Automatic analyzer and timing setting method

Abstract

In order to provide an automatic analysis device capable of improving measurement stability, the following configuration is adopted. A photometry waveform for each of a plurality of reaction cells is acquired from a photometry signal obtained by photometry of the plurality of reaction cells held in a reaction disc in an empty state or in a state in which blank water is accommodated, on the basis of a photometry trigger signal indicating that each of the plurality of reaction cells traverses the optical axis of a light source. A photometric value calculation period is determined on the basis of a time region representing a flat waveform obtained for the photometric waveform for each of the plurality of reaction cells.

Description

Technical Field

[0001] The present invention relates to an automatic analyzing device and a timing setting method thereof. Background Art

[0002] Automated analyzers mix a test substance in a sample such as blood, urine, or body fluid with a reagent corresponding to the test substance, illuminate the resulting reaction product with light, and measure absorbance, turbidity, reflectance, and other parameters to perform quantitative analysis of the test substance. The reaction unit that mixes the sample and reagent is placed on a disc-shaped reaction disk. By rotating the disk, multiple reaction units can be measured in a short period of time. Therefore, it is necessary to extract the waveform portion containing information about the reaction solution resulting from the sample and reagent mixing from the continuous waveform obtained from measuring multiple reaction units.

[0003] Patent Documents 1 to 3 are cited as technologies for optimizing photometric timing. Patent Document 1 discloses a technology for repeatedly performing photometric measurements while the reaction cells are filled with water, varying the photometric timing by a small amount each time. The photometric timing with the smallest fluctuation in the photometric values ​​across all reaction cells is determined as the optimal photometric timing. Patent Document 2 discloses a technology for calculating the optimal photometric region for each reaction vessel. Specifically, the following is disclosed: the point in the waveform that is half the time difference of the timing when light passes through the side of the reaction vessel, or the time difference of the timing when light passes through the portion that becomes a cavity between the reaction vessels, is set as the center value of the reaction vessel, and the optimal photometric region for each reaction vessel is determined based on the center value. Furthermore, Patent Document 3 discloses a technology for correcting the photometric start timing or photometric end timing for uneven rotation of the reaction disk.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Laid-Open No. 6-167505

[0007] Patent Document 2: Japanese Patent Application Laid-Open No. 2009-162719

[0008] Patent Document 3: Japanese Patent Application Laid-Open No. 2009-162720 Summary of the Invention

[0009] Problems to be solved by the invention

[0010] In Patent Document 1, photometry is repeatedly performed on a reaction cell filled with water while changing the photometry timing by a small amount. Therefore, multiple measurements are required to determine the optimal photometry timing, which is complicated.

[0011] On the other hand, Patent Document 2, for example, performs photometry with an empty reaction vessel, and determines the photometry timing based on its waveform. Specifically, the method describes determining the waveform's changing point as the timing when light passes through the side of the reaction vessel. However, the waveform shape varies from reaction vessel to reaction vessel due to variations in shape and mounting position on the reaction disk. Consequently, the slope of the waveform transitioning from the changing point to the flat portion suitable for photometry of the reaction solution varies considerably from reaction vessel to reaction vessel. The transition from the changing point to the flat portion can occur with a steep slope, while others can occur with a gentle slope. Therefore, in the method disclosed in Patent Document 2, which determines the measurable photometric area based on the center value of the reaction vessel, even for waveforms with a gentle slope, the measurable photometric area must be determined so that the photometric area converges to the flat portion, making it difficult to extend the length of the measurable photometric area.

[0012] Means for solving problems

[0013] An automatic analyzer according to one embodiment of the present invention includes: a reaction disk that holds a plurality of reaction cells on a circumference and rotates; a light source that irradiates light; a spectrophotometer that rotates along the reaction disk and detects light transmitted through the reaction cells that crosses the optical axis of the light source; and a control unit having a photometry unit that extracts a photometry waveform for a photometry value calculation period used for calculating the light intensity value of a liquid contained in the reaction cells from a photometry waveform obtained by sampling a photometry signal reflecting the light intensity value of the transmitted light output from the spectrophotometer. The control unit obtains a photometry waveform for each of the plurality of reaction cells from the photometry signals obtained by photometry of the plurality of reaction cells held on the reaction disk in an empty state or a state containing blank water, based on a photometry trigger signal indicating that each of the plurality of reaction cells crosses the optical axis of the light source. The control unit determines the photometry value calculation period based on a time region representing a flat waveform obtained for each of the photometry waveforms of the plurality of reaction cells.

[0014] Effects of the Invention

[0015] According to the present invention, the photometric value of the reaction solution can be calculated using the photometric value in the time region representing the flat waveform of the reaction unit, obtained before the sample is tested by the automatic analyzer, thereby improving the measurement stability of the device. Other issues and new features will become clear from the description and drawings of this specification. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a diagram showing the overall structure of an automatic analyzer.

[0017] Figure 2 It is a schematic diagram showing an outline of a position detection unit.

