The present invention relates to an analyzer for a clinical examination that performs qualitative and quantitative analysis of a biological sample such as blood or urine, and particularly relates to an automatic analyzer including a reaction tank circulation flow path.
For example, in a biochemical automatic analyzer, in order to perform component analysis of a biological sample such as serum or urine, a test sample and a reagent are caused to react with each other in a reaction vessel, and a change in color tone or turbidity caused by the reaction is optically measured by a photometry unit such as a spectral photometer at regular time intervals. In order to suppress a fluctuation in the chemical reaction rate of the sample and the reagent in the reaction vessel depending on a temperature fluctuation, the reaction vessel is immersed in constant temperature water where the temperature is stable. This constant temperature water is circulated through a heater and a cooling device to keep the reaction vessel at the stable temperature.
However, when bubbles are mixed in the constant temperature water and cross an optical axis during measurement of absorbance data of the sample in the reaction vessel, light is scattered or absorbed by the bubbles such that the measured absorbance data is a value different from that of a typical chemical reaction. Therefore, the automatic analyzer includes a degassing unit in a circulation flow path to suppress the formation of bubbles. When the degassing performance of the degassing unit decreases, bubbles are formed in circulating water.
However, the presence of bubbles does not always cause an abnormal value of an analysis result, and when an examination item is an item where absorbance values at two wavelengths are acquired to calculate a concentration using a difference therebetween, even if the measured absorbance values are affected by bubbles, the effects of the bubbles can be suppressed by acquiring the difference. Therefore, there is a case where an increase in the amount of the bubbles cannot be noticed from the analysis result.
PTL 1 discloses that whether disturbance related to a photometry portion of a reaction vessel occurs is determined by measuring light at a wavelength where there is no absorption by a reaction solution multiple times. Examples of the disturbance include scratches, contamination, and bubble attachment of the reaction vessel.
PTL 2 discloses that, when absorbance data in the same reaction vessel is measured at multiple points at predetermined time intervals in a chronological manner and a spike-like change in absorbance is detected, alarm information is added to the measurement data, and it is determined that there is an effect of an increase in the amount of foreign matter such as bubbles or scale in constant temperature water based on an alarm occurrence frequency.
PTL 3 discloses that reaction tank water is dispensed into a reaction vessel during an operation of an automatic analyzer and absorbance of the reaction tank water is measured to determine the water quality of the reaction tank water such that supply and drainage of the reaction tank water are performed depending on the water quality determination.
A main factor for the mixing of bubbles in constant temperature water is a decrease in the degassing performance of the degassing unit for the constant temperature water. When the concentration of dissolved oxygen in the reaction tank circulating water increases due to a decrease in the degassing performance of the degassing unit, a state where bubbles are likely to be formed is established. However, typically, the degassing unit is disposed in the analyzer, and it is difficult to frequently access the degassing unit. Further, the degassing unit is connected to a flow path, and thus it is difficult to check the internal state of the degassing unit.
In PTL 1 and PTL 2, an abnormality is determined from a change in absorbance at a wavelength where there is no absorption for a reaction solution obtained by a chemical reaction of a sample and a reagent.
In PTL 3, the water quality abnormality of the reaction tank circulating water is determined by measuring the reaction tank water (alternatively, a standard sample having a known absorbance). However, during an operation, dedicated measurement for the water quality determination of the reaction tank circulating water is performed, and the examination efficiency of the automatic analyzer may decrease.
An object of the present invention is to implement an automatic analyzer that can detect a water quality abnormality where bubbles are likely to be formed in reaction tank circulating water using an absorbance value obtained by an operation without adding a dedicated mechanism or measurement.
