WO2017006964A1 - Trousse d'analyse sanguine, éléments associés, et son procédé de production - Google Patents

Trousse d'analyse sanguine, éléments associés, et son procédé de production Download PDF

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Publication number
WO2017006964A1
WO2017006964A1 PCT/JP2016/070009 JP2016070009W WO2017006964A1 WO 2017006964 A1 WO2017006964 A1 WO 2017006964A1 JP 2016070009 W JP2016070009 W JP 2016070009W WO 2017006964 A1 WO2017006964 A1 WO 2017006964A1
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Prior art keywords
blood
test kit
diluent
plasma
standard component
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PCT/JP2016/070009
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English (en)
Japanese (ja)
Inventor
光 浦野
中津川　晴康
進 大澤
晋哉 杉本
Original Assignee
富士フイルム株式会社
株式会社リージャー
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Application filed by 富士フイルム株式会社, 株式会社リージャー filed Critical 富士フイルム株式会社
Priority to KR1020187000463A priority Critical patent/KR102080416B1/ko
Priority to CN201680039462.1A priority patent/CN108027359A/zh
Priority to EP16821433.6A priority patent/EP3321678A4/fr
Priority claimed from JP2016133958A external-priority patent/JP6522555B2/ja
Publication of WO2017006964A1 publication Critical patent/WO2017006964A1/fr
Priority to US15/861,875 priority patent/US10788478B2/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • 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
    • 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
    • G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard

Definitions

  • the present invention relates to a blood test kit for analyzing a target component in a very small amount of blood sample, a member for use in the kit, and a method for producing them.
  • a general qualified blood sample is collected by a doctor or other qualified person using a syringe to collect blood from the vein, and the subject is self-collected by inserting a blood collection needle into his / her finger or the like. There is blood sampling.
  • Blood collected by general blood collection is transported to a medical institution or inspection in a state of being sealed in a collection container, where it is inspected.
  • a test is performed after blood is separated into blood cells and plasma by a centrifuge at a medical institution or inspection institution.
  • the collected blood is separated into blood cells and plasma by a separation membrane and transported to the examination site in this separated state, where the examination is performed.
  • Patent Document 1 describes a method for examining a blood sample collected by self blood collection. Specifically, 1) Prepare a sample for quantification consisting of an unknown volume of a biological sample containing a component to be quantified collected without quantifying the volume and a fixed amount of an aqueous solution containing a fixed amount of an indicator substance.
  • Patent Document 2 the amount of the analysis target component in the sample is measured, and the amount of the standard component originally present in the sample other than this is measured.
  • a quantitative analysis method is described in which the amount of a sample is determined from a known concentration of a standard component, and the concentration of the analysis target component in the sample is determined from the sample amount and the analysis target component amount.
  • Patent Document 3 describes that a small amount of blood is collected from a human or animal using a blood dilution quantification instrument and is supplied as it is or after dilution to supply a constant amount to another device, container or reagent.
  • Patent Document 4 describes a method of quantifying the concentration of a component to be quantified in a biological sample using the absorbance of an indicator substance in an aqueous solution for dilution.
  • Patent Document 2 about 100 ⁇ L of whole blood of healthy subjects is dropped on a porous membrane, blood cells are separated and serum is developed, and then 150 ⁇ L of saline-buffered saline (pH 7.4) is added. The supernatant obtained by centrifuging the obtained liquid is analyzed as an analysis sample, but there is no description of blood collection of less than 100 ⁇ L.
  • the measurement method described in Patent Document 4 is a measurement with a dilution factor of about 10 times.
  • the measurement value is repeatedly reproduced as in Patent Document 1. There is a problem that the performance is lowered.
  • the present invention relates to a method for analyzing the concentration of a target component in a blood sample using a standard component that is constantly present in blood as a method for quantitatively analyzing a component by diluting a trace amount of blood with a buffer solution.
  • a concentration of standard components that are constantly present in the blood eluted from the kit members in the buffer solution for example, the dilution factor can be accurately determined with an accuracy that is not found in the prior art of Patent Document 1 and Patent Document 2.
  • a blood test kit capable of further improving accuracy by further using a method for obtaining a dilution ratio using an internal standard is provided.
  • the present inventors diluted a collected blood sample with a diluent, and determined the dilution ratio using the standard values of standard components that are constantly present in the blood.
  • the present invention provides the following.
  • a diluent for diluting a blood sample A first storage device in which the diluent is stored, a separation device for separating and recovering plasma from a blood sample diluted with the diluent, a holding device for holding the separation device, and storing the recovered plasma
  • a standard component that is continually present in blood comprising: a second storage device for: and a member selected from the group consisting of sealing devices for maintaining stored plasma in the second storage device
  • the blood test kit according to 1 wherein the amount of the standard component derived from the member that can be contained in the diluent is 0.5% by mass or less of the amount of the diluent.
  • the blood test kit according to 1 or 2 wherein the volume of the diluent is 15 times or less the volume of plasma.
  • the blood test kit according to any one of 1 to 3 wherein the standard component that is constantly present in blood is sodium ion or chloride ion.
  • the blood according to any one of 1 to 4 wherein the standard component that is constantly present in blood is a standard component that is permanently present in sodium or chloride ions and in another blood. Inspection kit.
  • An amino alcohol compound wherein the diluent is selected from the group consisting of 2-amino-2-methyl-1-propanol, 2-ethylaminoethanol, N-methyl-D-glucamine, diethanolamine, and triethanolamine 2- [4- (2-hydroxyethyl-1-piperazinyl] ethanesulfonic acid), also referred to as HEPES, N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid, also referred to as TES, 3-morpholino, also referred to as MOPS
  • the blood test according to any one of 1 to 9, comprising a buffer selected from the group consisting of propanesulfonic acid and BES (N, N-bis (2-hydroxyethyl) -2-aminoethanesulfonic acid kit.
  • the blood test kit according to 11, wherein the standard component not present in the blood is lithium ion or glycerol triphosphate.