[0018] Figure 3A This is a diagram for explaining a method of measuring the photometry of a reaction solution in a reaction cell.

[0019] Figure 3B This is a diagram for explaining a method of measuring the photometry of a reaction solution in a reaction cell.

[0020] Figure 4 This diagram shows the photometric waveform arranged in response units based on the rising edge of the photometric trigger signal T.

[0021] Figure 5 is the correction time t cal _st calculation process.

[0022] Figure 6 It is used to correct the time t cal _st calculation example.

[0023] Figure 7 It represents the period t calculated by extracting the photometric value according to the reaction unit cal Figure of an example of a light metering waveform.

[0024] Figure 8 It is used to correct the time t cal _st calculation example.

[0025] Figure 9 It is used to correct the time t cal A diagram illustrating the third example of _st calculation.

[0026] Figure 10A This is an example of the correction time storage memory in the third example.

[0027] Figure 10B This is an example of a memory used to store light-metered values ​​during calculation in the third example.

[0028] Figure 11 This diagram explains how to determine abnormal waveforms such as foreign matter, bubbles, and flaws.

[0029] Figure 12 This is a diagram for explaining the estimation of the foreign matter width.

[0030] Figure 13 This diagram explains the self-diagnosis of the beam width.

[0031] Figure 14 This is a diagram for explaining detection of poor stirring of a reaction solution and insufficient liquid volume. DETAILED DESCRIPTION

[0032] Hereinafter, embodiments will be described with reference to the accompanying drawings.

[0033] Example 1

[0034] The configuration and operation of the automatic analyzer will be described by taking an automatic analyzer 100 that performs colorimetric analysis using a biochemical reaction as an example.

[0035] Figure 1 The overall structure of the automatic analyzer 100 is shown. Here, an automatic analyzer that performs colorimetric analysis using biochemical reactions is used as an example. The automatic analyzer 100 comprises a transport line 101, a rotor 102, a reagent disk 103, a reaction disk 104, a dispensing mechanism 105, a stirring mechanism 106, a spectrophotometer 107, a reaction unit cleaning mechanism 108, a nozzle cleaning mechanism 109, a control unit 115, an input unit 123, a display unit 124, and the like. Subscripts are used to distinguish between multiple components.

[0036] The transport line 1011 transfers a specimen rack 111 holding a specimen container 110 containing a specimen to a specimen dispensing position 121. At the specimen dispensing position 121, a dispensing mechanism (specimen dispensing mechanism) 1051 dispenses the specimen from the specimen container 110 into the reaction unit (reaction container) 112 on the reaction disk 104. The transport line 1011 is also connected to the rotor 102. By placing a specimen rack 111 and rotating the rotor 102, the specimen rack 111 is exchanged between other transport lines 1012.

[0037] The reagent disk 103 holds reagent containers 113 containing reagents and rotates the reagent containers 113 to a position where a dispensing mechanism (reagent dispensing mechanism) 1052 can perform dispensing operations. The dispensing mechanism 1052 dispenses the reagents from the reagent containers 113 into the reaction cells 112 on the reaction disk 104 at the reagent dispensing position 122. The reagents are dispensed into the reaction cells 112 in the amount required for colorimetric analysis, where they react with components in the sample being analyzed.

[0038] The reaction disk 104 holds reaction cells 112 on its circumference. A spectrophotometer 107 for colorimetric analysis, a stirring mechanism 106, and a reaction cell cleaning mechanism 108 are positioned around the reaction disk 104. The reaction cells 112, which are the subject of various actions, are rotated and moved to their respective action positions. Furthermore, the reaction cells 112 are kept warm by a constant-temperature medium such as water, thereby promoting chemical reactions between components in the specimen and the reagents in the reaction solution, a mixture of the specimen and reagents.

[0039] The dispensing mechanism 1051 draws the specimen to be colorimetrically analyzed from the specimen container 110 and ejects it into the reaction unit 112. The dispensing mechanism 1052 draws the reagent corresponding to the analysis object from the reagent container 113 and ejects it into the reaction unit 112. The dispensing mechanism 105 (1051 to 1052) respectively includes: an arm 118, a nozzle 116, and a dispensing mechanism motor 119. The arm 118 holds the nozzle 116 and the 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 based on the change in electrostatic capacitance. A shielding portion 114 is provided near the position where the dispensing mechanism 105 performs the dispensing action. The dispensing mechanism motor 119 moves the dispensing mechanism 105 in the up and down direction or the rotational direction.

[0040] The stirring mechanism 106 stirs the reaction liquid in the reaction unit 112 to promote the reaction between the analyte component in the sample ejected from the sample container 110 to the reaction unit 112 and the reagent ejected from the reagent container 113 to the reaction unit 112 .

[0041] Light source 120 emits light onto the reaction solution that has been stirred and chemically reacted by stirring mechanism 106. For example, an LED (Light Emitting Diode) is used as light source 120. Spectrometer 107 spectrally separates the light transmitted through the reaction solution in reaction cell 112 and measures the intensity of the separated light. Colorimetric analysis based on absorbance measurement is performed based on the intensity of the separated light.

