the kind of the sample.
  • an amount of transmitted light when a tip is not mounted (hereinafter referred to as the unmounted-tip case) is larger than that when a tip is mounted and no sample is aspirated into the tip (hereinafter referred to as the mounted-tip case), and thus, it is possible to determine whether or not a tip is mounted by measuring an amount of transmitted light.
  • whole-blood-holding case since little light is transmitted when whole blood is aspirated into a tip (hereinafter referred to as whole-blood-holding case), an amount of transmitted light in the whole-blood-holding case becomes smaller than that in the mounted-tip case. In contrast, an amount of transmitted light when plasma or a serum is aspirated into a tip (hereinafter referred to as plasma-or-serum-holding case) becomes larger than that in the mounted-tip case, due to the lens effect caused by a tip, but does not exceed that in the unmounted-tip case.
  • plasma-or-serum-holding case an amount of transmitted light when plasma or a serum is aspirated into a tip
  • each threshold may vary according to conditions, such as the kind of an optical analyzing system, properties (for example, materials, the quality of materials, shape, or size) of a tip, or the like, and thus, is not particularly limited. Those skilled in the art can easily determine each threshold without undue experimentation by carrying out a pilot test, for example, by measuring amounts of transmitted light in these cases in accordance with the procedures described in Examples 1 to 2.
  • a pilot test using plural whole blood and plasma and/or sera is carried out to measure amounts of transmitted light when a sample is aspirated into a tip (i.e., an amount of transmitted light in the whole-blood-holding case, and an amount of transmitted light in the plasma-or-serum-holding case). Further, an amount of transmitted light (To) in the mounted-tip case (i.e., when no sample is aspirated into a tip) is measured.
  • the order of the decreasing amount of transmitted light is as follows:
  • the tip is irradiated with light to measure an amount of transmitted light (T).
  • T an amount of transmitted light
  • the amount of transmitted light T of the unknown sample is larger than the threshold a, it is possible to determine that this is the plasma-or-serum-holding case, i.e., that the unknown sample is plasma or a serum.
  • the amount of transmitted light T of the unknown sample is smaller than the threshold b, it is possible to determine that this is the plasma-or-serum-holding case, i.e., that the unknown sample is plasma or a serum.
  • the amount of transmitted light T of the unknown sample is between the threshold a and the threshold b, it is possible to determine that there is an inadequate operation.
  • the above logic for determination (hereinafter sometimes referred to as the one-step method) which may be used in the present invention comprises, for example, the steps of:
  • an optical intensity for example, an amount of transmitted light
  • a i.e., the threshold between an optical intensity when plasma or a serum is aspirated into the supplying means and an optical intensity when no sample is aspirated into the supplying means
  • the previously determined threshold b i.e., the threshold between an optical intensity when no sample is aspirated into the supplying means and an optical intensity when whole blood is aspirated into the supplying means
  • B determining that when the optical intensity of the sample is higher than the threshold a, the sample is plasma or a serum; when the optical intensity thereof is lower than the threshold b, the sample is whole blood; and when the optical intensity thereof is between the threshold a and the threshold b, no sample is aspirated into the supplying means (for example, an inadequate operation).
  • a sample is a hemolytic sample or a usual chyle sample (i.e., a whitish and opaque sample having a high lipid content)
  • plasma or a serum can be clearly discriminated from whole blood, as shown in the experimental data described in Example 2.
  • a chyle plasma or serum sample having an extremely high lipid content is used, it is sometimes difficult to discriminate the sample from whole blood.
  • an amount of transmitted light is sometimes a value between the threshold a and the threshold b (i.e., judged as an inadequate operation) or smaller than the threshold b (i.e., judged as whole blood) in the above-mentioned logic for determination.
  • samples to be analyzed include (or are suspected of including) one or more chyle samples having an extremely high lipid content
  • a chyle plasma or serum sample can be discriminated from whole blood by diluting the sample(s) to, for example, 1.2-fold to 10-fold, preferably 1.5-fold to 5-fold, more particularly 2-fold, and measuring again an amount of transmitted light of the diluted sample(s).
  • the amount of transmitted light T of an unknown sample is smaller than the threshold b (a usual sample is judged as whole blood) in the above-mentioned logic for determination, the unknown sample is diluted, and an amount of transmitted light of the diluted sample (hereinafter referred to as the amount of transmitted light T′) is measured again under the same conditions.
  • the amount of transmitted light T′ is measured again under the same conditions.
  • the unknown sample is a chyle plasma or serum sample
  • the amount of transmitted light measured after the dilution is increased.
  • the unknown sample is whole blood, there is little change between the values measured before the dilution and after the dilution.
