Automatic analysis device and timing setting method

Abstract

In order to provide an automatic analysis device that can improve measurement stability, the present invention is configured as follows. From photometric signals that are obtained by carrying out photometry on a plurality of reaction cells held by a reaction disc in an empty state or in a state of accommodating blank water, photometric waveforms for the respective plurality of reaction cells are acquired on the basis of photometric trigger signals which indicate that the respective plurality of reaction cells have crossed the optical axis of a light source. A photometric value calculation period is determined on the basis of time domains that each exhibit a flat waveform and that have been obtained for the photometric waveforms for the respective plurality of reaction cells.

Description

Automated analyzer and timing setting method

[0001] The present invention relates to an automatic analyzer and a timing setting method thereof.

[0002] Automated analyzers perform quantitative analysis of test substances by mixing test substances in samples such as blood, urine, and body fluids with reagents corresponding to the test substances, irradiating the resulting reaction product with light, and measuring absorbance, turbidity, reflectance, etc. The reaction cells in which the sample and reagent are mixed are placed on a circular reaction disk, and multiple reaction cells are measured in a short period of time by rotating the reaction disk. For this reason, it is necessary to extract the waveform portion containing information about the reaction solution obtained by mixing the sample and reagent from the continuous waveform obtained by measuring multiple reaction cells.

[0003] Patent Documents 1 to 3 are examples of techniques for optimizing photometry timing. Patent Document 1 discloses a technique in which, with water contained in reaction cells, photometry is repeatedly performed by changing the photometry timing in small increments, and the photometry timing with the smallest fluctuation range for all reaction cells is determined as the optimal photometry timing. Patent Document 2 discloses a technique for calculating the optimal photometry region for each reaction vessel. Specifically, it discloses that the point in the waveform that is half the time difference between the timing when light passes through the side of the reaction vessel or the time difference between the timing when light passes through the hollow portion between the reaction vessels is set as the center value of the reaction vessel, and the optimal photometry region for each reaction vessel is determined from the center value. Furthermore, Patent Document 3 discloses a technique for correcting the photometry start timing or photometry end timing to account for uneven rotation of the reaction disk.

[0004] Japanese Patent Laid-Open No. 6-167505 Japanese Patent Laid-Open No. 2009-162719 Japanese Patent Laid-Open No. 2009-162720

[0005] In Patent Document 1, photometry is repeatedly performed on a reaction cell filled with water by changing the photometry timing in small increments of time, which makes it cumbersome to determine the optimal photometry timing, requiring multiple measurements.

[0006] On the other hand, Patent Document 2, for example, performs photometry on an empty reaction vessel, and determines the photometry timing from the waveform. Specifically, an example is given in which the timing when light passes through the side of the reaction vessel is identified as the waveform change point. However, due to variations in the shape of each reaction vessel and variations in the mounting position on the reaction disk, the waveform shape varies from reaction vessel to reaction vessel. As a result, the slope of the waveform transitioning from the change point to the flat portion suitable for photometry of the reaction liquid varies considerably from reaction vessel to reaction vessel. In some cases, the transition from the change point to the flat portion is steep, while in other cases, the transition from the change point to the flat portion is gentle. Therefore, in the method of determining the photometric region from the center value of the reaction vessel disclosed in Patent Document 2, the photometric region must be determined so that it fits within the flat portion even for waveforms with a gentle slope, making it difficult to extend the length of the photometric region.

[0007] An automated analyzer according to one embodiment of the present invention comprises a reaction disk that holds multiple reaction cells on its circumference and rotates, a light source that irradiates light, a spectrometer that detects transmitted light that passes through reaction cells that cross the optical axis of the light source as the reaction disk rotates, and a control unit equipped with a photometric unit that extracts a photometric waveform for a photometric value calculation period used to calculate the light quantity value for the liquid contained in the reaction cells from the photometric waveform obtained by sampling a photometric signal that reflects the light quantity value of the transmitted light output from the spectrometer.The control unit acquires the photometric waveform for each of the multiple reaction cells from the photometric signal obtained by photometry of the multiple reaction cells held on the reaction disk when they are empty or contain blank water, based on a photometric trigger signal that indicates that each of the multiple reaction cells has crossed the optical axis of the light source, and determines the photometric value calculation period based on the time domain showing a flat waveform obtained for the photometric waveform for each of the multiple reaction cells.

[0008] According to the present invention, it is possible to calculate the photometric value of the reaction solution using the photometric value in the time domain showing a flat waveform of the reaction cell obtained before performing a sample test in an automatic analyzer, thereby improving the measurement stability of the device. Other objects and novel features will become apparent from the description of this specification and the accompanying drawings.

[0009] FIG. 1 is a diagram showing the overall configuration of an automatic analyzer; FIG. 2 is a schematic diagram showing an overview of a position detection unit; FIG. 3 is a diagram for explaining a photometric method for a reaction solution in a reaction cell; FIG. 4 is a diagram for explaining a photometric method for a reaction solution in a reaction cell; FIG. 5 is a diagram showing photometric waveforms arranged for each reaction cell, based on the rising edge of a photometric trigger signal T; ｃａｌ _st. ｃａｌ FIG. 10 is a diagram illustrating a first example of calculation of the photometric value calculation period t ｃａｌ 10 is a diagram illustrating an example of extracting a photometric waveform of a correction time t ｃａｌ FIG. 10 is a diagram illustrating a modification of the second example of calculation of the correction time t ｃａｌ 10 is a diagram for explaining a third example of calculation of _st. FIG. 11 is an example of a correction time storage memory in the third example. FIG. 12 is an example of a photometric value calculation period storage memory in the third example. FIG. 13 is a diagram for explaining abnormal waveform determination for foreign matter, bubbles, scratches, etc. FIG. 14 is a diagram for explaining estimation of foreign matter width. FIG. 15 is a diagram for explaining self-diagnosis of light beam width. FIG. 16 is a diagram for explaining detection of poor stirring of reaction liquid and insufficient liquid volume.

