JP2012008077A - Automatic analyzer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an automatic analyzer which can provide a user with a highly reliable inspection result by confirming during a progress of a reaction process that dispensation and agitation are actually properly carried out and then achieving proper dispensation and proper agitation.SOLUTION: The automatic analyzer includes: a photographing mechanism 400 which is provided separately from a measurement mechanism for measuring a chemical reaction in a reaction container 401, and photographs the reaction container 401; and control means 90 in which, during a measurement process for measuring the chemical reaction in the reaction container 401, the reaction container 401 is photographed by the photographing mechanism 400 in accordance with a preset predetermined timing, the photographed image is analyzed, and normal dispensation of at least one of a sample and a reagent in accordance with a kind of the reagent is confirmed.

Description

  The present invention relates to an automatic analyzer for measuring components in a biological sample such as blood, and more particularly to a technique for improving the accuracy thereof.

  2. Description of the Related Art Conventionally, techniques for automatically analyzing components of biological samples such as blood using an automatic analyzer have been provided. The chemical reaction between the specimen and the reagent is advanced in a dedicated reaction container, the absorbance of the mixture is measured at regular time intervals, and the concentration of a predetermined substance present in the biological sample is measured from the change in absorbance over time.

  In order to improve the reliability of the measured concentration, it is necessary to improve the accuracy of the absorbance data. However, data defects occur due to malfunctions in the mechanism for dispensing and stirring.

  Here, an example of data failure in the prior art will be described with reference to FIGS. 9 to 11 are explanatory diagrams for explaining an example of data failure in the prior art.

  For example, when a reagent shortage occurs due to a malfunction of the dispensing function or the like, the data tends to be generally higher than normal data (701 in FIG. 9) (702 in FIG. 9). Further, when scattering occurs due to a malfunction of the stirring function or the like, a discontinuous difference occurs in the data (703 in FIG. 10). Furthermore, sudden high values (spikes) may occur due to the presence of bubbles (704 in FIG. 11). These factors are known to affect the accuracy or accuracy of the measurement results.

  To solve such a problem, for example, Japanese Patent Laid-Open No. 10-227797 (Patent Document 1) describes an automatic analyzer that can confirm an analysis operation without opening a dust cover. Japanese Patent Laid-Open No. 2001-174469 (Patent Document 2) describes a technique for detecting suction and discharge of a liquid by providing a means for appropriately monitoring a dispensing operation.

  In addition, Japanese Patent Laid-Open No. 2002-162403 (Patent Document 3) maintains the accuracy of the dispensing amount by sampling at a constant depth by mounting a liquid level sensor at the tip of the dispensing nozzle. A method is described, and Japanese Patent Application Laid-Open No. 60-064256 (Patent Document 4) describes a method for suppressing the generation of bubbles per se by using a deaeration process.

Japanese Patent Laid-Open No. 10-227797 JP 2001-174469 A JP 2002-162403 A Japanese Patent Laid-Open No. 60-064256

  By the way, there are a plurality of items that can be measured by the automatic analyzer, and the type of reagent to be dispensed, the amount of the reagent, and the state of the reaction inside the container are different for each measurement item. Also, it is usual to use a plurality of types for one item, such as the first reagent and the second reagent.

  On the other hand, reaction containers are not different depending on measurement items, and all reaction containers used in the system have the same shape. Therefore, the ideal position of the liquid level differs for each analysis container used and for each kind of dispensed reagent. In addition, the amount of foam generated, the degree of turbidity, the color of the reaction, and the like are various for each measurement item, and the visual information obtained by observation inside the container is also different.

  Under this circumstance, in order to guarantee that the dispensing is correctly performed, it is necessary to confirm that the dispensing is correctly performed for each dispensing according to the reagent type.

  However, with the above-mentioned conventional method alone, it cannot be confirmed during the course of the reaction process that dispensing or stirring has actually been performed properly, and the final data must be output for confirmation. It took a lot of time.

  In this regard, as a means for detecting foreign matter during the analysis process, a method using an optical system detection method for measuring absorbance can be considered. Certainly, it may be possible to acquire an image that can detect the position of the liquid level and foreign matter simultaneously with the measurement of the absorbance by photographing the container using a photometer for measuring the absorbance. However, the field of view measured by the photometer is limited to a part of the region where the mixture in the reaction container exists, and there is a limit in detecting the liquid level and foreign matter alone.

  Therefore, the purpose of the present invention is to confirm that dispensing and stirring are actually performed properly during the course of the reaction process, realize appropriate dispensing and appropriate stirring, and provide a reliable test for the user. An object of the present invention is to provide an automatic analyzer capable of providing a result.

  The above and other objects and novel features of the present invention will be apparent from the description of this specification and the accompanying drawings.

  Of the inventions disclosed in the present application, the outline of typical ones will be briefly described as follows.