  • such an unknown sample can be discriminated by previously determining a threshold c, with respect to the difference (T′-T) between the amount of transmitted light after the dilution (T′) and that before the dilution (T). That is, when the difference “T′-T” is larger than the threshold c, the unknown sample may be judged as a chyle plasma or serum sample, and when the difference “T′-T” is not more than the threshold c, the unknown sample may be judged as whole blood.
  • the amount of transmitted light T of an unknown sample is between the threshold a and the threshold b (a usual sample is judged as that when no sample is aspirated into a tip) in the above-mentioned logic for determination, the unknown sample is diluted, and the amount of transmitted light T′ is measured again under the same conditions.
  • the unknown sample is a chyle plasma or serum sample, the amount of transmitted light measured after the dilution is increased.
  • no sample is aspirated into a tip, there is little change between the values measured before the dilution and after the dilution.
  • such an unknown sample can be discriminated by previously determining a threshold d, with respect to the difference (T′-T) between the amount of transmitted light after the dilution (T′) and that before the dilution (T). That is, when the difference “T′-T” is larger than the threshold d, the unknown sample may be judged as a chyle plasma or serum sample, and when the difference “T′-T” is not more than the threshold d, it may be judged that no sample is aspirated into a tip.
  • another logic for determination (hereinafter sometimes referred to as the two-step method) which may be used in the present invention comprises, for example, the steps of:
  • an optical intensity for example, an amount of transmitted light
  • T measured in a supplying step
  • the previously determined threshold a i.e., the threshold between an optical intensity when plasma or a serum is aspirated into the supplying means and an optical intensity when no sample is aspirated into the supplying means
  • the previously determined threshold b i.e., the threshold between an optical intensity when no sample is aspirated into the supplying means and an optical intensity when whole blood is aspirated into the supplying means
  • B′ determining that, when the optical intensity of the sample is higher than the threshold a, the sample is judged as plasma or a serum; when the optical intensity thereof is lower than the threshold b, the following step (C) is carried out; and when the optical intensity thereof is between the threshold a and the threshold b, the following step (D) is carried out; (C) diluting the sample, and comparing the difference (T′
  • Step B′ T ⁇ b to ⁇ ⁇ Step ⁇ ⁇ C b ⁇ T ⁇ a to ⁇ ⁇ Step ⁇ ⁇ D a ⁇ T P / S Step C ⁇ T ⁇ c WB c ⁇ ⁇ ⁇ T P / S Step D ⁇ T ⁇ d IO d ⁇ ⁇ ⁇ T P / S WB: whole blood P/S: plasma or a serum IO: inadequate operation
  • the one-step method or the two-step method may be appropriately selected and carried out according to the state of samples (a set of samples) to be analyzed.
  • the samples to be analyzed include no chyle sample having an extremely high lipid content
  • the one-step method is preferable.
  • a chyle sample can be identified by, for example, a visual check.
  • the one-step method a convenient and rapid analysis can be carried out, because the judgment is made in one step.
  • the samples to be analyzed include (or are suspected of including) one or more chyle samples having an extremely high lipid content
  • the two-step method is preferable. According to the two-step method, a more accurate analysis can be carried out, and a visual check of samples is not necessary.
  • the effect of chyle was examined using intrafat (20%, Takeda Chemical Industries, Ltd.) and, as a result, the type of samples having a lipid content of 300 mg/dL or less could be determined by the one-step method of the present invention. Further, with respect to samples having a lipid content of more than 300 mg/dL, it was confirmed that the type of samples having a lipid content of 1500 mg/dL or less could be determined (particularly, discriminated from whole blood) by the two-step method (2-fold dilution).
  • FIGS. 3 and 4 An embodiment of an optical analyzing system (transmission type) which may be used in the present invention is shown in FIGS. 3 and 4 .
  • a light emitting diode (LED) 11 and a photodiode (PD) 12 are located opposite to each other and spaced apart, so that a tip 4 can be placed therebetween.
  • a material through which light can be transmitted may be used, and there may be mentioned, for example, glass or transparent plastics, such as polyethylene, polystyrene, polycarbonate, polyacrylic plastics, or polypropylene.
  • the inner diameter, wall thickness, material, or the like of the tip, and the light intensity, optical path length, or the like of the light may be appropriately selected to optimize the optical system.
  • the portion to be irradiated with light has an outer diameter of preferably 2 to 10 mm, more preferably 3 to 6 mm, an inner diameter of preferably 1 to 8 mm, more preferably 2 to 4 mm, and a wall thickness of preferably 0.2 to 2 mm, more preferably 0.5 to 1 mm.
  • the present invention is not limited to these values.
  • the wavelength of the photodiode is not limited, so long as at least the unmounted-tip case, the plasma-or-serum-holding case, the mounted-tip case, and the whole-blood-holding case are optically discriminated from each other.
  • the wavelength of light emitted from a commonly used photodiode includes an ultraviolet region, a visible region, and an infrared region, and an appropriate wavelength may be selected therefrom.