[0010] Hereinafter, an embodiment will be described with reference to the drawings.

[0011] The configuration and operation of an automatic analyzer will be described using an automatic analyzer 100 that performs colorimetric analysis using biochemical reactions as an example.

[0012] 1 shows the overall configuration of an automatic analyzer 100. Here, an automatic analyzer that performs colorimetric analysis using biochemical reactions is shown as an example. The automatic analyzer 100 is composed of a conveying line 101, a rotor 102, a reagent disk 103, a reaction disk 104, a dispensing mechanism 105, a stirring mechanism 106, a spectroscopic analyzer 107, a reaction cell cleaning mechanism 108, a nozzle cleaning mechanism 109, a control unit 115, an input unit 123, a display unit 124, and the like. Note that when multiple mechanisms are to be distinguished from one another, they are distinguished by adding subscripts.

[0013] Conveyor line 101 １ The sample dispensing mechanism 105 transports a sample rack 111 holding sample containers 110 containing samples to a sample dispensing position 121. １The sample dispenser 101 dispenses the sample from the sample container 110 to the reaction cell (reaction container) 112 on the reaction disk 104 at the sample dispensing position 121. １ is further connected to the rotor 102. By rotating the rotor 102 with the sample rack 111 placed thereon, the other transport lines 101 ２ The sample rack 111 is transferred between the

[0014] The reagent disk 103 holds reagent containers 113 containing reagents, and a dispensing mechanism (reagent dispensing mechanism) 105 ２ The dispensing mechanism 105 rotates and transfers the reagent container 113 to a position where the dispensing operation can be performed. ２ dispenses a reagent from a reagent container 113 into a reaction cell 112 on the reaction disk 104 at a reagent dispensing position 122. The reagent is dispensed into the reaction cell 112 in an amount required for colorimetric analysis, and reacts with a component in the sample to be analyzed.

[0015] The reaction disk 104 holds reaction cells 112 on its circumference. A spectrophotometer 107 for performing colorimetric analysis, a stirring mechanism 106, a reaction cell cleaning mechanism 108, and the like are arranged around the reaction disk 104, and each of these rotates to transport the reaction cell 112 that is the target of each operation to an operating position where it operates. The reaction cell 112 is kept warm by a constant temperature medium such as water, which promotes chemical reactions between the components in the specimen and the reagent in the reaction solution, which is a mixture of the specimen and the reagent.

[0016] Dispensing mechanism 105 １ The dispensing mechanism 105 aspirates a sample to be subjected to colorimetric analysis from a sample container 110 and dispenses it into a reaction cell 112. ２ The dispensing mechanism 105 (105) aspirates a reagent according to the analysis target from a reagent container 113 and dispenses it into the reaction cell 112. １ ~105 ２) each include an arm 118, a nozzle 116, and a dispensing mechanism motor 119. The arm 118 holds the nozzle 116 and a liquid level sensor 117. The nozzle 116 is connected to the liquid level sensor 117. The liquid level sensor 117 detects the presence or absence of liquid by a change in capacitance. A shield part 114 is installed near the position where the dispensing mechanism 105 performs the dispensing operation. The dispensing mechanism motor 119 moves the dispensing mechanism 105 up and down or in a rotational direction.

[0017] The stirring mechanism 106 stirs the reaction liquid in the reaction cell 112 to promote the reaction between the components to be analyzed in the sample ejected from the sample container 110 into the reaction cell 112 and the reagent ejected from the reagent container 113 into the reaction cell 112.

[0018] The light source 120 irradiates output light onto the reaction solution that has undergone a chemical reaction while being stirred by the stirring mechanism 106. For example, an LED (Light Emitting Diode) is used as the light source 120. The spectroscopic analyzer 107 separates the transmitted light that has passed through the reaction solution in the reaction cell 112 and measures the light intensity of the separated transmitted light. Colorimetric analysis is performed by measuring absorbance based on the light intensity of the separated transmitted light.

[0019] The reaction cell washing mechanism 108 sucks the reaction liquid from the reaction cell 112 after the colorimetric analysis has been completed, and discharges a detergent or the like to wash the reaction cell 112 .

[0020] Nozzle cleaning mechanism 109 (109 １ ~109 ２ ) are the dispensing mechanisms 105 (105) that dispensed the specimen or reagent, respectively. １ ~105 ２ ) to clean the tip of the nozzle 116. This removes any residue adhering to the nozzle 116, preventing it from affecting the next analysis target.

[0021] The control unit 115 is composed of a processor, memory, etc., and controls each mechanism. The input unit 123 is composed of a keyboard, mouse, touch panel, etc., and inputs instructions from the user to the control unit 115. The display unit 124 is composed of an LCD (Liquid Crystal Display), etc., and displays an operation screen, etc.

