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WO2008050824A1 - Dispositif, appareil et procédé de mesure - Google Patents

Dispositif, appareil et procédé de mesure Download PDF

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Publication number
WO2008050824A1
WO2008050824A1 PCT/JP2007/070778 JP2007070778W WO2008050824A1 WO 2008050824 A1 WO2008050824 A1 WO 2008050824A1 JP 2007070778 W JP2007070778 W JP 2007070778W WO 2008050824 A1 WO2008050824 A1 WO 2008050824A1
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WO
WIPO (PCT)
Prior art keywords
light
sample
concentration
aggregation
intensity
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/JP2007/070778
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English (en)
Japanese (ja)
Inventor
Takahiro Nakaminami
Hiroaki Tachibana
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.)
Panasonic Corp
Panasonic Holdings Corp
Original Assignee
Panasonic Corp
Matsushita Electric Industrial Co Ltd
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 Panasonic Corp, Matsushita Electric Industrial Co Ltd filed Critical Panasonic Corp
Publication of WO2008050824A1 publication Critical patent/WO2008050824A1/fr
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
    • 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
    • G01N21/82—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 precipitate or turbidity
    • 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
    • G01N33/5304—Reaction vessels, e.g. agglutination plates

Definitions

  • the present invention relates to a measurement device, a measurement device, and a measurement method for analyzing a test substance contained in a sample.
  • POCT Point of Care Testing
  • Examples of the POCT device include a blood glucose sensor, a pregnancy diagnostic agent, an ovulation test agent, and an HbAlc-microalbumin measurement device (for example, DCA2000 manufactured by Bayer). Since the POCT instrument can focus on a marker substance specific to a certain disease state and measure the marker substance simply and quickly, it is effectively used for screening and monitoring of a subject.
  • the POCT equipment is small and excellent in portability, can be introduced at low cost, and does not require special expertise in operability, and can be used by anyone.
  • Patent Document 3 as an example of antigen measurement using an antibody, antigens such as albumin and CRP (C-reactive protein) are mixed together with the antibody and a polytheneglycol as an aggregation promoter. It has been proposed to produce antigen-antibody aggregates and measure turbidimetry using 470 nm light!
  • CRP C-reactive protein
  • Patent Document 1 Japanese Patent Application Laid-Open No. 07-248310
  • Patent Document 2 Japanese Patent Laid-Open No. 03-046566
  • Patent Document 3 Japanese Translation of Special Publication 2002-509247
  • the reagent particularly the aggregation promoter, is applied to the sample. Since dissolution is not always easy, the dissolution state varies from measurement to measurement, and as a result, the measurement of marker substances may be adversely affected.
  • the present invention has a simple configuration, and even if the state of dissolution of the aggregation promoter in the sample differs for each measurement, the measurement object can be measured quickly and accurately. It is an object of the present invention to provide a measuring device, a measuring apparatus, and a measuring method capable of measuring an antigen as a substance.
  • the measuring device of the present invention communicates with the sample holding unit, and a container-like substrate constituting a sample holding unit for holding a sample containing an antigen as a test substance in the internal space.
  • a sample supply port formed in the substrate, an antibody against the antigen arranged in contact with the sample in the sample holding part, and a sample in contact with the sample in the sample holding part and labeled with a dye
  • an aggregation promoter that promotes the formation of an aggregation complex containing the antigen and the antibody.
  • the measuring apparatus of the present invention includes a measuring device mounting portion for mounting the measuring device, and the sample held by the sample holding portion of the measuring device attached to the measuring device mounting portion.
  • a light emitter configured to emit light to the light receiving device
  • a light receiver configured to receive light that has passed through the sample held by the sample holding portion of the measurement device attached to the measurement device attachment portion.
  • the intensity of light reflecting the concentration of the aggregated complex received by the receiver and labeled with the dye And an arithmetic unit for quantifying the concentration of the test substance contained in the sample based on the intensity of light reflecting the concentration of the aggregation promoter dissolved in the sample.
  • the light emitter is configured to emit first light and second light
  • the light receiver emits from the light emitter.
  • a first light receiver for receiving the first light that has passed through the sample
  • a second light receiver for receiving the second light that has been emitted from the light emitter and passed through the sample.
  • the intensity of the first light received by the first light receiver reflects the concentration of the aggregated complex
  • the second light received by the second light receiver reflects the concentration of the aggregation accelerator labeled with the dye, and the concentration of the test substance and the first light receiver when the concentration of the aggregation accelerator is different.
  • a storage unit is further provided for storing a second calibration curve representing a relationship between the concentration of the accelerator and the intensity of the second light received by the second light receiver.
  • the light emitter is configured to emit first light and second light
  • the light receiver emits from the light emitter.
  • a first light receiver for receiving the first light that has passed through the sample
  • a second light receiver for receiving the second light that has been emitted from the light emitter and passed through the sample.
  • the intensity of the first light received by the first light receiver reflects the concentration of the aggregated complex
  • the second light received by the second light receiver The intensity of the light reflects the concentration of the aggregation accelerator labeled with the dye, and the concentration of the aggregation accelerator and the first light receiver when the concentration of the test substance is different.
  • the measurement method of the present invention is a measurement method using the above-described measurement device, and (A) supplying the sample into the sample holder of the measurement device, whereby the test substance and the antibody are A step of generating an agglomerated complex, (B) a step of emitting light to the sample held by the sample holding portion of the measuring device by a light emitter, and (C) a step of emitting light by a light receiver. A step of receiving light that has passed through the sample held by the sample holder of the measuring device; and (D) reflecting the concentration of the aggregated complex received by the light receiver in the step (B). A step of quantifying the concentration of the test substance contained in the sample based on the intensity of light and the intensity of light reflecting the concentration of the aggregation promoter labeled with the dye dissolved in the sample. And including.
  • the step (B) includes a first light emitter that emits the first light and a second light emitter that emits the second light.
  • the first and second light receivers have a step in which the light receiver receives the first and second light beams that have passed through the sample, and the step (D) is an aggregation promotion labeled with the dye.
  • a first calibration curve corresponding to the converted concentration of the aggregation promoter is extracted from a plurality of first calibration curves representing the relationship, and the extracted first calibration curve is referred to. Further, it may be a step of converting the intensity of the first light received by the first light receiver into the concentration of the test substance.
  • the step (B) includes light having a first light emitter that emits first light and a second light emitter that emits second light.
  • the emitter is a step of emitting the first and second lights to the sample held by the sample holder of the measurement device, and the step (C) receives the first and second lights.
  • the first and second light receivers have a step in which the light receiver receives the first and second light beams that have passed through the sample, and the step (D) is an aggregation promotion labeled with the dye.
  • the light intensity of 2 is converted into the concentration of the aggregation accelerator, and the concentration of the aggregation accelerator when the concentration of the test substance is different from the concentration of the aggregation accelerator.
  • a plurality of third units representing the relationship with the intensity of the first light received by the first receiver. From the calibration curve, a third calibration curve in which the converted concentration of the aggregation accelerator and the intensity of the first light received by the first light receiver coincide is extracted, and the extracted third The step of obtaining the concentration of the test substance corresponding to the calibration curve.
  • the concentration of an antigen as a measurement target substance can be measured quickly and accurately even if the aggregation state of the aggregation promoter in the sample differs for each measurement.
  • a measurement device, a measurement apparatus, and a measurement method that can be performed can be provided.
  • FIG. 1 is a perspective view showing a measuring device according to Embodiment 1 of the present invention.
  • FIG. 2 is a cross-sectional view taken along line AA in FIG.
  • FIG. 3 is an exploded perspective view showing the configuration of the measuring device according to the first embodiment of the present invention.
  • FIG. 4 is a diagram showing an absorption vector of a dye that labels the aggregation promoter in Embodiment 1 of the present invention.
  • FIG. 5 is a perspective view showing another example of the measuring device according to the first embodiment of the present invention.
  • FIG. 6 is a cross-sectional view taken along line BB in FIG.
  • FIG. 7 is a perspective view showing a measuring apparatus according to Embodiment 2 of the present invention.
  • FIG. 8 is a cross-sectional view showing an internal configuration when the measurement device of FIG. 1 is inserted into the measurement apparatus according to Embodiment 2 of the present invention.