  • a visible region of 380 to 780 nm may be preferably used, more preferably 400 to 700 nm, most preferably 470 to 635 nm.
  • the present invention is not limited to these wavelength ranges.
  • the present invention can be carried out by using a means for compensating a refractive index caused when the light is transmitted through the tip and the sample.
  • a well-known detecting means may be used, with appropriate modifications if desired.
  • the light output from the light source (LED) 11 is transmitted through the tip, the amounts of light (current value) detected with the photodetector (photodiode) 12 are current-voltage converted by the operational amplifier 13 , the analog values are digitalized with the AD converter 14 , and the digital values are processed with software.
  • an optical analyzing system other than that shown in FIGS. 3 and 4 , for example, an image processing system using a CCD camera may be used.
  • the detected light can be captured as color information by passing the light through an RGB primary-colors filter, and the sample can be determined by color.
  • the RGB primary-colors filter is not used, it can be determined from gradations in monochrome whether or not the light is transmitted.
  • LED light emitting diode
  • three types of LEDs i.e., an LED having a peak wavelength of 635 nm (GL3HD44; Stanley), an LED having a peak wavelength of 573 nm (NSPY800AS; NICHIA), and an LED having a peak wavelength of 470 nm (NSPB500S; NICHIA), were used.
  • a photodiode (PD) a PD having a sensitivity wavelength range of 320 to 1100 nm (S6775; Hamamatsu Photonics) was used.
  • a detected value of light was highest when the tip was not mounted (i.e., control), and the detected value of light was lowered by mounting the tip. Whereas the detected value of light was further lowered when whole blood was aspirated into the tip, the detected value of light was increased due to the lens effect caused by the tip when water or plasma was aspirated into the tip, in comparison with the case of the tip alone.
  • Example 2 the procedures described in Example 1 were repeated, except that an LED having a peak wavelength of 590 nm (EFY3863; Stanley) was used as an LED for a light source.
  • EY3863 an LED having a peak wavelength of 590 nm
  • Plasma plasma supplemented with commercially available interfering substances (purchased from Sysmex Corporation), whole blood, and water were used as samples.
  • the interfering substances used and final concentrations (or turbidity) thereof are as follows:
  • the present invention may be applied to an automatic analysis of samples such as body fluids.

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JP6030676B2 (ja) * 2015-01-30 2016-11-24 シャープ株式会社 試料分析装置及び試料分析方法
CN108738348B (zh) 2016-02-17 2023-09-01 贝克顿·迪金森公司 用于相同的诊断测试的自动化样品制备系统
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JP7111622B2 (ja) 2016-04-22 2022-08-02 ベクトン・ディキンソン・アンド・カンパニー 自動化された診断アナライザおよびその動作のための方法
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US20100285996A1 (en) * 2006-08-30 2010-11-11 Universal Bio Research Co. Ltd Segmented process apparatus for microplate and segmented process method for microplate
US8921282B2 (en) 2006-08-30 2014-12-30 Universal Bio Research Co., Ltd. Segmented process apparatus for microplate and segmented process method for microplate
US10012665B2 (en) 2010-02-09 2018-07-03 Microjet Corporation Discharge device for liquid material including particle-like bodies
US20150301018A1 (en) * 2012-07-18 2015-10-22 Theranos, Inc. Low-volume coagulation assay
US11119110B2 (en) * 2012-07-18 2021-09-14 Labrador Diagnotics LLC Low-volume coagulation assay
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US11079325B2 (en) * 2014-04-30 2021-08-03 Instrumentation Laboratory Company Methods and systems for point-of-care coagulation assays by optical detection
US20150316533A1 (en) * 2014-04-30 2015-11-05 Josef Kerimo Methods and systems for point-of-care coagulation assays by optical detection
US20160334429A1 (en) * 2015-05-11 2016-11-17 Kabushiki Kaisha Yaskawa Denki Rack for dispensing and dispensing system
US10837977B2 (en) * 2015-05-11 2020-11-17 Kabushiki Kaisha Yaskawa Denki Rack for dispensing and dispensing system
EP4105663A4 (en) * 2020-02-10 2024-03-06 I-Sens, Inc. METHOD FOR AUTOMATIC DISTINCTION OF WHOLE BLOOD/PLASMA/NON-ASPIRATION BY MEANS OF A REFLECTIVE PHOTOCENSOR

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EP1775574A4 (en) 2012-02-29
WO2006011531A1 (ja) 2006-02-02
JPWO2006011531A1 (ja) 2008-05-01
EP1775574B1 (en) 2018-03-14
JP4452277B2 (ja) 2010-04-21
CN102539737A (zh) 2012-07-04
US8557599B2 (en) 2013-10-15
US20120142043A1 (en) 2012-06-07
EP1775574A1 (en) 2007-04-18
CN101010579A (zh) 2007-08-01

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