Automated analyzer and sample analysis method

Abstract

A waveform acquisition unit 123 samples the amount of transmitted light measured by a transmitted light measuring instrument 202 while a reaction vessel 106 passes a light measurement point as a result of the rotation of a reaction disk 103, and acquires the amount of transmitted light as transmitted light amount waveform data, and a data processing unit 124 calculates a difference or derivative of the transmitted light amount waveform data of the first reaction vessel to acquire transmitted light amount difference waveform data or transmitted light amount differentiation waveform data, and determines the influence of air bubbles in a reaction liquid stored in the first reaction vessel on the basis of a change over time in the transmitted light amount difference waveform data or the transmitted light amount differentiation waveform data for each photometric sampling when the first reaction vessel passes the light measurement point. As a result, the analysis accuracy and reliability of the automated analysis are improved.

Description

[Technical Field]

[0001] The present invention relates to an automated analyzer and a method for analyzing specimens using the same. [Background technology]

[0002] The automated analyzer determines the presence and concentration of the target component based on light intensity data obtained by reacting a reagent corresponding to the target component with a biological sample (specimen) such as blood or urine, irradiating the reaction solution with light, and measuring the transmitted or scattered light. The reaction vessels containing the reaction solution are arranged continuously on the circumference of a rotatable reaction disk, and by rotating the reaction disk, light is continuously irradiated onto the reaction solutions contained in the numerous reaction vessels for measurement.

[0003] In recent years, there has been a growing demand for automated analyzers that can provide highly accurate and reliable analytical results at high speed. For example, if abnormalities such as bubbles or scratches occur in the reaction vessel, the analytical results may become abnormal, and there are prior technologies to detect such abnormalities.

[0004] Patent Document 1 discloses a technique for calculating the degree of matching using photometric data of the same cuvette and wavelength, comparing photometric waveforms from different photometric points within the same test, or the photometric waveform of a water blank that serves as a reference photometric waveform, and determining an error based on the calculated value or its change.

[0005] Patent Document 2 discloses a standard deviation calculation unit that calculates the standard deviation of the absorbances of multiple reaction solutions measured by the photometric unit each time the reaction vessel passes through the photometric unit once; a standard deviation determination unit that determines whether each of the multiple standard deviations calculated by the standard deviation calculation unit is smaller than a threshold determined based on the standard deviations of multiple absorbances in a uniformly stirred reaction solution; and an average value calculation unit that determines the average value of the multiple absorbances having a standard deviation that the standard deviation determination unit determined to be smaller than the threshold as the absorbance when analyzing a sample. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Japanese Patent Publication No. 2009-281941 [Patent Document 2] Japanese Patent Publication No. 2010-160116 [Overview of the project] [Problems that the invention aims to solve]

[0007] Thus, in absorbance and scattering light analysis using automated analyzers, if air bubbles are mixed into the reaction solution in the reaction vessel, the resulting interference may prevent accurate analysis results. Therefore, technologies like the prior art have been developed. However, the technology disclosed in Patent Document 1 requires the acquisition of a reference photometric waveform, and if air bubbles or scratches on the cell interfere with the acquisition of the reference photometric waveform, accurate error determination becomes difficult. Furthermore, the technology disclosed in Patent Document 2 calculates the standard deviation for each photometric point, but significant fluctuations in absorbance due to reagent dispensing before and after reagent dispensing may occur, potentially preventing the determination of an appropriate absorbance. [Means for solving the problem]

[0008] An automated analyzer, which is one embodiment of the present invention, comprises a reaction disk in which a plurality of reaction vessels, including a first reaction vessel, are arranged circumferentially and are capable of intermittent rotation; a photodetection system including a light source and a photometer, wherein the reaction vessels arranged on the reaction disk pass through a photometric point located on a straight line connecting the light source and the photometer; and a photometer data processing unit, wherein the reaction disk is equipped with a temperature bath for maintaining the reaction vessels at a predetermined temperature, the photometer is equipped with a transmitted light measuring instrument for measuring the amount of transmitted light that has passed through the reaction vessels in the irradiation direction from the light source, and the photometer data processing unit The system includes a waveform acquisition unit that samples the amount of transmitted light measured by a transmitted light measuring instrument as the reaction vessel passes a photometric point due to the rotation of a reaction disk, and acquires it as transmitted light amount waveform data, and a data processing unit that calculates the difference or derivative of the transmitted light amount waveform data of the first reaction vessel to acquire transmitted light amount difference waveform data or transmitted light amount derivative waveform data, and determines the effect of bubbles in the reaction liquid contained in the first reaction vessel based on the time-dependent change in the transmitted light amount difference waveform data or transmitted light amount derivative waveform data for each photometric sampling as the first reaction vessel passes the photometric point. [Effects of the Invention]