[0022] 2 is a schematic diagram showing an outline of a position detection unit provided on the reaction disk 104. The position detection unit 200 is an example including a detection plate 201 and a detection plate detector 202. As shown in FIG. 2, the reaction disk 104 is provided with the same number of detection plates 201 as the reaction cells 112 in a one-to-one relationship. In addition, the detection plates 201 that are crossed by the optical axis 205 of the light source 120 are １ The detection plate detector 202 is provided at a position where it can detect the passage of the detection plate 201. For example, the detection plate detector 202 includes a light-emitting unit 203 and a light-detecting unit 204, and detects the passage of the detection plate 201 when the detection plate 201 passes between the light-emitting unit 203 and the light-detecting unit 204 and the light from the light-emitting unit 203 is blocked. The position detecting unit 200 outputs a detection signal when the detection plate detector 202 detects the passage of the detection plate 201 as a photometry trigger signal indicating that the reaction cell 112 passes between the light source 120 and the spectroscopic analyzer 107.

[0023] 3A and 3B, a photometric method for a reaction solution in a reaction cell 112 in the automated analyzer 100 will be described. Light is irradiated from a light source 120 onto the reaction cell 112 containing the reaction solution, and the transmitted light that passes through the reaction cell 112 is incident on a spectroscopic analyzer 107. The spectroscopic analyzer 107 includes a spectroscope 301 and a photodetector 302. The transmitted light is separated into multiple wavelengths by the spectroscope 301, and the photodetector 302 detects the light intensity value of the transmitted light for each separated wavelength. Specifically, the photodetector 302 outputs a photometric signal S having a current value proportional to the light intensity value of the transmitted light, and the photometric signal S is input to a photometric unit 304 of the control unit 115.

[0024] The photometric unit 304 includes a current-voltage converter 305, an A / D converter 306, and a data processor 307. The current-voltage converter 305 converts the photometric signal S into a voltage value, the A / D converter 306 samples the photometric voltage value signal, which is an analog signal, at a predetermined sampling period and converts it into a digital signal, and the data processor 307 generates a photometric waveform indicating a change in the amount of transmitted light that has passed through the reaction cell 112 for the photometric voltage signal converted into a digital signal. In addition, a photometric trigger signal T is input to the data processor 307 from the position detector 200.

[0025] 3B shows a schematic diagram of the photometric signal S and photometric trigger signal T input to the photometric unit 304. It is assumed that photometric measurement is performed when the reaction cell 112 is empty or filled with blank water. Since photometric measurement is performed while the reaction disk 104 is rotating, the photometric waveform is a continuous waveform similar to the photometric signal S in FIG. 3B. The photometric waveform corresponding to one reaction cell 112 significantly attenuates the light intensity value when the optical axis 205 of the light source 120 passes through the side wall of the reaction cell 112. Therefore, the photometric waveform during the period sandwiched between the attenuated portions contains information on the transmitted light of the reaction solution contained in the reaction cell 112. For this reason, the data processing unit 307 calculates the photometric value during a predetermined photometric value calculation period t ｃａｌ The photometric waveform of the photometric value calculation period t ｃａｌ is a period used to calculate the light intensity value for the reaction solution contained in the reaction cell 112. The data processing unit 307 calculates the light intensity value of the light transmitted through the reaction solution based on the extracted photometric waveform. The calculated light intensity value is sent to the processor 303 of the control unit 115, and the reaction solution is analyzed.

[0026] 3A, a photometric signal S of the transmitted light for each separated wavelength is input from the photodetector 302 to the photometric unit 304. The photometric waveforms for each separated wavelength are processed in parallel by the current-voltage converter 305, the A / D converter 306, and the data processor 307.

[0027] FIG. 4 shows the photometric waveforms corresponding to the photometric signal S shown in FIG. 3B arranged for each reaction cell, based on the rising edge of the photometric trigger signal T. In the photometric waveform for each reaction cell, the time period during which the waveform is flat and the difference between the values ​​at adjacent sampling positions is less than a certain value is defined as the photometric period t, and the time from the rising edge of the photometric trigger signal T to the start of the photometric period t is defined as the photometric start time t_st. It is desirable to calculate the photometric period t after removing variations due to noise, etc. Thus, the photometric start time ta_st and the photometric period ta for waveform A (photometric waveform for reaction cell A), the photometric start time tb_st and the photometric period tb for waveform B (photometric waveform for reaction cell B), and the photometric start time tc_st and the photometric period tc for waveform C (photometric waveform for reaction cell C) all vary. The causes of these variations are variations in the container shape, variations in the mounting position on the reaction disk, and scattered light from adjacent containers. In this embodiment, the photometric period t and the photometric start time t_st are calculated for each photometric waveform of each reaction cell, which has such large variations, and the timing to start extracting the photometric waveform used to calculate the light quantity value for the reaction solution from the rising edge of the photometric trigger signal T, i.e., the photometric value calculation period t ｃａｌ In the following, the start timing of the photometric value calculation period t ｃａｌ The time until the start of the correction time t ｃａｌ It's called _st.

[0028] The correction time t ｃａｌ The calculation flow of the photometric value calculation period t ｃａｌ is assumed to be a period that is predetermined as a common period for the reaction cells 112 on the reaction disk 104. This flow is executed by the control unit 115.

