WO2021024535A1

WO2021024535A1 - Automatic analysis device

Info

Publication number: WO2021024535A1
Application number: PCT/JP2020/010994
Authority: WO
Inventors: 光加呂; 憲一西墻
Original assignee: 株式会社日立ハイテク
Priority date: 2019-08-05
Filing date: 2020-03-13
Publication date: 2021-02-11
Also published as: JP7229363B2; CN114174800B; JPWO2021024535A1; CN114174800A

Abstract

Provided is an automatic analysis device that can measure the amount of scattered light of a measurement object while removing the influence of bubbles and can improve the accuracy and reliability of analysis. This automatic analysis device has: an optical detection system provided with a transmitted light detector (42) for receiving transmitted light having transmitted through a measurement object (132) and a scattered light detector (43) for receiving scattered light scattered by the measurement object (132); a waveform acquisition unit (49) for acquiring first scan waveform data from the transmitted light detector (42) and second scan waveform data from the scattered light detector (43); and a data processing unit (48) for, by using the first scan waveform data and the second scan waveform data, specifying the presence/absence of bubbles in the measurement object (132) and a section subjected to the influence of bubbles in the second scan waveform data when there are bubbles.

Description

Automatic analyzer

The present invention relates to an automatic analyzer that performs qualitative and quantitative analysis of biological samples such as blood and urine.

The automatic analyzer irradiates a reaction solution obtained by reacting a biological sample such as blood or urine with a reagent, and determines the presence or absence and concentration of a target component based on the data obtained by measuring transmitted light or scattered light. It is a thing. The reaction vessels containing the reaction solution are continuously arranged on the circumference of the rotatable reaction disk, and the measurement is performed while moving the optical axis of light to be detected as the reaction disk rotates. ..

In recent years, automatic analyzers are required to provide more and more accurate and reliable analysis results at high speed. Here, for example, when bubbles are generated in the reaction vessel used for the analysis, it may cause an error in the analysis result. The following prior art discloses a technique for detecting the occurrence of such anomalies.

Patent Document 1 describes a technique for measuring transmitted light over the entire section from one end to the other end of a reaction vessel containing a reaction solution, and detecting a foreign substance based on a decrease in luminous intensity in the obtained photometric data. It is disclosed.

Patent Document 2 measures the photometry of the reaction solution in one cell for a predetermined time, divides the photometric range into a plurality of regions, and calculates and compares the integrated value of the photometric quantity corresponding to the region. The measuring unit discloses a technique for detecting an abnormality in the reaction solution or an abnormality in the cell from the result of comparison.

Patent Document 3 describes a plurality of detection values for the same sample of each luminosity detector for each luminosity detector of a plurality of luminosity detectors in an automatic analyzer having a plurality of luminosity detectors for analyzing a sample in a reaction vessel. Calculate the concentration of the sample from, calculate the fluctuation range of the calculated concentration, determine whether the calculated fluctuation range is within the predetermined allowable fluctuation range, and use one of the multiple luminosity detectors. A technique for displaying that the reaction process is abnormal unless the fluctuation range of the concentration calculated from the detected value of is within the permissible fluctuation range is disclosed.

JP-A-2007-198739 JP-A-2015-102428 Japanese Unexamined Patent Publication No. 2013-134139

Patent Document 1 makes it possible to determine the position of foreign matter such as air bubbles from the decrease in the amount of transmitted light. However, when the automatic analyzer measures the scattered light, the scattered light has the possibility of both decreasing or increasing due to the influence of foreign substances such as bubbles as described later, so that the position cannot be detected by the same technique. ..

In Patent Document 2, it is not possible to determine which section of the division has an abnormality such as air bubbles, but only the presence or absence of air bubbles can be determined.

In Patent Document 3, the presence or absence of an abnormality such as a bubble is detected from the variation of the measurement data at the same measurement position for the measurement target, and the position of the bubble cannot be determined.

The detector that measures the scattered light of the measurement target is affected by the change in the amount of light caused by the bubbles generated in the measurement target, which causes the measurement error. If the waveform section affected by bubbles can be grasped from the scattered light waveform data to be measured, the waveform data including the influence of bubbles that causes an error can be excluded, and the waveform data in a state where there are virtually no bubbles can be obtained. Obtainable. As a result, the accuracy and reliability of the analysis can be improved. Furthermore, if the reanalysis of the sample becomes unnecessary, the time required for the analysis can be shortened.

An automated analyzer according to an embodiment of the present invention includes a reaction disk in which a plurality of reaction vessels are arranged in the circumferential direction and can rotate intermittently, a light source and a photometer, and reacts between the light source and the photometer. It has a light detection system arranged so that the reaction container arranged on the disk can pass through, and a photometer data processing unit. The light detection system irradiates the measurement target housed in the reaction container with light from a light source. A transmitted light detector that receives transmitted light transmitted through the measurement target and a scattered light detector that irradiates the measurement target housed in the reaction vessel with light from a light source and receives the scattered light scattered by the measurement target. The photometer data processing unit scans the light from the light source with respect to the measurement target by rotating the reaction disk, and obtains the first scanning waveform data from the transmitted light detector and the scattered light detector. Using the waveform acquisition unit that acquires the second scanning waveform data, the first scanning waveform data, and the second scanning waveform data, the presence or absence of bubbles in the measurement target and the presence or absence of bubbles, the second It has a data processing unit that specifies a section affected by bubbles in the scanned waveform data.