[0009] Because sampling sections affected by air bubbles can be accurately identified, the analytical accuracy and reliability of automated analyzers can be improved. Other challenges and novel features will become apparent from the description and accompanying drawings in this specification. [Brief explanation of the drawing]

[0010] [Figure 1] This is an overall diagram of the automated analyzer. [Figure 2] This is an example of the configuration of the photodetector system and the photometer data processing unit. [Figure 3] This figure shows examples of fluctuations in the transmitted light scanning waveform of the reaction solution before and after reagent dispensing. [Figure 4] This figure shows an example of transmitted light waveform data when air bubbles are present in the reaction solution. [Figure 5] This figure shows the change in bubbles in the reaction vessel over time. [Figure 6] It is a diagram showing the change over time of the transmitted light amount waveform data when bubbles are present in the reaction vessel. [Figure 7] It is a flowchart in which the photometric data processing unit identifies the region where bubbles are present. [Figure 8] It is a diagram showing a method for calculating the difference in the transmitted light amount waveform data. [Figure 9] It is a diagram for explaining step S104 of the flowchart. [Figure 10] It is a diagram for explaining a method for identifying the influence range of bubbles. [Figure 11] It is a diagram for explaining a method for identifying the influence range of bubbles.

Embodiments for Carrying Out the Invention

[0011] Embodiments of the present invention will be described in detail based on the drawings. In the following embodiments, it is needless to say that the constituent elements (including element steps, etc.) are not necessarily essential unless specifically stated or considered to be clearly essential in principle. Also, for bubbles, light amount waveform data, etc., when they do not need to be uniquely identified in the description and in the figures, they are described with the reference signs omitted.

[0012] FIG. 1 is an overall configuration diagram of the automatic analyzer 1. The automatic analyzer 1 mainly includes a sample disk (specimen container 104 holding mechanism) 101, a reagent disk (reagent bottle 105 holding mechanism) 102, a reaction disk (reaction vessel 106 holding mechanism) 103, a specimen dispensing mechanism 107, a reagent dispensing mechanism 109, a stirring mechanism 111, a cleaning mechanism 112, a light source 121, a photometer 122, and a computer 132.

[0013] The reaction disk 103 is capable of intermittent rotation and is equipped with a temperature bath. Numerous reaction vessels (reaction cells) 106 made of a translucent material are arranged circumferentially on the reaction disk 103. The reaction vessels 106 on the reaction disk 103 are maintained at a predetermined temperature, for example, 37.5°C, by the temperature bath.

[0014] The sample disc 101 can accommodate numerous sample containers 104 containing biological samples such as blood and urine arranged around its circumference. A sample dispensing mechanism 107 is located near the sample disc 101. The sample dispensing mechanism 107 comprises a sample dispensing nozzle 108 and a drive unit. When dispensing a sample, the sample dispensing mechanism 107 rotates and moves the sample dispensing nozzle 108 up and down to move it to the dispensing position (aspiration position) on the sample disc 101, aspirates a predetermined amount of sample from the sample container 104 containing the sample, then moves it to the discharge position on the reaction disc 103, and discharges the sample into the reaction vessel 106.

[0015] The reagent disk 102 can accommodate numerous reagent bottles 105 arranged circumferentially. Each reagent bottle 105 contains reagents corresponding to the items that can be analyzed by the automated analyzer 1. A reagent dispensing mechanism 109, which has a mechanism generally similar to that of the sample dispensing mechanism 107, is located near the reagent disk 102. During reagent dispensing, the reagent dispensing mechanism 109 moves the reagent dispensing nozzle 110 to the dispensing position on the reagent disk 102 by rotating and moving it up and down, aspirates a predetermined amount of reagent from the reagent bottle 105 containing the reagent, then moves it to the discharge position on the reaction disk 103, and discharges the reagent into the reaction vessel 106.

[0016] The stirring mechanism 111 is positioned near the reaction disk 103. This stirring mechanism 111 stirs the mixture of sample and reagent (reaction solution) contained in the reaction vessel 106, thereby promoting the reaction.