  In other words, the outline of a typical one is provided separately from the measurement mechanism that measures the chemical reaction in the reaction container, and the imaging mechanism that photographs the reaction container and the progress of the measurement process for measuring the chemical reaction in the reaction container The reaction mechanism was photographed by the photographing mechanism according to a predetermined timing set in advance, and the photographed image was analyzed, and at least one of the sample and the reagent was normally dispensed according to the type of the reagent. Control means for confirming this.

  The effects obtained by typical ones of the inventions disclosed in the present application will be briefly described as follows.

  In other words, the effects obtained by typical products are checked in synchronization with the analysis process for the presence or absence of bubbles in each reaction container, the presence or absence of dirt adhering to the container, the presence or absence of splashes, and the amount dispensed. It can be guaranteed in real time that the process was performed under more optimal conditions. As a result, it is possible to remarkably increase confidence in safe operation and accuracy. It also contributes to cost reduction for users by reducing the number of re-measurements and re-inspections.

It is a block diagram which shows the whole structure of the automatic analyzer which concerns on one embodiment of this invention. It is a block diagram which shows the structure of the imaging mechanism of the automatic analyzer which concerns on one embodiment of this invention. It is a figure which shows an example which image | photographed the reaction container containing the mixture of the automatic analyzer which concerns on one embodiment of this invention. It is explanatory drawing for demonstrating the detection method of the bubble of the automatic analyzer which concerns on one embodiment of this invention. It is a figure which shows an example of scattering by the malfunction of the stirring operation | movement of the automatic analyzer which concerns on one embodiment of this invention. It is a figure which shows an example of scattering by the malfunction of the dispensing operation | movement of the automatic analyzer which concerns on one embodiment of this invention. It is a flowchart which shows the process which specifies the inconvenience of the automatic analyzer which concerns on one embodiment of this invention. It is a flowchart which shows the whole process including the imaging | photography mechanism of the automatic analyzer which concerns on one embodiment of this invention, and its process. It is explanatory drawing for demonstrating an example of the data defect in a prior art. It is explanatory drawing for demonstrating an example of the data defect in a prior art. It is explanatory drawing for demonstrating an example of the data defect in a prior art.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. Note that components having the same function are denoted by the same reference symbols throughout the drawings for describing the embodiment, and the repetitive description thereof will be omitted. In addition, this invention is not limited to the following embodiment, The following embodiment is a typical example for implement | achieving the basic concept in this invention.

<1. Automatic analysis system overview>
A configuration of an automatic analyzer according to an embodiment of the present invention will be described with reference to FIGS. 1 and 2. FIG. 1 is a block diagram showing the overall configuration of an automatic analyzer according to an embodiment of the present invention, and shows a top view. FIG. 2 is a configuration diagram showing the configuration of the imaging mechanism of the automatic analyzer according to the embodiment of the present invention.

  In FIG. 1, the automatic analyzer 1 has, as main functions, a biological sample transport unit 20 that transports a biological sample, a dispensing mechanism 30 a to 30 c that dispenses a sample and a reagent, a reaction mechanism 40 that reacts the sample and the reagent, and a reagent Are stored in the first cold reagent disk 50, the second cold reagent disk 60, and the control unit 90 for controlling the entire automatic analyzer 1. The basic measurement procedure by each part of the main functions is briefly shown below.

  A specimen container 203 containing a biological sample collected from a patient is placed on the transport table 204 and set in the automatic analyzer 1.

  In the biological sample transfer unit 20, a transfer path 201 of the transfer table 204 is secured, and the transfer table 204 is placed on the transfer path 201 along the rail 202 that prevents shaking and falling during transfer and adjusts the position difference. Moving.

  The transport table 204 is transported to the transport table storage unit 206 of the sample disk 205 according to the timing programmed in advance in the system. Thereafter, the transport table 204 moves to the vicinity of the dispensing mechanism 30 a by the rotation of the sample disk 205.

  In this case, the specimen sample is dispensed into the reaction container 401 by the dispensing mechanism 30a.

  A plurality of reaction vessels 401 are installed on the reaction disk 402 and can be moved in an annular shape by the rotation of the disk. During the movement, the reagent dispensing mechanisms 30 b to 30 c are operated, and the reagents installed in the reagent disks 50 and 60 are dispensed into the reaction container 401.

  It is assumed that the reagent disks 50 and 60 have a plurality of reagent container storage portions 501 and 601 and necessary reagents are arranged in advance. The sample and reagent mixture 410 (see FIG. 2) generated in the above-described dispensing process is stirred by the stirring mechanism 406.

  In some cases, since it is necessary to stir the reagent itself, the first cold reagent disk 50 and the second cold reagent disk 60 are respectively provided with stirring mechanisms 502 and 602 dedicated to the reagent.