The amount of scattered light to be measured can be measured excluding the influence of bubbles, and the accuracy and reliability of analysis can be improved.

Other issues and new features will become apparent from the description and accompanying drawings herein.

It is an overall block diagram of an automatic analyzer. This is a configuration example of a photodetector system and a photometer data processing unit. This is an example of a scanning waveform (scattered light) when bubbles are present in the reaction vessel. This is an example of a scanning waveform (scattered light) when bubbles are present in the reaction vessel. This is an example of a scanning waveform (scattered light and transmitted light) when bubbles are present in the reaction vessel. This is an example of a scanning waveform (scattered light and transmitted light) when bubbles are present in the reaction vessel. It is a flowchart for determining the waveform section without a bubble. It is a figure for demonstrating the threshold value setting method for determining the waveform section in which a bubble exists. It is a figure for demonstrating the threshold value setting method for determining the waveform section in which a bubble exists. It is a figure which added the mean value and the threshold value to the scan waveform of FIG. It is a figure which added the mean value and the threshold value to the scan waveform of FIG. It is a flowchart for determining the waveform section without a bubble. It is a flowchart for determining the waveform section without a bubble. It is a flowchart for determining the waveform section without a bubble. It is a figure for demonstrating the difference threshold setting method. It is a figure for demonstrating the difference threshold setting method. 11 is a diagram for explaining a procedure for determining a bubble-free waveform section from scanning waveforms (scattered light and transmitted light) according to the flowcharts of FIGS. 11A to 11C. 11 is a diagram for explaining a procedure for determining a bubble-free waveform section from scanning waveforms (scattered light and transmitted light) according to the flowcharts of FIGS. 11A to 11C.

FIG. 1 is an overall configuration diagram of the automatic analyzer. The automatic analyzer 1 mainly includes a reaction disk (reaction vessel holding mechanism) 30, a sample disk 10, a reagent disk (reagent container holding mechanism) 20, a light source 40, a photometer 41, and a computer 54. Be prepared.

The reaction disk 30 is rotatable intermittently, and a large number of reaction vessels 31 made of a translucent material are arranged along the circumferential direction on the reaction disk 30. The reaction vessel 31 is maintained at a predetermined temperature (for example, 37 ° C.) by the constant temperature bath 32.

On the sample disk 10, a large number of sample containers 11 for accommodating biological samples such as blood and urine are doubly placed along the circumferential direction in the illustrated example. Further, a sample dispensing mechanism (sample dispensing mechanism) 16 is arranged in the vicinity of the sample disk 10. The sample dispensing mechanism 16 includes a movable arm 15 and a pipette nozzle 17 attached to the movable arm 15. With the above configuration, the sample dispensing mechanism 16 moves the pipette nozzle 17 to the dispensing position by the movable arm 15 at the time of sample dispensing, and sucks a predetermined amount of the sample from the sample container 11 located at the suction position of the sample disk 10. Then, the sample is discharged into the reaction vessel 31 at the discharge position on the reaction disk 30.

In the reagent disc 20, the reagent cold storage 22 is arranged along the circumferential direction. In the reagent cold storage 22, a plurality of reagent bottles 21 to which labels displaying reagent identification information such as barcodes are affixed are placed along the circumferential direction of the reagent disc 20. The reagent bottle 21 contains a reagent solution corresponding to an analysis item that can be analyzed by the automatic analyzer 1. A barcode reading device 27 is attached to each reagent cold storage 22, and the barcode reading device 27 reads the barcode displayed on the outer wall of each reagent bottle 21 at the time of reagent registration. The read reagent information is registered in the memory 53 together with the position on the reagent disk 20.

A reagent dispensing mechanism 25 having a mechanism substantially similar to that of the sample dispensing mechanism 16 is arranged in the vicinity of the reagent disc 20. At the time of reagent dispensing, the reagent solution is sucked from the reagent bottle 21 according to the inspection item of the reaction vessel 31 positioned at the reagent receiving position on the reaction disk 30 by the pipette nozzle provided in the reagent dispensing mechanism 25, and the corresponding reaction vessel is used. Discharge into 31.

The stirring mechanism 36 is arranged at a position surrounded by the reaction disk 30, the reagent disk 20, and the reagent dispensing mechanism 25. The mixture of the sample and the reagent contained in the reaction vessel 31 is stirred by the stirring mechanism 36 to promote the reaction.

The photometer 41 composed of the scattered light detector 43 and the transmitted light detector 42 is arranged on the outer peripheral side of the reaction disk 30, and the light source 40 is arranged near the center of the reaction disk 30. The row of reaction vessels 31 after stirring rotates so as to pass through the photometric position sandwiched between the light source 40 and the photometer 41. The light source 40 and the photometer 41 constitute a photodetection system. The reaction solution of the sample and the reagent in each reaction vessel 31 is photometrically measured each time it crosses in front of the photometer 41 during the rotation operation of the reaction disk 30. The analog signals of the transmitted light and the scattered light measured for each sample are input to the photometer data processing unit 2. The photometer data processing unit 2 has a waveform acquisition unit 49, a data processing unit 48, and a data storage unit 47. The reaction vessel 31 whose measurement has been completed can be used repeatedly by cleaning the inside thereof by the reaction vessel cleaning mechanism 38 arranged in the vicinity of the reaction disk 30.