[0029] First, photometry is performed on the reaction cell 112 on the reaction disk 104 (S01). The reaction cell 112 may be empty or may contain blank water. This flow is performed when the reaction cell is replaced, but is not limited to this and may be performed at any timing.

[0030] Next, the photometry start time t_st and the photometry enable period t as shown in FIG. 4 are calculated from the photometry waveform for each reaction cell (S02). Based on the photometry start time t_st and the photometry enable period t of the reaction cell 112 on the reaction disk 104 calculated in step S02, a correction time t ｃａｌ The calculated correction time t ｃａｌ _st is stored in the control unit 115 and is used for the photometric value calculation period t ｃａｌ The correction time t ｃａｌ An example of calculating _st will be described.

[0031] (correction time t ｃａｌ First Example of Calculation of Correction Time t ｃａｌ 6 shows an example of calculating the correction time t ｃａｌ _st and photometric value calculation period t ｃａｌ That is, the correction time t ｃａｌ _st is the photometric value calculation period t ｃａｌ is set so that it is included in the photometric period t of the photometric waveform corresponding to the reaction cell on the reaction disk 104. For example, if the maximum value of the photometric start time t_st of the reaction cell on the reaction disk 104 is the latest photometric start time t_st_max, the correction time t ｃａｌ The time is set so as to satisfy the relationship: t_st>latest photometry start time t_st_max.

[0032] In the first example, a common correction time t ｃａｌ By setting the value _st, the photometric value calculation period t ｃａｌ This simplifies the extraction process of the photometric waveform. ｃａｌ However, the possible photometric value calculation period t ｃａｌHowever, it is unavoidable that the correction time t ｃａｌ An example of setting _st will be described.

[0033] (correction time t ｃａｌ In the second example, the correction time t ｃａｌ That is, for each reaction cell, the correction time t ｃａｌ _st>photometry start possible time t_st. This allows the photometry value calculation period t to be calculated from the photometry waveform corresponding to the reaction cell without being restricted by the variations in the reaction cell 112 on the reaction disk 104. ｃａｌ The photometric value calculation period t ｃａｌ Being able to obtain a longer time period means that, for example, even if there is an area affected by air bubbles when measuring a sample, it is more likely that a sufficient photometric waveform can be obtained even if the area affected by the air bubbles is removed, which has the effect of reducing the number of cases where remeasurement is necessary.

[0034] 7, the data processing unit 307 calculates the photometric value for each reaction cell during the photometric value calculation period t ｃａｌ An example of extracting a photometric waveform will be described below. The data processing unit 307 includes a photometric waveform extraction unit 401 and a photometric waveform extraction control unit 402 as functional units for extracting photometric waveforms. The photometric waveform extraction control unit 402 also includes a counter 403 and a correction time storage memory 404. The data processing unit 307 can be configured with a processor that executes a program, and in this case, by executing a predetermined program, the processor operates as a functional unit that executes a predetermined function.

[0035] Here, M reaction cells 112 are mounted on the reaction disk 104, and a number (cell number) that uniquely identifies the mounting position is set at each mounting position of the reaction cells 112. The counter 403 receives from the processor 303 the number of reaction cells (total number of cells) M mounted on the reaction disk 104, the cell number (initial value cell number) of the reaction cell 112 that first crosses the optical axis 205 of the light source 120 when the reaction disk 104 starts rotating, and the photometry trigger signal T. The counter 403 outputs a value obtained by adding 1 to the initial value cell number every time the photometry trigger signal T is input. When the cell number reaches the total number of cells M, the cell number is reset to 1 at the timing when the next photometry trigger signal T is input. The correction time storage memory 404 stores the correction time t for each reaction cell 112 identified by the cell number. ｃａｌ _st is stored.

[0036] When the photometric waveform i corresponding to the reaction cell of cell number i is input to the photometric waveform extraction unit 401, the photometric waveform extraction control unit 402 outputs the correction time t ｃａｌ _st and photometric value calculation period t ｃａｌ is input to the photometric waveform extraction unit 401. The photometric waveform extraction unit 401 uses this information to calculate the photometric value of the reaction cell with cell number i during the photometric value calculation period t ｃａｌ Extract the photometric waveform of

[0037] (correction time t ｃａｌ Modification of the second example of calculation of the correction time t ｃａｌ When setting the correction time t_st, the correction time t_st is set according to the waveform of the photometric waveform of the reaction cell 112 during the photometric period t. ｃａｌ _st, photometric value calculation period t ｃａｌ can be set.

[0038] In the case of waveform X shown in Figure 8, the slope of the waveform during the photometry period t is nearly zero in the latter half, but there is a gentle slope in the first half. Similarly, in the case of waveform Y, the slope of the waveform during the photometry period t is nearly zero in the first half, but there is a gentle slope in the second half. In such cases, it is desirable to set the correction time so that a waveform with a slope of nearly zero can be extracted from the waveform during the photometry period t.

[0039] In this case, for waveform X, the correction time is set so that the photometric value calculation period is set in the latter half of the waveform during the photometric period t, and for waveform Y, the correction time is set so that the photometric value calculation period is set in the first half of the waveform during the photometric period t.

[0040] (correction time t ｃａｌ In the third example, the correction time t ｃａｌ _st, photometric value calculation period t ｃａｌ Here, as in the second example, the correction time t ｃａｌ _st, photometric value calculation period t ｃａｌ An example of setting the above will be explained.