  The mixture 410 in the reaction vessel 401 passes through the photometric unit 405 at regular time intervals. In the photometry unit 405, the light emitted from the irradiation light source 403a is applied to the mixture 410, and the amount of transmitted light is measured. By repeating this a certain number of times, data on the change in absorbance with time is obtained, and the concentration of the measurement object contained in the biological sample is calculated based on the chemical reaction theory. The reaction vessel 401 that has finished the measurement is washed when it passes through the washing mechanism 407. The above operations are controlled by the control means 90.

<2. Unit according to the present invention>
(1) Unit Configuration In the automatic analyzer according to the present embodiment, the irradiation light source 403b and the reaction vessel 401 are photographed on the reaction disk 402 as a means different from the photometric unit 405 that measures the absorbance of the mixture 410. An imaging mechanism 400 including an imaging unit 404 is provided. A sensor such as a CCD, CMOS, or PMT is used for the imaging unit 404. The photographing means 404 is fixed in the reaction mechanism 40 together with the irradiation light source 403b in a state in which the positional accuracy is kept well.

  FIG. 2 shows details of the photographing mechanism. The photographing mechanism photographs the side surface 411 of the reaction container 401 at a predetermined timing, and acquires an image of the reaction container and the mixture 410 inside. Appropriate shooting timings are set for each measurement item, and therefore are set for each measurement item.

  Analyzing images taken with this unit, it is possible to proceed with analysis while confirming that the main operation is normal. For example, confirming the appropriateness of the dispensing operation based on the estimated dispensing volume by detecting the liquid level, confirming the appropriateness of the stirring operation by detecting the presence of bubbles or bubbles, or It is possible to detect the presence of the reaction container 401 by detecting its presence.

  For each dispensing, it is possible to check the dispensing amount (the position of the liquid level) and the presence or absence of foreign matter, and if a foreign matter is detected, the position can be specified. A similar method can be used at the start of measurement to confirm that the reaction vessel 401 is indeed empty or that no foreign matter such as dirt is attached.

  When the irradiation light source 403 b is on the side opposite to the imaging unit 404 via the reaction disk 402, the imaging unit 404 images the light 421 that the irradiation light 420 from the irradiation light source 403 b has transmitted through the mixture 410.

  On the other hand, when the irradiation light source 403 c is on the near side with the imaging unit 404 via the reaction disk 402, the imaging unit 404 images the light 423 reflected from the irradiation light 422 from the irradiation light source 403 c on the mixture 410.

(2) Arrangement of photographing means (i) Basic arrangement In the automatic analyzer shown in FIG. 1, there is one photographing means 404 to be installed, and the arrangement is such that photographing is performed from the outside of the reaction disk 402. On the contrary, the photographing means 404 may be arranged inside the reaction disk 402 and photographed from the inside of the reaction disk 402.

(Ii) Form using a plurality of imaging means Although not shown, a plurality of imaging means 404 are prepared, and the first reagent dispensing, the second reagent dispensing, the third reagent dispensing, and the agitation are performed at the positions. Each method may be installed. It is best to arrange so that there is a difference of n (integer) weeks between each operation. With this arrangement, it is possible to photograph the dispensing operation and stirring operation of each reagent at a time, and it is possible to proceed with analysis while confirming normal operation in each process.

(Iii) Form using movable imaging means Although not shown, the method using a plurality of imaging means 404 can be substituted by providing the imaging means 404 with a moving function. For example, an annular rail is provided on the outer frame of the reaction disk 402, and a vehicle is attached to the lower part of the photographing means 404 so that the rail can be moved in any direction on the left and right.

  By this mechanism, it is possible to move to the reaction container 401 where the operation to be photographed is performed each time. For example, when confirming the dispensing operation of the first reagent, the imaging unit 404 is moved to a position where the first reagent is dispensed. Moreover, when confirming stirring operation, it moves to the position where stirring is performed. This method is also effective for continuous monitoring of specific operations. In addition, since only one photographing unit 404 is required, the cost is reduced.

  Alternatively, a function of following a specific reaction vessel 401 is provided. This makes it possible to monitor a specific container in real time, which is particularly useful for detecting a phenomenon of time-developable defects. For example, the function of moving the imaging unit 404 is applied to follow the reaction containers individually, the reaction containers are periodically imaged, the difference between successive images is monitored over time, and the presence of foreign matter is detected in real time. It is also an effective method to grasp.

(Iv) Form using a camera with a wide imaging range Although not shown, a method of installing a camera with a wide imaging range is also effective. If such a camera is used, a plurality of reaction vessels 401 can be photographed at a time. If a plurality of reaction vessels 401 are shown in one image, it can be compared with the left and right reaction vessels 401, and stains and the like adhering to the unwashed residue can be found quickly and accurately. Note that it is convenient to specify the identification number on the reaction vessel in advance, and it is also convenient for maintenance such as specifying a position where dirt easily adheres.