  • FIG. 9 is a front view showing a measurement device removal mechanism of the measurement apparatus according to Embodiment 2 of the present invention.
  • FIG. 10 is a side view showing a measurement device removal mechanism of the measurement apparatus according to Embodiment 2 of the present invention.
  • FIG. 11 is a block diagram showing a configuration of a measuring apparatus according to Embodiment 2 of the present invention. 12] FIG. 12 is a diagram showing a second calibration curve stored in the memory of the measuring apparatus in the second embodiment of the present invention.
  • FIG. 13 is a diagram showing a first calibration curve group stored in the memory of the measuring apparatus according to the second embodiment of the present invention.
  • FIG. 14 is a diagram showing the first calibration curve extracted in the second embodiment of the present invention.
  • FIG. 15 is a diagram showing a third calibration curve group stored in the memory of the measuring apparatus according to Embodiment 3 of the present invention.
  • FIG. 16 is a flowchart schematically showing the characteristic operation of the measuring apparatus according to the second embodiment.
  • FIG. 17 is a flowchart schematically showing a characteristic operation of the measuring apparatus according to the third embodiment. Explanation of symbols
  • the measuring device includes a container-like base constituting a sample holding part for holding a sample containing an antigen as a test substance in the internal space, and the base so as to communicate with the sample holding part
  • an aggregation promoter that is labeled with a dye and promotes the generation of an aggregation complex containing the antigen and the antibody.
  • the dye since the dye is labeled on the aggregation promoter held in the sample holder, the dye is dissolved with the dissolution of the aggregation promoter in the sample.
  • the intensity of transmitted light (absorbed light), which is light after passing through the sample supplied into the sample holder, or fluorescence intensity depends on the amount of dye dissolved in the sample. For this reason, by measuring the intensity of light after passing through the sample, it is measured by the force to measure the amount of aggregation promoter dissolved in the sample.
  • the substrate is configured to emit light from the outside of the sample holder to the inside of the sample holder and light from the inside of the sample holder to the outside of the sample holder.
  • the antibody and the aggregation promoter are separately arranged in the sample holder.
  • the antibody and the aggregation promoter are arranged separately to facilitate the dissolution of the antibody and perform stable measurement. That's the power S.
  • the aggregation accelerator is preferably a polymer compound containing polyethylene glycol as a main chain.
  • the dye for labeling the aggregation promoter include phenoxazine and phenoxazine derivatives, phenazine and phenazine derivatives, atalidine and atalidine derivatives, fluorescein and fluorescein derivatives, and phenothiazine derivatives.
  • the above dyes are chemically stable, and their absorption coefficients, fluorescence yields, and absorption / excitation 'spectral properties such as fluorescence wavelength are well known, so they promote aggregation labeled with these dyes. The amount of the agent can be measured stably and accurately.
  • phenothiazine derivatives include thionine and thionine derivatives, azure A and azure A derivatives, azure C and azure C derivatives, and toluidine blue and toluidine blue derivatives.
  • the phenothiazine derivatives are chemically stable and well-known for their spectroscopic properties, and have an amino group in the molecule, so that they can be covalently labeled to aggregation promoters. Thus, the amount of the aggregation promoter labeled with these dyes can be measured stably and accurately.
  • the dye is one selected from the group consisting of thionine, azure eight, azure C, and toluidine blue.
  • the measuring apparatus includes a measuring device mounting portion for mounting the measuring device and the sample held by the sample holding portion of the measuring device attached to the measuring device mounting portion.
  • a light emitter configured to emit light
  • a light receiver for receiving light that has passed through the sample held by the sample holding portion of the measurement device attached to the measurement device attachment portion. Based on the intensity of light reflecting the concentration of the aggregation complex received by the light receiver and the intensity of light reflecting the concentration dissolved in the sample of the aggregation promoter labeled with the dye
  • a calculation unit for quantifying the concentration of the test substance contained in the sample is configured to emit first light and second light, and the light receiver receives the first light emitted from the light emitter and passed through the sample.
  • a second light receiver for receiving the second light emitted from the light emitter and passed through the sample, and received by the first light receiver.
  • the first light intensity reflected reflects the concentration of the aggregation complex
  • the second light intensity received by the second light receiver is labeled with the dye. Reflect the concentration of Is preferred.
  • the light emitter includes a first light emitter that emits the first light and a second light emitter that emits the second light! /, .
  • the measuring device receives light from the concentration of the test substance and the first light receiver when the concentration of the aggregation promoting agent is different.
  • a plurality of first calibration curves representing the relationship with the intensity of the first light, the concentration of the aggregation accelerator labeled with the dye, and the second light received by the second light receiver.
  • a storage unit for storing a second calibration curve representing the relationship between the intensity and the intensity.
  • the second calibration curve stored in the storage unit based on the signal from the second light receiver corresponding to the intensity of the second light that has passed through the sample held in the sample holding unit.
  • the dissolution concentration of the aggregation promoter labeled with the dye can be determined.
  • a first calibration curve corresponding to the determined concentration of the aggregation accelerator is extracted from the plurality of first calibration curves and extracted.
  • anti-antibody antibody aggregation is based on the concentration of the aggregation promoter in the sample.
  • the measuring apparatus receives light by the first light receiver and the concentration of the aggregation accelerator when the concentration of the test substance is different.
  • a plurality of third calibration curves representing a relationship with the intensity of the first light, and a relationship between the concentration of the aggregation accelerator and the intensity of the second light received by the second light receiver.
  • a storage unit for storing the second calibration curve to be expressed is further provided.
  • the second standard curve stored in the storage unit is referred to based on the signal output from the second light receiver corresponding to the intensity of the second light, and is labeled with a dye.
  • the concentration of the coagulation promoter dissolved can be determined.
  • the concentration of the aggregation accelerator determined from the plurality of third calibration curves and the measurement are measured.
  • a third calibration curve that matches the intensity of the first emitted light is extracted.
  • the concentration of the test substance corresponding to the extracted third calibration curve is the concentration of the test substance in the sample.
  • the concentration of the aggregation promoter dissolved in the sample (dissolution concentration C) is considered in consideration of the effect on the amount of antigen-antibody aggregation complex formed by the dissolution state of the aggregation promoter in the sample for each measurement. ) And based on the determined dissolution concentration of the aggregation promoter
  • the measurement apparatus of the present invention it is preferable to further include a suction unit for sucking the sample into the sample holding unit of the measurement device.
  • a suction unit for sucking the sample into the sample holding unit of the measurement device.
  • the measurement method of the present invention is a measurement method using the above-described measurement device, and (A) supplying the sample into the sample holder of the measurement device, whereby the test substance and the antibody are A step of generating an agglomerated complex; (B) a step of emitting light to the sample held by the sample holding portion of the measurement device by a light emitter; and (C) a step of emitting the light to the sample by the light receiver.
  • the concentration of the aggregation promoter is adjusted.
  • the concentration of the antigen-antibody aggregation complex the amount of the antigen to be measured (test substance) can be measured quickly and accurately.
  • the step (B) includes a first light emitting device that emits the first light and a second light emitting device that emits the second light.
  • the light receiver is a step of receiving the first and second lights that have passed through the sample, and the step (D) includes the concentration of the aggregation promoter labeled with the dye and the second light reception.
  • the intensity of the second light received by the second light receiver is referred to by referring to a second calibration curve representing the relationship between the intensity of the second light received by the light receiver and the aggregation promoter.
  • the intensity of the first light received by the first receiver May be converted to the concentration of the test substance.
  • the second calibration curve stored in the storage unit is referred to based on the signal from the second light receiver corresponding to the intensity of the second light that has passed through the sample held in the sample holding unit.
  • the dissolution concentration of the aggregation promoter labeled with the dye can be determined.
  • a first calibration curve corresponding to the determined concentration of the aggregation promoter is extracted from the plurality of first calibration curves, and the extracted first calibration curve is extracted.
  • the first receiver force signal corresponding to the intensity of the first light passing through the sample held in the sample holder can be converted into the concentration of the test substance. Can do.
  • the concentration of the antigen-antibody aggregation complex is determined based on the concentration of the aggregation accelerator in the sample. By determining the concentration, it is possible to quickly and accurately measure the antigen as the measurement target substance.
