JPS6073465A - Automatic analysis device - Google Patents

Abstract

PURPOSE:To judge easily whether a specimen such as a blood serum can be measured or not and to prevent to loss of the precious specimen by constituting the device in such a way that the difference between the measurable critical absorbance and the absorbance of a blank reagent liquid or the concn. converted from said difference can be displayed as the corrected measurable critical absorbance. CONSTITUTION:The 1st arithmetic and display means 8 is constituted of a multiplexer 17 consisting essentially of an electronic circuit, an absorbancy converting part 18 and an A/D converting part 19 as well as the 1st data processing part 20 consisting of a microcomputer and a printer 21. On the other hand, the 2nd arithmetic and display means 9 contains commonly the multiplexer 17, the absorbancy converting part 18 and the A/D converting part 19 and consists further of an arithmetic circuit 23 which calculates the absorbance difference Al-Ab between the measurable critical absorbance value Al of the reagent and the measured absorbance value Ab of the blank reagent liquid measured with a multiwavelength photometer 7 and which calculates further the equiv. concn. C by multiplying the calculated absorbance difference by a concn. conversion factor K and consists of a printer 24 as a display part which displays the equiv. concn. as the corrected measurable critical value C.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Field of Industrial Application This invention relates to an automatic analyzer, and particularly to an automatic analyzer suitably used in the field of clinical biochemistry.

(B) Prior Art Automated analyzers used in the field of clinical biochemistry generally perform analysis using the end point method and rate method based on the spectrophotometric method. Of course, these methods have measurable ranges, or measurement limits, and the factors that determine these measurement limits are reaction conditions (sample amount, analytical reagent component concentration and liquid volume, reaction time, etc.) and measurement conditions (measurement conditions). (cell length, photometer measurement wavelength, stray light at that wavelength, etc.)
can be mentioned. In other words, if these conditions do not change, the measurement limit value will hardly change.

However, among the above conditions, the analytical reagent component concentration (hereinafter sometimes simply referred to as reagent concentration) is the most variable, and depending on the analytical reagent (hereinafter sometimes simply referred to as reagent), the measurement limit can be reached within a few hours. (see Figure 2).

On the other hand, with conventional automatic analyzers, analytical reagents are prepared, the analysis is completed within a few hours or the same day, and the remaining reagents are discarded.However, recently, analytical reagents containing large amounts of expensive enzymes have been There is a trend towards storing reagents for a long period of time, as reagents have come to be used and automatic analyzers have built-in cold storage to prevent the activity of reagents from decreasing.

Therefore, it has become impossible to ignore the decrease in measurement limit values due to long-term storage of reagents.

To put this more specifically, conventional measurement limit values are determined by actually analyzing a dilution series of a high-concentration sample immediately after preparing the analytical reagent (when the reagent is most active) (Figure 4), or Examine the relationship between the concentration of the component (substrate, coenzyme, etc.) and the measured amount (concentration or activity unit) of the test component (Figure 3), and determine the limit value that can guarantee linearity. It is being However, if the analytical reagent is consumed several days, or even 2 to 3 weeks after its preparation, even if it is kept cold, the concentration of the reagent components will decrease, and the measurement limit value will inevitably become smaller. However, in the conventional measurement limit values, no consideration was given to this point.

(c) Purpose of the invention This invention was made in view of these circumstances, and its main purpose is to provide an automatic analyzer that can obtain information on correcting measurement limit values due to a decrease in reagent concentration. .

(D) Structure of the Invention The present invention includes a means for transporting a large number of reaction containers, a dispensing means for dispensing a fixed amount of a reagent for analyzing a sample and a test component of the sample into each reaction container, and a means for dispensing a predetermined amount of a reagent to each reaction container. Regarding absorption wavelength,
A measuring means for measuring the absorbance and absorbance change of the reaction solution in each reaction container; a storage section for pre-storing the measurable limit absorbance value of the reagent; and an absorbance difference between the limit absorbance value stored in the storage section and the absorbance value measured by the measuring means of the reagent blank solution. or further multiplies the absorbance difference by a concentration conversion constant to calculate the converted concentration, and a display section that displays the absorbance difference or the converted concentration as a corrected measurable limit value. This is an automatic analyzer equipped with a display means and a control means for controlling the operation of each of these means.

(e) Examples The present invention will be described in detail below based on examples shown in the drawings. However, this invention is not limited to this.

First, in Fig. 1, the automatic biochemical analyzer (1) is equipped with a conveyor (5
), a dispensing means (6) for dispensing a fixed amount of sample and reagent into each reaction container, and a multi-wavelength photometer (6) as a measurement means for measuring the absorbance and absorbance change of the reaction solution in each reaction container.
7), a first calculation/display means (8) that calculates the concentration of the test component in each sample based on the detection signal from the photometer and displays the calculated concentration value, and calculation of a corrected measurable limit value. and a second calculation/display means (9) for display, and a control means (not shown) for controlling the operation of each of these means.