[0017] The light source 121 is positioned near the center of the reaction disk 103. Here, the light from the light source 121 after it has passed through the reaction vessel 106 in the direction of irradiation is called transmitted light, and the light from the light source 121 after it has passed through the reaction vessel 106 in directions other than the direction of irradiation is called scattered light. The photometer 122 is equipped with a transmitted light measuring instrument 202 for measuring the intensity of transmitted light and a scattered light measuring instrument 203 for measuring the intensity of scattered light, and is positioned on the outer periphery of the reaction disk 103. The light source 121 and the photometer 122 constitute a photodetection system. After stirring is complete, the reaction vessel 106 rotates to pass through photometric points (photometric positions) that are located on a straight line connecting the light source 121 and the photometer 122. The reaction liquid present in each reaction vessel 106 after stirring is measured each time it passes through a photometric point during the rotation of the reaction disk 103. Analog signals indicating the amount of transmitted and scattered light measured are input to the photometer data processing unit 2. The photometer data processing unit 2 comprises a waveform acquisition unit 123 and a data processing unit 124. The waveform acquisition unit 123 converts the analog signal into data at a predetermined sampling period, and the data processing unit 124 processes it as a digital signal.

[0018] The cleaning mechanism 112 is located near the reaction disk 103. This cleaning mechanism 112 cleans the inside of the reaction vessel 106 after measurement is complete, making it reusable.

[0019] Computer 132 is connected via interface 131 to the sample disk 101, reagent disk 102, reaction disk 103, sample dispensing mechanism 107, reagent dispensing mechanism 109, stirring mechanism 111, washing mechanism 112, and photometer data processing unit 2. Computer 132 sends commands to all mechanisms and controls their operation accordingly, and performs sample analysis using light intensity data from the photometer data processing unit 2. Computer 132 also has a storage medium where information such as analysis parameters, analysis request details, and analysis results are recorded.

[0020] Furthermore, the interface 131 is connected to an input device 133 for inputting operation commands and other information, and a display device 134 for displaying analysis items, errors, and other information.

[0021] Next, the sample dispensing operation in the automated analyzer 1 will be described. The items that can be analyzed by the automated analyzer 1 are pre-entered via the input device 133 and stored in the computer 132. The operator uses the operation item display function of the display device 134 to select the analysis items corresponding to each sample and its request from the screen. At this time, information such as the patient ID is also entered into the computer 132 using the input device 133. In order to perform the instructed analysis items for each sample, the sample dispensing nozzle 108 of the sample dispensing mechanism 107 dispenses a predetermined amount of sample from the sample container 104 to the reaction vessel 106 according to the analysis parameters.

[0022] The reaction vessel 106, into which the sample has been dispensed, is moved to a position where the reagent can be dispensed by the rotation of the reaction disk 103. The reagent dispensing nozzle 110 of the reagent dispensing mechanism 109 dispenses a predetermined amount of reagent from the reagent bottle 105 into the reaction vessel 106 according to the analytical parameters. In some cases, the reagent may be dispensed before the sample, contrary to this example. Subsequently, the mixture is stirred by the stirring mechanism 111, and the sample and reagent are mixed.

[0023] When the reaction vessel 106, after mixing is complete, crosses a photometric point located on the straight line connecting the light source 121 and the photometer 122, the transmitted and scattered light of the reaction solution is measured by the photometer 122. The measured transmitted and scattered light is converted into numerical data for each sampling position by the waveform acquisition unit 123 of the photometer data processing unit 2, extracted as light intensity data for the target of measurement by the data processing unit 124, and then input to the computer 132 via the interface 131. Note that the processing in the data processing unit 124 may also be performed by the computer 132.

[0024] Concentration data is calculated based on the converted numerical data, the analytical method specified for each test item, and the calibration curve that has been measured in advance. The concentration data of the components of each analytical item, which are the analysis results, are stored inside the computer 132. In addition, the analysis results are displayed on the screen of the display device 134 after the analysis is completed.

[0025] Figure 2 shows an example configuration of the photodetection system and the photometer data processing unit 2. Light emitted from the light source 121 passes through the reaction liquid 201, which is the object to be measured and contained in the reaction vessel 106, and is received by the transmitted light measuring instrument 202, which is installed in a straight line with the light source 121. In addition, some of the light emitted from the light source 121 becomes scattered light as it passes through the reaction liquid 201. The scattered light is received by the scattered light measuring instrument 203, which is installed at a different angle from the transmitted light measuring instrument 202. Note that multiple scattered light measuring instruments installed at different angles to each other may be installed. Here, the waveform acquisition unit 123 synchronously samples the amount of transmitted light and scattered light from the reaction vessel 106 passing through the photometric points detected by the transmitted light measuring instrument 202 and the scattered light measuring instrument 203, respectively, and acquires the amount of light for each sampling position as scanned waveform data. The data processing unit 124 extracts data corresponding to the reaction liquid 201 from the scanned waveform data acquired by the waveform acquisition unit 123 for each photodetection timing (photometric sampling). Subsequently, data processing is performed to determine the effect of air bubbles in the reaction solution, and the results are stored internally in computer 132.