  • the step (B) includes a light emitter having a first light emitter that emits the first light and a second light emitter that emits the second light.
  • the second calibration curve representing the relationship between the intensity of the second light received by the second light receiver and the second light received by the second light receiver.
  • the strength of the aggregation promoter A plurality of third calibrations representing the relationship between the concentration of the aggregation accelerator and the intensity of the first light received by the first light receiver when the concentration of the test substance is converted.
  • a third calibration curve in which the converted concentration of the aggregation accelerator and the intensity of the first light received by the first light receiver coincide with each other is extracted from the line, and the extracted third It may be a step of obtaining the concentration of the test substance corresponding to the calibration curve
  • the aggregation accelerator labeled with the dye is referred to by referring to the second calibration curve stored in the storage unit.
  • the dissolution concentration of can be determined.
  • the concentration of the aggregation accelerator determined from the plurality of third calibration curves and the intensity of the first output light measured are measured.
  • a matching third calibration curve is extracted.
  • the concentration of the test substance corresponding to the extracted third calibration curve is the concentration of the test substance in the sample.
  • the concentration of the aggregation promoter dissolved in the sample is determined in consideration of the effect on the amount of antigen-antibody aggregation complex produced by the difference in the dissolution state of the aggregation promoter in the sample for each measurement.
  • concentration concentration is determined in consideration of the effect on the amount of antigen-antibody aggregation complex produced by the difference in the dissolution state of the aggregation promoter in the sample for each measurement.
  • concentration concentration of the antigen-antibody aggregation complex based on the determined dissolution concentration of the aggregation promoter, the measurement of the antigen as the measurement target substance can be performed quickly and accurately. .
  • Samples used in clinical tests include body fluids such as serum, plasma, urine, interstitial fluid, and lymph fluid, and liquid samples such as culture supernatant.
  • body fluids such as serum, plasma, urine, interstitial fluid, and lymph fluid
  • liquid samples such as culture supernatant.
  • urine is a very effective sample for non-invasive daily health management at home.
  • a reagent that reacts with a specific component in these body fluids, such as an enzyme, antibody, or dye, and a mixture of body fluids may be supplied as a sample to the measurement device.
  • albumin As test substances, albumin, hCG (human chorionic gonadotropin), LH (Luteinizing Hormone), CRP (C — Reactive Protein: C-reactive protein) ), IgG (Immunogloburin G).
  • optical measurement based on antigen-antibody reaction is suitable for the measurement.
  • examples of the optical measurement based on the antigen-antibody reaction include those that measure the turbidity generated in the sample based on the antigen-antibody reaction, such as an immunoratio method, an immunoturbidimetric method, and a latex immunoaggregation method.
  • an antibody against an antigen can be obtained by immunizing a mouse rabbit such as a protein such as albumin or CRP or a hormone such as hCG or LH as an antigen.
  • a mouse rabbit such as a protein such as albumin or CRP or a hormone such as hCG or LH as an antigen.
  • antibodies include antibodies against proteins contained in urine such as albumin and CRP, and antibodies against hormones contained in urine such as hCG and LH.
  • Embodiment 1 of the present invention exemplifies a case where the specimen sample is urine, the substance to be measured is human albumin, and the substance to be measured is detected by an immuno-ratio method.
  • FIG. 1 is a perspective view schematically showing a schematic configuration of the measurement device according to Embodiment 1 of the present invention
  • FIG. 2 is a cross-sectional view taken along line AA in FIG.
  • the measuring device 1 according to Embodiment 1 of the present invention includes a base body 2 having a space 2a made of a transparent material, for example, polystyrene.
  • the substrate 2 includes a hollow quadrangular prism portion 2d and a hollow quadrangular pyramid portion 2e, and the space portion 2a inside the substrate 2 functions as a sample holding portion 2a.
  • both ends of the base 2 are open to the outside, and the opening at the upper end of the hollow quadrangular prism portion 2d forms the suction port 2c, and the opening at the lower end of the hollow quadrangular pyramid portion 2e forms the sample supply port 2b. Yes.
  • the side surface of the hollow quadrangular prism portion 2d has four surfaces, that is, a first surface 3, a second surface 4, a third surface 5, and a fourth surface 6.
  • the second surface 4 functions as the light incident portion 4
  • the third surface 5 facing the second surface 4 functions as the light emitting portion 5.
  • the light incident part 4 and the light emitting part 5 constitute an optical measuring part 10.
  • the light incident part 4 and the light emitting part 5 are preferably formed of an optically transparent material or a material that does not substantially absorb visible light. For example, in addition to the above-mentioned polystyrene, quartz, glass, polymethyl methacrylate and the like can be mentioned.
  • the measuring device When the measuring device is disposable, it is preferable to use a resin material such as polystyrene from the viewpoint of cost. Further, in the measuring device, it is sufficient that at least the light incident part 4 and the light emitting part 5 are only optically transparent. Other parts than the above are not necessarily optically transparent.
  • the first reagent holding part 7 and the second reagent holding part are arranged on the inner wall face of the fourth face 6 of the hollow rectangular column part 2d among the inner wall faces surrounding the sample holding part 2a.
  • Part 8 is provided separately.
  • the first reagent holding unit 7 is provided in such a manner that the reagent comes into contact with the sample when the sample is supplied into the sample holding unit 2a.
  • the first reagent holding unit 7 includes a fourth reagent in the hollow square column part 2d. It is provided in the lower part of the surface 6.
  • the second reagent holding unit 8 is provided in such a manner that the reagent contacts the sample when the sample is supplied into the sample holding unit 2a. Specifically, it is provided between the lower end of the fourth surface 6 and the first reagent holding part 7 in the hollow quadrangular prism portion 2d.
  • the force that forms the second reagent holding part 8 at a position closer to the sample supply port 2b than the first reagent holding part 7 is not limited to this, and the first reagent holding part 7 may be formed at a position closer to the sample supply port 2b than the second reagent holding unit 8.
  • the first and second reagent holding portions 7 and 8 are each formed with a force formed on the inner wall surface of one surface (here, the fourth surface 6) of the hollow quadrangular prism portion 2d.
  • the first and second reagent holding portions 7 and 8 are not separately limited to the inner wall surfaces of two different surfaces (for example, the first surface 3 and the fourth surface 6) in the hollow rectangular column portion 2d. It may be formed.
  • the force for forming the first and second reagent holding portions 7 and 8 at different positions is not limited to this, and one reagent holding portion including an antibody and an aggregation promoter may be formed.
  • a reagent for reacting with the sample supplied in the sample holding unit 2a is held in a dry state.
  • a reagent an antibody that reacts with an antigen as a test substance in a sample is used.
  • a human albumin antibody is retained.
  • the second reagent holding unit 8 holds an agglutination promoter for promoting the agglutination reaction between the antigen and the antibody as a reagent in a dry state.
  • the aggregation promoter is labeled with a dye.
  • a dye for example, a compound having a structure represented by the following general formula (1) is used.
  • X and Y are each independently hydrogen (one H) or a methyl group (one CH).
  • n is preferably 30 to 350.
  • General formula (1) shows an example in which polyethylene glycol is used as the aggregation accelerator, and a phenothiazine derivative is used as the pigment for labeling the aggregation accelerator.
  • Polyethylene glycol and a phenothiazine derivative are bound by a peptide bond at the main chain end of polyethylene glycol, which is an aggregation promoter.
  • Examples of the aggregation promoter include compounds containing as a main chain a water-soluble polymer such as the above-mentioned polyethylene glycol and polysaccharides (dextran, cellulose, hyaluronic acid, chondroitin sulfate, etc.).
  • the binding form between the aggregation promoter and the dye may be a C—C bond, a C ⁇ C bond, a C ⁇ N bond, a S—S bond or the like in addition to the peptide (N—C) bond.
  • a side chain having 1 to 10 carbon atoms is bonded to the main chain of the aggregation accelerator!
  • Examples of the side chain include carboxyalkyl, alkyl, alkylamine, and alkylamide.
  • Examples of the dye for labeling the aggregation promoter include phenothiazine derivatives, phenoxazine and phenoxazine derivatives, phenazine and phenazine derivatives, atalidine and atalidine derivatives, and fluorescein and fluorescein derivatives.
  • Examples of phenothiazine derivatives include thionin and thionin derivatives.