(V) Form of providing an auxiliary function for imaging It reacts at a constant speed with the vertical direction as an axis for impurities such as fibrin that are difficult to optically detect and difficult to detect only from the front. A method of rotating the container 401 and photographing from a plurality of side surfaces is effective. This scheme can be substituted by a method in which the reaction vessel 401 is vibrated left and right or up and down. In addition, the method of illuminating the container from multiple directions using the scattered light by irradiating the scattering light with the scatter plate and irradiating the transmitted light through the reaction vessel to the scatter plate is also used to discover materials that are difficult to detect optically It is effective as a method for facilitating

<3. Image processing flow and data extraction method>
Next, the flow of image processing and the data extraction method of the automatic analyzer according to the embodiment of the present invention will be described with reference to FIGS. FIG. 3 is a diagram showing an example of a reaction vessel containing a mixture of an automatic analyzer according to an embodiment of the present invention, and FIG. 4 is a method for detecting bubbles in the automatic analyzer according to an embodiment of the present invention. FIG. 5 is a diagram showing an example of splattering due to a problem in the stirring operation of the automatic analyzer according to one embodiment of the present invention, and FIG. 6 is an automatic analysis according to one embodiment of the present invention. It is a figure which shows an example of scattering by the malfunction of the dispensing operation | movement of an apparatus.

  First, data obtained by photographing by the photographing unit 404 is sent to a control unit 90 configured by a computer or the like. Then, analysis is performed in the control means 90, information necessary for the subsequent operation is extracted, and feedback is given to the automatic analyzer. Below, a representative example is shown along the procedure.

(1) Liquid Level Detection FIG. 3 shows an example in which the reaction vessel 401 containing the mixture 410 is photographed. The subject is divided into a portion 410 where the mixture exists and a portion 411 where the mixture does not exist, and there is a difference in the amount of light detected from each region. They are separated by a boundary 412 having a finite thickness and a light intensity step.

  Here, the squares in FIG. 3 represent pixels. In the vicinity of the boundary 412, the light changes from a strong part to a weak part. This boundary line can be easily detected by using a feature extraction technique such as image differentiation in light amount difference image processing.

(2) Impurity detection Bubbles and bubbles may be generated and foreign substances may be mixed in during the analysis process. Here, taking a bubble as an example, the detection method will be described. The main cause of the generation of bubbles is a decrease in the amount of saturated gas dissolved in the solution. Many of these phenomena are caused by changes in the environment surrounding the solution such as temperature and pressure after dispensing. Therefore, even if the dispensing is correctly performed, bubbles may be generated during the analysis, which adversely affects the analysis result. The most effective way to avoid this is to monitor and discover the cells over time.

  An example of detecting bubbles by this method is shown in FIG. In the example shown in FIG. 4, the reaction container 401 is photographed over time. An image 401d photographed for the first time after a focused dispensing operation, an image 401e photographed next at regular intervals, and further periodically. The images 401 f photographed at regular time intervals are arranged in this order.

  If time passes after dispensing, a small bubble (801 of the image 401e) will generate | occur | produce. As time elapses, bubbles grow (802 in the image 401f). Of these images, the images 401g and 401h are obtained by taking the difference between the preceding and succeeding images, respectively. Since it is the difference between the images before and after, the cell itself and the mixture portion which are not changed are zero on average.

  In the differenced image, (i) the part where a new bubble is generated is an area having a positive luminance (image 401g and image 401 803).

  On the other hand, (ii) when the already generated bubble moves, or (iii) when the already generated bubble grows, the region has a negative value (804 in the image 401h).

  Next, for each image, the root sum square (difference in luminance) of the difference from the signal average amount of all images is calculated and recorded in the time series graph 810. The horizontal axis of the time series graph 810 is time 811, and the vertical axis is luminance fluctuation 812.

  When no bubble is generated, the luminance fluctuation keeps the value (camera-dependent value) 813 peculiar to the imaging system described above regardless of the passage of time (814 of the time series graph 810).

  On the other hand, when bubbles are generated, the above-described positive and negative irregularities are formed in the luminance of the image, so that the luminance fluctuation increases, and the graph (in the time-series graph 810 of the time-series graph 810) is in a state of rising right (in the time-series graph 810). 816).

  Here, a reference value 817 is set in advance, and when the luminance fluctuation of the photographed image exceeds the reference value, it is recognized as a bubble generation time 818. If there is a problem in the analysis, feedback to the automatic analyzer is performed by means such as an alarm display.

  In addition, the ease with which bubbles are generated and the amount of bubbles generated vary depending on the measurement item. For example, there is an item in which bubbles are always generated. If air bubbles cannot be detected during measurement of such items, there is a possibility of reagent misplacement. In this case as well, the function of issuing an alarm to the user and informing the content of the malfunction that is presumed to be malfunctioning is very effective.

(3) Confirmation of Normal Operation A method for identifying a foreign object using a physical quantity and determining whether the operation is normal will be described. Here, the scattering phenomenon will be described as an example.