[0026] Generally, automated analyzers often have separate photodetectors for transmitted light analysis and scattered light analysis. The photodetector shown in Figure 2 uses a photometer 122 equipped with a transmitted light detector 202 and a scattered light detector 203 in the photodetector for scattered light analysis, and therefore it is not intended to use the scanning waveform data of the transmitted light detector 202 for sample analysis. However, depending on the test item, it is possible to use the scanning waveform data of the transmitted light detector 202 for sample analysis.

[0027] Figure 3 shows an example of the fluctuation of transmitted light scanning waveforms in reaction solutions 301 and 302, contained in reaction vessel 106, before and after dispensing reagent 303. Reaction solution 301 is the reaction solution before dispensing reagent 303, and reaction solution 302 is the reaction solution obtained by dispensing reagent 303 into reaction solution 301 and stirring. Here, the scanning waveform of the transmitted light from light source 121 for reaction solution 301 is referred to as transmitted light intensity waveform data 304, and similarly, the scanning waveform of the transmitted light for reaction solution 302 is referred to as transmitted light intensity waveform data 305.

[0028] Mixing reaction solution 301 and reagent 303 causes a chemical change in the substances in reaction solution 301, resulting in a change in the amount of light scattered inside the reaction vessel 106 from the light source 121. As a result, in Figure 3, the transmitted light waveform data 305 of reaction solution 302 shows an increase in the light intensity in the flat region compared to the transmitted light waveform data 304 of reaction solution 301. Note that the light intensity in the flat region may decrease depending on the type of reagent 303 dispensed and the sample.

[0029] Figure 4 shows an example of transmitted light waveform data when bubbles 402 are present in the reaction liquid 401 contained in the reaction vessel 106. Light incident on bubbles 402 is scattered in other directions due to the influence of the bubbles, increasing the amount of light scattered in other directions. As a result, a region (i.e., a sampling interval where the amount of light decreases) 404 appears, as shown in the transmitted light waveform data 403 in Figure 4, due to the multidirectional scattering effect of bubbles 402. Note that the amount of light scattered in other directions differs depending on the size of the bubbles; the larger the bubbles, the greater the decrease in transmitted light, and the wider the region tends to be.

[0030] Figure 5 shows the change over time of bubbles 402 in the reaction solution 401 contained in the reaction vessel 106. The reaction solution 401 is always maintained at a predetermined temperature (e.g., 37.5°C) on the reaction disk 103. That is, in an air-conditioned environment such as a laboratory, the reaction vessel 106 and the reaction solution 401 are always kept at a higher temperature. Since gases expand with heat, if bubbles 402 are introduced when a sample or reagent is dispensed, the bubbles 402 will expand over time along with the fine gases present in the reaction solution 401.

[0031] Figure 6 shows the temporal changes in transmitted light intensity waveform data along with the temporal changes in bubble 402 shown in Figure 5. As described above, when bubble 402 is present inside the reaction vessel 106, a region of decreased light intensity 404 appears in the transmitted light intensity waveform data 403. As bubble 402 expands due to temporal changes caused by heat, the degree of decrease in the transmitted light intensity and the region of decrease (sampling interval) appearing in the transmitted light intensity waveform data 405 and 406 increase. In this embodiment, the region (sampling interval) where bubbles are present is identified based on the temporal changes in transmitted light intensity waveform data 403, 405, and 406 due to the effect of bubble expansion.

[0032] The flowchart in Figure 7 illustrates the procedure for identifying regions where bubbles exist within the scanned waveform data.

[0033] First, light from the light source 121 is shone into the reaction vessel 106 containing the reaction solution, and the waveform acquisition unit 123 acquires transmitted light waveform data and scattered light waveform data from the amount of light received by the photometer 122 (S101). Here, the scattered light waveform data is the scanning waveform of the scattered light from the light source 121 for the reaction solution, and the transmitted light waveform data and scattered light waveform data are acquired synchronously at the same sampling position. Hereafter, the transmitted light waveform data and scattered light waveform data will be collectively referred to as light intensity waveform data.

[0034] Next, the data processing unit 124 extracts light intensity waveform data for each photometric sampling, that is, each time the reaction vessel 106 passes a photometric point (S102). Subsequent processing is also performed by the data processing unit 124.