[0041] The reaction disk 104 rotates at a constant speed, but when it starts rotating and when it stops rotating, it moves faster and slower than the constant speed, respectively. Therefore, the photometric waveform of the reaction cell 112 that crosses the optical axis 205 immediately after the reaction disk 104 starts rotating, or the photometric waveform of the reaction cell 112 that crosses the optical axis 205 immediately before the reaction disk 104 stops rotating, is different from the photometric waveform of the reaction cell 112 that crosses the optical axis 205 when the reaction disk 104 is rotating at a constant speed. This is shown in Figure 9. Compared to the waveforms in a stable state, the photometry start time t_st and the photometry possible period t are shorter at high speeds and longer at low speeds.

[0042] Therefore, in the third example, the photometry start possible time t_st and the photometry possible period t are adjusted according to the rotation speed of the reaction disk 104. For this reason, the photometric waveform extraction control unit 402 has a correction time storage memory 411 shown in FIG. 10A and a photometric value calculation period storage memory 412 shown in FIG. 10B. As a result, if the photometric waveform to be extracted is a photometric waveform when the reaction disk 104 is operating at high speed immediately after starting rotation, the correction time at high speed (correction time t ｃａｌ _st_F) and the photometric value calculation period at high speed (photometric value calculation period t ｃａｌ _F), and if the photometric waveform is obtained when the reaction disk 104 is operating at a low speed just before the rotation stops, the correction time at the low speed (correction time t ｃａｌ _st_S) and the photometric value calculation period at low speed (photometric value calculation period t ｃａｌ The rotation speed of the reaction disk 104, whether stable, low speed, or high speed, can be determined by the cell number.

[0043] Here, the correction time t ｃａｌ _st, photometric value calculation period t ｃａｌ , but the correction time t ｃａｌ Even when setting the correction time t ｃａｌ _st, photometric value calculation period t ｃａｌ It is possible to set:

[0044] The present invention is not limited to the above-described embodiments and includes various modifications. For example, the above-described embodiments and modifications have been described in detail to make the present invention easier to understand, and are not necessarily limited to those including all of the described configurations. Furthermore, it is possible to replace part of the configuration of one embodiment or modification with the configuration of another embodiment or modification, and it is also possible to add the configuration of another embodiment or modification to the configuration of one embodiment or modification. Furthermore, it is possible to add, delete, or replace part of the configuration of each embodiment or modification with other configurations.

[0045] The first embodiment is characterized by determining the time when photometry can be started, the period during which photometry can be performed, etc. based on the photometry waveform. In the second embodiment, an example will be described in which the photometry waveform is applied to purposes other than determining the time when photometry can be started, the period during which photometry can be performed, etc.

[0046] Figure 11 (a) shows the photometric waveform when a uniform liquid is contained in the reaction vessel. It can be seen that a photometric output is obtained that is symmetrical about the central axis of the reaction vessel. In contrast, (b) shows the photometric waveform when a foreign object such as a bubble or scratch is present in the reaction vessel. It can be seen that the photometric intensity decreases around the foreign object because the light from the light source is scattered by the foreign object. By utilizing this phenomenon, it is possible to detect the presence of a foreign object in the reaction vessel.

[0047] Furthermore, although not shown in the drawings, since scratches and bubbles scatter light differently, a reaction vessel (reaction cell) that is determined to have a scratch can be skipped (cell skipped) so as not to be used in subsequent analyses, thereby improving the reliability of the measurement results. Alternatively, it is possible to notify the equipment operator that a reaction vessel needs to be replaced, urging them to replace the reaction vessel, thereby enabling more reliable analysis.

[0048] Furthermore, if it is determined that there are many bubbles in the liquid (reaction liquid) in the reaction vessel, it is possible that the analyzed sample is highly viscous and prone to generating bubbles, or that there is some problem with the reagent, such as reagent deterioration, and that normal analysis results may not be obtained.It is also effective to add an alarm to the analysis results or to add a comment urging the instrument operator to perform a reanalysis.In order to make the above determination, it is preferable to create and store reference data for identifying reaction vessels that have scratches or bubbles based on photometric waveforms measured in advance using reaction vessels that have been artificially scratched or in which bubbles have been generated, and to determine whether the reaction vessels have scratches or bubbles by comparing the reference data with the actual photometric waveform.

[0049] In making this judgment, a threshold value may be set for the photometric waveform, and if the photometric waveform drops below the threshold value, it may be determined that there is a scratch or bubble. Alternatively, to improve the accuracy of the judgment, a Mahalanobis distance may be used, i.e., the Mahalanobis distance may be calculated based on a normal photometric waveform to determine a threshold value for normal space, and if the photometric waveform exceeds that threshold value, it may be determined to be abnormal, or other well-known statistical methods may be used to make the judgment.

[0050] Figure 12 shows an example of estimating the size of a foreign object based on the diameter of the light beam from a light source. In Figure 12, the time when the foreign object and the light beam begin to overlap is t1, the time when the foreign object and the light beam completely overlap is t2, and the time when the foreign object and the light beam no longer overlap is t3. The abnormal section where the photometric waveform indicates an abnormality = foreign object width + (light beam width x 2), so the width (size) of the foreign object can be determined based on this formula.

