JP7522835B2 - Automatic analyzer and method for registering reagent in automatic analyzer - Google Patents

Description

The present invention relates to an automatic analyzer that measures the concentration or activity value of a target component in a sample containing multiple components, such as blood or urine, and a method for registering a reagent in the automatic analyzer, and to an automatic analyzer that uses multiple containers filled with multiple types of reagents by simultaneously installing them, and a method for registering a reagent in the automatic analyzer.

Patent document 1 describes a device that is provided with a recording medium that records information regarding the arrangement within the housing of multiple types of reagents contained in the reagent container, an information reading means that reads the information recorded on the recording medium, and a reagent dispensing control means that controls which reagent from the reagent container is to be dispensed by the reagent dispensing means based on the information read by the information reading means.

JP 2005-43137 A

In automated analyzers that analyze biological samples such as blood and urine, the reagents used to react with these samples are filled into reagent containers and placed on the circumference of a circular table (hereafter referred to as the reagent disk). Rotating the reagent disk minimizes nozzle movement and enables random access to the reagent containers. It is becoming mainstream to design analyzers that use this type of operation to maximize processing capacity.

The automated analyzer stores pre-registered reagent information, the analysis items to be measured using that reagent, and the position number of the reagent disk in which the reagent is placed.When performing a measurement, the reagent disk is rotated so that the reagent container containing the reagent to be used is positioned at the reagent aspiration position, and the reagent aspiration nozzle is moved over the target reagent container to aspirate the reagent.

Here, there are two types of reagent containers: one that contains one type of reagent in one container (reagent container), and one that is called a reagent container set, in which multiple reagent containers are combined into one container to accommodate analysis items that require the addition of multiple reagents to be measured (hereinafter, these will be collectively referred to as reagent bottles).

Methods for installing such reagent bottles include a method in which the user installs the reagent bottle directly on the reagent disk, and a method in which the device pulls the reagent bottle, which the user has installed in a specified position, onto the reagent disk.

If the user makes a mistake when installing the reagent container, the device will misidentify the reagent type, or the system will be unable to register the reagent container, leading to the output of incorrect data and cumbersome work for the user. In either case, the user would normally have to check the orientation of the reagent bottle before installing it, which is cumbersome work and prone to human error.

In particular, with the type of reagent bottles in the reagent cassette described above, it is necessary to identify the type of reagent (first reagent, second reagent, etc.) in the same bottle, so there is a higher demand for correct installation orientation.

However, reagent bottles are often symmetrical to make them smaller, which makes it difficult to distinguish between them. Also, installing the bottles in the wrong direction can lead to abnormal measurement results and require the test to be redone, so it is necessary to install the bottles in the correct direction or to identify the direction in which the reagent to be aspirated is located.

In order to reduce such workload for users, for example, Patent Document 1 describes an automatic analyzer that can perform analysis without considering the orientation of the reagent bottles during installation by controlling the dispensing order to change depending on the orientation of the reagent bottles.

Reagent bottles used in automated analyzers are typically equipped with information media such as barcodes that include expiration dates and lot information. The method described in Patent Document 1 assumes that in addition to the information media, the device is equipped with a medium such as a black-and-white label for identifying information to determine the orientation of the reagent bottle and a mechanism for reading this on the device side, and realizes a function for the device to determine the appropriate installation orientation from the orientation of the reagent bottle and other information. This allows the user to install the device without having to worry about the orientation of the reagent bottle.

However, with the technology described in Patent Document 1, if there is a problem such as scratches or dirt on the identification medium for determining the orientation of the reagent bottle or the reading mechanism on the device, the former means that the reagent bottle cannot be registered, and the latter means that all reagent bottles cannot be registered. In particular, the inside of the reagent storage mechanism is at high risk of reagent scattering and is an environment where dirt easily accumulates, making it a place at high risk of contamination.

In such cases, an alternative method would be for users to manually enter bottle information on the operation screen, allowing them to register reagent bottles, but this would be a very cumbersome operation, which would actually extend the work time and invite human error.

In addition, if it is assumed that, in addition to the reagent information identifier that is already equipped on conventional devices, media for identifying the orientation information of reagent bottles and reading mechanisms on the device side will be added, there will be an increase in costs associated with the addition of these mechanisms, as well as an increased risk of breakdowns and problems occurring during identification.

In view of the above problems, the present invention provides an automatic analyzer capable of identifying the installation orientation of a reagent bottle without adding any special mechanism, and a method for registering reagents in the automatic analyzer.

The present invention includes multiple means for solving the above problems, and one example is an automatic analyzer for analyzing samples, comprising a reagent holding mechanism capable of holding multiple reagent container sets, each of which is a collection of multiple reagent containers containing one type of reagent, an information medium reading mechanism for reading first reagent information recorded on an information medium attached to the reagent container sets, and an information acquisition unit capable of actually measuring, by at least two or more different methods, second reagent information for identifying the installation orientation of the reagent container set when placed in the reagent holding mechanism, and is characterized in that the installation orientation of the reagent container set is determined from the first reagent information read by the information medium reading mechanism and the second reagent information measured by the information acquisition unit.

According to the present invention, the orientation of a reagent bottle can be identified without adding any special mechanism. Other problems, configurations, and effects will become clear from the description of the following examples.