(I) Cause of Stirring Operation FIG. 5 shows an example of splattering due to a failure in the stirring operation. This phenomenon occurs when the stirring bar is not properly immersed in the liquid mixture due to insufficient liquid volume, etc., and stirring is performed near the liquid surface.A large amount of liquid is scattered when the liquid on the surface is agitated with the stirring bar. A continuous liquid is formed inside.

  Water droplets 805 due to scattering adhere to the inner side surface of the reaction vessel 401i. The area where the water droplet exists is the upper part of the liquid surface (805 in FIG. 5), unlike the bubble.

  In order to detect this feature, the position of the water droplet from the bottom surface is first represented in a graph 820. The horizontal axis of the graph 820 is the water droplet number (in the order of the detected water droplet number) 821, and the vertical axis is the position 822. The liquid level position 823 of the mixture is also listed. The positions of the water droplets are all present at the upper part of the water surface (824 in FIG. 5).

  From this data, it is determined that the bubble is different. Next, the histogram 830 about an area is calculated | required regarding a water drop. The horizontal axis of the histogram 830 indicates the area 831, and the vertical axis indicates the number distribution 832. Since the size of the water droplets adhering to the side surface of the reaction vessel 401i is different, the distribution is wide (833 in FIG. 5).

  With the above method, the mechanism causing the problem can be estimated from the scattering state, and feedback to the apparatus by an alarm or the like can be performed.

(Ii) Cause of dispensing operation FIG. 6 shows an example of scattering due to a defect in dispensing operation. Spattering occurs when the dispensed reagent bounces back into the mixture. Dot-like liquid particles are generated on the wall of the analysis container.

  Similar to the above-mentioned phenomenon caused by stirring, water droplets 806 due to scattering adhere to the inner side surface of the reaction vessel 401j. The area where the water droplets are present is the upper part of the liquid surface, unlike the bubbles (806 in FIG. 6). As described above, the position of the water droplet from the bottom surface is shown in the graph 820. The positions of the water droplets are all present at the top of the water surface (825 in FIG. 6).

  Again, it can be determined from this data that the bubble is different. Unlike the case of the agitation operation described above, the area histogram 830 has a single water drop size, and thus the histogram has a profile having a peak only at one location (834 in FIG. 6).

  With the above method, the mechanism causing the problem can be estimated from the scattering state, and feedback to the apparatus by an alarm or the like can be performed.

(Iii) Others A method of directly observing the operation using a moving image is also effective for the malfunction of the dispensing operation.

(4) Other effective methods (i) Form using reference value As another method, a method of extracting features using statistical data and specifying a foreign object will be described.

  First, a plurality of samples having foreign matters are prepared in advance and classified according to the cause of occurrence. Next, for each cause of occurrence, statistics such as the area, shape, number, and number distribution of the foreign matter are calculated and stored in advance in the apparatus as a standard pattern of the foreign matter. Since the standard pattern differs depending on the reagent, information is registered for each reagent.

  In addition, as the number of foreign material samples increases, the standard pattern can be expected to express features more accurately. A function to automatically update the standard pattern based on the sample information is provided.

  For example, information obtained from a sample regarded as a foreign object is recorded in a database, and once for every 1000 measurements, an average value and a variance value are calculated for each cause of failure, and those values are used for the next measurement. It will be adopted as the standard value from Since the value obtained in this way is a value obtained by utilizing a malfunction phenomenon that has occurred in actual operation of the apparatus, the apparatus is more appropriately used than the value stored in the apparatus as a general parameter at the time of shipment. It can be said that the value expresses a unique phenomenon.

  Therefore, it is possible to expect improvement in the accuracy of defect detection in subsequent measurements. In addition, although it depends on the capacity of the database provided in the apparatus, an automatic calculation method may be used when the number of stored samples increases and the database needs to be updated.

(Ii) A mode using a method of matching a standard image obtained by photographing a standard solution Further, as a simpler form than a method using a standard value, a standard image obtained by photographing a standard solution is stored as a reference and dispensed. It is also effective to confirm the presence of a foreign substance by comparing the actual sample immediately after that with a difference from the standard image. Naturally, since the standard image is different for each measurement item, all the items handled by the apparatus can be registered, and if necessary, a function of updating the standard image automatically or according to a user instruction is provided.

(Iii) A form in which the judgment criterion is changed depending on the item. In order to reduce the calculation time and the calculation capacity in the image analysis, the points to be checked are narrowed down using the specificity of the reagent, and all the points in the above flow are used. It is also effective to select and check the minimum necessary contents instead. For example, more accurate specification is possible by grasping in advance the form of a foreign substance that is likely to be generated for each of the standard solution, blank solution, and quality control substance, and intensively determining the cause of the occurrence. It is also effective to have a function of selecting an appropriate check method for each type of reagent to be dispensed as well as the characteristics of the reagent.