  • the blood test kit according to any one of 1 to 12, or 13 or 14, comprising a step of washing the member under conditions effective for removal of a standard component that is constantly present in blood.
  • the manufacturing method of this member comprising a step of washing the member under conditions effective for removal of a standard component that is constantly present in blood.
  • the manufacturing method of this member comprising a step of washing the member under conditions effective for removal of a standard component that is constantly present in blood.
  • the manufacturing method of this member comprising a step of washing the member under conditions effective for removal of a standard component that is constantly present in blood.
  • the manufacturing method of this member comprising a step of washing the member under conditions effective for removal of a standard component that is constantly present in blood.
  • the manufacturing method of this member comprising a step of washing the member under conditions effective for removal of a standard component that is constantly present in blood.
  • the manufacturing method of this member comprising a step of washing the member under conditions effective for removal of a standard component that is constantly present in blood.
  • the manufacturing method of this member
  • the blood test kit and its members of the present invention it is possible to accurately analyze the concentration of a target component in a blood sample using a standard component that is constantly present in blood. According to the production method of the present invention, it is possible to provide a blood test kit and its members capable of performing the above-described analysis with high accuracy.
  • FIG. 1 is a cross-sectional view of a blood test kit according to an embodiment of the present invention.
  • FIG. 2 is an example of the result of calculating the allowable elution concentration of sodium ions in the diluent (% by weight with respect to the diluent).
  • the range indicated by X to Y includes the upper limit X and the lower limit Y.
  • a standard component that is constantly present in blood may be referred to as an external standard substance or an external standard.
  • a standard component that does not exist in blood may be referred to as an internal standard substance or an internal standard.
  • Patent Document 2 discloses a method using a porous material having high blood retention instead of filter paper.
  • blood components absorbed in the material are extracted and measured with a buffer solution or the like, so that sodium ions, chloride ions, calcium ions, proteins, which are external standard substances that are constantly present in blood, are measured.
  • sodium ions, chloride ions, calcium ions, proteins, which are external standard substances that are constantly present in blood are measured.
  • the amount of blood collected varies, and if the collected blood dilution rate increases, the accuracy of the subsequent analysis decreases and the results vary, and the blood is agglutinated and solidified for analysis. Insufficient assurance of component stability.
  • a buffer solution for extracting a biological component from a dried sample it is necessary to use a buffer solution to which NaOH, NaCl, or HCl is added for pH adjustment or biological component stabilization. For this reason, the concentration of other diluted biological components is corrected using the concentration of sodium ions and chloride ions, which are present at a relatively high concentration of sample components, have homeostasis, and have small differences between individuals as an external standard. There was a problem that it could not be used to do.
  • Patent Document 1 a method described in Patent Document 1 is disclosed as a method for diluting a collected trace blood with a buffer solution containing an internal standard and quantifying the amount of a component having an unknown amount in diluted plasma from the dilution factor of the internal standard substance.
  • N- (2-Hydroxy-3-sulfopropyl) -3,5-dimethoxyaniline sodium salt (HSDA) or Acid Blue 9 (Brilliant Blue FCF) is used as an internal standard substance to stabilize blood. Buffering agents and preservatives are used for holding.
  • Such a prescription achieved the stability of its components by not coagulating the blood, but when the blood collection volume is also variable and the collection volume is small, the dilution rate of the internal standard substance after dilution
  • the problem is that the reliability of the test accuracy is lowered due to the decrease in the amount of blood and the blood component amount itself.
  • the method of diluting with a buffer solution is a biological component stored in a buffer solution with physiological conditions of pH 7.4 and is excellent in stability during transportation. There was a problem that measurement errors were likely to occur when the dilution rate was small and a small amount of sample was added.
  • phosphate buffered saline is used as the buffer solution to be extracted because it is excellent in the stable retention of biological components.
  • phosphate buffered saline contains sodium ions and chloride. Contain ions.
  • sodium ions and chloride ions cannot be used as external standards, and calcium ions, proteins, and the like are used. Therefore, in order to perform a blood test with a small amount of blood with high accuracy, the use of an external standard substance that corrects the dilution rate as in the prior art or the use of a buffer solution containing a conventionally proposed internal standard substance Insufficient inspection accuracy.
  • Patent Document 1 has a description regarding an internal standard, but there is no description regarding the combined use with an external standard. Therefore, there is no description regarding the contamination of the external standard, and no specific means for preventing the contamination has been proposed.
  • the present invention is a kit for analyzing a concentration of a target component by diluting a trace blood sample with a buffer solution, and when analyzing a control component using an external standard constantly present in blood,
  • An object of the present invention is to provide a blood test kit capable of obtaining the dilution rate with an accuracy not found in the prior art.
  • the amount of the standard component derived from the member that can be included in the diluent is defined.
  • not only an external standard is used but also an internal standard is used.
  • a synthetic resin in this specification, , Plastic is used synonymously with synthetic resin.
  • Measurement method that can accurately quantify the component to be analyzed by detecting standard components with homeostasis derived from blood with sufficiently high accuracy by suppressing the component as much as possible, or blood using the measurement method An inspection system can be realized.
  • a blood test kit capable of further improving accuracy by further using a method for obtaining a dilution ratio using an internal standard is provided.
  • the blood test kit of the present invention comprises: A diluent for diluting the blood sample; A first storage device containing the diluent, a separation device for separating and collecting plasma from a blood sample diluted with the diluent, a holding device for holding the separation device, and for storing the collected plasma A member selected from the group consisting of a second storage device and a sealing device for maintaining the stored plasma in the second storage device; A blood test kit for analyzing the concentration of a target component in a blood sample using a standard component that is constantly present in blood, The amount of the standard component derived from the member that can be contained in the diluent is defined.
  • Analyzing the concentration of the target component in the blood sample is to determine the concentration of the target component (that is, to quantify the target component) or whether the concentration of the target component is equal to or higher than a predetermined reference value. Including determination of whether or not, the form of analysis is not particularly limited.