1 is a schematic diagram of an automatic analyzer according to an embodiment of the present invention. FIG. 2 is a schematic diagram of a reagent disk in the automatic analyzer according to the present embodiment. FIG. 2 is a schematic diagram of a reagent bottle in the automatic analyzer according to the present embodiment. 4 is a schematic cross-sectional view of a reagent bottle in the automatic analyzer according to the present embodiment, in which a first reagent storage portion and a second reagent storage portion have the same shape. FIG. 4 is a schematic cross-sectional view of a reagent bottle in the automatic analyzer according to the present embodiment, in which a first reagent storage portion and a second reagent storage portion have different shapes. FIG. FIG. 4 is a control block diagram relating to determination of the orientation of a reagent bottle in the automatic analyzer according to the present embodiment. FIG. 4 is a conceptual diagram of linking analysis parameters and reagent bottles in the automatic analyzer according to the present embodiment. 5 is a flowchart of reagent bottle registration in the automatic analyzer according to the present embodiment. 5 is a flowchart for acquiring reagent bottle installation orientation information in the automatic analyzer according to the present embodiment. 5 is a flowchart showing a process for determining a liquid level in the automatic analyzer according to the present embodiment. FIG. 4 is a conceptual diagram showing the height at which a reagent is lowered in the automatic analyzer according to the present embodiment. FIG. 4 is a conceptual diagram showing the height at which a reagent is lowered in the automatic analyzer according to the present embodiment. 4 is a flowchart showing a procedure for determining the nature of a liquid in the automatic analyzer according to the present embodiment. 4 is a flowchart showing absorbance determination in the automatic analyzer according to the present embodiment. 4 shows details of absorbance determination in the automatic analyzer according to the present embodiment.

An embodiment of the automatic analyzer of the present invention and a method for registering a reagent in the automatic analyzer will be described with reference to Figures 1 to 15. Note that in the drawings used in this specification, identical or corresponding components are given the same or similar reference numerals, and repeated explanations of these components may be omitted.

<Basic configuration of the device>
First, the overall configuration of the automatic analyzer will be described with reference to Figures 1 to 5. Figure 1 is a schematic diagram showing an embodiment of an automatic analyzer to which the present invention is applied, viewed from above the device, Figure 2 is a schematic diagram of a reagent disk of the automatic analyzer, Figure 3 is a schematic diagram of a reagent bottle in the automatic analyzer according to this embodiment, and Figures 4 and 5 are schematic cross-sectional views of the reagent bottle.

The automatic analyzer 200 for analyzing a sample shown in Figure 1 includes a reaction disk 1, a sample transport mechanism 8, a sample dispensing mechanism 9, a reagent disk 3, reagent dispensing mechanisms 11, 13, a cleaning mechanism 15, a light source 16a, a spectrophotometer 16b, stirring mechanisms 17, 18, cleaning tanks 19, 20, 21, 22, 23, an operation unit 24, etc.

The reaction vessels 2 are arranged in a circle on the reaction disk 1 and are immersed in a reaction tank 5 (hereafter also called a thermostatic tank) filled with a thermally conductive medium (heat medium), such as water, whose temperature is controlled at 37 degrees. The temperature of the reaction vessels 2 is always kept at around 37 degrees by circulating the thermostatic water inside the reaction tank 5.

A sample transport mechanism 8 is installed near the reaction disk 1 to move a rack 7 carrying sample containers 6.

A sample dispensing mechanism 9 that can rotate and move up and down is installed between the reaction disk 1 and the sample transport mechanism 8, and is equipped with a sample nozzle 10.

<Basic configuration of reagent disk 3>
As shown in FIG. 2, reagent bottles 4 (see FIG. 3), each of which is an assembly of multiple reagent containers 4A, 4B containing one type of reagent, can be placed on the inner and outer periphery of a circle on the reagent disk 3.

This reagent disk 3 is provided with information medium reading mechanisms 27, 28, an opening (not shown), etc.

The information medium reading mechanisms 27 and 28 are capable of reading the first reagent information recorded on an information medium 29 (see FIG. 3) such as an RFID attached to the reagent bottle 4. In this embodiment, the information medium 29 is an RFID and the information medium reading mechanisms 27 and 28 are RFID readers, but the medium and reading method are not important as long as the system can read the necessary information. For example, the information medium 29 can be a barcode or an IC with the function of reading and writing information.

The openings are arranged on the cover of the reagent disk 3 to dispense the reagent. There are, for example, four openings, which correspond in position to the openings 26 of the reagent bottles 4 arranged on the outer and inner circumferences of the reagent disk 3.

In the case of the reagent disk 3, the reagent is aspirated by rotating the reagent disk 3 so that the reagent bottle 4 required for measurement is positioned under the opening of the reagent disk 3. The reagent is aspirated at the position where the opening of the reagent disk 3 and the opening 26 of the reagent bottle 4 overlap.

<Basic configuration of reagent bottle 4>
3, the reagent bottle 4 is configured by combining a plurality of reagent containers 4A, 4B, or by dividing the inside of the reagent bottle 4 with partitions. As shown in FIG. 3, the reagent bottle 4 has an information medium 29, for example, an RFID label, attached to its upper surface.

As shown in Figure 4 or Figure 5, the reagent bottle 4 can be filled with multiple types of reagents in one bottle. Here, we will explain the case where the bottle is filled with a first reagent and a second reagent as reagents for reacting the sample.

Reagent bottles 4 may be combined in the same shape as shown in Figure 4, or in different shapes as shown in Figure 5. For example, even if the first and second reagents are filled in the same amount, by changing the shape of the reagent bottles 4 to be filled, a difference in the reagent liquid height can be created, making it possible to determine the installation orientation of the reagent bottles 4 by judging the reagent liquid height, as described below.

The amount of reagent filled into the reagent bottle 4 is specified in advance, and the bottle is sold filled with the amount determined at the manufacturing stage.