Next, the control system and signal processing system of the automatic analyzer 1 will be briefly described. The computer 54 is connected to the sample dispensing control unit 19, the reagent dispensing control unit 29, and the photometer data processing unit 2 via the interface 50. The computer 54 sends a command to the sample dispensing control unit 19 to control the sample dispensing operation. Further, the computer 54 sends a command to the reagent dispensing control unit 29 to control the reagent dispensing operation.

A printer 56 for printing, a memory 53 as a storage device, an external output medium 55, an input device 52 for inputting an operation command, etc., and a display device 51 for displaying on a screen are connected to the interface 50. The memory 53 is composed of, for example, a hard disk memory or an external memory. Information such as a password of each operator, a display level of each screen, analysis parameters, analysis item request contents, calibration result, and analysis result is stored in the memory 53.

Next, the sample analysis operation in the automatic analyzer 1 will be described. The analysis parameters related to the items that can be analyzed by the automatic analyzer 1 are input in advance via the input device 52 such as a keyboard, and are stored in the memory 53. The operator selects the inspection item requested for each sample by using the operation function screen of the display device 51. At this time, information such as the patient ID is also input from the input device 52. In order to analyze the inspection items indicated for each sample, the pipette nozzle 17 of the sample dispensing mechanism 16 dispenses a predetermined amount of the sample from the sample container 11 to the reaction vessel 31 according to the analysis parameters.

The reaction vessel 31 into which the sample (sample) has been dispensed is transferred by the rotation of the reaction disk 30 and stops at the reagent receiving position. The pipette nozzle of the reagent dispensing mechanism 25 dispenses a predetermined amount of the reagent solution into the reaction vessel 31 according to the analysis parameters of the corresponding test items. The order of dispensing the sample and the reagent may be opposite to that of this example, and the reagent may precede the sample. After that, the sample and the reagent are stirred by the stirring mechanism 36 and mixed.

When the reaction vessel 31 crosses the photometric position, the transmitted light and scattered light of the reaction solution are measured by the photometer 41. The metered transmitted light and scattered light are converted into numerical data proportional to the amount of light by the waveform acquisition unit 49 of the photometer data processing unit 2, and after the data processing unit 48 extracts the light amount data to be measured, the interface 50 is used. It is taken into the computer 54 via. The numerical data acquired by the waveform acquisition unit 49 can also be stored in the data storage unit 47 via the data processing unit 48. The processing in the data processing unit 48 and the data storage unit 47 may be performed by the computer 54 and the memory 53.

Using this converted numerical value, the concentration data is calculated based on the calibration curve measured in advance by the analysis method specified for each inspection item. The component concentration data as the analysis result of each inspection item is output to the screen of the printer 56 or the display device 51.

FIG. 2 is a schematic diagram showing a configuration example of a photodetector system and a photometer data processing unit 2 in the automatic analyzer 1. The irradiation light from the light source 40 irradiates the measurement target 132, which is a mixed solution of the sample and the reagent contained in the reaction vessel 31. The transmitted transmitted light to be irradiated is received by the transmitted light detector 42 arranged on the optical axis 121. The scattered light from the measurement target 132 is received by the scattered light detector 43 arranged at an angle different from that of the transmitted light detector 42 with respect to the optical axis 121. The transmitted light detector 42 and the scattered light detector 43 are synchronized so that the scanning positions with respect to the measurement target 132 are the same, and the waveform acquisition unit 49 acquires the respective scanning waveforms. Specifically, the transmitted light detector 42 is arranged on the vertical line of the scattered light detector 43, or the transmitted light detector 42 is arranged with respect to the scattered light detector 43 in the scanning orbit direction of the optical axis 121. If so, data processing may be performed to compensate for the deviation. The data processing unit 48 executes data processing for determining a section in which bubbles exist from the data (scanning waveform) captured by the waveform acquisition unit 49. Further, the data acquired by the waveform acquisition unit 49 is arbitrarily stored in the data storage unit 47, and in this case, the data processing unit 48 can access the past waveform data from the data storage unit 47.

The automatic analyzer may have a transmitted light detector for performing analysis based on transmitted light, but in general, what is light used for analysis based on transmitted light and light used for analysis based on scattered light? It is different and the light source is usually another light source. The transmitted light detector 42 in this embodiment is a transmitted light detector provided so as to receive light from the light source 40 for the scattered light detector 43.

First, in the photodetector system of the automatic analyzer 1, the influence of the presence of air bubbles in the reaction vessel 31 on the scanning waveform will be described.