[0051] This allows, for example, if the measured foreign matter is a scratch and its size is greater than a predetermined value, to notify the device operator that the reaction vessel needs to be replaced, thereby preventing the reaction vessel from being used for sample measurement and an analysis that cannot be used for reporting results.Furthermore, if the size of the bubble is greater than a predetermined value, to notify the device operator to stop the analysis using that sample or reagent, thereby preventing the waste of sample and reagent.

[0052] Figure 13 shows an example in which the diameter of the light beam can be determined by attaching a foreign object (an object capable of blocking the light beam) of a known size to the reaction vessel, as opposed to Figure 12. The light path of the light from the light source is bent by a reflecting mirror, and a slit or the like is provided so that the light beam has a predetermined width and passes through the reaction vessel.

[0053] If an abnormality occurs in this optical system for some reason, the width of the light beam may change. However, because the automated analyzer simply measures the change in absorbance and automatically analyzes the reaction based on that change, it is unable to detect such an abnormality even if the width of the light beam changes. In other words, there is a risk that the analyzer may report incorrect analysis results. However, by periodically observing (inspecting) the diameter of the light beam, it is possible to detect abnormalities in the optical system.

[0054] In recent years, automated analyzers have emerged that use light-emitting diodes (LEDs) as light sources instead of conventional halogen lamps. Because LEDs generate white light, they sometimes use an optical system that combines white light generated by irradiating a phosphor with light from a blue-emitting LED and ultraviolet-emitting LEDs to create a combined irradiated light. When using a light source with such a complex optical system, there is a non-zero chance that the orientation of the LED may change for some reason, causing a change in the direction of the irradiated light. Even in such cases, abnormalities in the light source can be detected by periodically monitoring the diameter of the light beam.

[0055] The system may be configured to notify an abnormality when the width of the light beam exceeds a predetermined threshold, or it may be possible to record the change in the measured width of the light beam over time and, based on that change over time, predict how much time will pass before the predetermined threshold is exceeded if the automatic analyzer is continued to be used, and notify the user of this fact.

[0056] 13 shows an example in which a light-blocking foreign object of a known width is provided on the inner surface of the reaction vessel, but the thickness of the reaction vessel wall can also be considered as the light-blocking foreign object of a known width. Since the thickness of the reaction vessel wall varies slightly from vessel to vessel, one or more reaction vessels are set as reaction vessels for confirming the diameter of the light beam, and the change in the diameter of the light beam over time is measured based on the shape of the transmitted light waveform due to the thickness of the vessel wall.

[0057] The method of regarding the container wall as a foreign body has a long length (vertical length in Figure 13), so the amount of attenuation of transmitted light is large and the detection sensitivity may be lower than the method of providing a foreign body of a known width, but it has the advantage of not requiring the preparation of a separate reaction vessel with a foreign body provided therein.

[0058] Another method is to consider the gaps between reaction vessels as foreign matter. Some automated analyzers are constructed by molding multiple reaction vessels into a single block. In the case of such block-shaped reaction vessels, the distance between adjacent reaction vessels is constant, so the gaps can be considered as foreign matter. Compared to when the vessel wall is considered as foreign matter, this method allows for a larger amount of light, which may enable more accurate measurement of the beam diameter.

[0059] Figure 14 shows an example of detecting the state of the liquid in a reaction vessel based on a photometric waveform. In the reaction vessel, the sample and reagent are mixed and stirred to cause a sufficient reaction, and then the measurement results are calculated based on the change in absorbance measured by a photometer. However, there is a possibility that some kind of malfunction may occur in the stirring mechanism, resulting in measurement without sufficient stirring.

[0060] Although the agitator has various anomaly detection functions to detect its own anomalies, there are cases where anomalies below the anomaly detection sensitivity cannot be detected. Even in such cases, this embodiment can detect an agitation anomaly based on the output of the photometer.

[0061] Figure 14(a) shows the photometric waveform when a normal reaction solution is used. The photometric waveform is symmetrical about the central axis of the reaction vessel. In contrast, if the concentration of the reaction solution is low on the left side of the reaction vessel (i.e., bright because it transmits light easily) and high on the right side (i.e., dark because it transmits light less easily) due to insufficient stirring or other reasons, the photometric waveform will be asymmetric, with the light intensity high on the left side and low on the right side. In this way, it is possible to determine the degree of mixing of the reaction solution in the reaction vessel based on the symmetry of the photometric waveform.

[0062] There are various methods for determining whether mixing is poor when the difference between the left and right peak values ​​of the photometric waveform exceeds a predetermined threshold, or whether the determination is based on the slope of the photometric waveform (in Figure 14(b) , the detected altitude of the photometer monotonically decreases from left to right).

[0063] Furthermore, the optical axis of the light beam from the light source is set to pass as low as possible in the reaction vessel so that measurement is possible even when the reaction liquid in the reaction vessel is small. However, if the reaction liquid in the reaction vessel is so small that it is close to the position of the optical axis, accurate measurement results may not be obtained. Figure 14 (c) shows the photometric waveform when the liquid level of the reaction liquid is close to the optical axis. It can be seen that the photometric waveform is not flat, but rather has an upward convex shape. Even if the photometric waveform is symmetrical, if the waveform has a slope on the left and right, an alarm may be added to the analysis result, indicating that the liquid volume is small and the measurement result may not be accurate.

