JPS635267A - Biochemical automatic analyser - Google Patents

Abstract

PURPOSE:To simply check the activity of immobilized enzyme, by operating the difference between the high concn. value in a range wherein the linearity of the concn. of the component to be examined in a specimen and analytical output is held and a concn. value obtained by converting the analytical output at the measuring time of a high concn. standard solution prepared so as to have said high concn. value by a calibration curve. CONSTITUTION:The high concn. value in a range wherein the linearity of the concn. of the component to be examined in a specimen and analytical output is held is stored in a memory 72. From the relation of the concn.-analytical output of a standard solution for calibration with the low concn. in the range wherein said linearity is held, an analytical output-concn. converting calibration curve is corrected at every predetermined analytical cycle by a first operation part 73 and the analytical output at the measuring time of a high concn. standard solution prepared so as to have the high concn. value is converted to concn. by a correcting calibration curve. The difference between this converted concn. and the high concn. value is operated by a second operation part 74 to judge whether the concn. difference is 1/10 or less of the high concn. value and the activity of immobilized enzyme is checked simply. The use propriety of an immobilized enzyme column 5 is displayed on a display device 75.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application This invention relates to an automatic biochemical analyzer. More details: Regarding a biochemical automatic analyzer using an immobilized enzyme column.

(b) Conventional technology In recent years, attempts have been made to use immobilized enzymes as clinical bioreactors in fields such as biochemical analysis, and in particular, attempts have been made to use immobilized enzymes as bioreactors for clinical use. An automatic analyzer has been proposed that includes a carrier flow path and an analysis flow path extending from the immobilized enzyme column to an analysis section. The immobilized enzyme column is made by immobilizing enzymes corresponding to each measurement item such as glucose, uric acid, lactic acid, BUN, etc. on a porous carrier.

(c) Problems to be solved by the invention However, the enzyme activity of the immobilized enzyme in the column used in the above-mentioned device decreases while being used, especially in the high concentration range, and as a result, the enzyme activity decreases, especially in the high concentration range. The linearity of the calibration curve, which is determined based on the relationship between the concentration standard sample and the analytical output, is likely to be lost, leading to measurement errors. Since this decrease in activity is controlled by factors such as the environmental temperature, the number of samples to be measured, and the loft of the immobilized enzyme produced, it is not possible to uniformly determine the lifespan of an immobilized enzyme simply by the number of times it is used or the elapsed time. However, there was a problem in that it was extremely difficult to decide when to replace it.

The present invention has been made in view of the above circumstances, and particularly aims to provide an automatic biochemical analyzer equipped with an arithmetic control section that can easily check the activity of immobilized enzymes.

(d) Means for Solving the Problems Thus, according to the present invention, there is provided a carrier channel extending from the carrier supply section to the immobilized enzyme column via the sample introduction section, and a carrier channel extending from the immobilized enzyme column to the analysis section. A high concentration value C within the range that maintains linearity between the concentration of the analyte component in the sample and the analytical output during the initial stage of the analysis.
A calibration curve for analytical output-concentration conversion is prepared every predetermined analysis cycle based on the relationship between the concentration and analytical output of a low-concentration calibration standard solution within the range in which the linearity is maintained. a first calculation unit to calibrate; the high concentration value c+;
:'The analytical output during the measurement of the Aged high concentration standard solution is converted to the concentration C' based on the above calibration standard curve, and then the concentration C' is converted to the concentration C'.
a second calculation unit that calculates the difference ΔC between ° and the high concentration value C, and a second calculation unit that determines whether the concentration difference Δc from the second calculation unit is less than 1/1O of b<c, and determines whether the immobilized enzyme column is used. An automatic biochemical analyzer is provided, which has a calculation display section configured with a display section for displaying the suitability of the test.

In the present invention, the high density value C is not particularly limited as it varies depending on the item, but it is usually preferably set around a value of about 3 to 5 times the low density value. Further, it is usually appropriate to set the low concentration value to a concentration slightly higher than the normal value of the biological sample.

(E) Effect According to this invention, when the enzyme activity decreases, a significant difference occurs between the calculated high concentration value and the actual concentration, and based on this, a display indicating that continued use is not possible is made. If the enzyme activity does not substantially decrease and there is no significant difference in concentration (that is, 1/10 or less of the high concentration value), a statement indicating that continued use is possible will be made.

The present invention will be described in detail below with reference to Examples, but the present invention is not limited thereby.

(F) Embodiment FIG. 1 is an explanatory diagram of the configuration of an embodiment of the automatic biochemical analyzer of the present invention.

In the figure, (1) is the carrier, (2) is the liquid pump, (
3) is a sample introduction section, (4) is a sample supply section, (5) is an immobilized enzyme column, (6) is a chemiluminescence detector, (7) is a calculation display section, (a) is a carrier flow path, ( b) is the analysis channel. Note that (8) is a luminol solution, (9) is a red blood salt solution, and (10) and (]1) are drains.

The sample introduction section (3) consists of an injector (3]), a three-way solenoid valve (32), and a pipetter (33), and the sample supply section (4) consists of a turntable, a pull (41), and a large number of sample cups ( 42).

In addition, the calculation display section (7) includes an A/D converter (7''), a storage section (72), a first calculation section (73), and a second calculation section (74).
and a display section (75).