FIG. 3 shows an example of the case where the bubble 101 exists on the right side of the reaction vessel 31 and on the optical axis orbit 122 when viewed from the detector in the measurement target 132. Here, the trajectory in which the optical axis 121 of the light source 40 scans on the reaction vessel 31 by the rotation of the reaction disk 30 is referred to as an optical axis trajectory 122. The upper row is a side view, the middle row is a front view, and the lower row is a scanning waveform (scattered light) 151 acquired by the scattered light detector 43. In this case, if the bubbles 101 are not present, the light transmitted on the optical axis 121 is scattered in the other direction due to the presence of the bubbles 101. As a result, in the scanning waveform 151 of the scattered light detector 43, a region where the intensity of the scattered light increases due to the influence of the scattered light by the bubbles 101 appears. In the scanning waveform 151, if the region where the influence of the bubble 101 appears is section B and the other area is section A, the scattered light intensity of section B is larger than that of section A.

FIG. 4 shows an example in which the bubble 102 is present on the left side of the reaction vessel 31 as viewed from the detector and at a position shifted upward from the optical axis orbit 122 in the measurement target 132. The upper row is a side view, the middle row is a front view, and the lower row is a scanning waveform (scattered light) 153 acquired by the scattered light detector 43. If the bubbles 102 are not present, the light incident on the scattered light detector 43 is scattered in the other direction due to the presence of the bubbles 102. As a result, in the scanning waveform 153 of the scattered light detector 43, a region where the intensity of the scattered light is reduced due to the influence of the scattered light by the bubbles 102 appears. In the scanning waveform 153, if the region where the influence of the bubble 102 appears is the section C and the other area is the section D, the scattered light intensity of the section C is smaller than that of the section D.

As described above, the scanning waveform 151 and the scanning waveform 153 acquired by the scattered light detector 43 show the same light amount transition even though the positions of the bubbles are different in the cases of FIGS. 3 and 4.

5 shows the measurement target 132 as the measurement target 132x at the concentration X while keeping the bubble position in FIG. 3, and FIG. 6 shows the measurement target 132 at the concentration Y (concentration Y> concentration X) while keeping the bubble position in FIG. 4 as it is. An example when the measurement target is changed to 132y is shown. The upper left of FIG. 5 is a side view, the lower left is a front view, the upper right is a scanning waveform (scattered light) 151x acquired by the scattered light detector 43, and the lower right is acquired by the transmitted light detector 42. Scanning waveform (transmitted light) 161. The upper left of FIG. 6 is a side view, the lower left is a front view, the upper right is a scanning waveform (scattered light) 153y acquired by the scattered light detector 43, and the lower right is a transmitted light detector 42. It is the acquired scanning waveform (transmitted light) 163.

As the density of the measurement target changes, the scan waveform (scattered light) 151x and the scanning waveform (scattered light) 153y each cause a shift in the amount of scattered light corresponding to the change in density. As a result, the scanning waveform (scattered light) 151x and the scanning waveform (scattered light) 153y have not only the waveform transition but also the magnitude of the scattered light amount, and as a result, both have almost the same waveform in this example. It has been done. As described above, it is not possible to determine the section in which the bubble exists only from the scanning waveform of the scattered light detector 43.

On the other hand, even when the scanning waveforms of the scattered light detector 43 are substantially the same as in FIGS. 5 and 6, differences appear in the scanning waveforms of the transmitted light detector 42. In the case of FIG. 5, if the bubble 101 is not present, the light incident on the transmitted photodetector 42 is scattered in the other direction due to the presence of the bubble 101. As a result, in the scanning waveform 161 of the transmitted light detector 42, in the region where the bubbles 101 exist (section B), the light is transmitted under the influence of scattering by the bubbles 101 as compared with the region where the bubbles do not exist (section A). Light intensity is reduced. On the other hand, in the case of FIG. 6, the light incident on the scattered photodetector 43 if the bubble 102 does not exist is scattered in the other direction due to the presence of the bubble 102, and a part of the light is incident on the transmitted photodetector 42. To do. However, the amount of light incident on the transmitted photodetector 42 along the optical axis 121 is larger than the amount of light incident on the transmitted photodetector 42 due to scattering by the bubbles 102, and the region (section C) in which the bubbles 102 exist. There is almost no difference between the amount of light received by the transmitted photodetector 42 and the amount of light received by the transmitted photodetector 42 in the nonexistent region (section D).

To summarize the above, when there are air bubbles in front of the transmitted light detector 42, the incident light on the transmitted light detector 42 is scattered by the air bubbles, so that the amount of light is reduced as compared with the section without air bubbles, but the scattered light. The incident light on the detector 43 is affected by the scattered light by the bubbles, and the amount of light increases as compared with the section without bubbles. On the other hand, when there are air bubbles in front of the scattered light detector 43, the incident light on the scattered light detector 43 is scattered by the air bubbles, so that the amount of light is reduced as compared with the section without air bubbles, while the transmitted light is transmitted. The transmitted light is extremely large as the incident light to the detector 42, and the influence of scattered light by bubbles can be ignored. In this embodiment, the region where the bubbles exist in the reaction vessel 31 is determined based on the difference in the waveform transition between the scanning waveform of the transmitted photodetector 42 and the scanning waveform of the scattered light detector 43.