Returning to Figure 1, reagent dispensing mechanisms 11, 13 that can rotate and move up and down are installed between the reaction disk 1 and the reagent disk 3, and are equipped with reagent nozzles 12, 14 that dispense reagent from reagent containers 4A, 4B in the reagent bottle 4.

The reagent dispensing mechanisms 11, 13 are provided with liquid level sensors 11a, 13a (see Figure 6) for detecting the liquid level of the reagent in the reagent containers 4A, 4B of the reagent bottle 4, and pressure sensors 11b, 13b (see Figure 6) for detecting the pressure in the reagent nozzles 12, 14 when the reagent is being aspirated, thereby detecting whether the reagent is being aspirated and discharged normally.

The liquid level sensors 11a, 13a are configured, for example, to detect changes in the capacitance of the reagent nozzles 12, 14 to determine whether or not there is a liquid level, but any form is acceptable as long as they can detect the liquid height in the reagent bottle 4.

Around the reaction disk 1, there are arranged a cleaning mechanism 15, a light source 16a that irradiates light onto the reagent, a spectrophotometer 16b that measures the optical characteristics of the light irradiated from the light source 16a and passed through the reagent, and stirring mechanisms 17 and 18. Washing tanks 19, 20, 21, 22, and 23 are installed within the operating ranges of the specimen dispensing mechanism 9, the reagent dispensing mechanisms 11 and 13, and the stirring mechanisms 17 and 18, respectively.

The sample dispensing mechanism 9, the reagent dispensing mechanisms 11 and 13, and the cleaning mechanism 15 are each connected to a dedicated pump (not shown).

The operation unit 24 is responsible for managing the information of the entire automatic analyzer 200, and has an overall control unit 24-1, a memory unit 24-2, a display unit 24-3, and an input unit 24-4. This operation unit 24 may be realized using a general-purpose computer, or may be realized as a function of a program executed on a computer.

The overall control unit 24-1 in the operation unit 24 is connected to the analysis unit 100 via a wired or wireless network line and controls the operation of the entire automatic analysis device 200.

The processing of the overall control unit 24-1 may be realized by storing the program codes in a recording unit such as a memory and having a processor such as a CPU (Central Processing Unit) execute each program code. The overall control unit 24-1 may be configured by hardware such as a dedicated circuit board.

Display unit 24-3 is a section on which various screens are displayed, such as an operation screen for ordering the measurement items to be measured for the sample to be measured, a screen for confirming the measurement results, etc., and is configured as a liquid crystal display, etc. Note that it does not have to be a liquid crystal display, and may be replaced with a printer, etc., or may be configured as a display and a printer, etc., or may even be a touch panel type display that also serves as input unit 24-4 described below.

The input unit 24-4 is a part for inputting various parameters and settings, measurement results, measurement request information, instructions to start and stop analysis, etc. based on the operation screen displayed on the display unit 24-3, and is composed of a keyboard, mouse, etc.

The memory unit 24-2 is a part that stores time charts and operating parameters required for the operation of each device that constitutes the automatic analyzer, various information for identifying biological samples, measurement results, etc., and is composed of storage media such as semiconductor memory such as flash memory and magnetic disks such as HDDs.

In this embodiment, the automatic analyzer 200 is described as being configured to measure biochemical items, but the configuration is not limited to measuring biochemical items, and it can also be configured to measure other items, such as immune items or electrolyte items.

Although the automated analyzer 200 has been described as being composed of one analysis unit, it may be equipped with two or more analysis units. In this case, the type of analysis unit is not particularly limited, and it may be equipped with one or more of each type of analysis unit, such as a biochemical analysis unit, an immunological analysis unit, a blood coagulation analysis unit, etc.

Furthermore, the automatic analysis device 200 may be equipped with a transport unit.

Next, an outline of the mechanical operation of the automatic analysis device 200 shown in Figure 1 will be described.

For each sample placed in the sample transport mechanism 8, a dispensing operation is performed by the sample nozzle 10 according to the measurement items requested by the operation unit 24.

The specimen nozzle 10 ejects the aspirated specimen into a reaction vessel 2 on the reaction disk 1, and further reagent aspirated from a reagent bottle 4 on the reagent disk 3 by the reagent nozzles 12, 14 is added to the reaction vessel 2 and stirred. The optical properties of the reaction liquid adjusted by stirring are then measured by the spectrophotometer 16b, and the measurement results are sent to the overall control unit 24-1 of the operation unit 24.

The overall control unit 24-1 performs calculations based on the transmitted measurement results to determine the concentration of a specific component in the sample. The analysis results are notified to the user via the display unit 24-3 and are also recorded in the memory unit 24-2.

<Regarding reagent registration>
Next, the details of the registration operation of the reagent bottle 4 in this embodiment will be described with reference to FIGS.

Figure 6 is a control block diagram for determining the orientation of a reagent bottle, Figure 7 is a conceptual diagram of linking analytical parameters and reagent bottles, Figure 8 is a flowchart for registering reagent bottles, Figure 9 is a flowchart for obtaining reagent bottle installation orientation information, Figure 10 is a flowchart for determining the liquid level height, Figures 11 and 12 are conceptual diagrams of the reagent descent height, Figure 13 is a flowchart for determining the liquid property, Figure 14 is a flowchart for determining absorbance, and Figure 15 is a diagram showing the details of the absorbance determination.

First, the configuration related to reagent registration in the automatic analysis device 200 of this embodiment will be explained using Figure 6.