An automatic analyzer according to one embodiment of the present invention includes: a reaction tank; a reaction disk that holds a reaction vessel in a state of being immersed in a reaction tank circulating water in the reaction tank; a circulation flow path that adjusts a temperature of the reaction tank circulating water from the reaction tank and returns the reaction tank circulating water to the reaction tank; a degassing device provided in the circulation flow path to degas the reaction tank circulating water; a photometer including a light source lamp and a photodetector that detects light emitted from the light source lamp and transmitted through the reaction vessel; and a control unit that controls a sequence of analyzing a sample and analyzes the sample, in which, prior to dispensing the sample into the reaction vessel and performing sample measurement, the control unit dispenses pure water into the reaction vessel to perform water blank measurement, corrects absorbance data of a reaction solution of the sample and a reagent measured by sample measurement with water blank absorbance data measured by the water blank measurement, and analyzes the sample based on the corrected absorbance data, and the control unit determines a water quality abnormality of the reaction tank circulating water based on the water blank absorbance data measured by the water blank measurement.
According to the present invention, a water quality abnormality of reaction tank circulating water can be detected without adding a dedicated mechanism or check operation. Problems, configurations, and effects other than those described above will be clarified by the description of the following embodiments.
Hereinafter, one embodiment of the present invention will be described in detail with reference to the drawings.
An operation of an automatic analyzer will be described based on a configuration of the automatic analyzer illustrated in
First, reaction vessels 1 are cleaned by a cleaning mechanism 17 and a pure water pump for cleaning 15. Next, regarding each of the reaction vessels 1, pure water is dispensed into the reaction vessel, and the measurement is performed by a photometer configured by a light source lamp 3, a diffraction grating for spectroscopy 4, and a photodetector 5 to acquire photometry data (water blank value). Next, pure water is removed from the reaction vessel 1.
Next, a sample in a sample cup 7 placed on a sample disk 8 is dispensed into the reaction vessel 1 placed on a reaction disk 2 using a sample dispensing mechanism 11 and a sample dispensing pump 14. Likewise, a reagent in a reagent bottle 9 placed on a reagent disk 10 is dispensed into the reaction vessel 1 by a reagent dispensing mechanism 12 and a reagent dispensing pump 16, and both of the sample and the reagent are stirred using a stirring mechanism 13. In the reaction solution in the reaction vessel 1, color development of the chemical reaction is measured by the photometer at regular time intervals determined according to the rotation of the reaction disk 2. In order to stably accelerate the chemical reaction, the reaction vessel 1 is kept at a constant temperature by a constant temperature water supply device 6. After completion of the measurement, the reaction vessel 1 is cleaned by the cleaning mechanism 17 and the pure water pump for cleaning 15 and is used for next measurement of the sample.
A configuration of the photometer will be described. Light emitted from the light source lamp 3 transmits through the reaction vessel 1 and is separated into respective components by the diffraction grating wavelength for spectroscopy 4. Before the separation, the required number of the photodetectors 5 are installed and disposed at positions corresponding to wavelengths required for the measurement. The light incident on the photodetector 5 is converted into photoelectricity to generate a current in proportion to the light intensity, that is, the number of photons in the light. This current is called a photocurrent. In order to obtain an electric signal in proportion to a concentration of a component to be measured in a sample, the concentration is converted into a digital value by an AD conversion unit 20, is stored in a storage device 23 via an interface bus 27, and is analyzed by the control unit 22.
In order to calculate the concentration of the sample, absorbance data corrected by the water blank value is used. The absorbance varies due to the effect of scratches or attachment of contamination of a sample container and a change in the light intensity of the light source lamp. Therefore, in general, the water blank value is acquired immediately before the sample measurement.
This way, in the automatic analyzer, the reaction vessel 1 is repeatedly used in order of the cleaning, the water blank measurement, and the sample measurement. In the water blank measurement, blank water (purified water, pure water) is dispensed into the reaction vessel 1, and the measurement is performed at a timing at which the reaction vessel 1 crosses the front of the photometer due to the rotation operation of the reaction disk 2. Since the purified water has low wettability, bubbles are likely to be attached to a wall of the reaction vessel 1. When bubbles are attached to an inner wall of the reaction vessel, accurate absorbance cannot be obtained. Therefore, in the water blank measurement, water is discharged into the reaction vessel 1 and the stirring operation is not also performed to suppress the formation of bubbles. In addition, the surroundings of the reaction vessel 1 are kept at a constant temperature of 37° C. by circulating the reaction tank circulating water. When the temperature of the blank water increases, dissolved oxygen is likely to form bubbles, and thus the measurement is completed within a short period of time. Note that, in general, the measurement is performed multiple times in consideration of a variation in measured value. In the water blank absorbance measurement, the reaction vessel does not include a factor that causes a variation in absorbance. Therefore, a stable measured value can be obtained.