[0042] The reaction unit cleaning mechanism 108 sucks the reaction solution from the reaction unit 112 after the colorimetric analysis is completed, and cleans the reaction unit 112 by ejecting a cleaning agent or the like.

[0043] The nozzle cleaning mechanism 109 (1091-1092) cleans the tip of the nozzle 116 of each dispensing mechanism 105 (1051-1052) that dispenses the sample or reagent. This removes any residue adhering to the nozzle 116 and prevents it from affecting the next analysis object.

[0044] 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 user instructions to the control unit 115. The display unit 124 is composed of an LCD (Liquid Crystal Display), etc., and displays the operation screen, etc.

[0045] Figure 2 1 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 sensing plate 201 and a sensing plate detector 202. Figure 2As shown, the reaction disk 104 is provided with the same number of sensing plates 201 as reaction cells 112, in a one-to-one relationship. Furthermore, a sensing plate detector 202 is provided at a position capable of detecting the passage of sensing plates 2011 through which the optical axis 205 of the light source 120 intersects. For example, the sensing plate detector 202 includes a light-emitting section 203 and a light-sensing section 204. When the sensing plate 201 passes between the light-emitting section 203 and the light-sensing section 204, it blocks light from the light-emitting section 203, thereby detecting the passage of the sensing plate 201. The position detection unit 200 outputs a detection signal from the sensing plate detector 202 indicating the passage of the sensing plate 201 as a photometric trigger signal indicating the passage of the reaction cell 112 between the light source 120 and the spectroscopic analyzer 107.

[0046] use Figure 3A 、 Figure 3B The following describes a method for measuring the photometry of the reaction solution within the reaction cell 112 in the automated analyzer 100. Light is irradiated from the light source 120 onto the reaction cell 112 containing the reaction solution. The transmitted light, which has passed through the reaction cell 112, enters the spectrophotometer 107. The spectrophotometer 107 includes a spectrometer 301 and a photodetector 302. The transmitted light is separated into multiple wavelengths by the spectrophotometer 301, and the photodetector 302 detects the light intensity of each separated wavelength. Specifically, the photodetector 302 outputs a photometric signal S having a current value proportional to the light intensity of the transmitted light. This photometric signal S is then input to the photometric unit 304 of the control unit 115.

[0047] The photometry unit 304 includes a current-to-voltage converter 305, an A / D converter 306, and a data processing unit 307. The current-to-voltage converter 305 converts the photometry signal S into a voltage value. The A / D converter 306 samples the photometry voltage value signal, which is an analog signal, at a predetermined sampling cycle and converts it into a digital signal. The data processing unit 307 generates a photometry waveform representing changes in the amount of light transmitted through the reaction cell 112 based on the converted digital photometry voltage signal. The data processing unit 307 also receives a photometry trigger signal T from the position detection unit 200.

[0048] Figure 3B The photometric signal S and the photometric trigger signal T input to the photometric unit 304 are schematically shown. In addition, it is assumed that the photometric signal S is input to the photometric unit 304 in an empty state or in a state filled with blank water. The ... Figure 3BThe photometric signal S is a continuous waveform. The photometric waveform corresponding to one reaction cell 112 has a significantly attenuated light 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 by the attenuated portion contains information about the transmitted light of the reaction liquid contained in the reaction cell 112. Therefore, the data processing unit 307 extracts the predetermined photometric value calculation period t cal Metering waveform. Metering value calculation period t cal This period is used to calculate the light intensity of the reaction solution contained in reaction cell 112. Data processing unit 307 calculates the light intensity of the light transmitted through the reaction solution based on the extracted photometric waveform. The calculated light intensity is transmitted to processor 303 of control unit 115, which analyzes the reaction solution.

[0049] In addition, although Figure 3A Although omitted, the photometric signal S of the separated transmitted light of each wavelength is input from the photodetector 302 to the photometric unit 304. The processing performed by the above-mentioned current-voltage converter 305, A / D converter 306, and data processor 307 is performed in parallel on the photometric waveform of each separated wavelength.

[0050] Figure 4 Based on the rise of the photometric trigger signal T, the response units are arranged to indicate the equivalent Figure 3B The photometric waveform of the photometric signal S is shown. In the photometric waveform of each reaction cell, the period of the flat waveform where the difference from the value at the adjacent sampling position is a constant value or less is defined as the photometrically available period t, and the time from the rising edge of the photometric trigger signal T to the start of the photometrically available period t is defined as the photometrically available start time t_st. Furthermore, when determining the photometrically available period t, it is preferable to eliminate variations caused by noise, etc. Thus, variations occur in the photometrically available start time ta_st and the photometrically available period ta in waveform A (the photometric waveform of reaction cell A), the photometrically available start time tb_st and the photometrically available period tb in waveform B (the photometric waveform of reaction cell B), and the photometrically available start time tc_st and the photometrically available period tc in waveform C (the photometric waveform of reaction cell C). These variations are caused by variations in container shape, deviations in the mounting position on the reaction disk, and scattered light from adjacent containers. In this embodiment, for the photometric waveform of each reaction unit having such a large deviation, the photometric period t and the photometric start time t_st are respectively calculated, and the timing for extracting the photometric waveform for calculating the light quantity value of the reaction liquid from the rising edge of the photometric trigger signal T is determined, that is, the photometric value calculation period t cal The following describes the period from the rise of the photometric trigger signal T to the photometric value calculation period t cal The time from the start of timing to the start of the correction time is called t cal _st.