In the automatic analysis device 200 of this embodiment, reagent registration is performed using first reagent information read from the information medium 29 attached to the reagent bottle 4 by the information medium reading mechanisms 27, 28, and second reagent information for identifying the installation orientation of the reagent bottle 4 when placed on the reagent disk 3, which is actually measured by the information acquisition unit.

As shown in Figure 6, components related to reagent registration in the analysis unit 100 include information medium reading mechanisms 27, 28, spectrophotometer 16b, liquid level sensors 11a, 13a and pressure sensors 11b, 13b of reagent dispensing mechanisms 11, 13. In the overall control unit 24-1, components include a medium reading determination unit 241a, a bottle suitability determination unit 241b and a bottle installation orientation determination unit 241c. In the memory unit 24-2, components include a bottle information memory unit 242a, a position information memory unit 242a1 and a bottle code memory unit 242b.

The information acquisition unit is capable of measuring the second reagent information using at least two or more different methods, and can be measured by the reagent dispensing mechanisms 11, 13.

For example, it can be the reagent liquid level height actually measured by the liquid level sensors 11a, 13a provided in the reagent dispensing mechanisms 11, 13, or pressure waveform data actually measured by the pressure sensors 11b, 13b provided in the reagent dispensing mechanisms 11, 13 when the reagent is aspirated.

In addition, the second reagent information can be at least one of the absorbance actually measured by the spectrophotometer 16b, the calculation results 607, 609 of a relative comparison of absorbance between reagents filled in the same reagent bottle 4, and the deviation rate 608, 610 of an absolute comparison evaluating the deviation between the absorbance information stored in the bottle code memory unit 242b and the actually measured absorbance.

Regarding the actual measurement method of the second reagent information, if the method described above is adopted, when the detection of the reagent liquid level, the pressure waveform data when the reagent is aspirated, and the absorbance of the reagent are taken into consideration, the most prioritized method can be the detection of the reagent liquid level, followed by the pressure waveform data.

The media reading determination unit 241a of the overall control unit 24-1 determines whether the information medium 29 of the reagent bottle 4 has been read by the information medium reading mechanisms 27, 28, thereby determining whether the reagent bottle 4 has been placed at the reagent placement position.

The bottle suitability determination unit 241b compares the first reagent information read from the information medium 29 with the bottle code in the analysis parameters stored in the bottle code memory unit 242b in the memory unit 24-2, and determines whether the analysis parameters and bottle code match.

Here, the first reagent information of the reagent bottle 4 is information including the item name, bottle code, expiration date, lot, etc., as shown in Figure 7.

The bottle code is an identification number that links the reagent bottle 4 with the analytical parameters that use the reagent, and by comparing it with the bottle code and lot of the first reagent information, the analytical parameters related to the installed reagent are identified.

The analysis parameters are downloaded into the bottle code storage unit 242b using an online database or an external storage medium as shown in Figure 7. The analysis parameters store information necessary for analysis, such as the analysis parameter number, item name, wavelength, sample dispensed amount, and reagent dispensed amount. In addition to the above information, the analysis parameters also include analysis parameter bottle information.

Analysis parameter bottle information includes the bottle code, information on the amount of reagent filled in the target bottle, and viscosity and absorbance information used for the determination described below.

Furthermore, the analytical parameter bottle information also stores the determination method used to acquire the second reagent information. For example, in the case of Figure 7, the liquid level determination and liquid property determination can be performed, but the absorbance determination cannot be performed.

As for the determination method used to obtain the second reagent information, in the case of FIG. 7, it is possible to set it to use all or any of the three methods. In this case, it is possible to make it possible to select an available determination method. Furthermore, if two or more methods are selected, it is possible to assign a priority order to the methods. Furthermore, the determination may be made using a single mechanism or multiple mechanisms within the automatic analyzer 200, and is not particularly limited.

In addition, information regarding analytical parameters such as reagent filling volume, liquid information, absorbance information, etc. is not limited to being acquired online, but may be originally recorded on the information medium 29 of the reagent bottle 4 as first reagent information, and may be acquired collectively as first reagent information, or may be recorded in the memory unit 24-2.

The bottle installation orientation determination unit 241c determines the installation orientation of the reagent bottle 4 from the first reagent information read by the information medium reading mechanisms 27 and 28 and the second reagent information measured by the information acquisition unit. In this embodiment, the bottle installation orientation determination unit 241c includes a liquid level height determination unit 241c1, a liquid property determination unit 241c2, and an absorbance determination unit 241c3. Details of these will be described later.

Of the memory unit 24-2, the bottle information memory unit 242a stores the first reagent information of the reagent bottle 4 read by the information medium reading mechanisms 27 and 28. This bottle information memory unit 242a has a position information memory unit 242a1 that stores information on the installation orientation of the reagent bottle 4.

The bottle code storage unit 242b stores analysis parameters acquired from an online database or an external storage medium as shown in Fig. 7. This bottle code storage unit 242b may be an external configuration of the storage unit 24-2, i.e., the automatic analysis device 200, or may remain an online database or an external storage medium.

Next, the flow of the reagent registration method in the automatic analysis device 200 will be explained using Figures 8 and beyond.

First, as shown in Fig. 8, the user opens the lid of the reagent disk 3 (step S101) and places the reagent bottle 4 (step S102). These steps S101 and S102 correspond to the placement process.

The reagent bottle 4 is manually placed in step S102 by the user. Alternatively, the device may be equipped with a mechanism (autoloader) that automatically places the reagent bottle 4 on the reagent disk 3. Here, a case where the user manually places the reagent bottle 4 will be described. When placing the reagent bottle 4 on the reagent disk 3 as shown in Figure 2, it is possible to place the reagent bottle 4 without considering the orientation in which it is to be placed.

