JPH08219984A - Biochemical analyzer - Google Patents

Abstract

PURPOSE: To measure with high correctness even when the amount of a measuring liquid such as a reagent for measuring latex immunity or the like is small. CONSTITUTION: The apparatus is provided with a threshold value-setting means 4 for setting a threshold to extract a measured absorbance, an extracting means 3 for setting a reference measuring point and extracting an absorbance at a measuring point where a difference of absorbances from at the reference measuring point is within the threshold, and an operating means 6 for calculating a changing amount of the absorbance per unit time by the method of least squares from the absorbance of the measuring point extracted by the extracting means 3. A specimen and a reagent are distributed to react in a reaction cell. The absorbance at each of a plurality of measuring points is measured as time goes by, thereby to obtain the changing amount of the absorbance per unit time. Even when the absorbance of the specimen itself, for example, latex reagent or the like cannot be measured, a measuring area can be hence enlarged, enabling measurements with high correctness.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a biochemical analyzer for dispensing a sample and a reagent into a reaction cell, reacting them, measuring a plurality of absorbances over time, and obtaining the amount of change in absorbance per unit time. .

[0002]

2. Description of the Related Art Used in clinical, chemical and pharmaceutical fields,
In a biochemical analyzer that analyzes a sample such as serum or urine, a sample such as serum and a predetermined reagent are mixed in a transparent reaction cell to cause a color reaction, and white light is emitted from a light source. The transmitted light is dispersed by a spectroscope, the absorbance by the dye is determined, and then the concentration of the substance to be measured is determined based on the absorbance.

As a method for obtaining the concentration of the substance to be measured, the end point method EPA (End Point) has been conventionally used.
Assay) and reaction rate method RRA (Reaction R)
ateAssay) two types of methods are adopted. Among them, EPA is a method used when the amount of the dye produced by the color reaction is saturated with the lapse of reaction time, and the final absorbance after sufficiently reacting the sample and the reagent is measured and measured. Find the concentration of a substance. On the other hand, RR
A is a method used when the amount of the dye produced by the color development reaction increases with the elapse of the reaction time, as in the case of measuring the enzyme activity in the sample. In this case, the measurement is performed during the reaction. The linear function y = a + bt is approximated to the absorbance y by the least squares method, and the concentration of the substance to be measured is determined based on the value of the coefficient b obtained as a result, that is, the amount of change in the absorbance per unit time.

FIG. 4 is a diagram for explaining the absorbance at each measurement point and removal of the curved portion, and FIG. 5 is a diagram showing a conventional example of a biochemical analyzer employing RRA. In RRA, as shown in FIG. 4, the first reagent R1 and the sample S are dispensed into the reaction cell to measure the absorbance at the measurement point, and the second reagent R2 is further measured.
After dispensing, the absorbance at the measurement points to the measurement points of ∘10 is measured at predetermined time intervals as the reaction time t elapses. At this time, conventionally, a phenomenon occurs in which the reaction is saturated when the absorbance exceeds a certain level. Therefore, processing for removing this curved portion from the data when obtaining the coefficient b is performed.
This is the limit absorbance A, and the absorbance at the measurement points exceeding the limit absorbance A is automatically deleted, and the change b in the absorbance per unit time by the least square method is calculated from the absorbances at the remaining measurement points. In the example of FIG. 4A, the absorbance is shown on the vertical axis, the measurement points corresponding to time are shown on the horizontal axis, and the absorbance at each measurement point of the samples a to d is shown. If the limit absorbance A is used to remove the absorbance, the minimum absorptivity will be the minimum of two due to the absorbances of the samples a and b at 8 points from the measurement point to ○ 10, 6 at the sample c at the measurement point and 3 points at the sample d The amount of change b in the absorbance per unit time is calculated by the multiplication method. Further, since each of the absorbance had turbidity for each sample are different, so that use of the FIG. 4 (b) plus the absorbance a _s of sample blank limit absorbance A as shown in limits absorbance A '. By adjusting the limit absorbance A → A ′ in this way, the measurement region of the sample in the high concentration region can be expanded to the measurement point, and highly accurate measurement is possible. The absorbance a _s of the sample blank is
As shown in FIG. 4 (b), it is determined by subtracting the absorbance of the known first reagent blank that is measured in advance from the absorbance at the measurement point.

FIG. 5 shows a conventional example of a biochemical analyzer employing RRA. When the measurement data from the detector 31 having a spectroscope is stored in the measurement data 32, the effective data extractor 33 As compared with the limit absorbance 34, the absorbance at the measurement point exceeding the limit absorbance is deleted, and the absorbances at the remaining measurement points are stored in the valid data storage unit 35. Then, the absorbance calculation unit 36 calculates the change amount b of the absorbance per unit time by the least squares method, and the concentration calculation unit 37 converts it into the concentration.