FIG. 7 shows a flowchart for determining a waveform section from the scanning waveform that is not affected by bubbles for a measurement target having a known concentration. For this purpose, the determination of the increase or decrease in the amount of light due to the bubbles is performed using a predetermined threshold value. The data processing unit 48 stores these threshold values in advance. Examples of the case where the concentration to be measured is known include the case of calibration or blank measurement. In the case of calibration, measurement is performed on a standard substance having a known concentration in order to prepare a calibration curve, and in blank measurement, pure water is put into the reaction vessel 31 for measurement. An example of threshold setting is shown below. FIG. 8A is a scanning waveform 171 of the scattered photodetector 43 for a measurement object without bubbles, and FIG. 8B is a scanning waveform 173 of the transmitted photodetector 42 for a measurement object without bubbles. First, the fluctuation width V is calculated in the scanning waveform of each detector. The difference between the maximum value of the fluctuation range V _A of the scattered light amount detected by the scattered light detector 43 and the average value A _A is tripled, and the value added to the average value A _A is the upper limit threshold Th _AU , the fluctuation range V _A. The difference between the minimum value and the average value A _A is tripled, and the value subtracted from the average value A _{A is} defined as the lower limit threshold Th _AL . Similarly, based on the variation of the quantity of transmitted light detected by the transmitted light detector 42 width V _B and the average value A _B, to determine the upper threshold Th _BU and lower threshold Th _BL. The above is an example, and may be determined based on the upper and lower limits of the amplitude of the amount of light caused by the bubbles that are actually desired to be detected.

Taking the case where bubbles are present at the positions shown in FIG. 5 in the reaction vessel 31, a procedure for determining the waveform section in which the bubbles are present will be described with reference to the flowchart of FIG. 7. Figure 9 is the scanning waveform shown in FIG. 5, the average value _A A (A _B) of the amount of scattered light at a concentration X (the amount of transmitted light), the upper threshold Th _AU (Th _BU), the lower limit threshold value Th _AL (Th _BL ) Is added.

First, when the waveform acquisition unit 49 acquires the scanning waveform to be measured by the transmitted photodetector 42 and the scattered light detector 43, the data processing unit 48 starts determining the waveform section without bubbles (S100).

First, the scanning waveform 161 of the transmitted light amount is compared with the lower limit threshold value Th _BL (S101), and since the section B is equal to or less than the lower limit threshold value Th _BL , the transmitted light amount reduction flag Flg1 is given to the section B (S102). Subsequently, the scanning waveform 151x amount of scattered light compared to the lower threshold Th _AL (S103), the process proceeds to step S105 since there is no lower threshold Th _AL following section. The scanning waveform 151x is compared with the upper limit threshold value Th _AU, and since the section B is equal to or larger than the upper limit threshold value Th _AU , the scattered light amount increase flag Flg4 is given to the section B (S106).

Subsequently, in step S107, since the section B is a section to which both the transmitted light amount decrease flag Flg1 and the scattered light amount increase flag Flg4 are given, the section B is extracted as a waveform section in which bubbles are present, and is obtained from the scanned waveform data. , The data of the corresponding waveform section (here, section B) is removed (S108). In step S107, it is expected that the section to which the transmitted light amount decrease flag Flg1 is given and the section to which the scattered light amount increase flag Flg4 is given substantially overlap, but in reality, if both ends of the section are displaced. Conceivable. In this case, it can be said that the effect of air bubbles appears in the section where either the transmitted light amount decrease flag Flg1 or the scattered light amount increase flag Flg4 is given, so if either flag is given, it is targeted for removal. Is desirable. Subsequently, since there is no section to which the scattered light amount reduction flag Flg3 is given in step S109, the process proceeds to step S111, and the remaining waveform section A is determined as a waveform section without bubbles.

On the other hand, the procedure for determining the corrugated section in which the bubbles are present will be described from the flowchart of FIG. 7 by taking the case where the bubbles are present at the positions shown in FIG. 6 in the reaction vessel 31 as an example. Figure 10 is the scanning waveform shown in FIG. 6, the average value _A A (A _B) of the amount of scattered light at a concentration Y (transmitted light amount), the upper threshold Th _AU (Th _BU), the lower limit threshold value Th _AL (Th _BL ) Is added.

First, the scanning waveform 163 of the transmitted light amount is compared with the lower limit threshold value Th _BL (S101), and since there is no section below the upper limit threshold value Th _BL , the process proceeds to step S103. In step S103, the scanning waveform 153y amount of scattered light compared to the lower threshold Th _AL, section C is because it is below the lower threshold value Th _AL, imparts scattered light intensity decrease flag Flg3 in section C (S104). Subsequently, the scanning waveform 153y compared to upper threshold Th _AU (S105), the process proceeds to step S107 since there is no upper limit threshold Th _AU more sections.

In step S107, since there is no section to which both the transmitted light amount reduction flag Flg1 and the scattered light amount increase flag Flg4 are given, the process proceeds to step S109, and the section C is a section to which the scattered light amount reduction flag Flg3 is given. Extracts as a waveform section in which bubbles exist, removes the data of the corresponding waveform section (here, section C) from the scanned waveform data (S110), and determines the remaining waveform section D as a waveform section without bubbles (S110). S111).

FIGS. 11A to 11C show a flowchart for determining a waveform section without bubbles from the scanning waveform for the measurement target whose density is unknown. In this case, unlike the flow of FIG. 7, since the concentration is unknown, the threshold value cannot be set in advance. Therefore, in addition to the flow of FIG. 7, a flow for setting a threshold value for determining a waveform section without bubbles is included. Examples of cases where the concentration to be measured is unknown include the case of measurement in analysis of a sample.