Bubbles in the reaction tank circulating water 112 are disturbances in the absorbance measurement. Therefore, in the circulation flow path of
When the dissolved oxygen concentration in the reaction tank circulating water 112 is kept at 5.0 mg/L or less, a variation in absorbance caused by bubbles is not seen. With reference to
In
As an index for the dissolved oxygen concentration, the average value (
Next, the details of a process in which the automatic analyzer determines a water quality abnormality of the reaction tank circulating water based on the index for the water blank absorbance range will be described.
First, the control unit 22 measures a water blank absorbance (S01), and stores the measured water blank absorbance in the storage device 23 (S02). A water blank absorbance range for each water blank measurement is calculated from the obtained photometry data (S03), and is stored in the storage device 23 (S04). This water blank absorbance measurement is performed as the water blank measurement in the analytical sequence of the automatic analyzer described above with reference to
Whether a required number of pieces of data of the water blank absorbance range are stored is determined (S05), and the measurement and storage of the water blank absorbance and the calculation and storage of the water blank absorbance range are repeated until the required number of pieces of data are accumulated. When the required number of pieces of data are accumulated, the control unit 22 calculates an index value of the reaction tank circulating water based on the water blank absorbance range accumulated in the storage device 23, and stores the calculated index value in the storage device 23 (S06). As the index, the index for the dissolved oxygen concentration described above is used. The control unit 22 compares the index value to a threshold (S07), and when the index value exceeds the threshold, the control unit 22 notifies the user of a water quality abnormality of the reaction tank circulating water (S08). The threshold for the abnormality determination may be set to a fixed value, or may be set based on by requiring a distribution of normal data in the analyzer. For example, a standard deviation SD of the water blank absorbance range is calculated from a plurality of pieces of measurement data collected in a state where the analyzer is normal after maintenance of the reaction tank, and is multiplied by a set coefficient C to obtain a threshold (C×SD). The threshold is updated whenever the maintenance of the reaction tank is performed.
When the water quality abnormality of the reaction tank circulating water is detected, the water quality abnormality can be output to a display 24 or a printer 25 to warn the user. In addition, by imparting a function of adding and recording not only the measurement data but also the alarm information to the storage device 23 and subsequently referring to the accumulated data, abnormality history can be analyzed from the measurement data. As a result, the measurement reliability can be improved. Further, the accumulated data may be transmitted to a service location via a communication line to monitor the state of the automatic analyzer at the service location. As a result, a countermeasure such as an instruction for maintenance or component replacement can be taken at an early stage, and the reliability of the analyzer can be improved.
The water quality abnormality of the reaction tank circulating water is determined based on the water blank absorbance. Therefore, as factors that cause the abnormality, not only the malfunction of the degassing device but also deficiency in the surfactant concentration in the reaction tank circulating water can be considered. When the reaction tank circulating water 112 overflows from the reaction tank 18, water is replenished such that the surfactant concentration in the reaction tank circulating water 112 gradually decreases. When the surfactant concentration decreases, bubbles are likely to be attached to a window of the reaction vessel or the reaction tank. In this case, the water blank absorbance range is expected to be improved by the addition of the surfactant. Therefore, when the abnormality determination is made in Step S07, a step of adding the surfactant to the reaction tank circulating water 112 may be provided. The surfactant is added, the water blank absorbance is measured again, and the index value is calculated to perform the abnormality determination (S01 to S07). When the index value indicates an abnormality even after the abnormality determination, an alarm is generated and notified to the user (S08).
In addition, when floating matter such as trash is present in the reaction tank circulating water 112, the amount of the reaction tank circulating water 112 increases. Therefore, the reaction tank circulating water 112 may be improved by performing maintenance such as the water replacement of the reaction tank or the cleaning of the reaction tank. Therefore, by storing and monitoring the operational situation of the maintenance together with the water blank absorbance range, the determination of the water quality abnormality can be made more appropriately.
