JP2014153330A - Automatic blood coagulation analysis device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To allow a plurality of scattered light measurement sections to measure a plurality of analytes with high accuracy.SOLUTION: A computation process section 30 is provided that executes a computation process according to a preliminary installed program, and a storage section 32 is provided that stores data taken from an outside or data obtained through the computation process executed by the computation process section 30. The computation process section 30 comprises: Fbg calculation means 34; correction coefficient calculation means 36; reference value setting means 38; and difference means 40. The storage section 32 comprises: a standard specimen measurement value holding section 42; a base value holding section 44; a standard specimen difference value holding section 46; a reference value holding section 48; a correction coefficient holding section 50; an analyte measurement value holding section 52; and an analyte difference value holding section 54.

Description

  The present invention relates to an automatic blood coagulation analyzer that automatically analyzes a blood coagulation reaction in the field of clinical examination.

  An automatic blood coagulation analyzer that automatically measures the blood coagulation reaction collects the sample and reagent from the container containing the sample and reagent using a probe, dispenses it into an empty cuvette, and installs the cuvette in a predetermined measurement port. Thus, optical measurement is performed (see Patent Document 1). One of the measurement items of such an automatic blood coagulation analyzer is measurement of fibrinogen concentration (hereinafter referred to as Fbg concentration) in a specimen.

  The Fbg concentration is measured by adding a thromboplastin reagent (containing tissue thromboplastin and calcium; hereinafter referred to as PT reagent) to the specimen, irradiating the reaction solution with light, and measuring scattered light. When PT reagent is added to the specimen, fibrinogen in the specimen is changed to fibrin as a final reaction. Fibrinogen is soluble in water and hardly scattered when irradiated with light, whereas fibrin is insoluble in water and scattering occurs when irradiated with light. The scattered light intensity from the reaction solution added with the PT reagent is proportional to the amount of fibrin in the reaction solution, and the amount of fibrin in the reaction solution depends on the amount of fibrinogen in the sample. By measuring the typical scattered light intensity, the Fbg concentration in the specimen can be quantified.

Japanese Patent No. 3324560

  By providing a plurality of scattered light measurement units that irradiate light to the cuvette and measure the scattered light, it becomes possible to simultaneously measure the Fbg concentration of a plurality of specimens, and when there are many specimens. The analysis efficiency can be improved. However, the intensity of light irradiated to the cuvette, the distance from the light source to the cuvette, the distance from the cuvette to the light receiving sensor, etc. have individual differences for each scattered light measurement unit, so the same cuvette is measured by different scattered light measurement units. However, the scattered light intensity is not the same. Therefore, when multiple specimens are measured by multiple scattered light measurement units, the measurement results are affected by individual differences in each scattered light measurement unit, and multiple specimens are placed in a single scattered light measurement unit in order. There is a problem that the measurement accuracy is worse than in the case of doing so.

  Therefore, an object of the present invention is to make it possible to measure a plurality of specimens with a plurality of scattered light measurement units with high accuracy.

  The automatic blood coagulation analyzer according to the present invention includes a plurality of measurement ports that detachably hold cuvettes containing specimens and reaction reagents, irradiates light to the cuvettes held in the respective measurement ports, Each of the scattered light measurement units that measure the scattered light intensity with a photodetector, and each measured value obtained by each scattered light measurement unit is corrected to suppress variation in measured values due to individual differences between the scattered light measurement units A fibrinogen concentration is obtained using a correction coefficient holding unit that holds a correction coefficient for the scattered light measurement unit, and a corrected measurement value obtained by correcting the measurement value obtained by each scattered light measurement unit with each correction coefficient. Fbg calculating means.

  In the automatic blood coagulation analyzer of the present invention, a correction coefficient for each scattered light measurement unit is provided to correct the measurement value obtained by each scattered light measurement unit and suppress variation in the measured value due to individual differences between the scattered light measurement units. A correction coefficient holding unit for holding, and an Fbg calculating means for obtaining a fibrinogen concentration using a corrected measurement value obtained by correcting the measurement value obtained by each scattered light measurement unit with the respective correction coefficient. Therefore, variation in the measurement value due to individual differences between the scattered light measurement units is suppressed, and the Fbg concentration of the specimen can be quantified with high efficiency and high accuracy using a plurality of scattered light measurement units.