[0064] Furthermore, since the automated analyzer knows the reaction liquid volume for each analysis item, if the photometric waveform actually measured indicates that the reaction liquid volume is low compared to the set reaction liquid volume, it is possible that some kind of abnormality has occurred in the sample or reagent dispensing probe. In other words, by determining whether the actual liquid volume is insufficient compared to the liquid volume stored in the automated analyzer based on the photometric waveform, it is possible to detect an abnormality in the dispensing probe.

[0065] 100...automatic analyzer, 101...transport line, 102...rotor, 103...reagent disk, 104...reaction disk, 105...dispensing mechanism, 106...stirring mechanism, 107...spectroscopic analyzer, 108...reaction cell cleaning mechanism, 109...nozzle cleaning mechanism, 110...sample container, 111...sample rack, 112...reaction cell, 113...reagent container, 114...shield part, 115...control part, 116...nozzle, 117...liquid level sensor, 118...arm, 119...dispensing mechanism motor, 120...light source, 121...sample dispensing position, 12 2...reagent dispensing position, 123...input section, 124...display section, 200...position detection section, 201...detection plate, 202...detection plate detector, 203...light emitting section, 204...light detection section, 205...optical axis, 301...spectroscope, 302...photodetector, 303...processor, 304...photometric unit, 305...current-voltage conversion section, 306...A / D conversion section, 307...data processing section, 401...photometric waveform extraction section, 402...photometric waveform extraction control section, 403...counter, 404, 411...correction time storage memory, 412...photometric value calculation period storage memory.

Claims

1. a reaction disk that holds a plurality of reaction cells on its circumference and rotates; a light source that irradiates light; a spectroscopic analyzer that detects transmitted light that has passed through a reaction cell that crosses the optical axis of the light source as the reaction disk rotates; a control unit including a photometric unit that extracts a photometric waveform during a photometric value calculation period used to calculate a light quantity value for a liquid contained in a reaction cell from a photometric waveform obtained by sampling a photometric signal that reflects the light quantity value of the transmitted light output from the spectroscopic analyzer, The control unit acquires a photometric waveform for each of the plurality of reaction cells from a photometric signal obtained by measuring the plurality of reaction cells held on the reaction disk in an empty state or in a state where blank water is contained therein, based on a photometric trigger signal indicating that each of the plurality of reaction cells has crossed the optical axis of the light source, and determines an individual photometric value calculation period for each of the plurality of reaction cells based on a time region showing a flat waveform obtained for the photometric waveform for each of the plurality of reaction cells.

2. In claim 1, The control unit calculates, for the photometric waveform of each of the plurality of reaction cells, a photometric period, which is a time period when the waveform is flat, and a photometric start time from the rising edge of the photometric trigger signal to the start of the photometric period, and sets a correction time for starting the photometric value calculation period from the rising edge of the photometric trigger signal based on the photometric period and the photometric start time calculated for the photometric waveform of each of the plurality of reaction cells.

3. In claim 1, a position detection unit that outputs the photometry trigger signal; the position detection unit includes a plurality of detection plates provided corresponding to the plurality of reaction cells held on the reaction disk, respectively, and a detection plate detector that detects passage of the detection plates; The detection plate detector is installed in an automatic analyzer at a position where the detection plate passes when the reaction cell corresponding to the detection plate crosses the optical axis of the light source.

4. (delete)

5. (delete)

6. In claim 1, The control unit determines the photometric value calculation period in accordance with the slope of the photometric waveform in the time domain.

7. a reaction disk that holds a plurality of reaction cells on its circumference and rotates; a light source that irradiates light; a spectroscopic analyzer that detects transmitted light that has passed through a reaction cell that crosses the optical axis of the light source as the reaction disk rotates; a control unit including a photometric unit that extracts a photometric waveform during a photometric value calculation period used to calculate a light quantity value for a liquid contained in a reaction cell from a photometric waveform obtained by sampling a photometric signal that reflects the light quantity value of the transmitted light output from the spectroscopic analyzer, The control unit acquires a photometric waveform for each of the reaction cells held on the reaction disk from a photometric signal obtained by measuring the reaction cells in an empty state or when blank water is contained therein, based on a photometric trigger signal indicating that each of the reaction cells has crossed the optical axis of the light source, and determines the photometric value calculation period common to the reaction cells in accordance with the rotation speed of the reaction disk based on a time region showing a flat waveform obtained for the photometric waveform for each of the reaction cells.

8. In claim 1, The control unit detects the occurrence of an abnormality based on a local change in the photometric signal of the waveform obtained for each of the plurality of reaction cells in a time region showing a flat waveform.

9. In claim 8, When the control unit detects the occurrence of an abnormality, the automatic analyzer notifies the occurrence of the abnormality.

10. In claim 8, The control unit is an automatic analyzer that detects the size of the location where an abnormality has occurred based on a local change in the waveform of the photometric signal.

11. In claim 8, The control unit stores the flat waveforms obtained from the photometric waveforms of each of the plurality of reaction cells in chronological order as measurement results at least at two different points in time, and identifies the location of an abnormality in the reaction cell by comparing the flat waveforms of the photometric waveforms at the different points in time.

12. In claim 8, The control unit stores the flat waveforms obtained from the photometric waveforms for each of the plurality of reaction cells in chronological order as measurement results at least at two different points in time, compares the flat waveforms of the photometric waveforms at the different points in time to identify the degree of abnormality in the reaction cell, and determines when to replace the reaction cell based on the identification results.