That is, in the present embodiment, the water quality abnormality of the reaction tank circulating water 112 is determined based on the water blank absorbance range. As factors that worsen the water blank absorbance range, some factors can be considered, and methods of resolving abnormality caused by the factors are different. Accordingly, an alarm may be output by determining the water quality in consideration of past operation history in the automatic analyzer. As a result, when an abnormality is highly likely to occur in the degassing device, the abnormality can be narrowed to output an alarm. To that end, it can be considered to use an abnormality determination algorithm by machine learning for the determination of the water quality abnormality of the reaction tank circulating water 112.
The learning device 210 acquires information related to the water quality of the reaction tank circulating water, for example, water blank absorbance range data 201, maintenance history data 202, and alarm information data 203 (the information will be collectively referred to as water quality related data) from the storage device 23 of the automatic analyzer. In addition, the water quality related data may include the water blank absorbance range data or index data calculated based on the water blank absorbance range data.
An input unit 211 acquires these pieces of data directly or via a network. A training data generation unit 212 generates training data from the data acquired by the input unit 211.
A training data input unit 213 inputs the training data generated by the training data generation unit 212 to the learning model for determining the water quality abnormality, and a learning model update unit 214 updates the learning model. An updated learning model 220 is transmitted from an output unit 217 to the automatic analyzer, and the control unit 22 determines the performance of the degassing device using the learning model 220. An original form of the learning model used for determining the performance of the degassing device is accumulated in an algorithm database 215. In order to improve the accuracy of the learning model, it is necessary to learn using as much training data as possible. Therefore, the same data is collected from another automatic analyzer and is stored in other device data database 216. The learning model accumulated in the algorithm database 215 is generated based on the training data from the other device data database 216. When the learning model update unit 214 updates the learning model and the algorithm of the learning model is changed, change information is fed back to the training data generation unit 212, and a training data generation condition of the training data generation unit 212 is updated.
As the learning model 220, any learner such as a neural network, a regression tree, or a Bayes identifier can be used.
The learning model 90 is a learning model related to “degassing performance determination” as the output data, and is illustrated together with examples of input and output data. Both of the input and output data are exemplary. The water quality related data (or processed data thereof; hereinafter, also referred to as the water quality related data without being distinguished) is input to the input layer 91, and an operation result corresponding to the input is output from the output layer 93. Examples of the data input to the input layer 91 include the water blank absorbance and the water blank absorbance range (maximum value−minimum value) defined for each of the learning models and measurement result information 94 such as a frequency at which the value of the water blank absorbance range is an abnormal value, and device related information 95 including the operational situation of maintenance by the user and information on an alarm history that has been generated thus far. Examples of the maintenance include operations that may affect the degassing performance, for example, the water replacement of the reaction tank, the cleaning of the reaction tank, and the replacement of the degassing device. In addition, the information on the alarm history includes various levels of alarms. For example, there is a case where the maintenance is necessary to cancel the alarm or a case where the maintenance is not immediately necessary but the alarm is at an attention level that requires observation.
The output data from the output layer 93 is an inference result for a degassing performance determination result 97 and a cause of abnormality 98, and the necessity of an action on the degassing device 102 can be determined based on this result. An output value such as “degassing performance deteriorated (alarm level)”, “degassing performance attention required”, or “degassing performance normal” that is output data of a degassing performance determination result 97 is a probability value, and is determined based on whether the output probability value is a predetermined threshold or more. The cause of abnormality 98 implies the occurrence of an abnormality due to a factor other than the degassing device. For example, the occurrence of an abnormal value caused by a cause of abnormality other than the degassing performance, for example, the clogging of the reaction tank such as contamination or trash or the light source lamp can be inferred.
Number | Date | Country | Kind |
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2021-138598 | Aug 2021 | JP | national |
Filing Document | Filing Date | Country | Kind |
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PCT/JP2022/029846 | 8/3/2022 | WO |