In addition, QQ is a sample pipettor, (11)U is a reagent dispenser,
0→ is the flow cell, α4 is the diffraction grating, 0Fj (a)...
・ is a detector.

The first calculation/display means (8) includes a multiplexer (17) substantially consisting of an electronic circuit, an absorbance conversion section Q barrel and a /conversion section Ql, and a first data processing section consisting of a microcomputer. , printer. It is thoughtfully constructed.

On the other hand, the second calculation/display means (9) includes - the multiplexer aη, the absorbance converter (to), and the A/D converter oI, and further includes the measurable limit absorbance value (kl) of the reagent and the multiplexer aη, the absorbance converter (to), and the A/D converter oI. Absorbance difference with the measured absorbance value (Ab) of the reagent blank solution measured via the wavelength photometer (7) <he −Ab
), and then use the calculated absorbance difference as a concentration conversion constant @)
It consists of an arithmetic circuit (2) that calculates a converted density (C) by multiplying by , and a printer (c) that serves as a display unit that displays the converted density as a corrected measurable limit value (R).

Next, the operation of the automatic biochemical analyzer (1) having the above-mentioned configuration is performed to detect I and DH (lactate dehydrogenase) in the serum.
This will be explained using the measurement of .

First, the reaction formula that is the basis for the measurement of IIDI is pyruvate ten NADH---lactic acid ten NAD (IIDI). Note that NADH indicates the reduced form of nicotinamide adenine nucleotide, and NA'D indicates the oxidized form of nicotinamide adenine nucleotide. .Thus, the measured value of LDH is
This can be seen from the rate of decrease in the absorbance of HAD (which exhibits absorption at 340 nm) (NAD has no absorption at 340 nm).

For example, by dispensing means (6) into reaction vessels (2), (3), and so on, sample (serum) lopl and pure water 50/
11: was injected, and 2.1 minutes after the injection, the first reagent (R
J: NADH0.22m.

0.05 M phosphate buffer pH 7.4) 400) 1
1, and then the second reagent (R■: pyruvic acid 4 mM) at the same time for 9.3 minutes.

0.05 M phosphate buffer pH 7.4) 100 pl
Inject each. And 8.4 after stirring at the same 9.7 minutes
Rate measurements (37°C) are taken at ~8.7 minutes. In other words, the multi-wavelength photometer (7) detects the change in the absorbance of υMADE, and the optical signal at the wavelength of 340 is selected by the Yaruchi braker ←η, and the absorbance converter (c) and A/D converter D
The concentration of the component to be detected in the sample is calculated in the first data processing section (E) via I, and the concentration value is printed and displayed on the printer (C).

By the way, this automatic biochemical analyzer (1) can print and display the corrected measurable limit value (Cυ) on the printer (c) before the above-mentioned analysis.In other words, the reagent blank solution (instead of the sample, the same amount of pure water) can be displayed. is taken and the absorbance of RI and R [added] (A
When b) is measured with this device (1), the arithmetic circuit (e) calculates the measurable limit absorbance value (1', which will be determined later) stored in the memory circuit and the measured absorbance value of the reagent blank solution ( The absorbance difference (Ar-hb) with Ab) is calculated, and the absorbance difference is given a concentration conversion constant (K, a constant for converting the rate method measurement value into an activity value, which is a unique value depending on the device conditions) ff -Multiply to correct measurable limit value (
ax + K (to E-to)] is calculated, and the printer (
c) is printed and displayed. In other words, by subtracting the measured absorbance value (Ab) of the reagent blank solution from the measurable limit absorbance value (kl), it is possible to take into account the decrease in the concentration of unstable components in the reagent (see Figure 2). This enables lean analysis. To explain this more specifically, even if the reagent can be used for one week or two weeks after preparation,
Since reagent blank measurements are normally performed at least once a day on days when routine analysis is performed, the corrected measurable limit values are displayed accordingly, and the automatic analyzer operator can By confirming the measurable limit value (upper limit value or lower limit value), you can carry out analysis work with peace of mind.The graph in Figure 2 shows the RI of the LDH measurement reagent, 5
The changes in absorbance over time after storage at ℃ were investigated, and this change in absorbance can be regarded as the concentration of NADH (pyruvic acid also has absorption in 340 decoys.
'rlt' is changed to e〒01st, y is changed to 1-fi], then the graph in Figure 3 shows that in the TJDH reaction, R):R
1=4. :L(shows the LDH activity value when changing the NADH concentration in the mixed solution of filter ρ. From the figure, NADHo,
In the concentration range of x'ybraA or higher, an almost constant LDH activity value is obtained, 99% of that for 0.15 shrimp, and about 95% for 0.1 shrimp.