[0035] Next, the difference or derivative of the transmitted light intensity waveform data is calculated (S103). Figure 8 shows the method for calculating the difference of the transmitted light intensity waveform data. Since the transmitted light intensity waveform data 501 is a collection of data for each sampling position, the transmitted light intensity difference waveform data 502 can be calculated by calculating the difference ΔL of the light intensity data between consecutive sampling positions 503 and 504 at all sampling positions of the transmitted light intensity waveform data 501. Alternatively, the transmitted light intensity waveform data 501 may be approximated to a continuous value, and the transmitted light intensity derivative waveform data may be obtained by differentiating the continuous value approximated transmitted light intensity waveform data with respect to the sampling position. By using the transmitted light intensity difference waveform data or the transmitted light intensity derivative waveform data, the change in light intensity in the flat portion of the transmitted light intensity waveform data before and after reagent dispensing, as shown in Figure 3, can be ignored.

[0036] Next, it is determined whether the values ​​of the transmitted light intensity difference (differential) waveform data at all sampling positions are within a predetermined range (S104). The predetermined range is set as the range in which the values ​​of the transmitted light intensity difference (differential) waveform data can be considered as 0. If the values ​​of the transmitted light intensity difference (differential) waveform data are within the predetermined range (Yes in S104), it is determined that there is no effect of bubbles on the light intensity waveform data (S107). On the other hand, if the values ​​of the transmitted light intensity difference (differential) waveform data exceed the predetermined range (No in S104), it is determined that there is an effect of bubbles, and the process moves on to identifying the region (sampling interval) affected by bubbles.

[0037] The process of step S104 will be described with reference to FIG. 9. The transmitted light quantity waveform data 601 is affected by bubbles in some of its sampling intervals. In the transmitted light quantity waveform data 601, a sampling interval (flat portion) where the light quantity does not change much without the influence of bubbles or the like is referred to as section A, and a sampling interval where the light quantity decreases due to the influence of bubbles or the like is referred to as section B. At this time, in section A, the value of the transmitted light quantity difference waveform data 602 becomes almost 0, while in section B, the value of the transmitted light quantity difference waveform data 602 includes positive or negative values, that is, in section B, irregularities appear in the difference scanning waveform. Therefore, when an increase or decrease exceeding a predetermined range is observed in the value of the transmitted light quantity difference waveform data, it can be determined that there is a possibility of the influence of bubbles.

[0038] First, a method for specifying the influence range of bubbles in a certain reaction vessel (the first reaction vessel) arranged on the reaction disk will be described with reference to FIGS. 10 and 11. FIG. 10 shows the transmitted light quantity waveform data 611 obtained by the t1-th photometric sampling (t0 < t1) superimposed on the transmitted light quantity waveform data 601 assuming that the transmitted light quantity waveform data 601 shown in FIG. 9 is data obtained by the t0-th photometric sampling, and also shows the transmitted light quantity difference waveform data 602 and the transmitted light quantity difference waveform data 612 superimposed on each other.

[0039] As the bubble starts to cross the photometric point, the light quantity decreases from the light quantity of the flat portion, and as the bubble finishes crossing the photometric point, the light quantity increases and returns to the value of the original flat portion light quantity. The irregularities appearing in the difference scanning waveform or the differential scanning waveform represent this variation. Further, as described above, since the reaction vessel 106 on the reaction disk 103 is constantly heated, the bubble expands. The larger the bubble becomes, the greater the decrease in the light quantity of the transmitted light, and the area where the light quantity of the transmitted light decreases expands. In this embodiment, by capturing such a characteristic change over time of the influence of the bubble as the change over time of the difference or the differential of the light quantity of the transmitted light appearing in the difference scanning waveform or the differential scanning waveform, the sampling intervals affected by the bubble in the light quantity waveform data of a certain reaction vessel are specified.