Then, the necessary reagent bottles 4 are placed on the reagent disk 3 and the lid of the reagent disk 3 is closed (step S103).

After that, reading of the first reagent information of the reagent bottle 4 is started. The process may start automatically when the lid of the reagent disk 3 is closed, or the user may give an instruction to start reading the reagent bottle 4 information from the screen. When reading of the reagent bottle 4 information is started, the reagent disk 3 rotates so that the installation positions of all reagent bottles 4 pass the positions of the information medium reading mechanisms 27, 28 in order to read the information media 29 attached to the reagent bottles 4 (step S104). This step S104 corresponds to the information medium reading process.

The medium reading determination unit 241a then determines whether the information medium 29 could be read for position x (x = 1 to n, a natural number representing the total number of positions) (step S105). For the reagent disk 3 position for which the information medium 29 could be read, it is determined that a reagent bottle 4 is installed (step S107), and the process proceeds to step S108. On the other hand, if the information medium 29 cannot be read, it is determined that a reagent bottle 4 is not installed at that position (step S106), and the process ends.

Next, the bottle suitability determination unit 241b compares the bottle code in the analysis parameters stored in the bottle code memory unit 242b and determines whether the analysis parameters match the bottle code (step S108).

If the comparison shows that the analysis parameters stored in the bottle code storage unit 242b match the bottle code, the process proceeds to step S110, and the acquisition of reagent bottle 4 installation orientation information for the reagent bottle 4 (described later) is started (step S110). This step S110 corresponds to the information acquisition process and the determination process.

If the comparison shows that the analysis parameters and bottle code do not match, the reagent bottle 4 is not registered (step S109) and the process is terminated.

Next, the acquisition of reagent bottle 4 installation orientation information in step S110 will be described below with reference to Figure 9. Acquisition of reagent bottle 4 installation orientation information for the target reagent bottle 4 is performed through three determinations: "liquid level height determination," "liquid property determination," and "absorbance determination." Detailed methods for each determination will be described later with reference to Figure 10 onwards.

As an initial setting, as shown in Figure 7, the method for determining how to obtain the installation orientation information of the reagent bottle 4 is set in advance for the target bottle code in the analysis parameters. For example, if the liquid levels of the first and second reagents in the reagent bottle 4 are different, it is possible to determine this from the difference in the liquid levels.

If the liquid levels of the first and second reagents in the reagent bottle 4 are similar and it is difficult to distinguish them using "Liquid Level Determination", set "Liquid Property Determination". Liquid property determination is a method of distinguishing between the first and second reagents from the liquid properties of the reagents using the pressure waveform data of the reagents when the viscosities of the first and second reagents are different, as described below.

For reagent bottles 4 that are difficult to distinguish using "liquid level determination" and "liquid property determination", set "absorbance determination". The absorbance of each reagent has its own unique ultraviolet-visible absorption spectrum depending on the formulation of the reagent, so it is possible to distinguish the reagent by actually measuring the absorbance.

With these settings in place, when the process of acquiring reagent bottle 4 installation orientation information is started, first, as shown in Figure 9, it is determined whether liquid level height determination is enabled for the target bottle code in the analysis parameters (step S201).

If it is determined that the liquid level determination is enabled, the process proceeds to step S202A, where the liquid level determination is executed (step S202A), and it is determined whether the determination was successful (step S202B). If the liquid level was detected, the process proceeds to step S208, and if the liquid level was not detected (determination NG), the process proceeds to step S207.

On the other hand, if it is determined in step S201 that liquid level height determination is not enabled, processing proceeds to step S203, where it is determined whether liquid type determination is enabled for the target bottle code in the analysis parameters (step S203).

If it is determined that the liquid property determination is enabled, the process proceeds to step S204A, where the liquid property determination is performed (step S204A), and it is determined whether the determination was successful (step S204B). If the liquid property was determined, the process proceeds to step S208, and if the liquid property could not be determined (determination NG), the process proceeds to step S207.

On the other hand, if it is determined in step S203 that liquid determination is not enabled, processing proceeds to step S205, where it is determined whether absorbance determination is enabled for the target bottle code in the analysis parameters (step S205).

If it is determined that the liquid level determination is enabled, the process proceeds to step S206A, where an absorbance determination is performed (step S206A), and it is determined whether the determination was successful (step S206B). If the reagent can be identified by the absorbance measurement, the process proceeds to step S208, and if the reagent cannot be identified (determination NG), the process proceeds to step S207.

When various determinations make it possible to determine the orientation of the reagent bottle 4 (steps S202B, S204B, and S206B are OK), the reagent aspiration position, i.e., the orientation of the reagent bottle 4, is determined (step S208), and the acquisition of reagent bottle orientation information is terminated.

On the other hand, if the discrimination method is not set (No in step S205) or various judgments are NG (NG judgments in steps S202B, S204B, and S206B), the target reagent bottle 4 is deemed not eligible for registration (step S207), and acquisition of reagent bottle installation orientation information is terminated.

The procedure for the treatment is not limited to the above-mentioned flow, and for example, when it is determined in step S202B that the liquid level detection is NG, the process proceeds to step S203 to determine whether or not liquid property determination can be performed, and the procedure can be such that the installation orientation of the reagent bottle 4 is determined as much as possible.

Below, details of the liquid level determination in step S202A of Figure 9 are described using Figures 10 to 12.

The liquid level is determined using liquid level sensors 11a, 13a provided in the reagent dispensing mechanisms 11, 13.