[0051] Figure 5 represents the correction time t in this embodiment cal _st calculation process. In addition, the metering value calculation period t cal The period is predetermined to be shared by the reaction units 112 on the reaction disk 104. This process is executed by the control unit 115.

[0052] First, the photometry of the reaction cell 112 on the reaction disk 104 is performed (S01). The reaction cell 112 may be empty or filled with blank water. This process is performed when the reaction cell is replaced, but is not limited to this and may be performed at any time.

[0053] Next, according to the photometric waveform of each reaction unit, find Figure 4 The photometric start time t_st and the photometric start period t (S02) are shown as shown. Based on the photometric start time t_st and the photometric start period t of the reaction unit 112 on the reaction disk 104 obtained in step S02, the correction time t is obtained. cal _st(S03). The calculated correction time t cal _st is stored in the control unit 115 and is used for the light measurement value calculation period t in the data processing unit 307. cal Extraction of the photometric waveform. Next, the correction time t in step S03 is cal The calculation example of _st is explained below.

[0054] (Correction time t cal _st calculation example)

[0055] The first example is to calculate the common calibration time t for the reaction units 112 on the reaction disk 104 cal _st example. Figure 6 Overlapping representation Figure 4 The waveforms A to C are shown, and represent the correction time t cal _st and the exposure value calculation period t cal That is, the correction time t cal _st is set as the metering value calculation period t cal The light measurement period t of the light measurement waveform corresponding to the reaction unit on the reaction disk 104 is included. For example, if the maximum value of the light measurement start time t_st of the reaction unit on the reaction disk 104 is set as the latest light measurement start time t_st_max, it is set to satisfy the following relationship:

[0056] Correction time t cal _st>The latest time for starting light measurement is t_st_max.

[0057] In the first example, a common calibration time t is set for the reaction units 112 on the reaction disk 104. cal _st, thereby, the light measurement value calculation period t in the data processing unit 307 can be simplified. cal In addition, since it is obtained based on the actual waveform, the photometric value calculation period t can be extended as much as possible. cal However, it is unavoidable that the metering value calculation period t cal As a second example, the calibration time t is set for each reaction unit 112 on the reaction disk 104. cal _st example to illustrate.

[0058] (Correction time t cal Second example of _st calculation)

[0059] In the second example, the calibration time t is set according to the reaction unit 112 on the reaction disk 104. cal _st. That is, according to the reaction unit, it is set to satisfy the following relationship:

[0060] Correction time t cal _st>Time t_st at which light measurement can begin.

[0061] Thus, the photometric value calculation period t can be extended based on the photometric waveform corresponding to the reaction unit without being restricted by the variations of the reaction unit 112 on the reaction disk 104. cal . Extend the metering value calculation period t cal For example, even if a part of a specimen is affected by bubbles during measurement, the possibility of obtaining a sufficient photometric waveform other than the area affected by bubbles increases, thereby reducing the need for re-measurement.

[0062] use Figure 7 The data processing unit 307 extracts the photometric value for each reaction unit and calculates the period t cal The following describes an example of a photometric waveform. Furthermore, 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. Furthermore, the data processing unit 307 can be configured as a processor that executes a program. In this case, the processor operates as a functional unit that performs a predetermined function by executing a predetermined program.

[0063] Here, M reaction units 112 are mounted on the reaction disk 104, and numbers (unit numbers) that uniquely identify the mounting positions are set at the mounting positions of the reaction units 112. The number of reaction units (total number of units) M mounted on the reaction disk 104, the unit number (initial value unit number) of the reaction unit 112 that first crosses the optical axis 205 of the light source 120 when the reaction disk 104 starts rotating, and the photometric trigger signal T are input from the processor 303 to the counter 403. Each time the photometric trigger signal T is input, the counter 403 outputs a value obtained by adding 1 to the initial value unit number as the unit number. In addition, when the unit number reaches the total number of units M, the unit number is reset to 1 at the timing of the input of the next photometric trigger signal T. The correction time t of each reaction unit 112 identified by the unit number is stored in the correction time storage memory 404. cal _st.

[0064] When the photometric waveform i corresponding to the reaction unit of unit number i is input to the photometric waveform extraction unit 401, the correction time t of the unit number i is input from the photometric waveform extraction control unit 402 to the photometric waveform extraction unit 401. cal _st and exposure value calculation period t cal The photometric waveform extraction unit 401 uses this information to extract the photometric value calculation period t cal The metering waveform.