  • Azul A and Azul A derivatives, Azul C and Azul C derivatives, and Toluidine blue and Toluidine blue derivatives are used.
  • FIG. 4 shows an absorption spectrum of thionine, which is an example of a dye used for labeling.
  • the horizontal axis represents wavelength (nm) and the vertical axis represents absorbance (arbitrary intensity).
  • Figure 4 shows that the absorbance decreases with decreasing thionin concentration.
  • Phenothiazine derivatives, phenoxazine and phenoxazine derivatives, phenazine and phenazine derivatives, atalidine and atalidine derivatives, and fluorescein and fluorescein derivatives are chemically stable, their extinction coefficient, fluorescence yield, and absorption 'excitation. 'Because the spectroscopic properties such as fluorescence wavelength are well known, aggregation accelerators labeled with these dyes can be measured stably and accurately.
  • Thionin and thionine derivatives are chemically stable and well known for their spectroscopic properties.
  • these dyes have an amino group in the molecule and can be easily labeled with a covalent bond to an aggregation promoter.
  • the aggregation promoter is labeled from the viewpoint of excellent quantitativeness because the blue colorant is far from the urine absorption wavelength compared to other colorant dyes.
  • the dye is preferably selected from the group consisting of thionine, azure eight, azure C and toluidine blue.
  • the second reagent holding unit 8 may hold not only an aggregation promoter labeled with a dye but also an unlabeled aggregation promoter that is not labeled with a dye.
  • the molecular weight of the aggregation accelerator and the chemical structure of the side chain an appropriate one can be used depending on the type of the aggregation reaction.
  • the aggregation promoter for example, one having a molecular weight in the range of 1,000 to 10,000 is used. Since the aggregation promoter is used to promote the antigen-antibody reaction, the second reagent holding part 8 is preferably arranged in the vicinity of the first reagent holding part 7 containing the antibody.
  • the measuring device 1 immerses a part of the measuring device 1 in, for example, urine (sample) collected in a container, as will be described later.
  • the measuring device with the measuring device 1 attached is used to empty the sample holder 2a from the suction port 2c.
  • urine is supplied into the sample holder 2a.
  • albumin which is a test substance in urine supplied into the sample holding part 2a reacts with the anti-human albumin antibody carried on the first reagent holding part 7 to contain albumin and anti-human albumin antibody. Aggregated complexes are formed.
  • the aggregation promoter carried on the second reagent holding unit 8 promotes the formation of an aggregation complex containing albumin and an anti-human albumin antibody.
  • the first reagent holding unit 7 and the second reagent holding unit 8 provided in the sample holding unit 2a are each subjected to antibodies and coagulation.
  • the antibody is placed separately from the high-viscosity polymer such as polyethylene glycol, which is an aggregation promoter, so that the dissolution of the antibody in the sample is very smooth.
  • the measurement of the test substance can be performed stably.
  • the aggregation promoter is labeled with a dye, the aggregation promoter dissolved in the sample supplied to the sample holder 2a is measured by a measurement apparatus described later.
  • the concentration can be easily quantified. For this reason, it is not necessary to completely dissolve the undissolved aggregation promoter, so that the concentration of the test substance contained in the sample can be measured quickly, and the aggregation promoter dissolved in the sample can be measured.
  • concentration of the test substance the concentration of the test substance (antigen) contained in the sample can be accurately measured.
  • the surfaces functioning as the light incident portion and the light emitting portion are the second surface 4 and the third surface 5, but the present invention is not limited to this.
  • the second surface 4 functions as a light incident part
  • the fourth surface 6 functions as a light emitting part
  • the light scattered in the sample holding part 2a after entering the sample holding part 2a from the second surface 4 is measured later.
  • the device may detect it.
  • FIG. 3 is an exploded perspective view schematically showing a schematic configuration of the measuring device 1 according to the first embodiment.
  • the measuring device 1 includes a first member 31 and a second member 32.
  • the first member 31 and the second member 32 are each made of a transparent material such as polystyrene. And each has a recess. Then, the first member 31 and the second member 32 are joined to each other so that the force recesses face each other, whereby the base body 2 having the hollow quadrangular prism portion 2d and the hollow quadrangular pyramid portion 2e is configured.
  • the first member 31 and the second member 32 are obtained by molding using a mold.
  • a known resin molding technique may be used for this molding process.
  • the first member 31 and the second member 32 can be formed with one mold, and the cost S can be reduced.
  • the dimensions of the first member 31 and the second member 32 may be set as appropriate. In this embodiment, the width A is 10 mm, the length B is S84 mm, and the length C is Is 6mm and the wall thickness is lmm.
  • the first reagent holding unit 7 and the second reagent holding unit 8 are formed on the bottom surface of the recess of the second member 32 as follows. Provide.
  • the first reagent holding part 7 is formed by using an aqueous solution of an antibody against human albumin, which is a reagent for optical measurement, on the bottom surface of the recess of the second member 32 using a microsyringe or the like. A method of forming a certain amount of the solution by dropping it into a liquid and leaving it in an environment of room temperature to 30 ° C to evaporate the water.
  • the first reagent holding part 7 can be formed by supporting an antibody against human albumin in a dry state.
  • the first reagent holding unit 7 can be formed by using an aqueous solution of an antibody having a concentration of 8 mg / dL and dropping it in an area of 5 cm 2 in an amount of 0.7 mL.
  • the first reagent holding portion on the bottom surface of the concave portion of the second member 32 is obtained by using an aqueous solution of an aggregation promoter using a microphone mouth syringe or the like.
  • a certain amount is dropped at a position different from 32, and this is left in an environment of room temperature to 30 ° C to evaporate moisture.
  • the second reagent holding unit 8 can be formed by supporting the aggregation accelerator in a dry state.
  • the second reagent holding part 8 can be formed by using an aqueous solution of an aggregation promoter having a concentration of 16% by weight and dropping it into a region having an area of 5 cm 2 in a dropping amount of 0.7 mL. .
  • the concentration and amount of the aqueous solution containing the reagent to be applied may be appropriately selected according to the characteristics required of the measurement device 1 and the spatial restriction of the formation position in the second member 32. it can. Also, the first reagent holding unit 7 and the second reagent holding in the second member 32 The position and area of the part 8 can be appropriately selected in view of the solubility of the reagent in the sample and the position of the optical measurement part 10.
  • the force formed by applying the aqueous solution containing the reagent and drying the first reagent holding unit 7 and the second reagent holding unit 8 is not limited to this, and is made of glass fiber or filter paper.
  • the porous carrier is impregnated with each reagent solution and then dried to carry the reagent, and the carrier carrying the reagent is attached to the bottom surface of the recess of the second member 32, respectively.
  • the first reagent holding unit 7 and the second reagent holding unit 8 may be formed in the sample holding unit 2a.
  • a carrier carrying a lyophilized reagent outside the sample holder 2a may be placed in the sample holder 2a.
  • An antibody against human albumin can be obtained by a conventionally known method.
  • an anti-human albumin antibody can be obtained by purifying rabbit antiserum immunized with human albumin by protein A column chromatography and then dialysis using a dialysis tube.
  • the measuring device 1 is assembled by joining in the positional relationship indicated by the one-dot chain line.
  • an adhesive such as an epoxy resin is applied to the joint between the first member 31 and the second member 32, and the first member 31 and the second member 32 are bonded together. Then, it may be allowed to stand and dry for adhesion.
  • the joint portion between the first member 31 and the second member 32 is formed using a commercially available welding machine. It may be welded by heat or ultrasonic waves.
  • the first reagent holding unit 7 and the second reagent holding unit 8 provided in the sample holding unit 2a are respectively provided.
  • the antibody and the aggregation promoter By holding the antibody and the aggregation promoter separately, the antibody is placed separately from the high viscosity polymer such as polyethylene glycol, which is the aggregation promoter, so that the dissolution of the antibody in the sample is very high. Therefore, the measurement of the test substance can be performed stably.
  • the antigen as the test substance contained in the sample supplied in the sample holding unit 2a and the antibody held in the first reagent holding unit 7 Anti It is possible to realize the formation of aggregates by reaction.