Glucose oxidase is used for the immobilized enzyme column (5), and a photomultiplier tube is used for the chemiluminescence detector (6).

Further, the operation of the above device is configured to be completely controlled by a CPU (not shown).

Next, the specific operation of this device will be explained.

First, in the initial stage of analysis, the relationship between the concentration of the analyte in the sample and the analytical output is evaluated using a number of standard solutions, and a high concentration value C within a range that maintains linearity is keyed into the storage unit (72). memorize it. - On the other hand, the high concentration (C) standard solution is placed in a sample cup (4
2). Here, as the calibration standard solution, a low concentration solution within the range where the above-mentioned linearity is maintained is used.

Analysis is then performed and calibration is performed at every predetermined analysis cycle. That is, during analysis, the sample in the sample cup (42) on the turntable (4) is aspirated by the three-way solenoid valve (32) and pipetter (33), and the sample is transferred to the carrier channel (a) by the injector (31). ). The sample then passes through the immobilized enzyme column (5) together with the carrier. At this time, if the sample contains glucose (test component), hydrogen peroxide is generated in the column (5) by the reaction shown below. ) in which the luminol solution (8) and red blood salt solution (9) are combined to produce chemiluminescence. Chemiluminescence is detected by a chemiluminescence detector (6), and the detected output is converted into a digital quantity by an A/D converter (71) and processed by the CPU to provide an analytical output -
The glucose concentration is output based on the concentration conversion calibration curve.

On the other hand, during calibration, a low-concentration standard solution is introduced instead of the sample, and from the relationship between concentration and analytical output, the analytical output is
Setting and calibration of the concentration conversion calibration curve are performed in the first calculation section (73), and based on this, the calculation base is optimized.

Further, the calculation display section (7) is provided with a second calculation section (74) that performs column evaluation. After calibrating the calibration curve, the second calculation unit (74) converts the output when a highly concentrated C (concentration C) standard solution is introduced in place of the sample into a concentration C° based on the calibration curve; This C and C.

The difference ΔC (=IC'-CI) is calculated. The output of this ΔC is sent to display m (75).

The display section (75) has the following relationship; IC'-CI>0. IC
In the case of Ic'-CI≦0. In the case of an IC, a message indicating that continued use is possible is displayed.

Now, if the relationship between the analytical output and concentration of glucose oxidase used in the immobilized enzyme column in the fresh state holds the relationship shown in the output example of the standard solution dilution series in Figure 2, then A low concentration standard solution used for calibration (one example is one with a concentration close to the normal value of 200 mg/df2, and a glucose solution with a concentration of 1000 mg/dc (=C) as a high concentration standard solution (Sh) used for column evaluation. are each prepared and subjected to the above-mentioned analysis and calibration, and the immobilized enzyme in the device is checked, for example, according to the algorithm shown in FIG.

Note that the evaluation of the column may be displayed in rows or blanks with the indicator lamp being lit or not lit.

In this way, an automatic biochemical analyzer capable of evaluating immobilized enzyme columns can be obtained.

(G) Effects of the Invention According to the method of the present invention, in an analyzer using an immobilized enzyme, it is possible to measure the test component with good accuracy not only at low concentration values but also at high concentration values.

In addition, it is possible to accurately know when to replace the immobilized enzyme column. Furthermore, since the immobilized enzyme column can be used until the end of the life of the immobilized enzyme, running costs can be reduced.

[Brief explanation of drawings]

FIG. 1 is an explanatory diagram of the configuration of an embodiment of the biochemical automatic analyzer of the present invention, FIG. 2 is a graph diagram showing an output example of a glucose oxidase standard solution dilution series, and FIG. 3 is a diagram showing the configuration of an embodiment of the biochemical automatic analyzer of the present invention. FIG. 2 is a flowchart diagram illustrating an example of an algorithm for calibrating an analyzer and evaluating a column. (1)...Carrier, (2)...Liquid pump, (3)...Sample introduction section, (5)...
...immobilized enzyme column, (7) ...calculation display section (72) ...memory section, (73) ...
...first calculation section, (74) ...second calculation section,
(75)...Display section, (a)...Carrier flow path, (b)...
・Analysis flow path.

Claims (1)

[Claims] 1. A carrier channel extending from the carrier supply section to the immobilized enzyme column via the sample introduction section, and an analysis channel extending from the immobilized enzyme column to the analysis section. A first storage section that stores in advance a high concentration value C within a range where linearity between the concentration of the test component in the sample and the analytical output is maintained at the initial stage of analysis, and a high concentration value C within the range where the linearity is maintained. a first calculation unit that calibrates the analytical output-concentration conversion calibration curve for each predetermined analysis cycle based on the relationship between the concentration of the low-concentration calibration standard solution and the analytical output; and a high-concentration standard prepared to the high concentration value C. The analytical output during liquid measurement is converted to concentration C based on the above calibration standard curve, and then the difference Δ between the concentration C and the high concentration value C is calculated.
A second calculation unit that calculates C and a concentration difference Δ from the second calculation unit
An automatic biochemical analyzer comprising: a display section that determines whether C is 1/10 or less of C and displays whether or not the immobilized enzyme column is suitable for use;