JPH09127122A - Analyzing method and analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily and spontaneously calibrate the inter-lot difference and the change with time of a reagent and the inter-device difference by applying the correction equation data of the calibration curve generated by a reference machine when the reagent is inspected, the deterioration constant of the reagent, and the data on the inspection day to the correction equation generated by a user machine at the time of calibration. SOLUTION: The correction equation 1 of the calibration curve of a reagent of a certain lot is generated by a reference machine, and the data, the deterioration constant of the reagent, and the recording medium on the inspection day are delivered to a user together with the reagent. The user generates the correction equation 2 of the reagent of this lot with a user machine at the time of initial calibration, estimates the correction equation 3 of the user machine at the time of an inspection based on the data, the number of elapsed days since the inspection day, and the deterioration constant, calculates the relational expression 4 correcting the difference between both machines based on the correction equations 1, 3, and stores it in the user machine. When a specimen is actually measured, the correction equation 5 of the present reference machine is estimated based on the data of the correction equation 1, the number of elapsed days from the inspection day, and deterioration constant, the uncorrected measured value of the user machine is substituted into the relational expression 4 to resolve the inter-machine difference, and the correction value is collated with the correction equation 5 to resolve the change with time of the reagent.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an analysis method and an analysis device for calibrating with a data storage medium. This analyzer can be suitably used for quantitatively analyzing a specific component in a sample such as blood.

[0002]

2. Description of the Related Art A sample is reacted with a measuring reagent such as a coloring reagent to optically measure the change of the reagent, for example, the degree of color change,
An analyzer that detects the components in a sample by collating it with a calibration curve created based on the amount of change in the measurement reagent due to the reaction with a substance of known concentration is used in various analysis and inspection fields including clinical chemistry tests. It is commonly used.

In this type of analyzer, it is not always possible to make the same reagent, and there is a difference between reagent lots. Therefore, each time a user purchases a new lot of reagent, the substance of known concentration is measured with the reagent and the user's analyzer, and a calibration curve for each lot of the reagent is created from the known concentration and output value. It is stored in the device. For example, two types of substances are usually measured, such as a high-concentration standard solution and a low-concentration standard solution, and the measured values are connected by a straight line to create a calibration curve, and a magnetic medium such as a magnetic disk or magnetic card that can be inserted into the device. To be stored as a linear expression. Since this operation is troublesome, the apparatus manufacturer often creates a magnetic medium storing the calibration curve information for each reagent lot, and attaches the magnetic medium at the time of shipping the reagent. Or,
RA with at least two types of calibration curves built into the device
Information such as which calibration curve to use is stored in a storage unit such as M and attached to the reagent for each lot of the reagent, and the user specifies the calibration curve using the information input means such as the keyboard of the apparatus.

[0004]

However, since the reagent undergoes a change with time, the analytical accuracy decreases with the passage of time only with the calibration curve information prepared at the time of shipment. Also, attaching a calibration curve or correction formula for each lot to the reagent is
It will be a burden on the equipment manufacturer. In addition, even analyzers with the same design specifications have machine differences between individual machines, and the machine differences are not only purely hard, but there are also factors that appear only when used with reagents. The device manufacturer cannot directly correct the accompanying measurement error.

Therefore, an object of the present invention is to provide an analysis method and an analysis apparatus which can easily and spontaneously calibrate not only the difference between the reagent lots but also the change over time such as deterioration of the reagent and the instrumental difference. It is in.

[0006]

In order to achieve the object, the analysis method of the present invention detects a reaction between a sample and a measurement reagent (hereinafter referred to as "reagent") by using an analyzer. An analysis method for detecting a component in a sample by comparing it with a calibration curve created based on the reaction result of a substance with a known concentration and a reagent has the following features.

[0007] An analytical device (hereinafter referred to as "user machine") having a function equivalent to that of a reference machine which is a reference for calibration is defined.
That. ) Is a user machine. Then, first, when a reagent is inspected, a standard machine is used to create a calibration curve correction formula (1) for a reagent of a certain lot, and the created correction formula (1) data, the deterioration constant of the reagent, and the inspection date are recorded on a magnetic card. It is stored in a data storage medium such as a magnetic disk. This is usually done by the device manufacturer. The reagent of the lot is shipped to the user together with the data storage medium.

After that, at the time of calibration (usually the first calibration immediately after purchase by the user, but the second and subsequent calibrations may be performed), the correction formula (2) for the lot is created using the user machine, and A user estimated to be at the time of inspection from the correction formula (2) data created by reading the deterioration constant and the inspection date stored in the data storage medium, the number of days elapsed from the inspection date to the calibration date, and the deterioration constant. Machine correction formula
Calculate (3). This is usually done by the user.
The following operations are also the same.