[0065] (Correction time t cal (Variation of the second example of _st calculation)

[0066] The calibration time t is set by pressing the reaction unit 112 on the reaction disk 104. cal In the case of _st, the correction time t can be set based on the waveform of the light measurement period t of the light measurement waveform of the reaction unit 112. cal _st, exposure value calculation period t cal .

[0067] exist Figure 8 In the case of waveform X shown, the slope of the second half of the waveform during the photometric period t is nearly zero, while the first half is gentle but has a slope. Similarly, in the case of waveform Y, the slope of the first half of the waveform during the photometric period t is nearly zero, while the second half is gentle but has a slope. 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 photometric period t.

[0068] In this case, in the case of waveform X, the correction time is set so that the metering value calculation period is set in the second half of the waveform during the measurable period t, and in the case of waveform Y, the correction time is set so that the metering value calculation period is set in the first half of the waveform during the measurable period t.

[0069] (Correction time t cal _st calculation example 3)

[0070] In the third example, the correction time t can be set according to the rotation speed of the reaction disk 104. cal _st, exposure value calculation period t cal Here, similarly to the second example, a calibration time t is set for each reaction unit 112 on the reaction disk 104. cal _st, exposure value calculation period t cal The following example illustrates this.

[0071] Reaction disk 104 rotates at a constant speed, but moves at a speed higher than the constant speed when it starts rotating and at a speed lower than the constant speed when it stops rotating, respectively. Therefore, the photometric waveform of reaction cell 112 crossing optical axis 205 after reaction disk 104 starts rotating, or the photometric waveform of reaction cell 112 crossing optical axis 205 before reaction disk 104 stops rotating, differs from the photometric waveform of reaction cell 112 crossing optical axis 205 when reaction disk 104 rotates at a constant speed. Figure 9 Compared to the waveform in a stable state, the light measurement start time t_st and the light measurement period t are respectively shortened at high speeds and lengthened at low speeds.

[0072] Therefore, in the third example, the light measurement start time t_st and the light measurement period t are adjusted according to the rotation speed of the reaction disk 104. Therefore, the light measurement waveform extraction control unit 402 has Figure 10A The correction time storage memory 411 and Figure 10B The photometric value calculation period shown is stored in the memory 412. Therefore, if the photometric waveform to be extracted is the photometric waveform when the reaction disk 104 starts rotating and operates at high speed, the correction time (correction time t cal _st_F) and the metering value calculation period at high speed (metering value calculation period t cal _F) is extracted. If the waveform is a light measurement waveform when the reaction disk 104 is in a low-speed operation before it stops rotating, the correction time at low speed (correction time t cal _st_S) and the metering value calculation period at low speed (metering value calculation period t cal The rotation speed of the reaction disk 104, whether it is stable, low speed, or high speed, can be determined by the unit number.

[0073] In addition, here the correction time t is set for the reaction unit 112. cal _st, exposure value calculation period t calThe example of , however, even if a common correction time t is set for the reaction disk 104 cal In the case of _st, the same correction time t can be performed cal _st, exposure value calculation period t cal settings.

[0074] The present invention is not limited to the above-described embodiments and includes various variations. For example, the above-described embodiments and variations are examples described in detail to facilitate understanding of the present invention and are not necessarily limited to having all the structures described. In addition, a portion of the structure of a certain embodiment or variation can be replaced with the structure of another embodiment or variation, and the structure of another embodiment or variation can be added to the structure of a certain embodiment or variation. In addition, other structures can be added, deleted, or replaced with a portion of the structure of each embodiment or variation.

[0075] Example 2

[0076] The first embodiment is characterized in that the light measurement start time, the light measurement period, etc. are determined based on the light measurement waveform, but the second embodiment describes an example in which the light measurement waveform is used in addition to determining the light measurement start time, the light measurement period, etc.

[0077] Figure 11 (a) shows the photometric waveform when the reaction vessel is filled with a uniform liquid. It can be seen that the photometric output is symmetrical about the central axis of the reaction vessel. In contrast, (b) shows the photometric waveform when foreign matter, such as bubbles or damage, is present in the reaction vessel. It can be seen that the light from the light source is scattered by the foreign matter, so the photometric intensity decreases around the foreign matter. By utilizing this phenomenon, the presence of foreign matter in the reaction vessel can be detected.

[0078] Furthermore, although not shown in the accompanying figures, damage and bubbles scatter light differently. Therefore, damaged reaction vessels (reaction cells) are skipped (cell skipping) so that they are not used in subsequent analyses. This improves the reliability of measurement results. Alternatively, by notifying the device operator of a reaction vessel that needs replacement, replacement of the reaction vessel can be promoted, resulting in more reliable analysis.