[0006]

FIG. 6 is a diagram for explaining the problem of the conventional biochemical analyzer, in which 41 is a reaction cell, 42 is a light source, 43 is a detector, 44 is a sample, and R1 is a first sample. 1 reagent, R2 shows a 2nd reagent. As described above, at the measurement point, the absorbance at the time when the sample and the first reagent are dispensed is measured, and therefore, at that time, the measurement liquid amount is already required to be a specified amount or more, for example, 240 μl or more. However, in the case of a reagent for latex immunoassay, for example, since the amount of the measurement liquid is less than a specified amount, for example, 180 μl or less, two dotted lines between the light source 42 and the detector 43 in FIG. The measurement region shown is not filled with the sample 44 and the first reagent R1, and the measurement region between the light source 42 and the detector 43 is not measured until the second reagent is dispensed as shown in FIG. 6B. Filled with quantity. Therefore, at the measurement point, the exact absorbance of the sample and the first reagent, that is, the absorbance of the sample blank cannot be measured, and the limiting absorbance cannot be adjusted for each sample as described above. As a result, there is a problem that the measurement region cannot be expanded and the measurement accuracy cannot be improved for the sample in the high concentration region.

The present invention solves the above problems and provides a biochemical analyzer capable of performing accurate measurement even in the case of measurement with a small amount of measurement liquid such as a reagent for latex immunoassay. The purpose is to do.

[0008]

To this end, the present invention is designed to dispense a specimen and a reagent into a reaction cell and cause them to react with each other. The absorbance is measured at a plurality of measurement points over time, and the amount of change in the absorbance per unit time is measured. In the biochemical analyzer for obtaining, the threshold setting means for setting the threshold for extracting the measured absorbance, and the difference between the absorbance of the reference measurement point and the absorbance of each measurement point by setting the reference measurement point An extraction means for extracting the absorbance at the measurement point within the threshold range, and an operation means for calculating the amount of change in the absorbance per unit time by the least square method by the absorbance at the measurement point extracted by the extraction means were provided. It is characterized by that.

[0009]

In the biochemical analyzer of the present invention, the threshold setting means for setting the threshold for extracting the measured absorbance, the reference measurement point is set, and the absorbance at the reference measurement point and the absorbance at each measurement point are set. An extracting means for extracting the absorbance of a measurement point whose difference between the two is within a threshold range, and a computing means for calculating the amount of change in the absorbance per unit time by the least squares method based on the absorbance of the measurement point extracted by the extracting means. Since it is provided with, the measurement area can be expanded and the measurement can be performed with high accuracy even when the absorbance of the sample itself cannot be measured such as with a latex reagent.

[0010]

Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a diagram showing one embodiment of a biochemical analyzer according to the present invention, in which 1 is a detection unit, 2 is a measurement data storage unit,
3 is an effective data extraction unit, 4 is a threshold value storage unit, 5 is an effective data storage unit, 6 is an absorbance calculation unit, and 7 is a concentration calculation unit.
The detection unit 1 dispenses a sample and a reagent into a reaction cell, causes them to react with each other, measures the absorbance at a plurality of detection timings over time, converts the measurement data into a digital signal, and outputs the digital signal. The data storage unit 2 stores the measurement data of the absorbance from the detection unit 1 measured at a plurality of detection timings. The threshold storage unit 4 stores a threshold for extracting the target absorbance data when calculating the amount of change in absorbance per unit time. Since the threshold differs for each reagent lot, the reagent lot The effective data extraction unit 3 that is preset according to the above, and is rewritten when the reagent lot is updated, compares the difference between the absorbance at the measurement point set as a reference and the absorbance at each subsequent measurement point with a threshold value, and When the difference exceeds the threshold value, the data after the measurement point is deleted, and the data at the remaining measurement points is extracted as valid data for obtaining the amount of change in absorbance per unit time, and the valid data is stored. Is the valid data storage unit 5. The absorbance calculation unit 6 calculates the amount of change in absorbance per unit time by the least squares method using the valid data stored in the valid data storage unit 5, and converts the concentration based on the obtained amount of change in absorbance. The density calculation unit 7 performs the above.

Next, the operation will be described. FIG. 2 is a diagram for explaining the operation of the biochemical analyzer according to the present invention. The measurement data from the detection unit 1 is stored in the measurement data storage unit 2, and when the measurement is started, first, the threshold value is determined from the analysis conditions (step S11). Next, the measurement data is sequentially read from the measurement data storage unit 2 and the difference between the reference measurement point, for example, the absorbance and the absorbance of the measurement point to ∘10 is calculated (step S12). Subsequently, the difference in absorbance and the threshold value are compared (step S13). If the difference in absorbance is not larger than the threshold value, the valid data storage unit 5 is set as valid data to be calculated.
(Step S14), the process returns to step S12, and the same process is repeated for the absorbance at the next measurement point.
Then, if the difference in absorbance becomes larger than the threshold value, the amount of change in absorbance per unit time is calculated by the least square method based on the valid data stored in the valid data storage unit 5 (step S1).
5) Then, the concentration is converted based on the amount of change in the absorbance (step S16).

FIG. 3 is a diagram showing an outline of the system configuration of the biochemical analyzer according to the present invention, in which 11 is a cup transport unit and 1
2 is a sample pipette, 13 is a sampling valve, 1
4 is a switching valve, 15 is a cool box, 16 is a reagent pump, 17 is a reagent switching valve, 18 is a rotary reactor, 1
Reference numeral 9 is a detection unit, 20 is an analyzer, and 21 is a data processing unit.

In FIG. 3, the rotary reactor 18 has 30 to 40 reaction cells installed on the circumference thereof, and performs cleaning of the reaction cells and measurement of cell blanks while rotating in one step and 12 seconds, for example. Is. For each reaction cell of the rotary reactor 18, a fixed amount (about 1 μl to 10 μl) of a sample (specimen) such as serum or urine is weighed from the cup carrier 11 to the sampling valve 13. The first reagent and the sample are dispensed from this, and the second reagent is also dispensed. In this way, when a sample such as serum and a predetermined reagent are mixed in a transparent reaction cell using the rotary reactor 18 to cause a color reaction, a white light is emitted from the light source in the detection unit 19. The transmitted light is separated by a spectroscope. The measurement data of the detection unit 19 is converted from an analog signal to a digital signal by the analysis unit 20, processed by the data processing unit 21, and the data is stored in the memory, displayed on the CRT, or output from the printer. The data processing unit 21 is configured as shown in FIG. 1. As described above, the data processing unit 21 first extracts effective data using a threshold value, and then changes the absorbance per unit time of the dye. Then, the concentration of the substance to be measured is calculated based on the amount of change in the absorbance.

It should be noted that the present invention is not limited to the above embodiment, and various modifications are possible. For example, in the above-mentioned embodiment, the difference in absorbance is compared with the threshold value to determine the effective data stored in the memory one by one, but the difference in the absorbance is compared with the threshold value to detect the range of effective data, and the effective data in that range May be sequentially read from the memory when calculating the amount of change in absorbance. Further, although the difference between the absorbance at the reference measurement point and the absorbance at each measurement point is obtained and compared with a threshold value, the threshold value may be added to the absorbance at the reference measurement point to make a comparison with the absorbance at each measurement point. .

[0015]

As is apparent from the above description, according to the present invention, since the absorbance at the measurement point within the threshold range is taken from the absorbance at the reference measurement point, the first reagent amount becomes the specified amount. The measurement area can be expanded even with a latex reagent, for example, in which the absorbance of the sample cannot be measured at the measurement point without reaching it. Moreover, since the reference measurement point and the threshold are set, even if the absorbance of the sample cannot be measured, highly accurate measurement and expansion of the measurement region can be performed.

[Brief description of drawings]

FIG. 1 is a diagram showing one embodiment of a biochemical analyzer according to the present invention.

FIG. 2 is a diagram for explaining the operation of the biochemical analyzer according to the present invention.

FIG. 3 is a diagram showing an outline of a system configuration of a biochemical analyzer according to the present invention.

FIG. 4 is a diagram for explaining absorbance at a measurement point and removal of a curved portion.

FIG. 5 is a diagram showing a conventional example of a biochemical analysis device employing RRA.

FIG. 6 is a diagram for explaining a problem of a conventional biochemical analyzer.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Detection part, 2 ... Measurement data storage part, 3 ... Effective data extraction part, 4 ... Threshold value storage part, 5 ... Effective data storage part, 6 ... Absorbance calculation part, 7 ... Concentration calculation part

Claims (2)

[Claims] 1. A biochemical analyzer for dispensing a sample and a reagent into a reaction cell and reacting them to measure the absorbance at a plurality of measurement points over time and obtain the change amount of the absorbance per unit time. Threshold setting means for setting a threshold for extracting the absorbance, and a reference measurement point is set, and the absorbance at the measurement point where the difference between the absorbance at the reference measurement point and the absorbance at each measurement point is within the threshold range A biochemical analysis device, comprising: an extracting unit that extracts the above-mentioned value; and a calculating unit that calculates the amount of change in the absorbance per unit time by the least-squares method based on the absorbance at the measurement points extracted by the extracting unit. 2. The biochemical analyzer according to claim 1, wherein the threshold setting means resets the threshold when the reagent lot is changed.