(Iv) A mode in which a reaction vessel having a shape in which the liquid level after dispensing is always constant is used. Another method is to change the shape of the reaction vessel 401 for each measurement item, and to which item Alternatively, the liquid level may be the same when the reagent is dispensed appropriately. By setting in this way, it becomes possible to more easily determine an appropriate amount of dispensing.

<4. System processing>
Next, referring to FIG. 7, a process for identifying the inconvenience of the automatic analyzer according to the embodiment of the present invention will be described. FIG. 7 is a flowchart showing a process for identifying the inconvenience of the automatic analyzer according to the embodiment of the present invention, and determines the state of reagent dispensing based on the image of the reaction container, and causes a problem in the analysis process. Or the process which identifies the malfunction which has arisen in the automatic analyzer is shown. This process is performed by the control means 90.

  First, the dispensing amount of the reagent is calculated from the position information on the liquid level detected in the above analysis (S0). When the dispensed amount is lower than the preset amount, it is determined that the reagent is insufficient (S1). If there is a lack of reagent in S1, there is no guarantee that an effective analysis result will be obtained, so the reaction vessel 401 is excluded from the measurement process, and at the same time, an alarm is displayed indicating that the reagent is insufficient (S2).

  On the other hand, if it can be confirmed in S1 that a sufficient amount of reagent has been dispensed, then the presence of brightness shading is confirmed (S3). If there is no shading in S3, it is determined that there is no abnormality, and the reaction vessel is advanced to the next process (S4).

  If there is shading in S3, it is determined whether it is a foreign matter such as scattering, bubbles, bubbles, or other impurities based on the above-mentioned criteria (S5).

  If impurities exist in S5, the reaction vessel 401 is excluded from the measurement process in order to increase the reliability of the analysis result (S6). If the foreign matter such as bubbles or bubbles is scattered in S5, the positional relationship with the previously detected liquid surface is obtained, and it is confirmed whether the foreign matter is present in the reagent (S7).

  When the foreign substance exists inside the reagent in S7, it is determined as a bubble (S8). On the other hand, if it is outside in S7, it is confirmed whether the foreign matter is on the upper side or the surface of the liquid level (S9). When it exists in the upper side of a liquid level by S9, it determines that it is scattered (S10). Moreover, when it exists in the surface of a liquid level by S9, it is judged as a bubble (S11).

  Based on these determination results, it is possible to confirm whether the reagent is sufficiently dispensed or stirred, and when it is insufficient, feedback such as an alarm warning is performed.

  As another feedback method, when the reaction container 401 is confirmed to be dirty, a method of temporarily replacing the dirty reaction container 401 with the disposal reaction container 401 and operating the apparatus is not required to stop the apparatus. This is an effective means.

  In addition, when the presence of bubbles is confirmed, there is a method of controlling the photographing timing so that the absorbance can be measured while avoiding the positions of the bubbles.

  Next, referring to FIG. 8, the imaging mechanism of the automatic analyzer according to the embodiment of the present invention and the entire process including the process will be described. FIG. 8 is a flowchart showing the entire process including the imaging mechanism and the process of the automatic analyzer according to the embodiment of the present invention.

  By mounting the photographing mechanism on the automatic analyzer and providing the processing procedure of the flowchart shown in FIG. 8, the automatic analyzer can be mounted as a more effective analysis system.

  First, measurement is started after obtaining a biological sample (T0). First, a sample is dispensed into a predetermined container at a predetermined timing (T1), a reagent is dispensed (T2), and after an elapse of a predetermined time, an image obtained by photographing the reaction container 401 is analyzed (T4a). It is determined that the reagent has been dispensed (T5a).

  After confirming that the liquid is properly dispensed at T5a, the mixture is stirred as the next process (T3). After a certain period of time has elapsed, the image acquired by capturing the reaction container 401 is analyzed again (T4b). Here, from the analysis of the acquired image, the presence of brightness gradation is detected, and the presence of foreign matter is determined (T5b).

  When it is confirmed that the condition is normal at T5b, the process proceeds to a normal procedure, and the process is completed through absorbance measurement (T7), result acquisition (T8), and container cleaning (T9) (T10).

  On the other hand, when it is determined as abnormal in the results of T5a and T5b, the cause of the malfunction is estimated based on the analysis results in T4a and T4b (T11).

  Subsequent procedures are divided into the following two.

  (1) It is confirmed whether the number of abnormalities in which a failure is detected is within a predetermined number of times set in advance (T12). At this time, re-measurement is started from a step that affects the cause estimated from the result of the image analysis. For example, when the determination result that the liquid amount is small is obtained from the result of the image analysis, remeasurement is started from the liquid dispensing (T1) or the reagent dispensing (T2).

  When the result that the stirring is insufficient is obtained, the process is executed from the stirring step (T3).

  (2) When a malfunction more than the specified number of times is detected at T12, the automatic analyzer 1 performs self-maintenance (T13). Self-maintenance is a function provided in advance in the automatic analyzer 1. Maintenance such as cleaning of the mechanism that affects the cause of the defect estimated from the above image analysis result, operation check, etc. will be performed.