  • the intensity of the scattered light or transmitted light that is incident from the light incident part 4 of the measuring device 1 and transmitted through the sample supplied into the sample holding part 2a and then emitted from the light emitting part 5 of the measuring device 1 is Depends on the amount (concentration) of aggregates formed in the sample. For this reason, by measuring the emitted light, it is possible to measure the amount (concentration) of the aggregate, that is, the test substance in the sample.
  • the aggregation promoter is labeled with a dye
  • the dye is dissolved with the dissolution of the aggregation promoter in the sample.
  • Intensity of transmitted light (absorbed light) or fluorescence emitted from the light emitting part of the measurement device after entering through the light incident part of the measuring device 1 and passing through the sample supplied into the sample holding part 2a Depends on the amount (concentration) of the dye dissolved in the sample, that is, the amount (concentration) of the aggregation promoter. Therefore, by measuring the emitted light, it is necessary to measure the amount of the aggregation promoter dissolved in the sample.
  • the measuring device 1 can easily measure the amount of the aggregation promoter dissolved in the sample with a simple configuration. For this reason, it is not necessary to completely dissolve the undissolved aggregation promoter, so that the concentration of the test substance contained in the sample can be measured quickly, and the aggregation promoter dissolved in the sample can be measured.
  • concentration of the agent the concentration of the test substance (antigen) contained in the sample can be accurately measured.
  • the shape of the measuring device of the present invention is not limited to the measuring device 1 of the present embodiment as long as it satisfies the constituent requirements of the present invention and can obtain the effects of the present invention.
  • the measuring device 11 shown in FIGS. 5 and 6 may be used.
  • FIG. 5 is a perspective view showing another example of the measuring device according to Embodiment 1 of the present invention
  • FIG. 6 is a cross-sectional view taken along line BB in FIG.
  • the measuring device 11 is composed of a base 2 having a bottomed hollow rectangular parallelepiped shape having a sample holding portion 2a inside.
  • a sample supply port 2b is provided below the first surface 3 of the substrate 2.
  • the base 2 includes a first member 31 having three side surfaces and a bottom 33 corresponding to the first surface 3, the second surface 4, and the third surface 5, and a fourth surface. Consists of a second member 32 corresponding to 6 Has been. On the inner wall surface of the second member 32, a first reagent holding unit 7 and a second reagent holding unit 8 similar to the measurement device 1 of FIGS. 1 and 2 are provided.
  • the measuring device 11 configured as described above has the same operational effects as the measuring device 1.
  • FIG. 7 is a perspective view schematically showing the external appearance of the measuring apparatus according to the second embodiment
  • FIG. 11 is a block diagram schematically showing the functional configuration of the measuring apparatus shown in FIG.
  • the measurement apparatus 80 includes a housing 85, which includes the measurement device attachment unit 81, the display unit 82, the sample suction start button 83, and A measuring device removal button 84 is provided.
  • the measuring device mounting portion 81 is provided with a device mounting portion 94 (see FIG. 8) for removably joining the suction port 2c of the measuring device 1.
  • a display unit 82 which is a display for displaying measurement results, a sample suction start button 83, and a measurement device removal button 84 are provided.
  • the measuring device 1 is preferably attached to the measuring device 80 in a detachable state. Moreover, it is preferable that the measuring device 1 is disposable.
  • a measurement apparatus 80 includes a first light emitter 104 and a second light emitter 106 for emitting light incident on the optical measurement unit 10 of the measurement device 1. And a first light receiver 105 and a second light receiver 107 for receiving the light emitted from the optical measurement unit 10.
  • the first light emitter 104, the first light receiver 105, the second light emitter 106, and the second light receiver 10 7 are the light of the measurement device 1 when the measurement device 1 is attached to the measurement device 80.
  • the first light emitter 104 and the second light emitter 106 are a semiconductor laser (light source) that emits light of a predetermined wavelength (for example, 78 Onm and 600 nm), and the semiconductor laser is emitted from the semiconductor laser.
  • an optical system configured to irradiate the light incident portion 4 of the measurement device 1 with the optical system.
  • the first light receiver 105 and the second light receiver 107 use photodiodes.
  • the first light emitter 104 and the second light emitter 106 use a semiconductor laser as a light source here, but a light emitting diode (LED) or the like may be used.
  • the first light receiver 105 and the second light receiver 107 may use a charge coupled device (CCD), a photomultimeter, etc./.
  • the first light and the second light emitted from the first light emitter 104 and the second light emitter 106 are transmitted to the light incident portion 4 on the second surface 4 of the measuring device 1, and
  • the sample supplied to the sample holder 2a of the measuring device 1 and the light emitting unit 5 on the third surface 5 of the measuring device 1 are sequentially transmitted through the first light receiver 105 and the second light receiver 107. Each is received. Then, the first light receiver 105 and the second light receiver 107 each output an electric signal corresponding to the intensity of the received light to the calculation unit 121 described later.
  • the first light emitted from the first light emitter 104 and received by the first light receiver 105 is assumed to be applied to the measurement of albumin by immunoturbidimetry.
  • the wavelength of this light is 780 nm, but this wavelength may be appropriately selected according to the measurement method and the measurement object.
  • the second light emitted from the second light emitting device 106 and received by the second light receiving device 107 is a force that sets the wavelength of the second light to 600 nm. This wavelength is in the vicinity of the absorption peak of the dye that labels the aggregation accelerator.
  • An appropriate wavelength may be selected as appropriate according to the absorption characteristics of the dye used for the measurement in which the wavelength is preferred.
  • the first light emitter 104 and the second light emitter 106, the first light receiver 105 and the second light receiver 107, the two light emitters, and the two light receivers are used.
  • the present invention is not limited to this.
  • the first and second lights that is, light having an appropriate wavelength according to the absorption characteristics of the test substance (antibody) and the dye that labels the aggregation promoter are used.
  • the light may be emitted (one light source emits light of two different wavelengths) and received by one light receiver.
  • a single light source receives a wavelength selected for detection of the analyte in the sample
  • a second light receiver receives a wavelength selected according to the absorption characteristics of the dye. of A light receiver may be provided.
  • the first and second light emitters 104 and 106 are emitted from the light source and the optical system so that the first and second lights are emitted to the light incident portion 4 of the measuring device 1.
  • the present invention is not limited to this.
  • the first and second light emitted from the light source is guided into the sample holder 2a of the measuring device 1 and held there. You may comprise so that it may radiate
  • the first and second light receivers 105 and 107 are configured to receive the first and second lights emitted from the light emitting unit 5 of the measuring device 1, but the present invention is not limited to this.
  • the first and second lights that have passed through the sample held in the sample holding part 2a of the measuring device 1 are taken in at the tip of the optical fiber and guided to the first and second light receivers 105 and 107. These may be configured to receive light.
  • a calculation unit 121 composed of a CPU, a storage unit 122 composed of a memory, and a recording unit 124 for recording on a recording medium are provided. Further, the transmission unit 125 and the reception unit 126 are connected to the calculation unit 121.
  • the calculation unit 121 includes a first calculation unit for detecting or quantifying a test substance contained in a sample based on an electrical signal corresponding to the first light received by the first light receiver 105.
  • a second computing unit for detecting or quantifying the concentration of the aggregation promoter dissolved in the sample based on the electrical signal corresponding to the second light received by the second light receiver 107; have.
  • the storage unit 122 corrects the influence of the concentration of the aggregation promoter dissolved in the sample on the intensity of the first light received by the first light receiver 105, and examines the intensity of the emitted light. Stores data for conversion to the concentration of the substance antigen (human albumin).
  • the storage unit 122 of the measuring apparatus 80 stores the human albumin concentration and the first light receiver 105 that receives light at various aggregation promoter concentrations as data for conversion into the human albumin concentration.
  • 1 represents the relationship between the first calibration curve group representing the relationship between the light intensity of 1 and the concentration of the second light received by the second receiver 107 and the concentration of the aggregation promoter dissolved in the sample.
  • the second calibration curve is stored.
  • the calculation unit 121 refers to the second calibration curve stored (stored) in the storage unit 122 based on the intensity of the second light received by the second light receiver 107, and determines the dye.
  • the dissolution concentration of the aggregation promoter labeled with can be determined.
  • the calculation unit 121 includes the storage unit 1 By extracting a first calibration curve corresponding to the determined concentration of the aggregation promoter from the plurality of first calibration curves stored in 22 and referring to the extracted first calibration curve, The concentration of the test substance corresponding to the intensity of the first light received by the first light receiver 125 is calculated.