It is a top view which shows one Example of an automatic blood coagulation analyzer. It is a top view which shows roughly the scattered light measurement part of the Example. It is a block diagram which shows roughly the signal system | strain for Fbg density | concentration measurement of the Example. It is a figure which shows an example of the waveform of the signal obtained in a scattered light measurement part. It is a flowchart which shows the correction coefficient calculation operation | movement of the Example. It is a flowchart which shows the measurement operation | movement of Fbg density | concentration of the Example.

  In the automatic blood coagulation analyzer of the present invention, the measurement value of each scattered light measurement unit obtained by measuring the scattered light intensity while the cuvette containing the standard sample is held in the measurement port is used as the standard sample measurement value. Standard sample measurement value holding unit to be held, reference value setting means for setting the reference value used for calculating the correction coefficient based on the standard sample measurement value of each scattered light measurement unit, and standard sample measurement of each scattered light measurement unit It is preferable to further include correction coefficient calculation means for calculating a correction coefficient by dividing the value by the reference value. Then, the correction coefficient of each scattered light measurement unit can be calculated by the apparatus.

  In the above case, the reference value setting means may set one of the minimum value, maximum value, and average value of the standard sample measurement values as the reference value.

  In the present invention, the detection signal of the photodetector of each scattered light measurement unit obtained by measuring the scattered light intensity in a state where the cuvette is not held in the measurement port is held as the base value of each scattered light measurement unit. A base value holding unit, and a standard sample difference value holding unit that holds a value obtained by subtracting the base value from the standard sample measurement value of each scattered light measurement unit as a standard sample difference value of each scattered light measurement unit. In this case, the reference value setting means sets a reference value based on the standard sample difference value of each scattered light measurement unit held in the standard sample difference value holding unit, and calculates a correction coefficient. The means preferably calculates a correction coefficient by dividing the standard sample difference value of each scattered light measurement unit held in the standard sample difference value holding unit by a reference value set in the reference value setting unit. By using the detection signal of the light detector of each scattered light measurement unit obtained by measuring the scattered light intensity in a state where the cuvette is not held in the measurement port as a base value, and subtracting the base value from the sample measurement value, Pure scattered light from the sample can be accurately measured, and the measurement accuracy of the scattered light intensity can be increased.

  Even in the above case, the reference value setting means may set one of the minimum value, maximum value, and average value of the standard sample difference values as the reference value.

  Examples of standard samples include latex reagents or fibrin precipitation reaction solutions. The fibrin precipitation reaction solution is a reaction solution obtained by mixing a PT reagent with control plasma and leaving it to stand.

An embodiment of an automatic blood coagulation analyzer will be described with reference to FIG.
There are provided a sample table 2 in which a plurality of sample containers 6 for storing samples are arranged on the circumference, and a reagent table 4 in which a plurality of reagent containers 8 for containing reagents are arranged on the circumference. The reagent table 4 is a table having a circular planar shape, and is rotationally driven around the center, so that an arbitrary reagent storage portion 8 can be disposed at a predetermined reagent collection position. The sample table 2 is a table that surrounds the outer periphery of the reagent table 4 and has a sample storage unit 6 on a circumference concentric with the reagent table 4. The sample table 2 is driven to rotate independently of the reagent table 4, and a desired sample storage unit 6 can be arranged at a predetermined sample collection position.

  A sample arm 10 is provided on the side of the sample table 2 for collecting and transporting a sample from the sample storage unit 6. The sample arm 10 holds a sample collection probe 11 for inhaling and dispensing the sample at the distal end portion, and rotates around the axis of the proximal end portion so that the sample collection probe 11 is predetermined on the circumference of its movement locus. It can be moved to the position.

  A cuvette transport mechanism 14 that transports an empty cuvette 12 is provided near the sample arm 10. A sample dispensing position A is provided on the movement trajectory of the sample collection probe 11, and the cuvette transport mechanism 14 transports the cuvette to the sample dispensing position A. At the sample dispensing position A, the sample is dispensed from the sample collection probe 11 to the cuvette 12 that has been transported to this position A.

  A measuring unit 16 is provided in the vicinity of the sample table 2 and the reagent table 4. In the measurement unit 16, a plurality of transmitted light measurement units 18 and a plurality of scattered light measurement units 20 are arranged in a line so as to draw a common arc. Both the transmitted light measurement unit 18 and the scattered light measurement unit 20 are provided with a measurement port for installing the cuvette 12 containing the specimen.

Although the illustration of the transmitted light measurement unit 18 is omitted, the transmitted light measurement unit 18 irradiates the cuvette installed at the measurement port with light and measures the transmitted light intensity.
As shown in FIG. 2, the scattered light measurement unit 20 irradiates light from the light source 20b to the cuvette 12 installed in the measurement port 20a, and forms 90 ° with respect to the optical axis from the light source 20b. The scattered light from the cuvette 12 is measured by the detector 20c arranged at the position.