Usually, the known concentration substance used to create the correction formula (1) is stored in the equipment manufacturer, while the correction formula (1) is stored.
The substances of known concentration used when creating (2) are for users only, so the lots of both substances may differ. However, since the substance of known concentration is previously analyzed by another highly accurate analysis method, the difference between the lots can be ignored. Therefore, it is estimated that the correction formula (3) is for the inspection of the user machine. If you try, the correction formula
Both (1) and the correction formula (2) are values at the time of inspection of reagents in the same lot, and the only difference between them is the machine difference. Therefore, the relational expression (4) for correcting the machine difference between the reference machine and the user machine is calculated from the correction formulas (1) and (3) and stored in the user machine.

At the time of actually measuring the sample, the correction formula (1) data, the deterioration constant and the inspection date stored in the data storage medium are read, and the correction formula (1) data, the number of days elapsed from the inspection date to the present and the deterioration constant are read. From this, the correction equation (5) of the reference machine estimated to be the current one is calculated, and the uncorrected measurement value of the user machine is substituted into the relational expression (4) to perform the primary correction to eliminate the machine difference. By comparing the correction value with the correction formula (5), the secondary correction for eliminating the change with time of the reagent is performed, and the secondary correction value is output as the detection value.

Therefore, an analyzing apparatus suitable for carrying out the analyzing method of the present invention is a data receiving means for receiving information stored in a data storage medium, an arithmetic circuit such as a CPU for performing each of the above operations, and a correction formula. (3), a storage unit such as a RAM that stores the relational expression (4) and the correction expression (5) in an updatable manner, and an output circuit that outputs the detected value as an electric signal or the like.

According to the analysis method of the present invention, since the data storage medium storing the lot information of the reagent is attached to the reagent when the reagent is inspected, the difference between the lots of the reagent is eliminated. In addition, since all values are aggregated in the reference machine based on the relational expression (4), the machine difference is eliminated, and the change with time of the reagent is eliminated based on the correction equation (5). Therefore, the user can easily perform high-precision analysis without burdening the device maker. Correction formulas (1) (2) (3) (5) and relational expressions
(4) is stored in the device until the information stored in the new data storage medium is read, so when measuring the same measurement item with the reagent of the same lot, read the data storage medium again. Instead, it can be measured as it is.

As a means for receiving the information stored in the data storage medium, the device manufacturer generally supplies a magnetic card, a floppy disk, etc. to the user by providing the user with a magnetic card reader and a disk drive. However, when the data storage medium and the user device are connected by a telephone line or the like, the data can be received online and processed in the same manner.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described with reference to the drawings. FIG. 1 is a system configuration diagram showing an embodiment of an analyzer, FIG. 2 is a graph showing a correction formula by a substance having a known concentration (hereinafter, referred to as “calibrator”), and FIG. 3 is a calculation of a machine difference correction coefficient by initial calibration. FIG. 4 is a flow chart showing the method, and FIG. 4 is a flow chart showing the execution sequence of the arithmetic circuit when measuring with a new lot reagent.

The analyzer detects the reaction between the sample and the reagent and compares it with a calibration curve prepared based on the reaction result between the calibrator and the reagent to detect the components in the sample.

The analyzer is a magnetic card reader for reading the information stored in the magnetic card provided by the device manufacturer, and various arithmetic processing based on the information read by the magnetic card reader and the signal emitted from the photometric unit. And a controller having an arithmetic circuit such as a CPU for executing the above and transmitting it to an output circuit. The controller is a RAM that stores the above information and calculation results in an updatable manner.
Built-in.

The analyzer further comprises a reaction table for arranging reagents for reacting with the calibrator or sample,
A sampler that collects the calibrator or sample with a suction nozzle and drops it on the reagent placed on the reaction table, a sample changer that automatically replaces the pipette tip attached to the tip of the suction nozzle, and the degree of color change of the reagent due to the reaction. It is provided with a photometric section for optically measuring, an output circuit for transmitting an input signal from the arithmetic circuit to a display such as a liquid crystal display or a printer for displaying or printing, and a keyboard.

In this embodiment, the reagent and the analyzer are calibrated using two types of calibrators, a high concentration (YH) liquid and a low concentration (YL) liquid. First, one device that serves as a reference for calibration is always defined as a reference device, and an analyzer having a function equivalent to that of the reference device and owned by the user is defined as a user device.

[1] Outline of Analysis Method The outline of the analysis method with calibration is as follows. Inspection of reagent shipment by standard machine (implementation date: D1) Input of inspection information to magnetic card Initial calibration (due date: D2) of user machine = calculation of correction coefficient for machine difference When correcting reagent lot (when changing lot) Correction of series A detailed description will be given below.