[0079] Furthermore, if a large number of bubbles are determined to be present in the liquid (reaction solution) within the reaction vessel, it is possible that a normal analysis result may not be obtained, assuming that the sample being analyzed has high viscosity, is prone to bubble formation, or has a reagent problem, such as reagent deterioration. It is also effective to provide an alarm to this effect to the analysis result, or to add a note to the apparatus operator urging reanalysis. To perform this determination, it is preferable to create and store reference data for identifying damaged or bubbled reaction vessels based on photometric waveforms measured using reaction vessels that have been artificially damaged or bubbled. The presence of damage or bubbles is determined by comparing this reference data with the actual photometric waveform.

[0080] When making a judgment, a threshold value can be set for the photometric waveform. When the photometric waveform falls above the threshold value, it is judged as having damage or bubbles. In order to further improve the judgment accuracy, the Mahalanobis distance can also be used, that is, the Mahalanobis distance is calculated based on the normal photometric waveform to calculate the threshold value of the normal space. When the photometric waveform exceeds the threshold value, it is regarded as abnormal, etc., and the judgment is made using well-known statistical methods.

[0081] Figure 12 An embodiment is shown in which the size of a foreign object is estimated based on the diameter of a light beam from a light source.

[0082] exist Figure 12 In the figure, the time when the foreign matter and the light beam begin to overlap is set as t1, the time when the foreign matter and the light beam completely overlap is set as t2, and the time when the foreign matter and the light beam do not overlap is set as t3.

[0083] Since the abnormal section where the photometric waveform indicates an abnormality = the width of the foreign object + (the width of the light beam × 2), the width (size) of the foreign object can be known from this formula.

[0084] Thus, for example, if a detected foreign object is a damage and its size exceeds a predetermined value, the device operator is notified that the reaction container needs to be replaced. This prevents the reaction container from being used for sample analysis, leading to analysis that cannot be reported. Furthermore, if the size of a bubble exceeds a predetermined value, the device operator is notified to terminate the analysis using the sample or reagent, thereby preventing waste of samples and reagents.

[0085] Figure 13 If Figure 12 Conversely, by attaching a foreign object of known size (an object that can block the light beam) to the reaction vessel in advance, the diameter of the light beam can be determined. Light from a light source is designed so that its optical path is bent by a reflector and passes through the reaction vessel through a slit or other device so that the beam width is predetermined.

[0086] If an optical system anomaly occurs for some reason, the beam width may change. However, the automated analyzer only measures changes in absorbance and automatically analyzes the reaction based on these changes. Therefore, even if the beam width changes, the anomaly cannot be detected. This can lead to erroneous analysis results. Regularly observing (checking) the beam diameter can detect optical system anomalies.

[0087] In addition, in recent years, automatic analyzers that use light-emitting diodes (LEDs) as light sources to replace conventional halogen lamps have emerged. To produce white light, LEDs sometimes use an optical system that combines white light generated by irradiating a phosphor with light from a blue-emitting LED with light from an ultraviolet-emitting LED to create a composite irradiation light. When using a light source with such a complex optical system, there is a non-zero probability that the direction of the irradiation light will change if the LED changes direction for some reason. In such cases, it is also possible to detect abnormalities in the light source by regularly monitoring the diameter of the light beam.

[0088] It is also possible to report the occurrence of an abnormality when the width of the light beam exceeds a predetermined threshold, and to record the temporal changes in the measured light beam width. Based on the temporal changes, it is possible to predict how long it will take to exceed the predetermined threshold if the automatic analysis device is used directly, and to report this fact.

[0089] In addition, Figure 13 While the example in Figure 1 shows a light-blocking object of known width placed on the inner surface of a reaction vessel, the thickness of the reaction vessel wall can also be used as the light-blocking object of known width. Since the thickness of the reaction vessel wall varies slightly from vessel to vessel, one or more reaction vessels are used to confirm the diameter of the light beam. The temporal change in the diameter of the light beam is measured based on the shape of the transmitted light waveform, which is determined by the thickness of the vessel wall.

[0090] Regarding the method of treating the container wall as a foreign body, due to the length of the container wall (in Figure 13 Since the length (in the longitudinal direction) is long, the attenuation of the transmitted light is large. Compared with the method of setting a foreign body of known width, there is a possibility of poor detection sensitivity, but there is an advantage that there is no need to prepare a reaction container for setting a foreign body separately.

[0091] Another method involves treating the gaps between reaction vessels as foreign matter. Depending on the type of automated analyzer, some devices use a block of reaction vessels formed from multiple reaction vessels. In such a block-shaped reaction vessel, the gaps between adjacent reaction vessels are constant, so these gaps can be treated as foreign matter. Compared to treating the vessel walls as foreign matter, the amount of light is greater, sometimes enabling more accurate beam diameter measurements.

[0092] Figure 14 This example shows how the state of the liquid in a reaction vessel is detected based on a photometric waveform. In a reaction vessel, after the sample and reagent are mixed and stirred to allow for a thorough reaction, the measurement result is calculated based on the absorbance change measured by a photometer. However, if the stirring mechanism malfunctions, there is a non-zero chance that the measurement will be performed with insufficient stirring.

[0093] The stirring device has various abnormality sensing functions to detect abnormalities in itself, but may not be able to sense abnormalities below the abnormality detection sensitivity. Even in such cases, in this embodiment, stirring abnormalities can be detected based on the output of the photometer.