[0040] The first criterion for the method of specifying the sampling interval is that the absolute value of the value of the transmitted light amount difference waveform data or the transmitted light amount differential waveform data tends to increase with time. For example, in FIG. 10, in the transmitted light amount difference waveform data 602 obtained by the t0-th photometric sampling, the sampling position where the value changes from 0 to a negative value exceeding a predetermined range is P1 t0 , and the sampling position where the value changes from a positive value exceeding a predetermined range to 0 is P2 t0 . If the change in the difference (differential) scanning waveform at the sampling position P1 t0 is due to the influence of bubbles, the absolute value of the value at the sampling position P1 t0 in the transmitted light amount difference waveform data 612 obtained by the t1-th photometric sampling is larger than the absolute value of the value at the sampling position P1 t0 in the transmitted light amount difference waveform data 602. Similarly, the absolute value of the value at the sampling position P2 t0 in the transmitted light amount difference waveform data 612 obtained by the t1-th photometric sampling is larger than the absolute value of the value at the sampling position P2 t0 in the transmitted light amount difference waveform data 602. This is shown in FIG. 11. Each time the number of photometric measurements is repeated, the absolute value of the value of the transmitted light amount difference waveform data at the sampling position P1 t0 , and the sampling position P2 t0 becomes larger. Such a change over time in the absolute value of the transmitted light amount difference (differential) waveform data that conforms to the first criterion is observed in the sampling intervals located at both ends of the section where bubbles are present. Note that in FIG. 11, as a comparative example, the value of the transmitted light amount difference waveform data at the sampling position P0 (see FIG. 10) located in the flat portion of the transmitted light amount scanning waveform is shown. In this case, it shows a value of almost 0 regardless of the number of photometric measurements.

[0041] The second criterion for determining the sampling interval is that the sampling interval determined by the bubble end obtained by the first criterion tends to expand over time. For example, in Figure 10, in the transmitted light difference waveform data 602 obtained by the t0th photometric sampling, the sampling position where the value changes from 0 to a negative value exceeding a predetermined range is P1 t0 P2 is the sampling position where the value changes from a positive value exceeding a predetermined range to 0. t0 Similarly, in the transmitted light intensity difference waveform data 612 obtained from the t1 photometric sampling, the sampling position where the value changes from 0 to a negative value exceeding a predetermined range is P1 t1 P2 is the sampling position where the value changes from a positive value exceeding a predetermined range to 0. t1 And the sampling position P1 in the transmitted light intensity difference waveform data 602 t0 ,P2 t0 and sampling position P1 in transmitted light intensity difference waveform data 612 t1 ,P2 t1 All of these meet the first criterion and are recognized as candidate sampling locations located at both ends of the section where bubbles exist. At this time, the sampling section (P1 t1 ,P2 t1 ) is the sampling interval (P1 t0 ,P2 t0 It is wider than ). As a result, the sampling interval (P1) in the light intensity waveform data obtained from the t0th photometric sampling is wider. t0 ,P2 t0 ), sampling interval (P1 t1 ,P2 t1 ) can be identified as a sampling section affected by air bubbles.

[0042] When the bubble size becomes large enough, the transmitted light scanning waveform becomes smoother near the center of the bubble-containing section, causing the transmitted light difference (derivative) waveform data to be close to zero. Therefore, by using the second criterion, it is possible to identify the sampling section that is affected by the bubble, including the section where the transmitted light scanning waveform is smooth.

[0043] The identification of the bubble's influence range, as described above, is performed in steps S105 to S106. Specifically, a sampling position is searched for where the absolute value of the transmitted light intensity difference (differential) waveform data increases over time (S105). The sampling position extracted in step S105 is a sampling position that satisfies the first criterion, i.e., a sampling position that can be at both ends of the interval where bubbles exist. If no sampling position satisfies the first criterion exists (No in S105), it is determined that the light intensity waveform data is not affected by bubbles (S107). On the other hand, if a sampling position that satisfies the first criterion exists (Yes in S105), it is determined whether the sampling interval with the sampling position determined by the first criterion at both ends tends to expand with each photometric sampling (S106). If the sampling interval with the sampling position determined by the first criterion at both ends does not tend to expand (No in S106), it is determined that the light intensity waveform data is not affected by bubbles (S107). On the other hand, if the sampling interval with sampling positions that satisfy the first criterion at both ends is expanding (Yes in S106), then the sampling interval is identified as a sampling interval affected by bubbles (S108).

[0044] The presence or absence of the effect of bubbles in the light intensity waveform data is transmitted from the data processing unit 124 to the computer 132 via the interface 131. If the computer 132 determines that the light intensity waveform data is unaffected by bubbles, it uses the measured light intensity waveform data as is for sample analysis. On the other hand, if the light intensity waveform data is determined to be affected by bubbles, for example, the light intensity data for the sampling section where the effect of bubbles was determined to be present can be excluded from the measured light intensity waveform data and used for sample analysis. Alternatively, a light intensity correction index value can be calculated from the decrease in light intensity due to bubbles and the increase in the sampling section of the light intensity waveform data performed in steps S105 and S106, and the light intensity under conditions without the effect of bubbles can be estimated and sample analysis can be performed. This reduces the effect of bubbles on the analysis results and improves the accuracy and reliability of the analysis. Since the transmitted light intensity waveform data and scattered light intensity waveform data are acquired synchronously for the transmitted light intensity and scattered light intensity at the same sampling position, the sampling section affected by bubbles, which is determined using the transmitted light intensity difference (derivative) waveform data, can be applied to both the transmitted light intensity waveform data and the scattered light intensity waveform data.