  Returning to FIG. 1, a central axis 21 is provided at the center of an arc drawn by the transmitted light measurement unit 18 and the scattered light measurement unit 20. A cuvette transport arm 22 and a reagent arm 24 that are driven to rotate about the central shaft 21 are provided. The cuvette transport arm 22 and the reagent arm 24 are driven independently of each other.

  A cuvette holder (not shown) for holding the cuvette 12 is provided at the tip of the cuvette transport arm 22. The sample dispensing position A is on the movement locus of the cuvette holding part at the tip of the cuvette transport arm 22 as well as on the movement locus of the specimen collection probe 11 at the tip of the specimen arm 10. The cuvette transport arm 22 holds the cuvette 12 at the sample dispensing position A and transports it to an arbitrary scattered light measuring unit 20 or the stirring position B.

  Two reagent collection probes 25 a and 25 b are provided at the tip of the reagent arm 24. The reagent arm 24 moves the reagent collection probes 25a and 25b to predetermined reagent collection positions on the reagent table 4, and collects an arbitrary reagent by the reagent collection probes 25a and 25b in combination with the rotation of the reagent table 4. The reagent arm 24 moves the reagent collection probes 25 a and 25 b that have collected the reagent to the arbitrary scattered light measurement unit 20 or the position of the cuvette 12 installed at the stirring position B, and dispenses the reagent to the cuvette 12.

  Data obtained by the measuring units 18 and 20 is taken into a personal computer (PC) or a dedicated computer, and various arithmetic processes are executed. The computer that executes the arithmetic processing is configured to execute correction for increasing the accuracy of the measurement result in the measurement of the fibrinogen concentration (Fbg concentration) of the specimen.

  Here, in the measurement of the Fbg concentration, data as shown in FIG. 4 is obtained by adding a PT reagent to the specimen and measuring the temporal change in scattered light intensity. By this measurement, it is possible to measure the PT (prothrombin time) and Fbg concentration, which is the time until the specimen is coagulated. PT is defined as the time when the signal intensity becomes the intensity L0 of a preset ratio (for example, 40%) of the signal intensity L1 when the scattered light intensity is balanced. Further, the Fbg concentration can be obtained from the final signal intensity (scattered light intensity) L1 when the scattered light intensity is balanced.

  FIG. 3 shows an example of a signal system for Fbg concentration measurement in the automatic blood coagulation analyzer of this embodiment. In this example, a personal computer (PC) is used as a computer that performs calculation processing for Fbg concentration measurement.

  A PC 28 is connected to the automatic blood coagulation analyzer through a system controller 26 that controls the operations of the tables 2, 4, the arms 10, 22, 24 and the cuvette transport mechanism 14. Measurement data obtained by each scattered light measurement unit 20 is taken into the PC 28 via the system controller 26.

  In the PC 28, an arithmetic processing unit 30 that executes arithmetic processing according to a program incorporated in advance, and a storage unit 32 that stores data fetched from outside and data obtained by arithmetic processing by the arithmetic processing unit 30. Is provided. The arithmetic processing unit 30 includes an Fbg calculation unit 34, a correction coefficient calculation unit 36, a reference value setting unit 38, and a difference unit 40. The storage unit 32 includes a standard sample measurement value holding unit 42, a base value holding unit 44, a standard sample difference value holding unit 46, a reference value holding unit 48, a correction coefficient holding unit 50, a sample measurement value holding unit 52, and a sample difference value holding unit. 54.

The correction coefficient calculation operation of the embodiment will be described with reference to FIGS. 1 and 3 and FIG.
First, the empty cuvette 12 is transported to the reagent dispensing stirring position B by the cuvette transport arm. A latex reagent (standard sample) and a predetermined other reagent are collected by the reagent arm 24, dispensed into the cuvette 12, and stirred. The cuvette 12 is transported while being held by the cuvette transport arm 22 and is installed at one of the measurement ports of the scattered light measurement unit 20 to measure the scattered light intensity. The data (standard sample measurement value) acquired here is held in the standard sample measurement value holding unit 42 of the storage unit 32. When the measurement of the scattered light intensity is completed, the same cuvette 12 is transported to another scattered light measurement unit 20 by the cuvette transport arm 22, and the scattered light intensity is also measured in the other scattered light measurement unit 20. This standard sample measurement value acquisition operation is performed for all the scattered light measurement units 20, and the standard sample measurement values for each of the scattered light measurement units 20 are held in the standard sample measurement value holding unit 42. In addition to the latex reagent, a PT reaction solution in which fibrin is precipitated can be used as the standard sample. These are both reagents used in the blood coagulation apparatus. In addition, substances used as turbidity standard solutions such as formazine and polystyrene can also be applied.