[2] Reagent inspection data At the device manufacturer, the reagent to be inspected is placed on the reaction table of the standard machine, the substance is sampled by the sampler, and spotted and reacted on the reagent. The color of the reagent after the reaction is measured by the photometric unit, and the measured value is arithmetically processed and displayed on the display or printed on the printer. By using two kinds of low-concentration (L) liquid and high-concentration (H) liquid as calibrators, the following calibration curve correction formula (1) data are obtained. The calibrator display value is an analysis value obtained by another highly accurate analysis method in advance. K is the deterioration constant of the reagent per 1.5 years. The correction formula (1) is represented by Y = A2X + B2 in FIG.

XL1: Reference machine measurement value (L) at the time of inspection XH1: Reference machine measurement value (H) at the time of inspection YL1: Calibrator display value (L) at the time of inspection YH1: Calibrator display value (H) at the time of inspection KL : Deterioration constant (L,% / 1.5y) KH: Deterioration constant (H,% / 1.5y)

[3] Input of inspection information to magnetic card The inspection data such as the above-mentioned data (1) and inspection date (D1) are input to the magnetic card. The magnetic card is attached to the reagent and given to the user. The information is read by the magnetic card reader of the user machine at the time of calibration and stored in the RAM.

[4] Calculation of machine-difference correction coefficient by initial calibration (FIG. 3) The following correction formula (2) data is obtained by the user on the initial calibration using the user machine. The correction formula (2) is Y in FIG.
= A0X + B0. XL2: User machine measured value (L) at initial calibration XH2: User machine measured value at first calibration (H) YL2: Calibrator display value at initial calibration (L) YH2: Calibrator display value at first calibration (H)

The reagents used at this time are (D2-D
1) Since the day has passed, the user machine measured values XL and XH at the time of inspection are estimated as follows. XL3 = XL2 / {1- (KL / 100 / (365 ・ 1.5)) ・ (D2
-D1)} XH3 = XH2 / {1- (KH / 100 / (365 ・ 1.5)) ・ (D2
-D1)}

A correction formula showing an estimated correction formula (3) of the user machine at the time of reagent inspection by the above data Y = A1.X
+ B1 is obtained. A1 = (YH2-YL2) / (XH3-XL3) B1 = YL2-A1.XL3 or B1 = YH2-A1.X
H3

Since the calibrator is analyzed in advance by another highly accurate analysis method, the difference between the lots can be ignored. Therefore, the above correction formula is maintained even if the calibrator lot changes, so the display value of the calibrator at the time of inspection is substituted and the measurement value at the user machine is estimated as follows. XL4 = (YL1-B1) / A1 XH4 = (YH1-B1) / A1

It is recognized that this value is the result of the user's machine in which the reagent of the same lot as the above inspection data was measured by the calibrator of the same lot at the same time. Therefore, the difference from the inspection data is only due to the machine difference. Therefore, XL1 and XH1 (RA of the user machine) read from the magnetic card
By using (stored in M), the relational expression (4) (reference machine = α / user machine + β) for correcting the machine difference from the reference machine can be calculated.
The relational expression (4) obtained by the calculation is stored in the RAM. α = (XH1−XL1) / (XH4−XL4) β = XL1−α · XL4

[5] Correction of reagent lot (Fig. 4) The uncorrected measurement value X1 (concentration conversion value by the standard calibration curve) measured by the user machine is substituted into the relational expression (4) to eliminate the machine difference first. The primary correction is made and becomes X2. X2 = α ・ X1 + β

From the inspection information read from the magnetic card, X2 is collated with the correction formula (1) in the reference machine to become X3, and the difference between the lots of the reagent is eliminated. X3 = A2.X2 + B2 However, A2 = (YH1-YL1) / XH1-XL1) B2 = YL1-A2.XL1

[6] Time-series correction (FIG. 4) The above-mentioned [5] corresponds to the calibration at the time of inspection. When the actual measurement time (currently: D3) of the sample is (D3-D1) days from the inspection time, the reagent has changed over time, and therefore the calculation of [5] is not actually performed. Then, the inspection information read from the magnetic card and the number of days elapsed until the present (D3-
Calculated from D1) and measured by the current standard machine XL
Estimate 1'and XH1 'as follows. XL1 '= XL1 ・ {1- (KL / 100 / (365 ・ 1.5)) ・ (D2
-D1)} XH1 '= XH1 ・ {1- (KH / 100 / (365 ・ 1.5)) ・ (D2
-D1)}

Therefore, the correction equation (5) Y = A3X + B3 estimated to be the current one by the reference machine is obtained. However, A3 = (YH1-YL1) / (XH1'-XL1 ') B3 = YL1-A3.XL1' This is stored in the RAM.