[0094] Figure 14 (a) shows the photometric waveform when a normal reaction solution is used. The photometric waveform is bilaterally symmetrical about the central axis of the reaction vessel. In contrast, if the reaction solution on the left side of the reaction vessel is less concentrated (i.e., bright due to easy transmission of light) and the reaction solution on the right side is more concentrated (i.e., dark due to poor transmission of light) due to factors such as insufficient stirring, the photometric waveform becomes asymmetrical, with higher luminosity on the left side and lower luminosity on the right side. The symmetry of the photometric waveform allows the mixing status of the reaction solutions in the reaction vessel to be determined.

[0095] As a determination method, a method of determining that mixing is poor when the difference between the left and right peaks of the photometric waveform exceeds a predetermined threshold value, a method of determining that mixing is poor based on the slope of the photometric waveform (in Figure 14 The method of judging the detection height of the photometer is monotonically decreasing from left to right, etc.

[0096] In addition, the optical axis of the light beam from the light source is set so that it passes through the lowest possible position of the reaction container, so that measurement can be performed even if the reaction liquid in the reaction container is small. However, if the reaction liquid in the reaction container is smaller as it approaches the optical axis, there may be a situation where correct measurement results cannot be obtained. Figure 14 (c) shows the photometric waveform when the reaction solution surface is close to the optical axis. It can be seen that the photometric waveform is not flat but rather convex. Thus, even if the photometric waveform is bilaterally symmetrical, if the waveform has a left-right tilt, it indicates that the liquid volume is low and accurate measurement results may not be obtained. Therefore, an alarm can be added to the analysis results.

[0097] Furthermore, the automated analyzer identifies the reaction solution volume for each analysis item. Therefore, if the actual measured photometric waveform indicates a smaller reaction solution volume than the set volume, it is possible that a dispensing probe for the specimen or reagent has some abnormality. In other words, by determining whether the actual solution volume is insufficient relative to the volume stored in the automated analyzer based on the photometric waveform, any abnormality in the dispensing probe can be detected.

[0098] Description of Reference Numerals

[0099] 100...Automatic analyzer, 101...Transfer line, 102...Rotor, 103...Reagent disk, 104...Reaction disk, 105...Dispensing mechanism, 106...Stirring mechanism, 107...Spectrophotometer, 108...Reaction unit cleaning mechanism, 109...Nozzle cleaning mechanism, 110...Specimen container, 111...Specimen rack, 112...Reaction unit, 113...Reagent container, 114...Shield, 115...Control unit, 116...Nozzle, 117...Liquid level sensor, 118...Arm, 119...Dispensing mechanism motor, 120...Light source, 121...Specimen dispensing position, 122...Reagent dispensing position , 123…input unit, 124…display unit, 200…position detection unit, 201…sensing plate, 202…sensing plate detector, 203…light emitting unit, 204…light sensing unit, 205…optical axis, 301…spectrometer, 302…light detector, 303…processor, 304…photometric unit, 305…current-voltage conversion unit, 306…A / D conversion unit, 307…data processing unit, 401…photometric waveform extraction unit, 402…photometric waveform extraction control unit, 403…counter, 404, 411…correction time storage memory, 412…photometric value calculation period storage memory.

Claims

1. An automatic analysis device, characterized in that have: A reaction disk, which holds a plurality of reaction units on a circumference and performs a rotating motion; a light source, which radiates light; a spectroscopic analyzer that detects transmitted light that has passed through the reaction unit that crosses the optical axis of the light source by rotating the reaction disk; as well as a control unit including a photometric unit for extracting a photometric waveform during a photometric value calculation period used for calculating a light intensity value of the liquid contained in the reaction cell from a photometric waveform obtained by sampling a photometric signal reflecting a light intensity value of the transmitted light output from the spectroscopic analyzer; The control unit obtains a photometric waveform for each of the plurality of reaction cells from photometric signals obtained by photometrically measuring the plurality of reaction cells held on the reaction disk in an empty state or a state containing blank water, 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 the photometric value calculation period based on a time region representing a flat waveform obtained for the photometric waveform of each of the plurality of reaction cells.

2. The automatic analysis device according to claim 1, characterized in that The control unit calculates, for the photometry waveform of each of the multiple reaction units, a time period as a flat waveform, namely, a photometry period, and a photometry startable time from the rise of the photometry trigger signal to the start of the photometry startable period, and sets a correction time for the photometry value calculation period starting from the rise of the photometry trigger signal based on the photometry startable period and the photometry startable time calculated for the photometry waveform of each of the multiple reaction units.

3. The automatic analysis device according to claim 1, characterized in that The automatic analysis device includes: a position detection unit that outputs the photometry trigger signal; The position detection unit includes: a plurality of sensing plates provided corresponding to each of the plurality of reaction units held on the reaction disk; and a sensing plate detector for sensing the passage of the sensing plates. The sensing plate detector is disposed at a position where the sensing plate passes when a reaction unit corresponding to the sensing plate crosses the optical axis of the light source.