  For example, when a malfunction in the liquid volume reduction is detected from the result of the image analysis, the nozzle pressure is checked to check for clogging. If clogging is present, cleaning or air jet elimination is attempted. If abnormal stirring is observed, various functions such as the number of rotations of stirring are checked, and if necessary, recovery to a normal state is attempted.

  Thereafter, the user's intention to continue the measurement is confirmed (T14). If there is an intention to continue the measurement at T14, the process returns to T1 and the analysis is continued. If there is no intention to continue the measurement at T14, the cleaning process (T9). Then, the apparatus is stopped and finished (T10).

  Since this embodiment is a technique using an image, the amount of data handled is enormous. Therefore, a storage function for saving data is installed. In order to ensure that the dispensing operation and the stirring operation are correctly performed, an image obtained by photographing the final state after both operations are performed is stored in the storage device.

  As described above, in the present embodiment, as an imaging unit different from the photometer, an imaging mechanism capable of imaging the entire reaction container is used, and a dispensing operation and a stirring operation or a container are performed in synchronization with the measurement process. Take a picture of the inside of each reagent, and take into consideration that each reagent has different characteristics, and prepare appropriate judgment criteria for each reagent. The confirmation result can be displayed with an alarm warning for each reagent, and the information of the confirmed result is fed back to the automatic analyzer and re-examination is performed as necessary. By adding the processing procedure, appropriate dispensing and proper stirring can be performed, and the reliability of reliable operation and accuracy can be greatly increased.

  As mentioned above, the invention made by the present inventor has been specifically described based on the embodiment. However, the present invention is not limited to the embodiment, and various modifications can be made without departing from the scope of the invention. Needless to say.

  The present invention relates to an automatic analyzer for measuring a component in a biological sample such as blood, and can be widely applied to an apparatus or system that needs to improve the accuracy of the analysis.

  DESCRIPTION OF SYMBOLS 1 ... Automatic analyzer, 20 ... Biological sample conveyance part, 30 ... Dispensing mechanism, 40 ... Reaction mechanism, 50 ... 1st cold storage reagent disk, 60 ... 2nd cold storage reagent disk, 90 ... Control means, 201 ... Transfer route, 202 ... Rail, 203 ... Sample container, 204 ... Transport table, 205 ... Sample disk, 206 ... Transport table storage section, 400 ... Imaging mechanism, 401 ... Reaction container, 402 ... Reaction disk, 403a, 403b, 403c ... Irradiation light source, 404: photographing means, 405 ... photometry unit, 406 ... stirring mechanism, 407 ... cleaning mechanism, 410 ... mixture, 411 ... side surface of reaction vessel, 412 ... boundary (liquid surface), 420 ... irradiation light (when photographing with transmitted light) , 421 ... transmitted light, 422 ... irradiation light (when photographing with reflected light), 423 ... reflected light, 501 ... storage part of reagent container (first reagent), 502 ... reagent stirring mechanism (first Medicine), storage section (second reagent 601 ... reagent container), stirring mechanism (second reagent 602 ... reagent).

Claims (22)