The graph in FIG. 4 shows the linearity of LDH measurement using this device (1) by adding serum to a mixed solution of IDH0, 22 (R) and Takanashi (2). When the amount of LI)1 (MAD consumed within unit time as the activity value increases) increases and the NADH concentration decreases, linearity is gradually lost and the correct LDH activity value is no longer indicated. Note that the concentration of pyruvic acid in the reaction solution is 1 m or more, and under this condition, it does not affect the LDH activity value.

From Figures 2 to 4 above, it can be seen that MADH, which is the substrate for the LDH reaction in the LDH measurement reagent, changes over time, and that the LDH activity value depends on the 1liADH concentration, which changes the measurable limit value (linearity). I understand.

By the way, the measurable limit absorbance value (A/) is determined by calculating the absorbance value corresponding to the point where the linearity in FIG. 3 or 4 breaks down. For example, in FIG. 3, the NADH concentration at which a value of 99% or more of the maximum activity value is obtained, that is, the absorbance division value iA/ is assumed.

Unlike the above embodiment, only the difference (Al-Ab) between the measurable limit absorbance value and the measured absorbance value of the reagent blank solution may be displayed as the corrected measurable limit value.

Also, unlike transferring the reaction solution to a flow cell and measuring the rate, it is possible to measure the absorbance of the Mako Test Blank Solution in the same reaction container, then dispense the sample and then measure the absorbance or absorbance change. A so-called reaction vessel direct photometry method may be adopted.

Note that GO measures the rate of decrease in absorbance in the same way as LDH.
T (glutamate/oxaloacetate transaminase i UV-MDH method), GOT (glutamate/pyruvate transaminase i UV-LDH method λ or ALP (alkaline phosphatase; p-nitrophenyl phosphate substrate method) that measures the rate of increase in absorbance), 7-G
TP (7-geltamine transpeptidase; L-T-
It can be applied to measurements such as glutamyl-p-nitroanilide substrate method). Also, glucose (hexokinase, NAD
The same concept can be applied to analysis items by endpoint measurement methods such as PH method) and cholesterol (cholesterol oxidase method).

(f) Effects of the Invention This invention enables the difference between the measurable limit absorbance and the absorbance of the reagent blank solution, or the concentration converted from the difference, to be displayed as the corrected measurable limit absorbance.
It is possible to easily determine whether or not a sample such as serum can be measured, and the loss of valuable samples can be prevented. In particular, since absorbance measurement of a reagent blank solution is carried out at least once a day, it is convenient to use this measurement to perform the above display.

[Brief explanation of the drawing]

Fig. 1 is a functional explanatory diagram showing one embodiment of the automatic analyzer according to the present invention, Fig. 2 is a graph showing the relationship between the storage period and absorbance of the LBH measurement reagent, and Fig. 3 is a graph showing the relationship between NAD in the LDH reagent.
A graph showing the relationship between H concentration and LDH activity value, and FIG. 4 is a graph showing linearity of LDH measurement. (1)・・・Automatic biochemical analyzer, (2)(3)
...Reaction container, (5) ...Transportation conveyor, (6) ...Dispensing means, (7) ...
...Multi-wavelength photometer, (8)...First calculation/display means, (9)...Second calculation/display means, Iwa.
...Memory circuit, Kan...Arithmetic circuit, (c)
...Printer. ,,yIJ,: , ””::,! Agent: Patent attorney Shintabe Nogawa, Pa. 1, ・ : 5.゛Figure 1

Claims (1)

[Scope of Claims] 1. A transport means for a large number of reaction vessels, a dispensing means for dispensing a fixed amount of a reagent for analyzing a sample and a test component of the sample into each reaction vessel, and a predetermined absorption wavelength. , a measuring means for measuring the absorbance and absorbance change of the reaction solution in each reaction container, and a first measuring means for calculating the concentration of the test component in each sample based on the measurement signal from the measuring means and displaying the calculated concentration value. a storage section for pre-storing the measurable limit absorbance value of the reagent, and a storage section for storing in advance the measurable limit absorbance value of the reagent, and a combination of the limit absorbance value stored in the storage section and the absorbance value measured for the reagent blank solution by the measuring means; A second comprising a calculation section that calculates the absorbance difference or further multiplies the absorbance difference by a concentration conversion constant to calculate a converted concentration, and a display section that displays the absorbance difference or the converted concentration as a corrected measurable limit value. An automatic analyzer equipped with calculation/display means and control means for controlling the operation of each of these means.