  • the antigen is determined based on the concentration of the aggregation promoter in the sample.
  • a device mounting portion 94 for removably joining the suction port 2c of the measuring device 1, a piston mechanism 103 as a suction portion, and a measuring device for removing the measuring device 1 A detaching mechanism 117 is provided!
  • FIG. 8 is a longitudinal sectional view schematically showing the internal configuration of the measuring device 80 according to the second embodiment when the measuring device 1 is inserted.
  • FIG. 9 is a front view schematically showing a measurement device removal mechanism 117 in the measurement apparatus 80 according to the second embodiment
  • FIG. 10 is a measurement device removal in the measurement apparatus 80 according to the second embodiment.
  • 3 is a side view schematically showing a mechanism 117.
  • the measuring device 80 includes a base member 92.
  • the base member 92 has a short columnar main body 92c, and a columnar device mounting boss 92a and a cylinder mounting boss 92b project from the central portion of both main surfaces of the main body 92c.
  • a through hole 92d is formed in the center of the main body member 92c so as to penetrate the device mounting boss 92a, the main body 92c, and the cylinder mounting boss 92b in the axial direction.
  • a step portion having a small diameter is formed at the tip of the device mounting boss portion 92a, and an annular device mounting sealing member 93 is fitted to the step portion.
  • the step portion of the device mounting sealing member 93 and the device mounting boss portion 92a constitutes a device mounting portion 94! /.
  • the outer peripheral surface of the device mounting sealing member 93 is formed to be similar to the inner surface shape of the suction port 2c of the measuring device 1, and has a taper.
  • the device mounting sealing member 93 has elasticity, and the outer diameter thereof is formed to be slightly larger than the diameter of the suction port 2c of the measuring device 1. For this reason, the adhesion between the device mounting sealing member 93 and the suction port 2c is improved, and air leakage at the joint portion can be prevented.
  • the device mounting sealing member 93 for example, an elastic material such as isoprene rubber, fluorine rubber, silicon rubber, or Teflon (registered trademark) -coated rubber is used. Further, the device mounting portion 94 in which the device mounting protrusion 92a and the device mounting sealing member 93 are integrated may be used, and the device mounting portion 94 itself may be made of an elastic material such as isoprene rubber. .
  • a slide member 91 is slidably fitted to the base of the device mounting projection 92a.
  • the slide member 91 is configured to contact the upper end of the base 2 of the measuring device 1 and retract in the axial direction.
  • the slide member 91 has a contact 91a, and the contact 91a is configured to press the measuring device insertion detection switch 95 when the slide member 91 is retracted! / RU
  • the slide member 91 comes into contact with the upper end of the base 2 of the measuring device 1 and is retracted. Then, the contact 91a of the slide member 91 presses the measurement device insertion detection switch 95, and the measurement device insertion detection switch 95 transmits to the calculation unit 121 that the measurement device 1 is attached.
  • the piston mechanism 103 includes a cylinder 100 having a piston 99 to which a piston rod 98 is fixed, a male screw rod 102 that is screwed into a female screw hole 98a provided in the piston rod 98, and a male screw. And a motor 101 to which a rod 102 is fixed.
  • annular cylinder mounting sealing member 97 made of a material having elasticity similar to that of the device mounting sealing member 93 is fitted into the cylinder mounting protrusion 92b.
  • the cylinder mounting sealing member 97 is fitted with the cylinder 100 of the piston mechanism 103.
  • the cylinder 100 and the base member 92 are attached with airtightness.
  • the cylinder 100 is formed in a cylindrical shape, and one end portion of the cylinder 100 is fitted to the cylinder mounting sealing member 97 as described above, and the other end portion is covered by the lid plate 100a. It is closed.
  • a through-hole in the thickness direction is provided at the center of the cover plate 100a, and an engaging portion for guiding a piston rod, which will be described later, projects from the opening that forms the through-hole.
  • the lid plate 100a is provided with a hole 100b for removing air from the cylinder 100 that flows in as the piston 99 moves.
  • a piston 99 is disposed inside the cylinder 100, and one end of a piston rod 98 is fixed to the piston 99.
  • a female screw hole 98a is provided at the other end of the piston rod 98 so as to extend along its central axis, and a guide groove 98b is provided at the outer periphery of the piston rod 98 so as to extend in the axial direction. Is formed.
  • the piston rod 98 is passed through the through hole of the lid member 100a of the cylinder 100 so that the guide groove 98b engages with the engaging portion of the lid member 100a. As a result, the piston rod 98 moves straight without rotating.
  • the motor 101 and the cylinder 100 are fixed to a casing 85 that houses the piston mechanism 103 and the like, and a male screw rod 102 is fixed to the rotation shaft of the motor 101.
  • the male threaded rod 102 is screwed into the female threaded hole 98a of the piston rod 98.
  • the piston rod 98 advances and retracts linearly along the center line 96 of the base member 92 due to the rotation of the male screw rod 102 accompanying the rotation of the motor 101.
  • piston mechanism 103 may be manually operated or automatically operated.
  • an automatic method there is a method in which the piston 99 is operated by the motor 101 as described above.
  • the motor 101 a step motor, a DC motor, or the like is used.
  • the step motor is a motor that rotates by a specific rotation angle per one input pulse signal, and since the rotation angle can be determined by the number of pulses, an encoder for positioning is not required. In other words, the operating distance of the piston 99 can be controlled by the number of input canons.
  • This type of motor incorporates a linear mechanism that combines male and female screws in the motor, and the rod-shaped movable part is configured to move linearly depending on the number of input canons. For this reason, this rod shape If the piston 99 is connected directly to the movable part, the construction can be simplified.
  • the piston mechanism 103 in the measurement apparatus of the present embodiment uses a step motor as the motor 101, and the piston
  • the sample of measurement device 1 is measured by piston mechanism 103 in a state where measurement device 1 is attached so that suction port 2c of measurement device 1 is connected to measurement device 80.
  • the sample can be sucked from the supply port 2b, and the sample can be easily supplied into the sample holder 2a of the measuring device 1.
  • the measurement device removal mechanism 117 is provided in the lower part (front part) of the base member 92 in the measurement apparatus 80.
  • the measuring device removing mechanism 117 includes a slide member 91, a pair of connecting plates 111 and 112, a support shaft 113, an operating pin 114, and a solenoid 115 having a plunger 116.
  • receiving pins 91b and 91c are provided on the surface of the slide member 91 on the first surface 3 side of the measuring device 1 and on the surface of the fourth surface 6 opposite thereto, respectively. It has been. Further, on the outside of the slide member 91, a pair of connecting plates 111, 112 are directed so as to sandwich the slide member 91 therebetween.
  • the receiving pin 91b is slidably fitted to an elongated hole 111a provided on the end side of the connecting plate 111.
  • the receiving pin 91c is slidably fitted in an elongated hole (not shown) provided on the end side of the connecting plate 112. Further, pressing protrusions 91d and 91e are provided on the lower surface of the slide member 91 on the side where the receiving pins 91b and 91c are formed.
  • the connecting plates 111 and 112 are formed with bent portions in the intermediate portions.
  • the connecting plates 111 and 112 have an elongated hole 11 lb provided between the proximal end of the connecting plate 111 and the bent portion and an elongated hole provided between the proximal end of the connecting plate 112 and the bent portion (not shown).
  • they are overlapped with each other and are slidably fitted to the actuating pin 114 so as to be slidable.
  • the operating pin 114 is also fitted with the plunger 116 of the solenoid 115. Therefore, the connecting plates 111, 112 and the plunger 116 are connected by the operating pin 114.
  • connection plate 111 Hole in connecting plate 111
  • the part 11 lc and the hole (not shown) of the connecting plate 112 are provided at the end of the connecting plate 111 opposite to the long hole 11 la and the long hole of the connecting plate 112, respectively, and are opposed to each other. Thus, they are overlapped with each other and pivotally fitted to the support shaft 113. Accordingly, the connecting plates 111 and 112 can swing around the support shaft 113 as a fulcrum.
  • the calculation unit 121 operates the piston mechanism 103 to discharge the urine in the sample holding unit 2a from the suction port 2c of the measurement device 1.
  • the measuring device removal mechanism 117 is activated, current is supplied to the solenoid 115, and the plunger 116 is attracted by the solenoid 115, so that the coupling plates 111 and 112 are moved back and forth with the support shaft 113 as a fulcrum. Swing clockwise. By this swinging, the receiving pins 91b and 91c are pressed downward (forward), and the slide member 91 is moved downward.
  • the pressing protrusions 91d and 91e are in direct contact with the upper end surface of the measuring device 1 and move the measuring device 1 downward. In this way, the measuring device 1 can be detached from the device mounting portion 94, and the measuring device 1 can be automatically removed from the measuring apparatus 80.
  • the piston mechanism 103 and the device removal mechanism 117 are provided so that the sample can be sucked and discharged and the device can be automatically removed.
  • the present invention is not limited to this.
  • the user may manually remove the measurement device 1 from the measurement device mounting portion 81 and suck and discharge the sample.
  • FIG. 16 is a flowchart schematically showing a characteristic operation of the measuring apparatus according to the second embodiment.
  • the operator's operation accompanying the operation of the measuring apparatus and accompanying chemicals are also shown! /.
  • the operator attaches the measuring device 1 to the measuring device 80 by joining the suction port 2c of the measuring device 1 to the device mounting portion 94 in the measuring device mounting portion 81 of the measuring device 80 ( Step S l).
  • the measurement measurement mounting device 8800 cannot be installed in the measurement measurement mounting attachment 8888.
  • the detected measurement device input / detection detection switch 9955 is activated and the operation unit 112211 detects the input of the measurement device 11 To know. .
  • the power source of the measuring and measuring device 8800 is set to the OONN state ((step SS22)). .
  • the operator for example, left the urine container or the urine container provided in the toilet bowl, for example. Any device such as paper, paper, etc. can be transported to a urine sample, which is collected in a container that can be transported.
  • the specimen inlet / outlet 22bb should be immersed and immersed in the position where it will be immersed (step SS33). .
  • the operator makes the pipette tone machine mechanism structure 110033 by pressing and holding down the sample button 8833 at the beginning of the sample suction and suction opening. Let it move. .
  • the Pippistonton 9999 installed in the inner part of the Pippistonton machine mechanism 110033 is retracted, and the sample material for the measurement measurement device 11 is supplied.
  • a predetermined fixed amount ((for example, 33 mm UU of urine and urine, for example, is introduced ((supplied supply)) from the inlet 22bb into the sample specimen holder 22aa. It will be done.
  • the urine urine supplied and supplied to the sample specimen holding and holding unit 22aa is transferred to the eleventh reagent reagent holding and holding unit 77.
  • the anti-anti-hihitoalbububuminmin anti-antibody body and the 22nd reagent reagent holding part 88 which are the dry and dry state reagent reagents held and held, Dissolve and dissolve the coagulation-accelerating accelerator, which is the reagent in the dry and dry state that is held and held. .
  • the measurement is performed.
  • the operation / calculation unit 112211 of the measurement set-up device 8800 is operated according to the operation of the timing unit 112233 which is a timer. Obtain and obtain TTdd for the elapsed time after the sample fee is introduced into the sample charge holder 22aa ((Step SS SS 77)) . .
  • the operation / calculation unit 112211 of the measuring and measuring set-up device 8800 holds the test sample fee according to the output power signal of the time measuring unit 112233.
  • Step Step SS88 After the completion of the supply of the sample material to the part 22aa, it is determined whether the TTdd has reached the TTppdd for the predetermined elapsed time (Step Step SS88)). .
  • the arithmetic operation unit 112211 reaches the TTppdd during the elapsed time TTdd reaches the predetermined elapsed time TTppdd.
  • the performance calculation unit 112211 determines that the elapsed time TTdd has reached the predetermined elapsed time TTppdd.
  • Optical measurement of the sample held by the sample holding unit 2a of the measuring device 1 is started (step S9). Specifically, the calculation unit 121 emits the first light from the first light emitter 104 and enters the sample holding unit 2a through the second surface 4 of the measurement device 1, that is, the light incident unit 4. Make it incident. The first light incident on the sample holding part 2a is transmitted and scattered in the urine held in the sample holding part 2a, and from the third surface 5, that is, the light emitting part 5 of the measuring device 1. Exit. Then, the first light emitted from the light emitting unit 5 is received by the first light receiver 105 provided in the measuring device 80 for a predetermined time (for example, 3 minutes), and the intensity of the light is measured. Control the stock so that it does.
  • a predetermined time for example, 3 minutes
  • the calculation unit 121 emits the second light from the second light emitter 106 and makes it enter the sample holding unit 2a through the light incident unit 4.
  • the second light incident on the sample holder 2a is absorbed by the dye labeled with the aggregation accelerator in proportion to the concentration of the aggregation accelerator dissolved in the urine.
  • the second light that has not been absorbed by the pigment is emitted from the light emitting unit 5.
  • the second light emitted from the light emitting section 5 is received by a second light receiver 107 provided in the measuring device 80 for a predetermined time (for example, 3 minutes), and the intensity of the light is measured. taking measurement.
  • the calculation unit 121 correlates the intensity of the second light received by the second light receiver 107 stored in the storage unit 122 and the concentration of the aggregation accelerator labeled with the dye.
  • a second calibration curve indicating is read (step S10).
  • the computing unit 121 refers to the second calibration curve to determine the intensity of the second light received by the second light receiver 107 as the dissolution concentration (C) of the dye-labeled aggregation promoter. Convert to (step S11).
  • FIG. 12 is a schematic diagram showing the correlation between the concentration of the aggregation promoter (polyethylene glycol) and the second light intensity when the human albumin concentration is 20 mg / dL.
  • the horizontal axis represents the polyethylene glycol concentration (wt%) in the sample, and the vertical axis represents the absorbance of the second light received by the second receiver 107 (arbitrary intensity, hereinafter abbreviated as au). Show. For example, if the intensity (absorbance) of the second light received by the second receiver 107 is 1.5, the concentration of the polyethylene glycol labeled with the second calibration curve is 3. Owt%. .
  • the concentration of the aggregation promoter when the human albumin concentration is 20 mg / dL.
  • the relationship between the concentration of the aggregation promoter and the emitted light intensity does not depend on the human albumin concentration.
  • the calculation unit 121 stores the concentration of human albumin at various dye-labeled aggregation promoter concentrations stored in the storage unit 122 and the first light received by the first light receiver 105.
  • the first calibration curve at the dissolution concentration C of the dye-labeled aggregation promoter converted in step S11 is selected from a plurality of first calibration curve groups showing a correlation with the light intensity.
  • Step SI 2 Read (Step SI 2).
  • the calculation unit 121 converts the intensity of the first light received by the first light receiver 105 into the concentration of human albumin, which is the test substance (step S13).
  • FIG. 13 is a diagram showing the correlation between the concentration of human albumin and the intensity of the first light received by the first light receiver 105 at various dye-labeled aggregation promoter concentrations.
  • FIG. 14 is a schematic diagram showing a first calibration curve extracted from the first calibration curve group shown in FIG. 13 and 14, the horizontal axis is the human albumin concentration (mg / dL) in the sample, and the vertical axis is the intensity of the first light (scattered light intensity) received by the first light receiver 105 (au ). 13, a first calibration curve A ⁇ G constituting the first calibration line group, respectively dyes-labeled polyethylene glycol Honoré concentration (wt 0/0) force 1.0, 1.5, 2. The calibration curves for 0, 2.5, 3.0, 3.5, and 4.0 are shown.
  • the calculation unit 121 uses the first calibration curves A to G stored in the storage unit 122. Then, the first calibration curve E is selected and read (step S12). Then, as shown in FIG. 14, by estimating the human albumin concentration on the horizontal axis from the point on the first calibration curve E indicating the intensity of the first light received by the first light receiver 105, The human albumin concentration corresponding to the first light intensity can be obtained (step S13). For example, if the intensity of the first light (scattered light intensity) received by the first receiver 105 is 66 a.u., the human albumin concentration corresponding to the first light intensity is 14 mg / u.