As shown in FIG. 10, after starting the liquid level height determination, the liquid level height determination unit 241c1 first acquires the set height information of the first reagent and the second reagent set in the analysis parameters (step S301).

Then, based on the acquired set height information, the liquid level determination unit 241c1 determines the amount of descent of the reagent nozzles 12, 14 into the reagent bottle 4. The amount of descent of the reagent nozzles 12, 14 varies depending on the relationship between the liquid heights of the first and second reagents.

For example, if the set liquid height of the first reagent is higher than that of the second reagent, the liquid level determination unit 241c1 lowers either the reagent nozzle 12 or 14 (step S302) toward the set liquid height of the first reagent (case 1 in FIG. 10), or if the set liquid height of the second reagent is higher than that of the first reagent, toward the set liquid height of the second reagent (case 2 in FIG. 10). Hereinafter, it is assumed that the reagent nozzle 12 is lowered.

In this embodiment, the side closer to the center of the reagent disk 3 is designated position A and the side furthest from it is designated position B, and the reagent nozzle 12 is lowered to position A to a height where the reagent nozzle 12 is immersed in the liquid surface at either position A or position B, as shown in Figure 11.

Methods for detecting the liquid level include (1) lowering the device while searching for the liquid level, and (2) lowering the device to the liquid level that is obtained in advance from the analysis parameters using software. Here, if the reagent containers 4A and 4B are open and have no caps, it is desirable to lower the device while searching for the liquid level and check whether the detected position matches the expected position.

After the reagent nozzle 12 descends to position A by the set descending amount in step S302, the liquid level sensors 11a and 13a check for the presence or absence of the liquid level (step S303) and determine whether the liquid level has been detected (step S304). If the liquid level has been detected, in case 1, position A is determined to be the position for the first reagent and position B is determined to be the position for the second reagent, and in case 2, position A is determined to be the position for the second reagent and position B is determined to be the position for the first reagent (step S305).

On the other hand, if the liquid level cannot be confirmed at the lowered position of the reagent nozzle 12 for position A, the reagent nozzle 12 is lowered to the liquid height of the first reagent for position B, and the liquid level is confirmed (step S306), and it is determined whether the liquid level has been detected (step S307).

Here, the reason for accessing the higher reagent first in step S302 is that, as shown in Figure 11, if the set liquid height of the first reagent is higher than that of the second reagent, when the reagent nozzle 12 is lowered toward the liquid height of the first reagent on the higher side, only one of the reagents will enter the liquid surface, but when the reagent nozzle 12 is lowered toward the liquid height of the second reagent on the lower side as shown in Figure 12, both reagents will enter the liquid, and both will result in liquid surface detection. Also, this is to avoid the reagent nozzle 12 plunging too far into the reagent, which would require more cleaning.

Note that if a system is adopted in which the device descends while searching for the liquid level, the former problem does not arise, but the latter problem does exist, so it is still preferable to have a system that accesses the higher level first.

This step S306 is a process to confirm that it is the second reagent, and it is also possible to omit it and register only the judgment results of steps S303 and S304.

However, if the reagent bottle 4 is composed of three or more reagent containers, it is desirable to perform this step S306 and subsequent steps such as step S307 at least once.

If the liquid level can be confirmed in step S306, in case 1, position A is determined to be the position for the second reagent and position B is determined to be the position for the first reagent, and in case 2, position A is determined to be the position for the first reagent and position B is determined to be the position for the second reagent (step S308).

On the other hand, if the liquid level cannot be confirmed at the lowered position of the reagent nozzle 12 even in position B, it is highly likely that an inappropriate reagent is contained, so the reagent bottle 4 in question is deemed ineligible for registration (step S309).

The reagent position information determined in steps S305 and S308 is registered in the position information memory unit 242a1 as installation orientation information of the reagent bottle 4 (reagent suction position information) (step S310), and the processing ends.

Next, details of the liquid type determination in step S204A of Figure 9 will be described using Figure 13.

Liquid properties are determined using pressure sensors 11b and 13b provided in the reagent dispensing mechanism 11.

13, after starting the liquid property determination, the liquid property determination unit 241c2 first acquires the liquid level height and liquid property information of the first and second reagents set in the analysis parameters (step S401). In this embodiment, viscosity information is used as the liquid property information. This viscosity information indicates pressure waveform data when the device aspirates the first and second reagents in the reagent bottle 4.

After acquiring the information, the liquid property determination unit 241c2 lowers one of the reagent nozzles 12 to one of the positions in the reagent bottle 4 (step S402). In this case, it is assumed that the reagent nozzle 12 is lowered to position A. The amount of descent of the reagent nozzle 12 at this time is set to the lower of the set height of the first reagent and the set liquid height of the second reagent so as to reliably reach the liquid surface, as shown in FIG.

After that, the liquid level is checked (step S403), and it is determined whether or not the liquid level has been checked (step S404). If the liquid level has been checked, the reagent is aspirated (step S405), and pressure data is acquired (step S406). The amount of reagent aspirated at this time is a specified amount that allows pressure data to be acquired. Here, this is specified as 50 μL.

Then, the same operation as described above is performed for position B to obtain pressure data (steps S407, S408, S409, S410, S411).

If the liquid level is not detected in steps S403 and S408 and the judgment in steps S404 and S409 is No, it is highly likely that an inappropriate reagent is contained, so the reagent bottle 4 in question is not eligible for registration (step S414).

After acquiring the pressure data for positions A and B, a comparative analysis is performed with the pressure waveform data previously stored in the bottle code memory unit 242b to determine whether positions A and B are classified as the first reagent or the second reagent, respectively (step S412).