  After the standard sample measurement values are acquired for all the scattered light measurement units 20, the scattered light intensity (base value) in a state where no cuvette is installed in the measurement port is measured and acquired for each scattered light measurement unit 20. The base value is held in the base value holding unit 44 of the storage unit 32. Note that this base value acquisition operation may be executed before the standard sample measurement value acquisition operation. Further, the base value acquisition operation and the standard sample measurement value acquisition operation may be executed before each scattered light measurement unit 20 measures the scattered light of the specimen. By doing so, the influence of fluctuations in the light source intensity can be eliminated.

  The difference means 40 of the arithmetic processing unit 30 takes the difference between the standard sample measurement value and the base value of each scattered light measurement unit 20, and the difference value (standard sample difference value) is stored in the standard sample difference value holding unit 46 of the storage unit 32. Retained. The reference value setting means 38 sets the smallest one of the obtained standard sample difference values as the reference value, and the set reference value is held in the reference value holding unit 48. In addition, this invention is not limited to this, The largest standard sample difference value may be set as a reference value, and the average value of all the standard sample difference values may be set as a reference value.

  The correction coefficient calculation means 36 calculates the correction coefficient by dividing the standard sample difference value of each scattered light measurement unit 20 by the reference value. The correction coefficient obtained here is held in the correction coefficient holding unit 50. An example of data obtained by the above operation is shown in Table 1.

  In Table 1, the top row is the number of the photometric unit (scattered light measuring unit), and in this embodiment, there are 1 to 14 scattered light measuring units 20. The second row from the top is the measured value (standard sample measured value) of the cuvette containing the latex reagent, the third row from the top is the base value obtained by measurement without the cuvette, and the top 4 The row in the row is the standard sample difference value (standard sample measurement value−base value), and the row in the bottom row is the correction coefficient. In this example, the standard sample difference value of the number 14 scattered light measurement unit 20 is the minimum, and the standard sample difference value of each scattered light measurement unit 20 is divided by the reference value 4794 with this standard sample difference value 4794 as a reference. Thus, the correction coefficient is obtained.

Next, the Fbg concentration measuring operation of the same embodiment will be described with reference to FIGS. 1 and 3 and FIG.
The empty cuvette 12 is transported to the sample dispensing position A. A sample is collected from a predetermined sample container 6 by the sample arm 10 and dispensed into the cuvette 12 at the sample dispensing position A. The cuvette 12 is held and transported by the cuvette transport arm 22, installed in a measurement port of a predetermined scattered light measurement unit 20, the PT reagent is collected by the reagent arm 24, and dispensed into the cuvette 12, and the scattered light intensity is measured. To do. The measurement data (sample measurement value) obtained here is held in the sample measurement value holding unit 52 of the storage unit 32.

  The difference means 40 of the arithmetic processing unit 30 obtains a sample difference value obtained by subtracting the base value of the scattered light measurement unit 20 that performed the measurement from the sample measurement value obtained by the above measurement. The obtained sample difference value is held in the sample difference value holding unit 54 of the storage unit 32. The Fbg calculation means 34 of the arithmetic processing unit 30 calculates the fibrinogen concentration of the sample based on the value obtained by dividing the sample difference value obtained here by the correction coefficient of the scattered light measurement unit 20 (measured value after correction), and the PC 28 To a display device such as a monitor (not shown). The base value used when obtaining the sample difference value may be a value measured when calculating the correction coefficient, or a new value measured immediately before or after measurement of scattered light from the sample. May be.

  In the calculation operation of the correction coefficient and the measurement operation of the Fbg concentration, it is not always necessary to subtract the base value of each scattered light measurement unit from the standard sample measurement value and the sample measurement value. For example, when it can be determined from the measurement result of the base value that the difference between the base values of the scattered light measurement units 20 is negligibly small, the base value is not subtracted from the standard sample measurement value in the correction coefficient calculation operation. The correction coefficient may be obtained by using it as it is. Then, during the measurement operation of the Fbg concentration, the sample measurement value from which the base value is not subtracted may be corrected using the correction coefficient, and the Fbg concentration may be obtained using the correction value.