  • the aggregation promoter is changed for each measurement. Considering the effect on the amount of antigen-antibody aggregation complex produced by different dissolution states in the sample, the dissolution concentration of the aggregation promoter in the sample is determined, and the antigen concentration is determined based on the dissolution concentration of the aggregation promoter. By determining the concentration of the antibody aggregation complex, it is possible to accurately measure the antigen as the measurement target substance.
  • the human albumin concentration obtained by the quantification operation is displayed on the display unit 82 of the measuring device 80. Thereby, the user of the measuring device 80 can know the completion of the measurement of the human albumin concentration contained in the urine.
  • the human albumin concentration obtained by the quantitative operation is preferably stored in the storage unit 122 together with the time measured by the time measuring unit 123.
  • measuring apparatus 80 According to the configuration of measuring apparatus 80 according to the present embodiment, data relating to the human albumin concentration obtained by the quantitative operation is recorded on a removable storage medium such as an SD card by recording unit 124. Can do. As a result, the measurement result can be easily taken out from the measurement device 80, so that it is possible to bring the storage medium to an analysis specialist or mail it for a detailed analysis.
  • measuring apparatus 80 it is possible to transmit the data related to the human albumin concentration obtained by the quantitative operation to the outside of measuring apparatus 80 by transmitting unit 125. .
  • the measurement results can be sent to the analysis-related departments or analysis-related companies in the hospital It is possible to reduce the time required from measurement to analysis because the data can be sent to and analyzed by analysis-related departments or analysis-related contractors.
  • receiving section 126 is provided for receiving the results of analysis in an analysis-related department or analysis-related contractor or the like, analysis results are provided. Can be quickly fed back to the user.
  • the measuring device insertion detection switch 95 provided inside the measuring device mounting portion 81 is activated, and the computing unit 121 is disconnected from the measuring device 1. Detects separation. As a result, the power source of the measuring device 80 is turned off (step S15).
  • light irradiation by the first light emitter 104 and the second light emitter 106 is performed after a predetermined time after supplying the sample (urine) into the sample holder 2a.
  • the light irradiation may be started simultaneously with the detection of the completion of the sample supply.
  • the electrical signals from the first light receiver 105 and the second light receiver 107 that receive the light emitted from the first light emitter 104 and the second light emitter 106 are transmitted from the sample supply completion to a predetermined value.
  • the antigen-antibody due to the difference in the dissolution state of the aggregation promoter in the sample for each measurement is determined, and the concentration of the antigen-antibody aggregation complex is determined based on the dissolution concentration of this aggregation promoter. It is possible to accurately measure an antigen as a measurement target substance.
  • the measurement device according to the second preferred embodiment of the present invention and the measurement device are used.
  • An example of the second measurement method of the present invention will be described.
  • the storage unit 122 has the same second calibration curve as in the second embodiment, and an aggregation promoter labeled with a dye at various antigen concentrations (test substances). And the third calibration curve group indicating the correlation between the first light intensity received by the first light receiver 105 and the third calibration curve group. .
  • the storage unit 122 stores, for example, a second calibration curve shown in FIG. 12 and a third calibration curve group shown in FIG.
  • FIG. 15 shows a third calibration curve showing the relationship between the concentration of the aggregation promoter labeled with the dye and the intensity of the first emitted light received by the first receiver 105 at various human albumin concentrations.
  • the horizontal axis represents the polyethylene glycol concentration (wt%) in the sample, and the vertical axis represents the scattered light intensity (a.u.) of the first light received by the first light receiver 105.
  • the third calibration curves A to K constituting the third calibration curve group have human albumin concentrations (mg / dL) of 0, 2, 4, 6, 8, 10, 12, 14 , 16, 18, and 20 are calibration curves.
  • FIG. 17 is a flowchart schematically showing the characteristic operation of the measuring apparatus according to the third embodiment.
  • the measurement method using the measurement apparatus of the third embodiment in FIG. 17 is the same as the measurement method using the measurement apparatus of the second embodiment shown in FIG. 16 except for step S12 and step S13. Therefore, the description is omitted.
  • the calculation unit 121 calculates the correlation between the intensity of the second light received by the second light receiver 107 stored in the storage unit 122 and the concentration of the aggregation accelerator labeled with the dye.
  • the second calibration curve shown is read (step S10), and by referring to this second calibration curve, the intensity (absorbance) of the second light received by the second receiver 107 is labeled with a dye. Convert to the dissolved concentration (C) of the aggregation promoter (step Sll).
  • the calculation unit 121 calculates the correlation between the concentration of the aggregation promoter labeled with the dye and the intensity of the first light received by the first light receiver 105 at various human albumin concentrations.
  • the third calibration curve group shown is read from the storage unit 122 (step S12).
  • the computing unit 121 refers to the third calibration curve group to thereby obtain the first light receiver 105.
  • the intensity of the first light is converted into a human albumin concentration.
  • the concentration of polyethylene glycol converted in step S11 and the intensity of the first light received by the first receiver 105 are A matching third calibration curve is extracted, and the concentration of the test substance corresponding to the extracted third calibration curve is converted (step S13).
  • the calculation unit 121 15 shows the polyethylene glycol concentration (3 ⁇ Owt%) calculated by the second calibration curve from the third calibration curve group A to K shown in FIG. 15 (converted in step S11).
  • the third calibration curve H that matches the value and the vertical axis value indicating the intensity (66) of the first outgoing light is extracted.
  • the calculation unit 121 obtains the human albumin concentration (here, 14 mg / dU) in the third calibration curve H from the storage unit 122, and the human albumin concentration in the sample is converted to 14 mg / dL.
  • the measuring apparatus 80 by using the measuring apparatus 80 according to the third embodiment, the influence on the production amount of the antigen-antibody aggregation complex due to the difference in the dissolution state of the aggregation promoter in the sample for each measurement is taken into consideration.
  • the concentration of the aggregation promoter in the sample is determined, and the concentration of the antigen-antibody aggregation complex is determined based on the dissolution concentration of the aggregation promoter. Can be done.
  • the measurement device, the measurement apparatus, and the measurement method according to the present invention include an antigen-antibody aggregation complex due to different dissolution states of the aggregation promoter in the sample supplied to the measurement device.
  • the concentration of the aggregation promoter in the sample is determined in consideration of the effect on the production amount of the body, and the concentration of the antigen-antibody aggregation complex is determined based on the dissolution concentration of the aggregation promoter. Because it can accurately measure the target antigen, it is useful in medical and medical-related examination fields, especially when measuring the amount of a test substance in a urine sample.

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Abstract

La présente invention concerne un dispositif de mesure qui comprend : un corps en forme de conteneur (2) dont l'espace interne constitue une partie qui conserve l'échantillon (2a) pour conserver un échantillon contenant un antigène qui est une substance de test qui doit être mesurée ; un orifice d'introduction de l'échantillon (2b) qui est formé dans le corps (2) de manière à être raccordé à la partie qui conserve l'échantillon (2a) ; une partie de mesure optique (10) pour mesurer optiquement la substance de test maintenue dans la partie qui conserve l'échantillon (2a) ; un anticorps dirigé contre l'antigène qui est disposé à une position où il est en contact avec l'échantillon disposé dans la partie qui conserve l'échantillon (2a) ; et une substance favorisant l'agglutination disposée à une position où elle est en contact avec l'échantillon disposé dans la partie qui conserve l'échantillon (2a), ladite substance favorise la formation d'un complexe d'agglutination comprenant l'antigène et l'anticorps et qui a été marquée avec un pigment.
PCT/JP2007/070778 2006-10-26 2007-10-25 Dispositif, appareil et procédé de mesure Ceased WO2008050824A1 (fr)

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JP2005345464A (ja) * 2004-05-06 2005-12-15 Matsushita Electric Ind Co Ltd センサ、測定装置および測定方法
JP2006519376A (ja) * 2003-02-27 2006-08-24 ダコサイトメーション・デンマーク・アクティーゼルスカブ 免疫組織化学、免疫細胞化学および分子細胞遺伝学のための標準

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JP2006519376A (ja) * 2003-02-27 2006-08-24 ダコサイトメーション・デンマーク・アクティーゼルスカブ 免疫組織化学、免疫細胞化学および分子細胞遺伝学のための標準
JP2005345464A (ja) * 2004-05-06 2005-12-15 Matsushita Electric Ind Co Ltd センサ、測定装置および測定方法

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