The method for comparing and discriminating the pressure waveforms in step S412 is not important as long as it can quantitatively determine the similarity between the referenced pressure waveform data and the actually measured pressure waveform data.

If the determination is possible, the suction position information is registered (step S413). If the determination is not possible, registration is not possible (step S414).

Since the viscosity information of the reagent used as the judgment criteria may change depending on the reagent lot, the reference pressure waveform information may be updated for each reagent lot using an online database or external media.

If it is known from prior information that there will be no difference in pressure, it is advisable not to check the liquid properties in the settings shown in Figure 7, or to devise a way to intentionally create a difference in the liquid level by modifying the reagent bottle 4 side.

Next, details of the absorbance determination in step S206A of Figure 9 will be described using Figures 14 and 15.

The absorbance determination is performed using the reagent dispensing mechanisms 11, 13, the reaction vessel 2 on the reaction disk 1, the light source 16a, and the spectrophotometer 16b.

As shown in FIG. 14, after the absorbance determination starts, the absorbance determination unit 241c3 first acquires the liquid level height and absorbance information set in the analysis parameters (step S501).

12, the absorbance determination unit 241c3 lowers the reagent nozzle 12 to the lower of the set liquid height of the first reagent and the set liquid height of the second reagent with respect to position A (step S502). After the reagent nozzle 12 is lowered, the presence or absence of the liquid level is confirmed (step S503), and it is determined whether the liquid level has been confirmed (step S504).

If this is confirmed, the absorbance determination unit 241c3 aspirates the reagent (step S505). The amount of reagent aspirated at this time is the "minimum amount of liquid that can be measured in the reaction vessel + excess amount." The excess amount refers to the amount of reagent aspirated in excess to avoid dilution of the reagent by the pure water that fills the reagent nozzle. The minimum amount of liquid is determined by the shape of the reaction vessel, and is 75 μL in this case. The absorbance determination unit 241c3 then ejects the aspirated reagent into the reaction vessel 2 (step S506).

For position B, the reagent nozzle 12 is lowered to the same liquid height as in step S502 (step S507), the liquid level is checked (step S508), and it is determined whether the liquid level has been checked (step S509).

If this is confirmed, the absorbance determination unit 241c3 aspirates the reagent (step S510) and ejects the reagent into a reaction vessel 2 different from the reagent in position A (step S511). The amount of reagent aspirated and ejected at this time is the same as that at position A.

After the reagents at positions A and B are dispensed into the reaction vessel 2, the reaction disk 1 is rotated and absorbance measurement is performed (step S512). The absorbance measurement is an operation in which the reaction disk 1 is rotated, the amount of light emitted from the light source 16a and transmitted through the dispensed reagent is measured by the spectrophotometer 16b, and the absorbance of each reagent is obtained.

Here, if there are multiple new reagent bottles 4 in the reagent disk 3 that are set for absorbance determination, the process transitions to absorbance measurement after all reagent ejection from the target reagent bottles 4 into the reaction vessels 2 is completed.

In addition, if the liquid level is not detected in steps S503 and S508 and the judgment in steps S504 and S509 is No, it is highly likely that an inappropriate reagent is contained, so the reagent bottle 4 in question cannot be registered (step S515).

After the absorbance measurement, the absorbance is judged (step S513). The wavelength to be acquired during the absorbance measurement may be either a specified wavelength or any wavelength that can be acquired by the device. The absorbance is judged by comparing the absorbance information previously set in the analysis parameters with the actually measured absorbance.

Figure 15 shows an example of absorbance determination. Figure 15 shows the actual absorbance 601 of reagent containers 4A and 4B of reagent bottle 4, and in-apparatus absorbance information 602 of bottle code "10001" stored in bottle code memory unit 242b. Here, the actual absorbance 601 indicates the actual absorbance of all 12 wavelengths that can be measured by spectrophotometer 16b. In-apparatus absorbance information 602 is the theoretical value of absorbance at a specific wavelength or a value actually measured before the reagent is shipped, and is shown here as theoretical values at two wavelengths. The difference between the theoretical value of in-apparatus absorbance information 602 and the actual absorbance 601 is used to determine absorbance.

Note that the absorbance of some reagents varies depending on the reagent lot. For this reason, the absorbance information in the device can be updated for each reagent lot using an online database or external media. In addition, since the absorbance of some reagents gradually changes after production, it is also possible to determine this from the ratio or difference of the absorbance between the first and second reagents at a certain wavelength.

In the first reagent judgment, the differences 603, 604 between the absorbance of the first reagent set in the analysis parameter bottle information and the actual absorbance at the corresponding wavelengths a and b are calculated. Then, a relative judgment of a and b is performed. In the relative judgment, the smaller of the calculation results 607, 609 of the absorbance difference is selected. In the example of Figure 15, the calculation result 607 is selected.

Next, absolute judgment is performed. In absolute judgment, it is confirmed whether the deviation rate 608 of the actual absorbance of the selected side, a in FIG. 15, is within ±20% with respect to the absorbance information in the device. If the deviation rate 608 is within ±20%, in the example of FIG. 15, a is judged to be the first reagent.

Similarly, in the second reagent judgment, the difference 605, 606 between the absorbance of the second reagent set in the analysis parameter bottle information and the actual absorbance at the corresponding wavelengths of a and b is calculated. Then, a relative judgment of a and b is performed. In the relative judgment, the smaller of the calculation results 607, 609 of the absorbance difference is selected. In the example of Figure 15, the calculation result 609 is selected.