  • the blood test kit of the present invention is used for collecting a blood sample. Collection of blood using the blood test kit of the present invention may be performed by the subject himself or by a qualified person such as a doctor.
  • the patient himself / herself collects blood that has come out of the skin by damaging a fingertip or the like using an instrument with a knife such as a lancet.
  • the concentration of the standard component that is constantly present in the blood that can be eluted in the diluent is regulated to be low, and the blood is constantly present in the blood.
  • sodium ions or chloride ions as existing standard components, it is possible to provide a method for measuring an analyte with high measurement accuracy.
  • the blood test kit of the present invention is a blood test kit for analyzing the concentration of a target component in a blood sample using a standard component that is constantly present in blood.
  • using means determining the dilution factor for analyzing the concentration of the target component based on the standard value (constant value) of the standard component. Therefore, analyzing the concentration of a target component in a blood sample using a standard component that is constantly present in blood is based on the constant value (standard value) of the standard component that is constantly present in blood. Is to analyze the concentration of the target component.
  • Standard components that are constantly present in blood include sodium ions, chloride ions, potassium ions, magnesium ions, calcium ions, total protein, and albumin.
  • the concentration of these standard components contained in the serum and plasma of the blood sample is such that the sodium ion concentration is 134 to 146 mmol / L (average value: 142 mmol / L), and the chloride ion concentration is 97 to 107 mmol / L (average) Value: 102 mmol / L), potassium ion concentration is 3.2 to 4.8 mmol / L (average value: 4.0 mmol / L), and magnesium ion concentration is 0.75 to 1.0 mmol / L (average value: 0.9 mmol / L), calcium ion concentration is 4.2 to 5.1 mmol / L (average value: 4.65 mmol / L), and total protein concentration is 6.7 to 8.3 g / 100 ml (average value: 7.5 g / 100 ml), and the albumin concentration is
  • the present invention is intended to enable measurement of a target component when the amount of blood collected to relieve pain of a patient is very small.
  • a very small amount of blood is diluted with a diluent, It is necessary to accurately measure the concentration of “a standard component that is continually present in blood”.
  • the concentration of components originally present in the blood decreases in the diluted solution, and depending on the dilution rate, there is a possibility that a measurement error is included in the concentration measurement. Therefore, in order to detect the above-mentioned standard component with sufficient accuracy when a very small amount of blood component is diluted at a high dilution rate, it is preferable to measure a standard component present at a high concentration in a very small amount of blood.
  • sodium ions Na +
  • chloride ions Cl ⁇
  • sodium ion having the highest amount in the blood among the standard components that are constantly present in the blood.
  • the average value of sodium ion represents a standard value (median value of the reference range), and the value is 142 mmol / L, which accounts for 90 mol% or more of the total cations in plasma.
  • the occupation ratio of plasma components in the blood of the subject is about 55% in terms of volume, but varies depending on changes in the amount of salt intake of the subject. Therefore, when using the kit of the present invention, the dilution ratio of plasma is determined using the standard values of standard components that are constantly present in plasma, and the target in the blood sample plasma is determined using the determined dilution ratio. Analyze component concentrations. As a method for determining the dilution rate, a measured value (concentration X) of an external standard substance (for example, sodium ion) in a diluted plasma solution and the external standard substance (for example, sodium) contained in the blood sample plasma.
  • concentration X concentration a measured value of an external standard substance (for example, sodium ion) in a diluted plasma solution and the external standard substance (for example, sodium) contained in the blood sample plasma.
  • the dilution factor can be obtained by calculating the dilution factor (Y / X) of the plasma component in the blood sample from the known concentration value (concentration Y; 142 mmol / L in the case of sodium ion) of ions, etc. . Using this dilution factor, the measurement value (concentration Z) of the target component in the plasma dilution is measured, and this measurement value is multiplied by the dilution factor, so that the analyte actually contained in the plasma of the blood sample The component concentration [Z ⁇ (Y / X)] can be measured.
  • the sodium ion concentration and chloride ion concentration can be measured by, for example, flame photometry, glass electrode method, titration method, ion selective electrode method, enzyme activity method and the like.
  • the enzyme activity of the enzyme galactosidase is activated by sodium ion. Therefore, an enzymatic measurement method that measures a very low concentration sodium ion (24 mmol / L or less) sample diluted with a buffer solution in several ⁇ L Can be used. This method can be applied to a biochemical / immunological automatic analyzer and is highly efficient and economical in that it does not require a separate measuring instrument for measuring sodium ions.
  • a dilution factor independently from the other standard components and confirm that the value matches the dilution factor obtained above.
  • the coincidence means that in two measured values (a, b), the ratio of their difference to their average value, that is,
  • a standard component that is constantly present in plasma other than sodium ions or chloride ions it is preferably selected from total protein or albumin, and more preferably total protein.
  • Methods for measuring total protein include known methods such as the Burette method, the ultraviolet absorption method, the Breadford method, the Raleigh method, the bicinchoninic acid (BCA) method, and the fluorescence method.
  • a method to be used as appropriate can be selected according to the amount and the like.
  • the kit is for analyzing the concentration of a target component in a blood sample using a standard component that is not present in blood together with a standard component that is constantly present in blood.
  • Standard components that are not present in the blood can be used by adding them to a diluent (described later) in the kit so as to have a predetermined concentration.
  • a diluent described later
  • Standard components that are not present in blood include substances that do not interfere with the measurement of target components in blood samples, substances that do not degrade due to the action of biological enzymes in blood samples, substances that are stable in dilution, and blood cell membranes. It is preferable to use a substance that does not permeate and is not contained in blood cells, a substance that does not adsorb to a buffer storage container, and a substance that can use a detection system that can measure with high accuracy.
  • a substance that is stable even if stored for a long time in a state of being added to a diluent is preferable.
  • standard components not present in the blood include glycerol triphosphate, Li, Rb, Cs, or Fr as alkali metals, and Sr, Ba, or Ra as alkaline earth metals, among these , Li and glycerol triphosphate are preferred.
  • These standard components that are not present in blood can be colored by adding a second reagent during concentration measurement after blood dilution, and the concentration in the diluted blood can be determined from the color density.
  • concentration in the diluted blood can be determined from the color density.
  • the measurement of lithium ions added to the diluting solution is performed by biochemistry using a chelate colorimetric method (halogenated porphyrin chelate method: perfluoro-5,10,15,20-tetraphenyl-21H, 23H-porphyrin).
  • a chelate colorimetric method halogenated porphyrin chelate method: perfluoro-5,10,15,20-tetraphenyl-21H, 23H-porphyrin.
  • sodium ion is used as a standard component that is continually present in blood
  • lithium ion is used as a standard component that is not present in blood
  • sodium ion measurement is proportional to ⁇ -galactosidase activity.
  • the dilution factor of the blood sample is calculated by any one of the following formulas 1 to 4. be able to.
  • A, B, C, D, B ′ and X are defined as follows.
  • the blood sample component is calculated by calculating with Equation 5 using the root-mean-square method, and multiplying the concentration of the analysis target component in the diluted solution by the dilution rate calculated with Equation 5.
  • An embodiment in which the concentration of the target component is analyzed is also preferable.
  • the concentration of the target component in the blood sample component can be calculated from the concentration of the target component in the diluent based on the dilution factor.
  • the blood test kit of the present invention includes a diluent for diluting the collected blood sample.
  • a diluent for diluting a blood sample is a diluent that does not contain standard components that are constantly present in the blood used to determine the dilution factor.
  • does not contain means “does not contain substantially”.
  • substantially does not contain means that it does not contain a substance having homeostasis used at the time of determining the dilution factor, or even if it is contained, the homeostasis of the diluted solution after diluting the blood sample It means a case where it is contained at a very small concentration that does not affect the measurement of a toxic substance.
  • sodium ions or chloride ions are used as a standard component that is constantly present in blood, a diluent that does not substantially contain sodium ions or chloride ions is used as the diluent.
  • the diluting solution is pH 6.5 to pH 8.0, preferably pH 7.0 to pH 7.5, more preferably pH 7.3 to pH 7.4.
  • a buffer solution having a buffering action is preferable, and the diluent is preferably a buffer solution containing a buffer component that suppresses fluctuations in pH.
  • the types of buffer include acetate buffer (Na), phosphate buffer (Na), citrate buffer (Na), borate buffer (Na), tartrate buffer (Na), Tris (Tris (hydroxy Methyl) aminoethane) buffer (Cl), Hepes ([2- [4- (2-hydroxyethyl) -1-piperazinyl] ethanesulfonic acid]) buffer, phosphate buffered saline (Na), etc. ing.
  • phosphate buffers, Tris buffers, and Hepes buffers are representative examples of buffers around pH 7.0 to pH 8.0.
  • the phosphate buffer contains a sodium salt of phosphate
  • the Tris buffer has a dissociated pKa of 8.08, so that it has a buffer capacity around pH 7.0 to pH 8.0.
  • a buffer solution that does not contain sodium ions or chloride ions.
  • the diluent used in the present invention is preferably selected from the group consisting of 2-amino-2-methyl-1-propanol (AMP), 2-ethylaminoethanol, N-methyl-D-glucamine, diethanolamine, and triethanolamine.
  • AMP 2-amino-2-methyl-1-propanol
  • 2-ethylaminoethanol N-methyl-D-glucamine
  • diethanolamine diethanolamine
  • triethanolamine triethanolamine.
  • 2- [4- (2-hydroxyethyl-1-piperazinyl] also referred to as HEPES, which is a Good's buffer (Good buffer) and has a pKa of around 7.4.
  • the concentration ratio of amino alcohol and Good's buffer solution is 1: 2 to 2: 1, preferably 1: 1.5 to 1.5: 1, more preferably 1: 1.
  • the concentration of the buffer is not limited, but the concentration of amino alcohol or Good's buffer is 0.1 to 1000 mmol / L, preferably 1 to 500 mmol / L, more preferably 10 to 100 mmol / L.
  • the buffer solution may contain a chelating agent, a surfactant, an antibacterial agent, a preservative, a coenzyme, a saccharide and the like for the purpose of keeping the analysis target component stable.
  • chelating agents include ethylenediaminetetraacetate (EDTA), citrate, and oxalate.
  • the surfactant include a cationic surfactant, an anionic surfactant, an amphoteric surfactant, and a nonionic surfactant.
  • the preservative include sodium azide and an antimicrobial substance.
  • the coenzyme include pyridoxal phosphate, magnesium, zinc and the like.
  • saccharide of the erythrocyte stabilizer examples include mannitol, dextrose, oligosaccharide and the like.
  • by adding antibiotics it is possible to suppress the growth of bacteria partially mixed from the finger surface at the time of hand blood collection, to suppress the degradation of the biological components by bacteria, and to stabilize the biological components.
  • buffer solutions do not contain standard components and internal standard substances that are constantly present in blood and do not interfere with the measurement system.
  • components diluted with these buffer solutions do not interfere with measurement even with various measurement methods using biochemical / immunoimmune analyzers, and blood cells do not undergo hemolysis, and biological components can be stored stably even at 37 ° C. Is preferred.
  • the osmotic pressure of the buffer solution is equivalent to that of blood (285 mOsm / kg (mOsm / kg is 1 kg of water of the solution).
  • the osmotic pressure represents the number of millimoles of ions)) or more, so that hemolysis of blood cells can be prevented.
  • the osmotic pressure can be adjusted to be isotonic with salts, sugars, buffers or the like that do not affect the measurement of the target component and the measurement of the standard component that is constantly present in the blood.
  • a flame photometer an atomic absorption method, and an ion selective electrode method as a method for measuring plasma sodium ions diluted with a buffer as a standard component that is constantly present in blood.