Therefore, X2 is compared with the correction equation (5) to be subjected to the secondary correction for eliminating the change with time of the reagent, and becomes X3. X3 = A3.X2 + B3 This X3 is output as a detection value to the display or printer by the output circuit. In this way, a value in which all the differences between the lots of the reagents, the machine differences, and the changes with time of the reagents are corrected can be obtained. Since the device manufacturer only stores the test information of the reagent in the magnetic card, the burden is small. Also, for the user, after performing the calibration, as long as the reagents are in the same lot, the change over time is voluntarily performed, and even if the lot changes, all that is required is for the magnetic card to be read by the analyzer. I won't. Moreover, since the machine difference is corrected, the accuracy of the obtained detection value is high.

FIG. 5 shows a flowchart from the inspection of the reagent to the measurement.

[0034]

EFFECTS OF THE INVENTION It is possible to obtain a highly accurate detection value in which all of the difference between lots of reagents, the difference between machines, and the change with time of the reagent are eliminated without burdening both the apparatus maker and the user.

[Brief description of the drawings]

FIG. 1 is a system configuration diagram showing an embodiment of an analyzer of the present invention.

FIG. 2 is a graph showing each correction formula.

FIG. 3 is a flowchart showing an order of calculating machine difference correction coefficients by calibration.

FIG. 4 is a flowchart showing a calculation sequence for calibration when measuring a new lot reagent with a user machine.

FIG. 5 is a flowchart showing a flow from inspection of a reagent to measurement.

Claims (3)

[Claims] 1. A reaction between a sample and a measurement reagent (hereinafter referred to as “reagent”) is detected, and the reaction is compared with a calibration curve created based on the reaction result between a substance having a known concentration and the reagent,
In the analysis method for detecting components in a sample, when a reference machine is defined and an analyzer with the same function as the reference machine is used as the user machine, the calibration curve correction formula (1 ) Is created, the created correction formula (1) data, the deterioration constant of the reagent and the inspection date are stored in a data storage medium, and the correction formula (2) is created using a user machine during calibration. User's machine estimated to be at the time of inspection based on the correction formula (2) data created by reading the deterioration constant and inspection date stored in the data storage medium, the number of days elapsed from the inspection date to the calibration date, and the deterioration constant. The correction formula (3) is calculated, and from the correction formula (1) and the correction formula (3), the relational formula (4) that corrects the machine difference between the reference machine and the user machine is calculated and stored in the user machine. When measuring the sample, the correction formula (1) data stored in the data storage medium, Of reading constants and test date, correction equation (1) data, from the age and the deterioration constant of the examination date to the present, the reference machine correction equation is estimated that the current
By calculating (5) and substituting the uncorrected measurement value of the user machine into the relational expression (4), the primary correction is made to eliminate the machine difference, and the correction value is compared with the correction expression (5) to make the reagent The method of analysis is characterized in that secondary correction is performed to eliminate the change over time and the secondary correction value is output as a detection value. 2. A reaction between a sample and a measurement reagent (hereinafter referred to as “reagent”) is detected, and the reaction is compared with a calibration curve prepared based on the reaction result between a substance having a known concentration and the reagent,
In an analyzer that detects components in a sample, when a reference device is defined and an analyzer with the same function as the reference device is used as the user device, the calibration curve created using the reference device when testing reagents is corrected. Formula (1) Data storage medium that stores data, reagent deterioration constant and test date, data receiving means that receives information stored in the data storage medium, correction formula (2) data or correction formula (1) at the time of calibration ) Based on the data, the number of days elapsed from the date of inspection to the date of calibration or the present and the deterioration constant, the correction formula for the user machine estimated to be at the time of inspection (3) or the correction formula for the reference machine estimated to be the current one (3) The relational expression (4) that calculates the difference 5 between the reference machine and the user machine from the correction expression (1) and the correction expression (3)
An arithmetic circuit for calculating, and a storage means for storing the correction formula (3), the relational formula (4) and the correction formula (5) in an updatable manner, and the uncorrected measurement value in the relational formula (4) when the sample is actually measured. By performing the primary correction to eliminate the machine difference by substituting it, and by performing the secondary correction to eliminate the change over time of the reagent by checking the correction value with the correction formula (5), the secondary correction value is output as the detected value. And an output circuit for performing the analysis. 3. The data storage medium is a magnetic card,
The analyzer according to claim 2, wherein the data receiving means is a magnetic card reader.