Measurement method and measurement device

• US 9,778,184 B2
• Filed: 02/23/2015
• Issued: 10/03/2017
• Est. Priority Date: 02/25/2014
• Status: Active Grant

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Konica Minolta Inc.
• Inventors: Tamura, Tsuruki, Ootani, Makiko, Aoki, Youichi
• Primary Examiner(s): Chowdhury, Tarifur
• Assistant Examiner(s): Akanbi, Isiaka
• Application Number:
  US15/120,505
• Publication Number:
  US 20170016823A1
• Time in Patent Office: 953 Days
• Field of Search: 356445-446
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/554 detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/553 Metal or metal coated

Abstract

With a blood-derived specimen on top of a metal film on a measurement chip, the intensity of reflected excitation light, the resonance angle of excitation light, the intensity of plasmon-scattered light, or the enhancement angle of excitation light is measured, and the acquired measurement is used to obtain a whole-blood hematocrit value. Using the obtained whole-blood hematocrit value, a first signal value that indicates how much of an analyte the specimen contains is converted to a second signal value that indicates how much of said analyte the liquid part of the specimen contains.

Claims

1. A method of measuring an amount of a measurement object substance in a sample containing at least a part of blood by utilizing surface plasmon resonance, the method comprising:

coupling a measurement object substance contained in the sample and a capturing body by supplying the sample onto a metal film of a measurement chip, the measurement chip including a prism having an incidence surface and a film formation surface, the metal film disposed on the film formation surface, and the capturing body fixed on the metal film;

irradiating the metal film with excitation light from the prism side in a state where the sample is present on the metal film and measuring a quantity of excitation light reflected by the film formation surface, a resonance angle of the excitation light, a quantity of plasmon scattering light or an enhanced angle of the excitation light to determine whether the sample is whole blood or diluted solution of whole blood with use of an obtained measurement value, and, when the sample is determined to be whole blood or diluted solution of whole blood, acquire a hematocrit value of the whole blood with use of the obtained measurement value;

irradiating the metal film with excitation light from the prism side in a state where the measurement object substance and the capturing body are coupled together and the sample is not present on the metal film and measuring a quantity of fluorescence emitted from a vicinity of a surface of the metal film which faces away from the prism or a quantity of excitation light reflected by the film formation surface to acquire a first signal value representing an amount of the measurement object substance in the sample; and

,

when the sample is determined to be whole blood or diluted solution of whole blood, converting the first signal value to a second signal value representing an amount of the measurement object substance in the liquid component of the sample with use of the hematocrit value of the whole blood.

2. The method according to claim 1, wherein,

when converting the first signal value to the second signal value,

the first signal value is converted to the second signal value by multiplying the first signal value by conversion coefficient c₁ of Expression (1) when the sample is whole blood which is not diluted, and

the first signal value is converted to the second signal value by multiplying the first signal value by conversion coefficient c₂ of Expression (2) when the sample is diluted solution of whole blood,

3. A measurement device configured to measure an amount of a measurement object substance in a sample containing at least a part of blood by utilizing surface plasmon resonance, the measurement device comprising:

a holder configured to hold a measurement chip including a prism having an incidence surface and a film formation surface, a metal film disposed on the film formation surface, and a capturing body disposed on the metal film;

an excitation light irradiation section configured to emit excitation light toward the incidence surface;

a light detection section configured to detect a quantity of light emitted from a vicinity of a surface of the metal film which faces away from the prism, or a quantity of excitation light reflected by the film formation surface of the prism;

a processing section configured to determine whether the sample is whole blood or diluted solution of whole blood from a detection result of the light detection section, and calculate a first signal value representing an amount of the measurement object substance in the sample from the detection result of the light detection section, wherein, when the sample is determined to be whole blood or diluted solution of whole blood, the processing section calculates a hematocrit value of the whole blood from the detection result of the light detection section and converts the first signal value to a second signal value representing an amount of the measurement object substance in the liquid component of the sample with use of the hematocrit value of the whole blood, wherein;

the processing section determines whether the sample is whole blood or diluted solution of whole blood with use of a quantity of excitation light reflected by the film formation surface and measured by the light detection section, a resonance angle of the excitation light measured by the light detection section, a quantity of plasmon scattering light measured by the light detection section or an enhanced angle of the excitation light measured by the light detection section when the excitation light irradiation section irradiates the metal film with excitation light from the prism side in a state where the sample is present on the metal film; and

,

when the sample is determined to be whole blood or diluted solution of whole blood, the processing section acquires a hematocrit value of the whole blood with use of the quantity of the excitation light reflected by the film formation surface and measured by the light detection section, the resonance angle of the excitation light measured by the light detection section, the quantity of the plasmon scattering light measured by the light detection section or the enhanced angle of the excitation light measured by the light detection section.

4. The measurement device according to claim 3, wherein the processing section

converts the first signal value to the second signal value by multiplying the first signal value by conversion coefficient c₁ of Expression (1) when the sample is whole blood which is not diluted, and

converts the first signal value to the second signal value by multiplying the first signal value by conversion coefficient c₂ of Expression (2) when the sample is diluted solution of whole blood,