[0045] Furthermore, if most of the light intensity waveform data is determined to be affected by air bubbles, it is difficult to output accurate analysis results. Therefore, for example, if the sampling interval identified in step S108 reaches a predetermined proportion or more of the total interval, photometric sampling for the corresponding reaction vessel 106 may be terminated, and an error indicating the presence of air bubbles may be displayed on the display device 134. This makes it possible to shorten the time until re-analysis can be started.

[0046] In the above embodiment, by determining the interval affected by bubbles based on the temporal changes in the difference or derivative waveform data of the measured transmitted light intensity waveform data, it becomes unnecessary to set reference values, average values, or thresholds for each light intensity data with different characteristics for each reagent. This makes it possible to obtain light intensity data with the effect of bubbles removed and to shorten the time until a re-analysis alert is issued to the operator.

[0047] The present invention is not limited to the embodiments described above, and various modifications are included. For example, the embodiments described above are explained in detail to make the present invention easier to understand, and are not necessarily limited to those having all the configurations described. Furthermore, it is possible to add, delete, or replace some of the configurations in the embodiments with other configurations. [Explanation of Symbols]

[0048] 1: Automated analyzer, 2: Photometer data processing unit, 101: Sample disc, 102: Reagent disc, 103: Reaction disc, 104: Sample container, 105: Reagent bottle, 106: Reaction vessel, 107: Sample dispensing mechanism, 108: Sample dispensing nozzle, 109: Reagent dispensing mechanism, 110: Reagent dispensing nozzle, 111: Stirring mechanism, 121: Light source, 122: Photometer, 123: Waveform acquisition unit, 124: Data processing unit, 131: Inter Face, 132: Computer, 133: Input device, 134: Display device, 201, 301, 302, 401: Reaction solution, 202: Transmitted light meter, 203: Scattered light meter, 303: Reagent, 304, 305, 403, 405, 406, 501, 601, 611: Transmitted light intensity waveform data, 402: Bubbles, 404: Light intensity reduction region, 502, 602, 612: Transmitted light intensity difference waveform data, 503, 504: Sampling position.

Claims

1. Multiple reaction vessels, including a first reaction vessel, are arranged circumferentially, and a reaction disk capable of intermittent rotation is provided. A photodetection system including a light source and a photometer, wherein the reaction vessel located on the reaction disk passes through a photometric point located on a straight line connecting the light source and the photometer, In an automated analyzer equipped with a photometer data processing unit, The reaction disk includes a temperature bath for maintaining the reaction vessel at a predetermined temperature. The photometer includes a transmitted light measuring instrument that measures the amount of transmitted light that has passed through the reaction vessel in the irradiation direction from the light source. The photometer data processing unit comprises a waveform acquisition unit that samples the amount of transmitted light measured by the transmitted light measuring instrument while the reaction vessel passes the photometric point as the reaction disk rotates, and acquires it as transmitted light amount waveform data; and a data processing unit that calculates the difference or derivative of the transmitted light amount waveform data of the first reaction vessel to acquire transmitted light amount difference waveform data or transmitted light amount derivative waveform data, and determines the effect of bubbles in the reaction liquid contained in the first reaction vessel based on the time-dependent change in the transmitted light amount difference waveform data or transmitted light amount derivative waveform data for each photometric sampling as the first reaction vessel passes the photometric point.

2. In claim 1, The data processing unit determines that if the values ​​of the transmitted light difference waveform data or the transmitted light differential waveform data of the t0th photometric sampling of the first reaction vessel are within a predetermined range at all sampling positions, there is no influence of bubbles in the reaction liquid contained in the first reaction vessel. If a sampling position with a value exceeding the predetermined range is extracted, the automated analyzer identifies the sampling section in the reaction liquid contained in the first reaction vessel that is affected by bubbles.

3. In claim 2, The data processing unit determines, at the extracted sampling position, that the absolute value of the transmitted light intensity difference waveform data or the transmitted light intensity differential waveform data of the t1th (t0 < t1) photometric sampling of the first reaction vessel is increasing relative to the absolute value of the transmitted light intensity difference waveform data or the transmitted light intensity differential waveform data of the t0th photometric sampling of the first reaction vessel, and that the extracted sampling position is included in a sampling section affected by bubbles in the reaction liquid contained in the first reaction vessel.