In the scanning waveform 271 of the scattered light detector 43 for the measurement target without bubbles shown in FIG. 12A, the difference d of the scattered light amount at the sampling positions before and after is calculated, and the difference waveform 272 shown in FIG. 12B is obtained. When there are no bubbles in the measurement target, the light amount transition of the difference waveform 272 is almost constant regardless of the position and the density of the measurement target, so that the difference is extremely small in the data of the front and back positions of the received light waveform. Therefore, the value obtained by multiplying the maximum value of the fluctuation width DV _A of the difference in the scattered light amount detected by the scattered light detector 43 by 3 is the difference upper limit threshold value DTh _AU , and the value obtained by multiplying the minimum value of the fluctuation width DV _A by 3 is the difference lower limit threshold value. Let it be DTh _AL .

The data processing unit 48 stores these threshold values in advance prior to the analysis of the sample. The cause of the difference d in the amount of scattered light is considered to be the distortion and scratches of the reaction vessel 31 in addition to the background noise. While the background noise is assumed to be substantially constant, the distortion and scratches of the reaction vessel 31 appear as abnormal values, so the threshold value may be obtained by excluding the influence of these abnormal values. Further, it is desirable to calculate these threshold values based on the result of blank measurement for each reaction vessel 31. For example, by calculating and updating these threshold values for each blank measurement, the determination can be maintained with high accuracy. Further, by storing these threshold values for each reaction vessel 31, the determination can be maintained with high accuracy.

Taking the case where bubbles are present at the positions shown in FIG. 5 in the reaction vessel 31 (however, the concentration to be measured is unknown) as an example, the procedure for determining the waveform section in which the bubbles are present will be described by the flowcharts of FIGS. 11A to 11C. .. The scanning waveform 151 of the scattered light detector 43 is shown in the upper left of FIG. 13, and the scanning waveform 161 of the transmitted light detector 42 is shown in the lower left of FIG. For each, the average value _A A of the scattered light intensity at a concentration of the measurement target (the amount of transmitted light) (A _B), the upper threshold Th _AU (Th _BU), which are indicated by the lower threshold Th _AL (Th _BL). However, in this case, since the concentration to be measured is unknown, these values are also unknown.

First, when the waveform acquisition unit 49 acquires the scanning waveform to be measured by the transmitted photodetector 42 and the scattered light detector 43, the data processing unit 48 starts determining the waveform section without bubbles (S200).

The difference waveform 152 is calculated from the scanning waveform 151 of the scattered light detector 43 (S201). The obtained difference waveform 152 is shown in the upper right corner of FIG. The difference waveform of the scattered light is compared with the difference upper limit threshold DTh _AU and the difference lower limit threshold DTh _AL, and a section exceeding this is obtained and used as a waveform data removal section. In the difference waveform 152 in the upper right of FIG. 13, the removal section is shaded. The same applies to the scattered light waveform and the transmitted light waveform in the middle right and lower right of FIG.

Subsequently, the waveform section (removal section) exceeding the difference upper limit threshold / lower limit is removed from the scanned waveform of the transmitted light (S203). This state is shown in the lower right of FIG. Similarly, the waveform section (removal section) exceeding the difference upper limit threshold / lower limit is removed from the scanned waveform of the scattered light (S204). The scanning waveform of the scattered light from which the removed section has been removed is shown in the middle right of FIG.

The average value is calculated for each continuous waveform section in the scanning waveform of the transmitted light from which the removal section has been removed (S205). In this example, since it has two continuous waveform sections, the

average values

203 and 204 are calculated. The large average value 203 of the most value among the calculated average value 203 and the average value A _B scan waveform of the transmitted light (S206). This is because the amount of transmitted light decreases if air bubbles are present so as to block between the light source and the transmitted light detector 42.

Subsequently, the lower limit threshold value Th _BL of the transmitted light amount is set (S207). Specifically, as in FIG. 8B, calculated fluctuation range V in the continuous wave segment of the mean value A _B and the calculated average value 203 transmitted light, based on the average value A _B and fluctuation width V, the transmitted light quantity The lower limit threshold Th _BL can be set.

Subsequently, the scanning waveform 161 of the transmitted light (lower left column of FIG. 13) is compared with the lower limit threshold value Th _BL (S208), and since the section B is equal to or less than the lower limit threshold value Th _BL , the transmitted light amount reduction flag Flg1 is given to the section B. (S209). Subsequently, of the continuous sections in which the scattered light remains, the section to which the transmitted light amount reduction flag Flg1 is given is removed (S210). In this case, the continuous section included in the section B is excluded from the subsequent processing.

The average value was calculated for each of the continuous waveform sections in the scanned waveform of the scattered light from which the removed section and the section to which the transmitted light amount reduction flag Flg1 was added were removed (S211), and the highest value among the calculated average values was calculated. Let a large average value be the average value A _A of the scanning waveforms of scattered light (S212). This is because the amount of scattered light decreases if bubbles are present so as to block between the light source and the scattered light detector 43. In this example, as shown in the middle right of FIG. 13, since there is only one continuous section remaining, the average value 201 of the continuous section is the average value A _A of the scanning waveform of the scattered light.