13. In claim 1, The control unit is an automatic analyzer that detects the beam diameter of the transmitted light passing through the reaction cell based on a photometric waveform for a portion of the reaction cell having a known size.

14. In claim 13, The control unit stores the detected light beam diameter in chronological order as measurement results at least at two different points in time, and detects abnormalities in the optical system of the transmitted light by comparing the light beam diameters at the different points in time.

15. In claim 14, When the control unit detects an abnormality in the optical system of the transmitted light, the automatic analyzer notifies the user of the abnormality.

16. In claim 13, The control unit stores the detected light beam diameter in chronological order as measurement results at least at two different points in time, and predicts the time for maintenance based on changes in the light beam diameter at the different points in time.

17. In claim 1, The control unit of the automatic analyzer detects that poor stirring of the reaction solution in the reaction cell has occurred when the photometric signal of the waveform obtained for each of the multiple reaction cells generally monotonically decreases or increases in a time region showing a flat waveform.

18. In claim 1, The control unit detects that measurement is being performed with insufficient reaction solution in the reaction cell when the photometric signal of the waveform obtained for each of the plurality of reaction cells changes in a generally upward convex shape within a time domain showing a flat waveform.

19. A timing setting method for an automatic analyzer having a reaction disk that holds a plurality of reaction cells on its circumference and rotates, a light source that irradiates light, a spectroscopic analyzer that detects transmitted light that has passed through reaction cells that cross an optical axis of the light source as the reaction disk rotates, and a control unit having a photometric unit that extracts a photometric waveform during a photometric value calculation period used to calculate a light quantity value for a liquid contained in a reaction cell from a photometric waveform obtained by sampling a photometric signal that reflects the light quantity value of the transmitted light output from the spectroscopic analyzer, The control unit a photometric waveform for each of the reaction cells is acquired from a photometric signal obtained by measuring the reaction cells in an empty state or in a state where blank water is contained therein, based on a photometric trigger signal indicating that each of the reaction cells has crossed the optical axis of the light source; A timing setting method for determining an individual photometric value calculation period for each of the plurality of reaction cells based on a time region showing a flat waveform obtained from the photometric waveform for each of the plurality of reaction cells.

20. In claim 19, The control unit For the photometric waveform of each of the plurality of reaction cells, a photometric period, which is a time period in which the waveform is flat, and a photometric start time from the rising edge of the photometric trigger signal to the start of the photometric period are obtained; A timing setting method for setting a correction time for starting the photometric value calculation period from the rising edge of the photometric trigger signal based on the photometric period and the photometric start time obtained for the photometric waveform for each of the plurality of reaction cells.

21. (delete)

22. (delete)

23. In claim 19, The control unit determines the photometric value calculation period in accordance with a slope of a photometric waveform in the time domain.

24. A timing setting method for an automatic analyzer having a reaction disk that holds a plurality of reaction cells on its circumference and rotates, a light source that irradiates light, a spectroscopic analyzer that detects transmitted light that has passed through reaction cells that cross an optical axis of the light source as the reaction disk rotates, and a control unit having a photometric unit that extracts a photometric waveform during a photometric value calculation period used to calculate a light quantity value for a liquid contained in a reaction cell from a photometric waveform obtained by sampling a photometric signal that reflects a light quantity value of the transmitted light output from the spectroscopic analyzer, The control unit a photometric waveform for each of the reaction cells is acquired from a photometric signal obtained by measuring the reaction cells in an empty state or in a state where blank water is contained therein, based on a photometric trigger signal indicating that each of the reaction cells has crossed the optical axis of the light source; Based on a time region showing a flat waveform obtained for the photometric waveform for each of the plurality of reaction cells, A timing setting method for determining the photometric value calculation period common to the plurality of reaction cells in accordance with the rotation speed of the reaction disk.

25. a reaction disk that holds a plurality of reaction cells on its circumference and rotates; a light source that irradiates light; a spectroscopic analyzer that detects transmitted light that has passed through a reaction cell that crosses the optical axis of the light source as the reaction disk rotates; a control unit including a photometric unit that extracts a photometric waveform during a photometric value calculation period used to calculate a light quantity value for a liquid contained in a reaction cell from a photometric waveform obtained by sampling a photometric signal that reflects the light quantity value of the transmitted light output from the spectroscopic analyzer, The control unit From the photometric signals obtained by photometry of the plurality of reaction cells held on the reaction disk in an empty state or in a state where blank water is contained therein, a photometric period, which is a time period in which the waveform is flat, and a photometric start time from the rising edge of the photometric trigger signal to the start of the photometric period are calculated for the photometric waveforms obtained for each of the plurality of reaction cells based on a photometric trigger signal indicating that each of the plurality of reaction cells has crossed the optical axis of the light source; setting a correction time, which is a photometry start time common to the plurality of reaction cells, to a value greater than the maximum value of the photometry start time obtained for each of the plurality of reaction cells; An automatic analyzer that determines the photometric value calculation period based on the set correction time.

26. 26. In claim 25, an automatic analyzer that determines the photometric value calculation period common to the plurality of reaction cells based on the correction time;

27. In claim 1, The control unit determines an individual photometric value calculation period for each of the plurality of reaction cells in accordance with the rotation speed of the reaction disk.

28. In claim 19, A timing setting method in which the control unit determines the photometric value calculation period individually for each of the plurality of reaction cells according to the rotation speed of the reaction disk.