4. The automatic analysis device according to claim 1, characterized in that The control unit determines the photometric value calculation period shared by the plurality of reaction units.

5. The automatic analysis device according to claim 1, characterized in that The control unit determines the photometric value calculation period for each of the plurality of reaction units.

6. The automatic analysis device according to claim 5, characterized in that The control section determines the photometric value calculation period based on the slope of the photometric waveform in the time zone.

7. The automatic analysis device according to claim 4 or 5, characterized in that The control unit determines the photometric value calculation period according to the rotation speed of the reaction disk.

8. The automatic analysis device according to claim 1, characterized in that The control unit detects the occurrence of an abnormality based on a local change in a photometric signal of a flat waveform obtained for each of the plurality of reaction cells in a time region representing the waveform.

9. The automatic analysis device according to claim 8, characterized in that When the control unit detects the occurrence of the abnormality, it notifies the occurrence of the abnormality.

10. The automatic analysis device according to claim 8, characterized in that The control unit detects the size of the abnormality occurrence site based on a local change in the waveform of the photometric signal.

11. The automatic analysis device according to claim 8, characterized in that The control unit stores the flat waveform obtained for the photometric waveform of each of the plurality of reaction cells as measurement results at at least two different time points in a time series, and identifies a location of the reaction cell where an abnormality has occurred by comparing the flat waveforms of the photometric waveforms at the different time points.

12. The automatic analysis device according to claim 8, characterized in that The control unit stores the flat waveforms obtained for the photometric waveforms of each of the plurality of reaction units as measurement results at at least two different time points in a time series, identifies the degree of abnormality of the reaction unit by comparing the flat waveforms of the photometric waveforms at the different time points, and determines the replacement time of the reaction unit based on the identification result.

13. The automatic analysis device according to claim 1, characterized in that The control unit detects the beam diameter of the transmitted light passing through the reaction cell based on a photometric waveform of a portion of the reaction cell having a known size.

14. The automatic analysis device according to claim 13, characterized in that The control unit stores the detected beam diameters as measurement results at at least two different time points in a time series, and detects abnormality in the optical system of the transmitted light by comparing the beam diameters at the different time points.

15. The automatic analysis device according to claim 14, characterized in that When the control unit detects an abnormality in the optical system transmitting light, it notifies the abnormality.

16. The automatic analysis device according to claim 13, characterized in that The control unit stores the detected beam diameter as measurement results at at least two different time points in a time series, and predicts a maintenance period based on changes in the beam diameter at the different time points.

17. The automatic analysis device according to claim 1, characterized in that The control unit detects that stirring of the reaction solution in the reaction cell is poor when the photometric signal of the waveform decreases or increases substantially monotonically in a time region representing the flat waveform obtained for each of the plurality of reaction cells.

18. The automatic analysis device according to claim 1, characterized in that When the photometric signal of the waveform changes substantially upward in a convex shape in a time region representing the flat waveform obtained for each of the plurality of reaction cells, the control unit detects that measurement was performed in a state where the reaction liquid in the reaction cell is insufficient.

19. A timing setting method in an automatic analyzer, the automatic analyzer comprising: a reaction disk that holds a plurality of reaction cells on a circumference and rotates; a light source that irradiates light; a spectrophotometer that rotates through the reaction disk and detects transmitted light from the reaction cells that crosses the optical axis of the light source; and a control unit comprising a photometric unit that extracts a photometric waveform during a photometric value calculation period used for calculating the light intensity value of a liquid contained in the reaction cells from a photometric waveform obtained by sampling a photometric signal reflecting the light intensity value of the transmitted light output from the spectrophotometer, wherein: The control unit obtains a photometric waveform for each of the plurality of reaction cells from photometric signals obtained by photometrically measuring the plurality of reaction cells held on the reaction disk in an empty state or a state containing blank water, 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 the photometric value calculation period based on a time region representing a flat waveform obtained for the photometric waveform of each of the plurality of reaction cells.

20. The timing setting method according to claim 19, wherein: The control unit calculates, for the photometry waveform of each of the multiple reaction units, a time period as a flat waveform, namely, a photometry period, and a photometry startable time from the rise of the photometry trigger signal to the start of the photometry startable period, and sets a correction time for the photometry value calculation period starting from the rise of the photometry trigger signal based on the photometry startable period and the photometry startable time calculated for the photometry waveform of each of the multiple reaction units.

21. The timing setting method according to claim 19, wherein: The control unit determines the photometric value calculation period shared by the plurality of reaction units.

22. The timing setting method according to claim 19, wherein: The control unit determines the photometric value calculation period for each of the plurality of reaction units.

23. The timing setting method according to claim 22, wherein: The control unit determines the photometric value calculation period based on the slope of the photometric waveform in the time zone.

24. The timing setting method according to claim 21 or 22, characterized in that: The control unit determines the photometric value calculation period according to the rotation speed of the reaction disk.

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