  • a sample obtained by collecting a small amount of blood from a finger and diluting with a buffer is only about 150 ⁇ L, and more than 10 biochemical components and immunological test items are measured. It is preferable that the measurement can be performed with a minute amount of several ⁇ L.
  • biochemical / immunological automatic analyzer since it is necessary to analyze a large number of samples, it is preferable to be able to adapt to a commercially available biochemical / immunological automatic analyzer.
  • ALT alanine transaminase
  • AST anaspartate aminotransferase
  • ⁇ -GTP ⁇ glutamyl transpeptidase
  • ALP alkaline phosphatase
  • total bilirubin The concentration in the blood of several or more substances such as total protein and albumin is measured.
  • the amount of the diluted solution in the kit is preferably 20 times or less of the volume of plasma (that is, the dilution rate is 20 times or less of the volume of plasma), and more preferably 15 times or less. For example, if the amount of blood collected is 50 ⁇ L, the volume of plasma can be calculated as 28 ⁇ L. If the diluent is 360 ⁇ L, the dilution factor is 14 times.
  • the dilution factor based on the blood sample can be estimated by multiplying the dilution factor based on plasma by 50 / (50 + 50).
  • the amount of the diluted solution in the kit is preferably 10 times or less with respect to the volume of the blood sample (that is, the dilution rate is 10 times or less of the volume of the blood sample), and is 7.5 times or less. Is more preferable. That is, the present invention provides, as one embodiment, the above-described blood test kit in which the volume of the diluted solution is 7.5 times or less the volume of the blood sample.
  • kits for separating and collecting plasma from diluted blood samples A blood sample collected by the kit of the present invention may elapse for a long time in a diluted state until analysis is performed. In the meantime, for example, when hemolysis of erythrocytes occurs, substances or enzymes present in the blood cells elute into the plasma or serum and affect the test results, or the absorption of the eluted hemoglobin causes the optical properties of the analyte to be analyzed. This may have an impact on the measurement of the amount of analysis target components using optical information such as typical absorption. Therefore, it is preferable to prevent hemolysis. Therefore, it is preferable that the kit includes a separation device for separating and collecting plasma from a diluted blood sample.
  • a preferred example of the separation device is a separation membrane.
  • the separation membrane can be used, for example, by applying pressure to a diluted solution of a blood sample to capture blood cell components with the separation membrane, allowing the plasma components to pass through, separating the blood cells, and collecting the plasma components.
  • an anticoagulant it is preferable to use an anticoagulant.
  • the plasma that has passed through the separation membrane does not flow back to the blood cell side.
  • a backflow prevention means described in JP-A-2003-270239 is used. It can be a component of a kit.
  • the amount of standard components that are constantly present in the blood derived from the members of the blood kit that can be included in the diluent is defined.
  • the amount that can be contained in the diluted solution is to measure the amount of standard components that are derived from the member and contained in the diluted solution by exposing the target member to an appropriate amount of the diluted solution for a certain period of time. It can ask for.
  • the amount of the standard component derived from this member is not particularly limited as long as it can accurately analyze the concentration of the target component without greatly affecting the measurement of the dilution rate of the blood sample.
  • the amount derived from the standard component member constantly present in the blood is 0.5% by mass or less, preferably 0.4% by weight or less, more preferably, less than the amount of the diluted solution. 0.3 wt% or less.
  • the amount of the standard component that is constantly present in the blood derived from the members of the blood kit that can be contained in the diluent is preferably small, and the lower limit is not particularly limited.
  • a fiber lot is usually used for an aspirator for collecting blood, and a sodium salt of ethylenediaminetetraacetic acid (EDTA) is used as an anticoagulant in the fiber lot.
  • EDTA ethylenediaminetetraacetic acid
  • a glass filter is used as an instrument for separating and collecting plasma, and this contains a trace amount of sodium ions such as soda glass and sodium carbonate. Soda glass is obtained by mixing and melting silica sand (SiO2), sodium carbonate (Na2CO3), and calcium carbonate (CaCO3).
  • gasket material for holding the glass filter and the sealing device for maintaining the stored plasma in the second storage device are made of rubber, NaOH cleaning for deproteinization and molding
  • a trace amount of sodium ions may be contained as a residue of a release agent (a mixture of sodium nitrate, sodium nitrite, etc.) used.
  • a member that is a plastic (resin) molded product may contain a trace amount of Na on its surface. This is because the release agent used for resin molding contains sodium as a metal element together with tin, zinc, calcium and the like.
  • the amount of sodium ions eluted in the diluted solution is preferably ⁇ 2% or less with respect to the amount of sodium ions in plasma, dilution It is possible to maintain the high accuracy of magnification calculation.
  • the blood test kit of the present invention comprises a blood collection device for collecting blood, a first storage device containing a diluent, a separation device for separating and collecting plasma from a blood sample diluted with the diluent, and a separation device. At least a member selected from the group consisting of a holding device for holding, a second storage device for storing the collected plasma, and a sealing device for maintaining the stored plasma in the second storage device Have one.
  • a diluent for diluting a component of a blood sample a first storage device containing the diluent, and plasma for separating and collecting plasma from a blood sample diluted with the diluent Separation device, holding device for holding the separation device, second storage device for storing the collected plasma, sealing device for maintaining the stored plasma in the second storage device, on the skin Needle that bleeds blood out of skin, lancet, adhesive bandage or disinfecting member (for example, nonwoven fabric impregnated with isopropanol (70% isopropanol) or ethanol), instruction manual, etc.
  • a separation instrument for recovering plasma components from a diluted blood sample an embodiment that is a separation membrane is preferable, and a filter having pores that can separate blood cell components is more preferable.
  • the first storage device and the second storage device may be used as a first storage device and a second storage device, or may be provided with separate devices.
  • the first storage device and the second storage device The instrument is preferably made of a transparent material.
  • the holding device for holding the separation device is a gasket
  • the sealing device when the storage device is a tube-shaped device, a cap that can cover the opening, a cover having a spiral groove, or a rubber plug is used. can do.
  • the blood component stability and the fluctuation of the component due to hemolysis from the blood cell are reduced by providing the blood and diluent mixture container with the function of immediately separating plasma blood cells after diluting the blood with the diluent.
  • the influence can be eliminated and the stability of the sample after blood collection can be imparted.
  • the kit of the present invention makes it possible to realize a method capable of analyzing a component to be analyzed with high measurement accuracy even with a blood collection volume of 100 ⁇ L or less, and to accurately measure a patient with a small blood collection volume of 100 ⁇ L or less. It is preferable that the kit includes an instruction manual in which information indicating that it is possible is described.
  • the kit includes a diluted solution, a first storage device that stores the diluted solution (also a storage device for storing a diluted blood sample), and a blood sample diluted with the diluted solution.
  • Separation device for separating and recovering plasma from blood holding device for holding the separation device, second storage device for storing the recovered plasma, and maintaining the stored plasma in the second storage device A sealing device.
  • FIGS. 1 to 13 of Japanese Patent No. 3597827 can be used.
  • FIG. 1 of Japanese Patent No. 3597827 is incorporated as FIG. 1 of the present application.
  • the blood separation device 1 includes a blood collection container 2 (a storage device in which a diluent is stored, or a first storage device. It is also a storage device for storing a diluted blood sample) and a blood collection container 2.
  • a cylindrical body 3 that can be inserted (second storage device for storing the collected plasma), a cap piston 4 that can be attached to the cylindrical body 3, and a sealing lid 5 provided at the lower end of the cap piston 4 ( Before use, the upper end opening of the blood collection container 2 is sealed with a cap 6 via a packing 7 before use.
  • the storage device for storing the diluted blood sample in the present invention corresponds to the combination of the blood collection container 2 and the cylinder 3 in the configuration of FIG. That is, the number of storage devices for storing the diluted blood sample may be one or a combination of two or more.
  • the blood collection container 2 is made of a transparent material and has a cylindrical shape.
  • a screw portion 8 is formed on the outer surface of the blood collection container 2 and an engaging portion 9 is projected on the inner surface.
  • an inverted conical bottom portion 10 is formed at the lower end portion of the blood collection container 2, and a cylindrical leg portion 11 is formed around the bottom portion 10.
  • the legs 11 have the same outer diameter as the sample cup used at the time of blood analysis and testing, and preferably, slit grooves 12 are formed in the vertical direction at positions opposite to the lower ends thereof. Further, as shown in FIG. 1, a required amount, for example, a diluted solution 13 of 500 mm 3 may be placed in the blood collection container 2 in advance.
  • the cylindrical body 3 is made of a transparent material and has a cylindrical shape, and an enlarged diameter portion 14 is formed at an upper end portion thereof.
  • the enlarged diameter portion 14 is connected to the main body portion 16 through a thin portion 15.
  • a reduced diameter portion 18 is formed at the lower end of the cylindrical body 3, and a locking projection 19 is formed on the inner surface of the reduced diameter portion 18.
  • the outer flange portion 20 (holding device) is formed at the lower end portion of the reduced diameter portion 18, the lower end opening portion of the outer flange portion 20 is covered with a filtration membrane 21 (separation device), and the filtration membrane 21 is in the blood. It allows passage of plasma and prevents passage of blood cells.
  • a silicon rubber cover 22 is attached to the outer periphery of the reduced diameter portion 18 (FIG. 1).
  • the cap piston 4 includes a substantially cylindrical knob 26 and a mandrel 27 that is concentric with the knob 26 and extends downward.
  • a cylindrical space 28 into which the enlarged diameter portion 14 of the cylindrical body 3 can be fitted is formed at the inner upper end portion of the knob portion 26, and the lower portion thereof is screwed and can be screwed into the screw.
  • the lower end portion 29 of the mandrel portion 27 is formed in a pin shape, and the sealing lid 5 is detachably provided on the lower end portion 29 (see FIG. 1).
  • the sealing lid 5 is made of silicon rubber.
  • the operation of separating and collecting plasma from a diluted blood sample is performed as follows. After the collected blood is put into the blood collection container 2 containing the dilution liquid, the blood and the dilution liquid are sufficiently shaken and mixed while taking care not to foam while holding the upper part of the blood collection container 2. Next, the cylindrical body 3 holding the filtration membrane 21 (preventing liquid leakage due to sneaking into the side surface of the cylinder when separating blood plasma and blood cells) is inserted into the blood collection container 2 so that the filtration membrane is below, and slowly and constantly The filtration membrane is pushed down to the bottom of the blood collection container 2 at a speed. At this time, plasma goes up through the filtration membrane of the cylinder 3, and blood cells remain in the lower part of the blood collection container 2. Thereafter, the cap piston 4 is slowly inserted into the cylinder 3, and the sealing plug 5 prevents plasma and blood cells from being mixed by backflow.
  • the number of each element included in the blood test kit of the present invention is not particularly limited, and may be one each or two or more.
  • the material of the member included in the blood test kit of the present invention is preferably a synthetic resin from the viewpoint of resistance to breakage, hygiene, price, and the like.
  • a synthetic resin for example, polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride, polystyrene, polyvinyl acetate, polyurethane, polyethylene terephthalate, polylactic acid, acrylonitrile butadiene styrene resin (ABS resin), acrylonitrile styrene resin (AS resin), acrylic resin (PMMA) , Polycarbonate, silicone resin and the like.
  • ABS resin acrylonitrile butadiene styrene resin
  • AS resin acrylonitrile styrene resin
  • PMMA acrylic resin
  • Polycarbonate silicone resin and the like.
  • the blood test kit of the present invention can be provided in a form in which all of various members are stored in a storage container.
  • the present invention also provides a method for producing the kit and member described above.
  • the production method of the present invention includes a step of washing a member under conditions effective for removing standard components that are constantly present in blood.
  • the members used in the blood test kit of the present invention are made of plastic, glass or rubber, but the present inventors have used standard components that are constantly present in blood that would be eluted from these members as members.
  • the blood test kit manufacturing process including the above manufacturing process, it was found that the blood test kit can be effectively removed by a predetermined method.
  • the effective conditions for removing the standard components that are constantly present in the blood include a step of washing the target member with pure water having an electric conductivity of 1 ⁇ S / cm or less, preferably the target member This is a step of applying pure water having a conductivity of 1 ⁇ S / cm or less in a shower shape.
  • the present inventors have found that the elution concentration can be lowered to 0.5% by weight or less with respect to the diluted solution by sufficiently washing by such a process.
  • the standard component that is constantly present in the blood is sodium ion or chloride ion that is present at a high concentration in a very small amount of blood.
  • sodium ion or chloride ion that is present at a high concentration in a very small amount of blood.
  • it may be washed with high-level pure water (for example, 0.1 ⁇ S / cm or less) or ultrapure water (0.06 ⁇ S / cm or less). It is.
  • the present invention also provides a blood analysis method using the kit having the configuration described in [1] above.
  • the blood analysis method includes a mode that is a medical act on a human (an act performed by a doctor) and a mode that is not a medical act on a human (for example, a mode in which a blood sampler is a patient himself and an analyst is a person other than a doctor, Embodiments for human animals, etc.).
  • the blood analysis method of the present invention may be performed by self-collection in which the subject himself collects blood, or may be performed in general blood collection in which a qualified person such as a doctor collects blood using a syringe. Good.
  • the patient himself / herself collects blood exuded outside the skin by damaging a fingertip or the like using a knife-equipped instrument.
  • the biological sample to be analyzed using the kit of the present invention is blood, and blood is a concept including serum or plasma.
  • the origin of blood is not limited to humans, and it may be mammals, birds, fish, etc., which are non-human animals (non-human animals). Examples of animals other than humans include horses, cows, pigs, sheep, goats, dogs, cats, mice, bears, pandas, and the like.
  • the source of the biological sample is human.
  • the target component of analysis is not limited, and any substance contained in blood is targeted.
  • examples include biochemical test items in blood used for clinical diagnosis, markers for various diseases such as tumor markers and hepatitis markers, and include proteins, sugars, lipids, low molecular weight compounds, and the like.
  • the measurement includes not only the substance concentration but also the activity of substances having an activity such as an enzyme.
  • Each target component can be analyzed by a known method.
  • the allowable concentration of sodium ions derived from the members in the diluted solution is 1.7% by mass, that is, the allowable elution amount of sodium ions is ⁇ 6.1 ⁇ g with respect to 360 ⁇ L of the diluted solution
  • the allowable elution concentration of sodium ions in the diluent is 0.35% by mass, that is, ⁇ 1.3 ⁇ g with respect to 360 ⁇ L of the diluent, and rapidly increases as the dilution factor increases. It can be seen that the permissible elution amount of sodium ions eluted in the diluted solution becomes stricter, and the elution amount of the smaller diluted solution becomes a contaminant and reduces the accuracy of the dilution factor.
  • Diluent-1 prepared as described below was placed in a bottle, the filter held by the gasket was pushed into the bottle, the dilute liquid was filtered, and the amount of sodium ions in the liquid that passed through the filter was measured. Cleaning was performed by applying water to the member in a shower.
  • Dilution liquid was prepared with the following composition.
  • osmotic pressure a value measured using OSMOATAT OM-6040 (manufactured by ARKRAY, Inc.) was displayed.
  • the unit of osmotic pressure is the osmotic pressure of 1 kg of solution water, and represents the number of millimoles of ions.
  • HEPES 50mmol / L 2-Amino-2-methyl-1-propanol (AMP) 50mmol / L D-mannitol 284 mmol / L Lithium chloride 1mmol / L EDTA-2K 0.8mmol / L PALP (pyridoxal phosphate) 0.05mmol / L Thiabendazole 0.0001 mass% Amikacin sulfate 0.0003 mass% Kanamycin sulfate 0.0005% by mass Meropenem trihydrate 0.0005% by mass Osmotic pressure 355mOsm / kg pH 7.4
  • the sodium concentration was measured for each diluted solution prepared in (1).
  • ⁇ -galactosidase was activated by sodium, and the enzyme activity method using the fact that the sodium concentration in each diluted solution and ⁇ -galactosidase activity were in a proportional relationship was measured. Specifically, after diluting the diluted blood solution 5 times with purified water not containing sodium ions, 3 ⁇ L was weighed, 52 ⁇ L of the first reagent prepared as follows was added, and the mixture was heated at 37 ° C. for 5 minutes.
  • the concentration level of the sodium test substance (bottle, gasket, filter) of the blood test kit (bottle, gasket, filter) with respect to the diluted solution of sodium ions eluted in the diluted solution in tap water cleaning is indicated by a dotted line.
  • Example 1 Measurement of lithium ion in diluted solution
  • the lithium ion concentration was measured as follows.
  • the lithium ion added to the diluted solution was measured by a chelate colorimetric method (halogenated polyphyrin chelate method: perfluoro-5,10,15,20-tetraphenyl-21H, 23H, -porphyrin).
  • a chelate colorimetric method halogenated polyphyrin chelate method: perfluoro-5,10,15,20-tetraphenyl-21H, 23H, -porphyrin.
  • the temperature was determined by measuring the absorbance at a main wavelength of 545 nm and a sub wavelength of 596 nm using a JCA-BM6050 type biochemical automatic analyzer (manufactured by JEOL Ltd.).
  • the concentration of lithium ions can be measured from a calibration curve prepared in advance.
  • a lithium ion titration reagent having the following composition was prepared.
  • A Absorbance when the buffer solution is developed
  • B Absorbance change after plasma addition
  • C Absorbance of plasma sodium median of 142 mmol / L
  • D Absorbance at sodium concentration after plasma dilution
  • X Plasma dilution fold Plasma buffer The following dilution formula (1) was used as the dilution factor with the liquid.