Subsequently, the upper limit threshold Th _AU and the lower limit threshold Th _AL of the scattered light amount are set (S213). Specifically, as in FIG. 8A, obtains the variation width V in the continuous wave segment of the mean value A _A and the calculated average value 201 scattered light, based on the average value A _A and variation width V, the amount of scattered light The upper limit threshold Th _AU and the lower limit threshold Th _AL can be set.

Thus, the average value _A A of the scattered light intensity to be measured (the amount of transmitted light) (A _B), the upper threshold value Th _AU, the lower threshold Th _AL (Th _BL) was calculated. In step S214, the scanning waveform 151 of the scattered light (upper left in FIG. 13) is compared with the lower limit threshold Th _AL, and since there is no waveform section below the lower limit threshold Th _{AL, the process} proceeds to step S216, and section B is equal to or higher than the upper limit threshold Th _AU. Therefore, the scattered light amount increase flag Flg4 is added to the section B (S217).

Subsequently, in step S218, since the section B is a section to which both the transmitted light amount decrease flag Flg1 and the scattered light amount increase flag Flg4 are given, the section B is extracted as a waveform section in which bubbles exist, and is obtained from the scanned waveform data. , The data of the corresponding waveform section (here, section B) is removed (S219). Subsequently, since there is no section to which the scattered light amount reduction flag Flg3 is given in step S220, the process proceeds to step S222, and the remaining waveform section A is determined as a waveform section without bubbles.

On the other hand, the procedure for determining the waveform section in which the bubbles are present will be described by the flowcharts of FIGS. 11A to 11C, taking as an example the case where the bubbles are present at the positions shown in FIG. 6 in the reaction vessel 31. The scanning waveform 153 of the scattered light detector 43 is shown in the upper left of FIG. 14, and the scanning waveform 163 of the transmitted light detector 42 is shown in the lower left of FIG. For each, the average value _A A of the scattered light intensity at a concentration of the measurement target (the amount of transmitted light) (A _B), the upper threshold Th _AU (Th _BU), which are indicated by the lower threshold Th _AL (Th _BL). However, in this case, since the concentration to be measured is unknown, these values are also unknown.

The difference waveform 154 is calculated from the scanning waveform 153 of the scattered light detector 43 (S201). The obtained difference waveform 154 is shown in the upper right corner of FIG. The difference waveform of the scattered light is compared with the difference upper limit threshold DTh _AU and the difference lower limit threshold DTh _AL, and a section exceeding this is obtained and used as a waveform data removal section. In the difference waveform 154 in the upper right corner of FIG. 14, the removal section is shaded. The same applies to the scattered light waveform and the transmitted light waveform in the middle right and lower right of FIG.

The average value is calculated for each continuous waveform section in the scanning waveform of the transmitted light from which the removal section has been removed (S205). In this example, since there are two continuous waveform sections, the

average values

207 and 208 are calculated. The large average value 207 of the most value among the calculated

average value

207, 208 and the average value A _B scan waveform of the transmitted light (S206). This is because the amount of transmitted light decreases if air bubbles are present so as to block between the light source and the transmitted light detector 42.

Then, set the lower threshold Th _BL transmission light (S207), the scan waveform 163 of the transmitted light (left lower column of FIG. 14) compared to the lower threshold Th _BL (S208), the lower limit threshold value Th _BL following waveform segment Since there is no such thing, the process proceeds to step S211.

The average value was calculated for each of the continuous waveform sections in the scanned waveform of the scattered light from which the removed section and the section to which the transmitted light amount reduction flag Flg1 was added were removed (S211), and the highest value among the calculated average values was calculated. Let a large average value be the average value A _A of the scanning waveforms of scattered light (S212). This is because the amount of scattered light decreases if bubbles are present so as to block between the light source and the scattered light detector 43. In this example, as shown in the middle right of FIG. 14, since there are two continuous sections remaining, the average values 205 and 206 are calculated, and the average value 206 having the largest value among the average values 205 and 206 is scattered. The average value of the light scanning waveforms is A _A.

Subsequently, the upper limit threshold Th _AU and the lower limit threshold Th _AL of the scattered light amount are set (S213). Thus, the average value _A A of the scattered light intensity to be measured (the amount of transmitted light) (A _B), the upper threshold value Th _AU, the lower threshold Th _AL (Th _BL) was calculated.

Scan waveform 153 of the scattered light in step S214 (left upper part of FIG. 14) compared to the lower threshold Th _AL, section C is because it is below the lower threshold value Th _AL, imparts scattered light intensity decrease flag Flg3 in section C (S215 ). On the other hand, since there is no waveform section above the upper limit threshold value Th _AU (S216), the process proceeds to step S218.

In step S218, since there is no section to which both the transmitted light amount reduction flag Flg1 and the scattered light amount increase flag Flg4 are given, the process proceeds to step S220, and since the section C is a section to which the scattered light amount reduction flag Flg3 is given, the section C Is extracted as a waveform section in which bubbles are present, and the data of the corresponding waveform section (here, section C) is removed from the scanning waveform data (S221). Subsequently, the process proceeds to step S222, and the remaining waveform section D is determined as a waveform section without bubbles.