An automatic analyzer that measures a chemical reaction in the reaction container by reacting a sample and a reagent in the reaction container,
An imaging mechanism that is provided separately from a measurement mechanism that measures a chemical reaction in the reaction container, and photographs the reaction container;
During the progress of the measurement process for measuring the chemical reaction in the reaction vessel, the imaging mechanism is imaged by the imaging mechanism according to a predetermined timing set in advance, the captured image is analyzed, and the reagent An automatic analyzer comprising: control means for confirming that at least one of the sample and the reagent is normally dispensed according to the type. An automatic analyzer that measures a chemical reaction in the reaction container by reacting a sample and a reagent in the reaction container,
An imaging mechanism that is provided separately from a measurement mechanism that measures a chemical reaction in the reaction container, and photographs the reaction container;
During the progress of the measurement process for measuring the chemical reaction in the reaction vessel, the imaging mechanism is imaged by the imaging mechanism according to a predetermined timing set in advance, the captured image is analyzed, and the reagent An automatic analyzer comprising control means for confirming that the sample and the reagent are normally stirred according to the type. The automatic analyzer according to claim 1 or 2,
The control means analyzes an image photographed by the photographing mechanism, the reaction container is empty before dispensing of the sample, and whether or not the reaction container is contaminated during the measurement process An automatic analyzer characterized by confirming. In the automatic analyzer according to claim 1, 2, or 3,
The automatic analyzer is characterized in that a plurality of the imaging mechanisms are arranged at a position where at least one dispensing operation of the sample and the reagent can be imaged and at a position where the agitation operation of the reaction container can be imaged. In the automatic analyzer according to claim 1, 2, or 3,
Moving means for moving the imaging mechanism along a disk storing the reaction container;
The control means controls the moving means, moves the imaging mechanism to the position of the reaction container where the operation to be imaged is performed, and then follows the movement according to the movement of the reaction container. An automatic analyzer characterized in that the reaction vessel is photographed according to timing. In the automatic analyzer according to claim 1, 2, or 3,
The automatic analyzer is characterized in that the photographing mechanism can photograph a horizontally long range and is installed at a position where a plurality of the reaction containers can be photographed by one photographing. In the automatic analyzer according to any one of claims 3 to 6,
At least one of a mechanism for rotating the reaction vessel at a constant speed around the vertical direction, a mechanism for vibrating the reaction vessel back and forth or up and down, and a mechanism for scattering light emitted from a light source and passing through the vessel ,
The automatic control apparatus characterized in that the control means causes the reaction container to rotate, vibrate, or scatter light transmitted through the reaction container when the photographing mechanism photographs the reaction container. In the automatic analyzer of any one of Claims 1-7,
The control means causes the imaging mechanism to take an image of the reaction vessel after a predetermined time has elapsed after dispensing of the reagent, analyzes the taken image, and determines the position of the liquid level in the reaction vessel and An automatic analyzer characterized by detecting the presence or absence of foreign matter. The automatic analyzer according to claim 5 or 7,
The control means causes the imaging mechanism to periodically image the reaction container at a predetermined timing, monitors a difference between images before and after the imaged over time, and determines the liquid in the reaction container based on the change in the image. An automatic analyzer characterized by detecting the position of the surface, the appropriate amount of dispensing, the generation of bubbles and bubbles, and the presence or absence of foreign matter. The automatic analyzer according to claim 1,
The control means causes the imaging mechanism to continuously image the reaction container at a predetermined time interval from the start to the end of the dispensing operation of at least one of the sample and the reagent. An automatic analyzer characterized by confirming that the dispensing operation is normally performed based on a change over time or a part of images of the continuous image. The automatic analyzer according to claim 2,
The control means causes the imaging mechanism to continuously image the reaction container at a predetermined time interval from the start to the end of the stirring operation of the sample and the reagent, or the temporal change of the captured continuous images, or the An automatic analyzer that confirms that the stirring operation has been normally performed based on a partial image of the continuous image. The automatic analyzer according to claim 8 or 9,
Based on the detected information, the control means acquires the positional relationship between the position of the liquid surface and the foreign matter, the area of the foreign matter, the symmetry of the shape, the number, the number distribution, and the physical quantity of continuity. An automatic analyzer that compares a physical quantity with a reference value to distinguish the foreign matter for each type and estimates the cause of occurrence based on the distinguished type. The automatic analyzer according to claim 12,
The control means holds the reference value for each type of the reagent in advance,
An automatic analyzer that changes the reference value for each type of the reagent during the measurement process. In the automatic analyzer of any one of Claims 1-7,
The control means holds, as a reference image, an ideal pattern image in which the shape of the reaction container and the standard solution are correctly dispensed in the reaction container in advance, and is photographed by the photographing mechanism during the measurement process. An automatic analyzer that compares the image with the reference image and detects the position of the liquid surface obtained by dispensing and the presence of foreign matter. The automatic analyzer according to claim 14, wherein
The control unit holds the reference image corresponding to the type of the reagent in advance, and selects the reference image based on the reagent to be dispensed. The automatic analyzer according to claim 14, wherein
The automatic analysis apparatus characterized in that the control means updates the ideal pattern image according to the number of times the measurement process is performed. In the automatic analyzer of any one of Claims 1-7,
The control means holds in advance information on specificity found for each of the items of standard solution, blank solution, quality control substance, and calibration substance, and depends on the dispensed reagent based on the specificity information. An automatic analyzer characterized by selecting checkpoints. In the automatic analyzer of any one of Claims 1-7,
The reaction vessel is composed of a plurality of reaction vessels having a plurality of different shapes,
The control means has a dedicated shape for each of the analysis items from the plurality of reaction containers so that the liquid level is constant when the dispensing amount of the reagent that is different for each analysis item is correctly dispensed. An automatic analyzer characterized by selecting the reaction container. The automatic analyzer according to claim 3,
When the control unit confirms the contamination of the reaction container, the control unit replaces the reaction container in which the contamination is confirmed with a temporarily used reaction container for temporary use. In the automatic analyzer according to any one of claims 1 to 18,
The control means displays a warning and determines the necessity for reinspection based on the confirmed or detected information. If it is determined that reinspection is necessary, the control unit turns the reaction container for reinspection. An automatic analyzer characterized by that. In the automatic analyzer according to any one of claims 1 to 18,
The automatic analysis apparatus characterized in that the control means sets the timing of imaging by the imaging mechanism for each type of reagent. In the automatic analyzer according to any one of claims 1 to 18,
The automatic analyzer according to the imaging mechanism, wherein the light used for imaging is transmitted light passing through the reaction container or reflected light from the reaction container.