  • the square root of the sum of the squares of the lithium ion information of the internal standard substance existing in the diluent and the sodium ion information as the standard component that is constantly present in the blood It is possible to obtain the dilution rate from the information of both the internal standard substance and the standard component that is constantly present in the blood, and the elution amount of the standard component that is constantly present in the blood is specified. It can be seen that measurement of the dilution rate with high accuracy becomes possible by using.
  • Example 2 After volunteering informed consent from a volunteer patient, 10 ⁇ L of blood collected with a syringe from the vein was collected in a sponge, and in the same manner as in Reference Example 1, a bottle, filter, and gasket that had been subjected to pure water cleaning in advance were used. The collected blood was mixed with the diluted solution prepared using the kit, and blood cells were separated with a filter. The concentration of sodium ions was measured in the same manner as in Reference Example 1 for the diluted plasma after blood cell separation obtained in this manner. Further, the total protein concentration was measured for the same diluted plasma by the method shown below.
  • the dilution ratio of plasma was calculated from the measured values of sodium ion concentration and total protein concentration measured as described above, and the concentration of standard components of sodium ion concentration and total protein concentration that are constantly present in plasma. However, a consistent dilution factor was obtained. Therefore, in addition to the sodium ion concentration, the concentration of the target component in the blood sample that defines the amount of the standard component derived from the member by determining the dilution factor using at least one type of homeostatic substance different from sodium ion It was found that the analysis was successfully performed, and the measurement results could be verified.

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Abstract

La présente invention aborde le problème consistant à effectuer une analyse de haute précision d'un constituant cible contenu dans un échantillon de sang à l'état de trace à l'aide d'un constituant de référence qui est présent en permanence dans le sang. L'invention concerne une trousse d'analyse sanguine qui utilise un constituant de référence présent en permanence dans le sang pour analyser la concentration d'un constituant cible contenu dans un échantillon de sang, et qui comprend une solution de dilution permettant de diluer un échantillon de sang, et des éléments choisis dans le groupe constitué par : un premier instrument de stockage dans lequel est stockée la solution de dilution ; un instrument de séparation destiné à séparer et à collecter le plasma sanguin de l'échantillon de sang dilué à l'aide de la solution de dilution ; un instrument de support destiné à supporter l'instrument de séparation ; un second instrument de stockage destiné à stocker le plasma sanguin collecté ; et un instrument d'étanchéité destiné à maintenir le plasma sanguin stocké à l'intérieur de second instrument de stockage. Ladite trousse d'analyse sanguine est caractérisée en ce qu'elle comprend une quantité définie de constituant de référence, attribuable aux éléments, qui peut être inclue dans la solution de dilution.
PCT/JP2016/070009 2015-07-06 2016-07-06 Trousse d'analyse sanguine, éléments associés, et son procédé de production WO2017006964A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
KR1020187000463A KR102080416B1 (ko) 2015-07-06 2016-07-06 혈액 검사 키트, 그 부재 및 그 제조 방법
CN201680039462.1A CN108027359A (zh) 2015-07-06 2016-07-06 血液检查试剂盒、其部件及它们的制造方法
EP16821433.6A EP3321678A4 (fr) 2015-07-06 2016-07-06 Trousse d'analyse sanguine, éléments associés, et son procédé de production
US15/861,875 US10788478B2 (en) 2015-07-06 2018-01-04 Blood test kit, member thereof, and method for manufacturing the same

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JP2015-135065 2015-07-06
JP2015135065 2015-07-06
JP2016-133958 2016-07-06
JP2016133958A JP6522555B2 (ja) 2015-07-06 2016-07-06 血液検査キット、その部材及びそれらの製造方法

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7109597B2 (ja) 2018-06-01 2022-07-29 ラボラトリー コーポレイション オブ アメリカ ホールディングス Ｌｃ－ｍｓ／ｍｓのための簡易化した生体試料の処理

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11347017A (ja) * 1998-04-10 1999-12-21 Fuji Photo Film Co Ltd ガラス繊維濾紙の製造方法
JP2000254461A (ja) * 1999-03-09 2000-09-19 Fuji Photo Film Co Ltd ガラスフィルター
JP2001330603A (ja) * 2000-05-18 2001-11-30 Arkray Inc 定量分析法
WO2003005039A1 (fr) * 2001-07-04 2003-01-16 Kyowa Medex Co., Ltd. Procede de preparation d'une solution de quantification, procede de quantification utilisant la solution de quantification, instrument de preparation de solutions de quantification et procede d'utilisation correspondant
JP2003270239A (ja) * 2002-03-18 2003-09-25 Leisure Inc 生体試料分離器具及びその分離方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11347017A (ja) * 1998-04-10 1999-12-21 Fuji Photo Film Co Ltd ガラス繊維濾紙の製造方法
JP2000254461A (ja) * 1999-03-09 2000-09-19 Fuji Photo Film Co Ltd ガラスフィルター
JP2001330603A (ja) * 2000-05-18 2001-11-30 Arkray Inc 定量分析法
WO2003005039A1 (fr) * 2001-07-04 2003-01-16 Kyowa Medex Co., Ltd. Procede de preparation d'une solution de quantification, procede de quantification utilisant la solution de quantification, instrument de preparation de solutions de quantification et procede d'utilisation correspondant
JP2003270239A (ja) * 2002-03-18 2003-09-25 Leisure Inc 生体試料分離器具及びその分離方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
See also references of EP3321678A4 *
SUSUMU OSAWA ET AL.: "Revolution of medical services at home using a small amount of blood collected from the fingertip", CLINICAL TESTING, vol. 59, no. 5, 15 May 2015 (2015-05-15), pages 397 - 404, XP009503398 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7109597B2 (ja) 2018-06-01 2022-07-29 ラボラトリー コーポレイション オブ アメリカ ホールディングス Ｌｃ－ｍｓ／ｍｓのための簡易化した生体試料の処理

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