The automatic analyzer 1 extracts a section not affected by bubbles from the scanned waveform of the scattered light detected by the scattered light detector 43 in this way, and performs an analysis based on the amount of scattered light using the extracted waveform data. This makes it possible to improve the accuracy and reliability of the analysis by performing the analysis without the influence of bubbles.

1: Automatic analyzer, 2: Photometer data processing unit, 10: Sample disk, 11: Sample container, 15: Movable arm, 16: Sample dispensing mechanism, 17: Pipet nozzle, 19: Sample dispensing control unit, 20 : Reagent disc, 21: Reagent bottle, 22: Reagent cooler, 25: Reagent dispensing mechanism, 27: Bar code reader, 29: Reagent dispensing control unit, 30: Reaction disc, 31: Reaction vessel, 32: Constant temperature Tank, 36: Stirring mechanism, 38: Reaction vessel cleaning mechanism, 40: Light source, 41: Photometer, 42: Transmitted light detector, 43: Scattered light detector, 47: Data storage unit, 48: Data processing unit, 49 : Wave acquisition unit, 50: Interface, 51: Display device, 52: Input device, 53: Memory, 54: Computer, 55: External output media, 56: Printer, 101, 102: Bubbles, 121: Optical axis, 122: Optical axis orbit, 132: Measurement target, 151,153,171,271: Scattered light scanning waveform, 161,163,173: Transmitted light scanning waveform, 152,154,272: Difference waveform, 201,203,204,205, 206, 207, 208: Average value.

Claims

Multiple reaction vessels are arranged in the circumferential direction, and a reaction disk that can rotate intermittently and
A photodetector system including a light source and a photometer, which is arranged so that the reaction vessel arranged on the reaction disk passes between the light source and the photometer.
It has a photometer data processing unit and
The light detection system includes a transmitted light detector that irradiates a measurement target housed in the reaction vessel with light from the light source and receives the transmitted light transmitted through the measurement target, and the measurement housed in the reaction vessel. The object is provided with a scattered light detector that irradiates the object with light from the light source and receives the scattered light scattered by the measurement object.
The photometric data processing unit scans the light from the light source with respect to the measurement target by rotating the reaction disk, and obtains the first scanning waveform data from the transmitted light detector and the scattering. Using the waveform acquisition unit that acquires the second scanning waveform data from the optical detector, the first scanning waveform data, and the second scanning waveform data, the presence or absence of bubbles in the measurement target and the bubbles. An automatic analyzer having a data processing unit that identifies a section affected by the bubbles in the second scanning waveform data when is present.
In claim 1,
The transmitted light detector and the scattered light detector are automatic analyzers that are synchronized so that the scanning positions with respect to the measurement target are the same.
In claim 1,
An automatic analyzer that performs analysis based on the amount of scattered light of the measurement target by removing the scanning waveform data of the section specified by the data processing unit from the second scanning waveform data.
In claim 1,
The data processing unit stores a transmitted light lower limit of the transmitted light amount detected by the transmitted light detector, a scattered light upper limit threshold of the scattered light amount detected by the scattered light detector, and a scattered light lower limit threshold.
A first section of the first scanning waveform data in which the transmitted light amount is equal to or less than the transmitted light lower limit threshold value or the scattered light amount in the second scanning waveform data is equal to or greater than the scattered light upper limit threshold value is specified.
Among the second scanning waveform data, the second section in which the scattered light amount is equal to or less than the scattered light lower limit threshold value is specified.
An automatic analyzer that identifies the first section and the second section as the sections affected by the bubbles.
In claim 1,
The data processing unit stores the difference upper limit threshold value and the difference lower limit threshold value for the difference waveform obtained by calculating the difference in the amount of scattered light at the preceding and following sampling positions from the scanning waveform data from the scattered light detector.
A section in which the difference waveform obtained for the second scanning waveform data exceeds the difference upper limit threshold value or the difference lower limit threshold value is specified as a removal section.
Of the first scanning waveform data, the transmission light lower limit threshold value of the transmitted light amount is set based on the transmitted light amount of the section excluding the removal section.
An automatic analyzer that sets a scattered light upper limit threshold value and a scattered light lower limit threshold value of the scattered light amount based on the scattered light amount of the section excluding the removal section of the second scanning waveform data.
In claim 5,
The data processing unit has a first scan waveform data in which the amount of transmitted light is equal to or less than the lower limit of transmitted light, or the amount of scattered light in the second scanned waveform data is equal to or greater than the upper limit of scattered light. Identify the section and
Among the second scanning waveform data, the second section in which the scattered light amount is equal to or less than the scattered light lower limit threshold value is specified.
An automatic analyzer that identifies the first section and the second section as the sections affected by the bubbles.
In claim 5,
The data processing unit is an automatic analyzer that stores the difference upper limit threshold value and the difference lower limit threshold value for each reaction vessel.
In claim 5,
The data processing unit is an automatic analyzer that obtains the difference waveform from the scanning waveform data from the scattered light detector using pure water as the measurement target, and sets the difference upper limit threshold value and the difference lower limit threshold value.
In claim 8.
The data processing unit is an automatic analyzer that resets the difference upper limit threshold value and the difference lower limit threshold value when a blank measurement is performed with pure water as the measurement target.