4. In claim 3, The data processing unit determines that the first sampling position extracted for the transmitted light intensity difference waveform data or transmitted light intensity differential waveform data of the t0th photometric sampling of the first reaction vessel, and the second sampling position extracted for the transmitted light intensity difference waveform data or transmitted light intensity differential waveform data of the t1th photometric sampling of the first reaction vessel, are included in a sampling section affected by bubbles, and if the second sampling section, which has the second sampling position at both ends, tends to expand with respect to the first sampling section, which has the first sampling position at both ends, the automatic analyzer identifies the first sampling section and the second sampling section as sampling sections affected by bubbles in the reaction liquid contained in the first reaction vessel.

5. In claim 1, The photometer includes a scattered light measuring instrument that measures the amount of scattered light that passes through the reaction vessel in directions other than the irradiation direction from the light source. The waveform acquisition unit is an automated analyzer that synchronously samples the amount of transmitted light measured by the transmitted light measuring instrument and the amount of scattered light measured by the scattered light measuring instrument, and acquires the amount of light at each sampling position as transmitted light waveform data and scattered light waveform data.

6. In claim 5, The data processing unit is an automated analyzer that, when it determines that there is an effect of bubbles in the reaction liquid contained in the first reaction vessel, identifies the sampling section affected by bubbles in the transmitted light waveform data and the scattered light waveform data.

7. In claim 6, Equipped with a computer, The computer is an automated analyzer that stops processing the first reaction vessel when the sampling section affected by bubbles, as identified by the data processing unit, reaches a predetermined proportion or more of the total section.

8. In claim 6, Equipped with a computer, The computer is an automated analyzer that performs sample analysis by removing data from the transmitted light waveform data or the scattered light waveform data that is affected by bubbles identified by the data processing unit.

9. In claim 6, Equipped with a computer, The computer is an automated analyzer that performs sample analysis by applying light intensity correction to the data of the sampling section affected by bubbles identified by the data processing unit in the transmitted light intensity waveform data or the scattered light intensity waveform data.

10. A method for analyzing specimens using an automated analyzer, The automated analyzer comprises a reaction disk in which a plurality of reaction vessels, including a first reaction vessel, are arranged circumferentially and are capable of intermittent rotation; a photodetection system including a light source and a photometer, arranged such that the reaction vessels arranged on the reaction disk pass through photometric points located on a straight line connecting the light source and the photometer; and a photometer data processing unit. The reaction disk includes a temperature bath for maintaining the reaction vessel at a predetermined temperature. The photometer includes a transmitted light measuring instrument that measures the amount of transmitted light that has passed through the reaction vessel in the irradiation direction from the light source. The photometer data processing unit comprises a waveform acquisition unit and a data processing unit, The waveform acquisition unit samples the amount of transmitted light measured by the transmitted light measuring instrument while the reaction vessel passes the photometric point as the reaction disk rotates, and acquires it as transmitted light amount waveform data. The data processing unit calculates the difference or derivative of the transmitted light intensity waveform data of the first reaction vessel to obtain transmitted light intensity difference waveform data or transmitted light intensity derivative waveform data, and determines the effect of bubbles in the reaction solution contained in the first reaction vessel based on the time-dependent changes in the transmitted light intensity difference waveform data or transmitted light intensity derivative waveform data for each photometric sampling in which the first reaction vessel passes through the photometric point.

11. In claim 10, The photometer includes a scattered light measuring instrument that measures the amount of scattered light that passes through the reaction vessel in directions other than the irradiation direction from the light source. The waveform acquisition unit synchronously samples the amount of transmitted light measured by the transmitted light measuring instrument and the amount of scattered light measured by the scattered light measuring instrument, and acquires the amount of light for each sampling position as transmitted light waveform data and scattered light waveform data in this sample analysis method.

12. In claim 11, A sample analysis method in which the data processing unit determines that there is an effect of bubbles in the reaction solution contained in the first reaction vessel, and identifies the sampling section affected by bubbles in the transmitted light waveform data and the scattered light waveform data.

13. In claim 12, The aforementioned automated analyzer is equipped with a computer, A sample analysis method in which the computer performs sample analysis by removing data from the transmitted light waveform data or the scattered light waveform data that is affected by bubbles identified by the data processing unit.

14. In claim 12, The aforementioned automated analyzer is equipped with a computer, A sample analysis method in which the computer performs light intensity correction on the data of the sampling section affected by bubbles identified by the data processing unit in the transmitted light intensity waveform data or the scattered light intensity waveform data to perform sample analysis.

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