Next, an absolute judgment is made. In the absolute judgment, it is confirmed whether the deviation rate 610 of the actual absorbance of the selected side, b in Figure 15, is within ±20% with respect to the absorbance information in the device. If the deviation rate 610 is within ±20%, in the example of Figure 15, b is judged to be the second reagent. Note that the deviation rate value can be set to any value for each reagent, taking into account the measurement performance of the device, the reagent formulation, and variations in the manufacturing process. Also, the judgment may be made using the difference from the absorbance in the device rather than a ratio.

If there is no contradiction in the position allocation of a and b as a result of the first reagent judgment and the second reagent judgment, the absorbance judgment unit 241c3 determines the position information of the first reagent and the second reagent as the final judgment 611. In the case of Figure 15, a is the first reagent and b is the second reagent.

In this way, the absorbance determination unit 241c3 determines whether it was possible to distinguish between the first and second reagents (step S513), and if it is determined that it is possible to distinguish, registers the reagent aspirating position information in the position information storage unit 242a1 (step S514). If it is determined that it is not possible to distinguish between the first and second reagents due to an abnormality in the measured absorbance, the corresponding reagent bottle 4 is not allowed to be registered (step S515).

In FIG. 15, we have explained the case where the relative judgment and the absolute judgment are the same, but it is desirable to not allow registration if the two judgment results differ. Note that the absolute judgment may be given priority.

Although we have explained the case of an AND condition in which the relative judgment and absolute judgment coincide, it is also possible to have an OR condition in which either a relative judgment or an absolute judgment is performed.

Next, the effects of this embodiment will be explained.

The automated analyzer 200 for analyzing samples in the present embodiment described above comprises a reagent disk 3 on which multiple reagent bottles 4, each of which contains multiple reagent containers 4A, 4B containing one type of reagent, can be placed, information medium reading mechanisms 27, 28 that read first reagent information recorded on an information medium 29 attached to the reagent bottle 4, and an information acquisition unit that measures second reagent information to determine the installation orientation of the reagent bottle 4 when placed on the reagent disk 3, and determines the installation orientation of the reagent bottle 4 from the first reagent information read by the information medium reading mechanisms 27, 28 and the second reagent information measured by the information acquisition unit.

Automated analyzers are required to operate reliably with few problems and reduce user work, especially tedious tasks, and the above-mentioned configuration for automatically determining the installation orientation of the reagent bottle 4 reduces the burden on the user. In addition, there is no need to provide a dedicated recording medium and reading mechanism for identifying the installation orientation of the reagent bottle 4, which reduces the cost increase due to additional media and mechanisms and the risk of being unable to read due to breakdowns or other problems, allowing users to operate this function reliably.

In addition, since the information acquisition unit can actually measure the second reagent information using at least two or more different methods, it can accommodate reagent bottles 4 of various shapes and conditions, making it possible to make the device more capable of reducing the burden on the user.

Furthermore, by further providing a memory unit 24-2 that stores information on which of two or more second reagent information measurement methods to use, it is possible to determine the installation orientation of the reagent bottle 4 according to the characteristics of the corresponding reagent and reagent bottle 4, thereby enabling more accurate and stable determination.

In addition, the device further includes reagent dispensing mechanisms 11, 13 equipped with reagent nozzles 12, 14 that dispense reagent from reagent containers 4A, 4B in the reagent bottle 4, and the second reagent information is actually measured by the reagent dispensing mechanisms 11, 13, for example, the reagent liquid level height actually measured by liquid level sensors 11a, 13a provided in the reagent dispensing mechanisms 11, 13, or pressure waveform data actually measured by pressure sensors 11b, 13b provided in the reagent dispensing mechanisms 11, 13 when the reagent is aspirated.This makes it possible to determine the installation orientation using the configuration originally provided in the device, which is necessary for reagent dispensing, and therefore makes it possible to realize inexpensive and reliable installation orientation determination.

Furthermore, by further providing a light source 16a that irradiates light onto the reagent and a spectrophotometer 16b that measures the optical characteristics of the light irradiated from the light source 16a and passed through the reagent, and by setting the second reagent information to the absorbance actually measured by the spectrophotometer 16b, the installation orientation determination can be performed using only the components originally provided in the analytical device.

Furthermore, by configuring the second reagent information as at least one of a relative comparison of absorbance between reagents filled in the same reagent bottle 4 and an absolute comparison that evaluates the deviation between the absorbance information stored in the bottle code memory unit 242b and the actually measured absorbance, a more accurate determination of the installation orientation can be performed.

Furthermore, when the actual measurement method for the second reagent information is detection of the reagent liquid level, pressure waveform data when the reagent is aspirated, and reagent absorbance, the highest priority method is detection of the reagent liquid level, followed by pressure waveform data, so that the installation orientation determination can be performed in the order that provides the easiest post-processing after the determination is performed.

＜Other＞
The present invention is not limited to the above-mentioned embodiment, and various modifications and applications are possible. The above-mentioned embodiment has been described in detail to explain the present invention in an easily understandable manner, and the present invention is not necessarily limited to having all of the described configurations.

1... reaction disk 2... reaction container 3... reagent disk (reagent holding mechanism)
4... Reagent bottles 4A, 4B... Reagent container 5... Reaction tank 6... Sample container 7... Rack 8... Sample transport mechanism 9... Sample dispensing mechanism 10... Sample nozzle 11, 13... Reagent dispensing mechanism 11a, 13a... Liquid level sensor 11b, 13b... Pressure sensor 12, 14... Reagent nozzle 15... Cleaning mechanism 16a... Light source 16b... Spectrophotometer 17, 18... