JP2013079888A - Automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic analyzer enabling stable measurement because of less occurrence of a specific change (careless mistake) by optimizing an agitation condition even in measurement of a standard sample and an accurate control sample.SOLUTION: An automatic analyzer includes: a reaction vessel which mixes a sample and a reagent; an agitating mechanism which agitates a mixed solution of the sample and the reagent in the reaction vessel; and measurement means which optically measures the mixed solution in the reaction vessel by irradiating the reaction vessel with light. The analyzer also includes a control mechanism which is controlled so that an agitation condition on the agitating mechanism in the mixed solution using the same kind of the reagent is changed in accordance with a kind of the reagent to be agitated.

Description

  The present invention relates to an automatic analyzer for analyzing components contained in a sample by measuring the absorbance of a mixture of a sample such as blood or urine and an analytical reagent, and in particular, reagent blank measurement for preparing a calibration curve The present invention relates to an automatic analyzer that can improve the measurement accuracy.

  The present invention dispenses a sample to be measured into a reaction vessel, dispenses a reagent suitable for the measurement item into the reaction vessel, and stirs and mixes the reaction solution of the sample and the reagent. It is intended for an automatic blood analyzer that measures absorbance by an optical system including a light source, a spectroscope, a detector, and the like, and acquires component information in a sample. Hereinafter, a specific configuration of the automatic blood analyzer will be described. A plurality of reaction vessels are arranged on a rotating reaction table, and a plurality of samples are continuously measured. In addition, the reaction container that has been analyzed is cleaned by a cleaning mechanism so that the analysis can be performed again. In such an automatic analyzer, when a predetermined amount of sample or reagent is dispensed into a reaction container, there is a possibility that bubbles are involved in the liquid or bubbles are involved during stirring. The presence of such bubbles may cause a change (also referred to as “poca”) specific to the time change of absorbance as described in Patent Document 1. Japanese Patent Laid-Open No. 2004-228561 describes that the density calculation is not affected by deleting data in which this specific change (poca) has occurred at the data processing stage.

JP 2002-196005 A

  If the occurrence of specific changes (poca) is small, or when the specific change (poca) occurs is a time that does not significantly affect the concentration calculation, the technique described in Patent Document 1 can be used with a certain degree of accuracy. It is possible to calculate the concentration with However, some types of reagents tend to generate bubbles. If a large number of spots are generated or if spots occur at a time point that affects density calculation, even if correction is performed using the technique described in Patent Document 1, accurate density calculation may be difficult.

  In addition, when a specific change (poca) occurs in the measurement of a standard sample with a known concentration for drawing a calibration curve or a quality control sample for periodically checking the analysis accuracy of the analyzer, the standard sample Because the accuracy of the calibration curve created using this method decreases, there is a risk that the measurement result of the general sample calculated using the calibration curve may decrease, and it is impossible to accurately detect reagent deterioration and changes in the instrument status There was a fear.

  The purpose of the present invention is to provide an automatic analyzer that can perform stable measurement with few specific changes (poca) by optimizing the stirring conditions even when measuring standard samples and quality control samples There is to do.

  A typical configuration of the present invention for solving the above-described problems is as follows.

  A reaction vessel for mixing the sample and the reagent, a stirring mechanism for stirring the mixed solution of the sample and the reagent in the reaction vessel, and optically measuring the mixed solution in the reaction vessel by irradiating the reaction vessel with light And a control mechanism for controlling the stirring conditions of the stirring mechanism in a mixed solution using the same type of reagent to change according to the type of sample to be stirred. Automatic analyzer.

  The type of the sample may be a standard sample, a quality control sample, or a general sample.

  The control mechanism may control not to perform stirring when the type of sample to be stirred is a standard sample.

  As the stirring mechanism, various stirring mechanisms such as a mechanism for inserting a spatula into a liquid to be stirred and rotating or moving the spatula vertically, or a mechanism for stirring by irradiation with sound waves can be applied.

  Stirring conditions refer to various conditions that change the stirring efficiency (operation speed) of the mechanism that rotates or moves the spatula, the stirring intensity of the sound wave (sound wave output), the stirring efficiency, and the like.

  According to the present invention, it is possible to increase the measurement accuracy when measuring a standard sample with a known concentration or a quality control sample, and to obtain a more reliable measurement result. It is also possible to accurately grasp the state of the reagent and device.

It is a figure explaining one Example of an automatic analysis system. It is a figure explaining the phenomenon occurrence example regarding this invention. It is a figure explaining the operation | movement flow Example regarding this invention.

  An embodiment of the present invention will be described below. FIG. 1 shows a schematic diagram of an automatic analyzer embodying the present invention.

  A plurality of reaction vessels 101 for holding a mixed solution of a sample and a reagent, a reaction table 103 for holding and rotating the reaction vessels 101, and a photometer 102 for measuring the absorbance of the rotating reaction vessel 101 are arranged on the circumference. A predetermined liquid amount required for analysis of the sample 104 to be measured is dispensed into the reaction container by the sample dispensing mechanism 105 on the apparatus, and then the target is received from the reagent cold-retention mechanism 106 according to the item to be measured. The reagent is dispensed by the reagent dispensing 1 mechanism 107 and the reagent dispensing 2 mechanism 108 into the reaction vessel 101 into which the sample has been dispensed, and the agitation placed on the circumference of the reaction table 103 after each dispensing is performed. Agitation and mixing are performed by the mechanism 109. The mixed liquid is rotated by the reaction table 103, and the absorbance due to the time change of the liquid mixture is measured by the photometer 102. The photometer 102 is a measuring means for optically measuring a mixed solution in a reaction solution by irradiating the reaction container with light as shown in FIG. After the absorbance measurement is performed for a certain period of time and the measurement is completed, the cleaning mechanism 110 discards the mixed solution and cleans the container, and then returns to a state where it can be used for sample measurement. The reaction table 103, the photometer 102, the sample dispensing mechanism 105, and the stirring mechanism 109 are controlled by a control mechanism (not shown).

  FIG. 2 shows an example of the phenomenon that is the subject of the present invention regarding the measurement of the absorbance of the mixed solution. The liquid mixture 204 of the sample and the reagent held in the reaction vessel 203 is kept at a constant temperature of about 37 ° C. in the reaction vessel 202. A glass window A 206 and a glass window B 207 capable of transmitting light to the reaction tank 202 are provided at a site of the photometer 102 for measuring the absorbance. The light emitted from the light source 201 inside the photometer 102 passes through a lens and a slit (not shown), passes through the glass window A206 as a photometric region 205, and passes through the sample 204 which is a mixed liquid held in the reaction vessel 203. Thereafter, the light transmitted through the glass window B207 is guided to the detector 209. In the detector 209, photometry is performed for each predetermined wavelength using a slit or diffraction grating (not shown), the absorbance of the sample 204 is measured, the components contained in the sample 204 are analyzed from the absorbance, and the result is output to the output unit 210. To do.

  At this time, in order to perform the component analysis from the absorbance, it is necessary to prepare a calibration curve for clarifying the relationship between the absorbance and the concentration before the analysis. An example of the graph is shown in a calibration curve graph 221. Absorbance is plotted on the vertical axis, and concentration is plotted on the horizontal axis. For example, the absorbances of two substances, standard substances STD1 and STD2, whose concentrations are already known, can be measured, and a calibration curve can be drawn by these two points. However, for example, when the standard substance is measured, if the bubble 208 is attached to the photometric region 205 of the reaction vessel 203, the original calibration curve graph 221 shows the STD1A position of the absorbance B at the concentration C1. For example, the absorbance increases due to the bubble 208, indicating the STD1B position. As a result, the calibration curve that is the original calibration curve A is erroneously drawn to the calibration curve B. When the sample is measured as it is, the concentration result of the sample with the absorbance Ax is originally output as CxB. Result in erroneously outputting CxA.

  In order to solve this problem, it is necessary to remove or not generate the bubbles 208 when performing photometry with the photometer 102. The main cause of bubbles generated in the reaction vessel 203 is a stirring and mixing operation performed by the stirring mechanism 109 after dispensing the sample and the reagent. The stirring operation is performed by, for example, immersing a stirring rod with a twist like a plate or a screw in the mixed liquid 204, and rotating the stirring rod to mix the liquid by causing the liquid to rotate, up and down, or outside the reaction vessel. From the surface of the liquid mixture, bubbles are drawn into the liquid by the action of acoustic radiation pressure due to sound waves, and the upstream and downstream are generated to perform mixing.

  However, during this mixing operation, if the bubbles entrained in the liquid adhere to the wall surface of the reaction vessel 203 and the adhering bubbles adhere to the photometric region 205, an erroneous absorbance is measured. Therefore, according to the methods proposed so far, the acoustic radiation pressure generated by the sound waves from the outside of the reaction vessel is applied to the bubbles adhering to the wall surface by the stirring and mixing, similarly to the sound wave stirring shown in the example of the previous stirring method. By utilizing the action, a method has been proposed in which bubbles attached to the reaction vessel wall surface are separated from the wall surface or moved upward from the reaction vessel to remove bubbles from the photometric region. According to this method of removing bubbles by acoustic radiation pressure, the effect of removing bubbles is greatly influenced by the liquidity of the liquid mixture. Therefore, the liquidity of the target reagent is known in advance, and the sound pressure is determined by the liquidity of the reagent. For example, stable bubble removal can be performed by controlling.

  However, particularly when a liquid mixture having low wettability is targeted, the effect of removing bubbles by sound waves is not high, and the bubbles may remain in the photometric region. Generally, when serum or urine is used as a sample, even if the wettability of the reagent is low, the wettability of the mixed liquid is removed due to the liquidity of the sample so that it can be removed by sound waves. It can be carried out.

  On the other hand, when preparing a calibration curve, a sodium chloride aqueous solution is often used as a reagent blank solution for measuring STD1 for creating a calibration curve graph 221, and mixing is performed when serum or urine is used. There is no effect of improving the wettability of the liquid. Therefore, there are cases where a method such as preparing a special standard material with improved wettability as a reagent blank solution may be taken, but when this method is used, a standard material suitable for each target reagent is prepared. There are problems such as an increase in preparatory work such as necessity, and the necessity of purchasing a dedicated reagent blank solution.

  Therefore, in particular, we propose a solution technique that solves the problem of bubbles when performing reagent blank measurement and does not increase the amount of work.

  So far, in the mixed liquid stirring operation, methods such as changing the stirring parameter depending on the reagent item and changing depending on the liquid volume have been performed, but in the case of the same type of reagent and liquid volume, there is one stirring parameter. It was only. When stirring viscous serum or the like, it is necessary to stir the sample dispensed to the bottom of the reaction vessel vigorously and raise and mix it. However, since the viscosity of the aqueous sodium chloride solution used for the reagent blank measurement is lower than that of serum, it is not necessary to stir with the same strength as serum. Therefore, in the case of the calibration operation for creating a calibration curve, items that are considered to be sufficient only by the mixing effect of the reagent and the reagent blank solution in the reaction vessel by stirring at a lower intensity than that of a general specimen or the discharge flow of the reagent In this case, the stirring operation is not performed, and even if the same type of reagent is used, by changing the stirring conditions, bubbles are generated due to the stirring operation that occurred during the measurement of the standard substance, and bubbles on the reaction vessel wall surface. Reduce adhesion.

  FIG. 3 shows an operation determination flow of the present invention. After the start of measurement by the automatic analyzer (301), the target measurement item is confirmed (302), and it is determined whether the request is a calibration operation, other general sample measurement or a quality control sample (303), not a calibration operation. In this case, the same stirring parameter A306 is adopted and executed. In the case of the calibration operation, it is confirmed whether or not it has a stirring parameter dedicated for calibration depending on the item (304), and if it does not have a dedicated parameter, the stirring parameter A306 is executed in the same manner as for a general sample.

  In the case of having the dedicated parameter, it is determined whether or not the STD1 analysis using the reagent blank solution is performed (305). In the case of other standard samples that are not STD1, the stirring parameter B308 is executed. Run.

  In the agitation parameter, for example, the blank solution and other standard reagents are distinguished, and the agitation parameter C and B are controlled so that the agitation intensity of the agitation parameter C is smaller than the agitation intensity of the agitation parameter B. May control the stirring mechanism, or the stirring parameter B may be stirred but the stirring parameter C may not be stirred. In addition, when the sample is a general sample, stirring is performed as stirring parameter stirring A in the relationship between stirring parameters A, B, and C, but in the case of a standard sample, stirring is not performed as stirring parameters B and C. There is also. Further, the control mechanism may control the stirring mechanism so that the stirring intensity decreases in the order of the stirring parameter A, the stirring parameter B, and the stirring parameter C in the order of the stirring parameters A, B, and C.

  With this operation flow, there is no need to increase the stirring intensity, and in the calibration operation when there is a risk of bubbles adhering to the reaction container when stirring strongly, the stirring operation is used differently depending on the reagent item and the standard substance. It is possible to provide an automatic analyzer that can reduce generation and thereby can create a calibration curve with high reliability and can output a reliable analysis result.

  In the example shown above, the usage when a sodium chloride aqueous solution is used as a reagent blank solution has been explained. For example, in the case of creating a calibration curve by measuring a plurality of standard substances, it was adjusted to each standard substance. It is also possible to prepare a plurality of stirring parameters.

  According to the present invention, in the stirring of a mixed solution using the same type of reagent, by optimizing the stirring conditions according to the type of sample, it is possible to suppress bubbles generated by stirring and suppress a decrease in accuracy of measurement results. can do.

101, 203 Reaction vessel 102 Photometer 103 Reaction table 104, 204 Sample 105 Sample dispensing mechanism 106 Reagent cooling mechanism 107 Reagent dispensing 1 mechanism 108 Reagent dispensing 2 mechanism 109 Stirring mechanism 110 Washing mechanism 201 Light source 202 Reaction tank 205 Photometric area 206 Glass window A
207 Glass window B
208 Bubbles in reaction vessel 209 Detector 210 Output unit 221 Calibration curve graph 301 Measurement start 302 Measurement item confirmation 303 Measurement content determination 304 Calibration determination 305 Sample content determination 306 Stirring parameter A
307 Stirring parameter C
308 Stirring parameter B

Claims (6)

A reaction vessel for mixing the sample and the reagent, a stirring mechanism for stirring the mixed solution of the sample and the reagent in the reaction vessel, and optically measuring the mixed solution in the reaction vessel by irradiating the reaction vessel with light In an automatic analyzer equipped with a measuring means for
An automatic analyzer comprising a control mechanism for controlling the stirring condition of the stirring mechanism in a mixed solution using the same type of reagent so as to change according to the type of sample to be stirred. The automatic analyzer according to claim 1, wherein
The automatic analyzer according to claim 1, wherein the sample type is a standard sample, a quality control sample, or a general sample. The automatic analyzer according to claim 1, wherein
The automatic analysis apparatus characterized in that the control mechanism controls so as not to perform stirring when the type of the sample to be stirred is a standard sample. The automatic analyzer according to claim 1, wherein
The sample type is a standard sample,
The automatic analyzer is characterized in that the control mechanism controls the stirring conditions of the blank solution and other standard reagents in the standard sample. The automatic analyzer according to claim 4,
The stirring condition is stirring intensity,
The automatic analyzer is characterized in that the control mechanism controls the stirring strength of the blank solution to be smaller than the stirring strength of the other standard reagents. The automatic analyzer according to claim 5, wherein
The automatic analyzer is characterized in that the control mechanism controls so as not to stir the blank solution.