なお、上記の変動率ＣＶ（％）は、
ＣＶ＝（標準偏差／平均値）×１００
により求められる。 Table 2 shows the results of verifying the variation in the measured value of the scattered light intensity in each scattered light measurement unit 20 with and without using the correction coefficient in the lowermost row of Table 1.

The rate of change CV (%) is
CV = (standard deviation / average value) × 100
Is required.

  In the above verification, the Fbg concentration is measured in all the scattered light measurement units 20 for the specimen 1 and the specimen 2, and the variation in the measurement result is obtained as the variation rate CV (%). The left side of Table 2 (correction coefficient) obtained from the measurement data of the scattered light intensity obtained by measuring the cuvette containing the specimen 1 and the scattered light intensity obtained by measuring the cuvette containing the specimen 2 (Not used), the value obtained by subtracting the base value of each scattered light measurement unit 20 from the measurement data and then dividing by the correction coefficient is the right side of Table 2 (use of correction coefficient). As shown in this verification result, by using the value obtained by subtracting the base value from the measurement data and dividing by the correction coefficient, the variation between the scattered light measurement units 20 is reduced, and the difference between the scattered light measurement units 20 is reduced. The reproducibility of the measurement result of the Fgb concentration is improved.

2 Specimen Table 4 Reagent Table 6 Specimen Storage Unit 8 Reagent Storage Unit 10 Specimen Arm 11 Specimen Collection Probe 12 Cuvette 14 Cuvette Transport Mechanism 16 Measurement Unit 18 Transmitted Light Measurement Unit 20 Scattered Light Measurement Unit 21 Central Axis 22 Cuvette Transport Arm 24 Reagent Arm 25a, 25b Reagent collection probe 26 System controller 28 Personal computer 30 Arithmetic processing unit 32 Storage unit 34 Fbg calculation unit 36 Correction coefficient calculation unit 38 Reference value setting unit 40 Difference unit 42 Standard sample measurement value holding unit 44 Base value holding unit 46 Standard Sample difference value holding unit 48 Reference value holding unit 50 Correction coefficient holding unit 52 Sample measurement value holding unit 54 Sample difference value holding unit

Claims (6)

A plurality of measurement ports for detachably holding cuvettes containing specimens and reaction reagents are provided, light is irradiated to the cuvettes held in the respective measurement ports, and the scattered light intensity is measured by a photodetector. A plurality of scattered light measurement units;
A correction coefficient holding unit that holds a correction coefficient for each of the scattered light measurement units that corrects the measurement value obtained by each of the scattered light measurement units and suppresses variation in the measurement value due to individual differences between the scattered light measurement units; ,
An automatic blood coagulation analyzer comprising: an Fbg calculating means for obtaining a fibrinogen concentration using a corrected measurement value obtained by correcting a measurement value obtained by each of the scattered light measurement units with the correction coefficient. Standard sample measurement value holding unit for holding the measurement value of each scattered light measurement unit obtained by measuring the scattered light intensity in a state where the cuvette containing the standard sample is held in the measurement port as the standard sample measurement value When,
A reference value setting means for setting a reference value used for calculation of the correction coefficient based on the standard sample measurement value of each scattered light measurement unit;
The automatic blood coagulation analyzer according to claim 1, further comprising correction coefficient calculation means for calculating a correction coefficient by dividing the standard sample measurement value of each scattered light measurement unit by the reference value.   The automatic blood coagulation analyzer according to claim 2, wherein the reference value setting means sets one of a minimum value, a maximum value, and an average value of the standard sample measurement values as the reference value. The detection signal of the photodetector of each of the scattered light measurement units obtained by measuring the scattered light intensity in a state where no cuvette is held at the measurement port is held as the base value of each of the scattered light measurement units. A base value holding unit;
A standard sample difference value holding unit that holds a value obtained by subtracting the base value from the standard sample measurement value of each scattered light measurement unit as a standard sample difference value of each scattered light measurement unit, and
The reference value setting means sets the reference value based on the standard sample difference value of each scattered light measurement unit held in the standard sample difference value holding unit,
3. The correction coefficient calculation unit calculates the correction coefficient by dividing the standard sample difference value of each scattered light measurement unit held in the standard sample difference value holding unit by the reference value. The automatic blood coagulation analyzer described in 1.   5. The automatic blood coagulation analyzer according to claim 4, wherein the reference value setting means sets one of a minimum value, a maximum value, and an average value of the standard sample difference values as the reference value.   The blood coagulation analyzer according to any one of claims 2 to 5, wherein the standard sample is a latex reagent or a fibrin precipitation reaction solution.

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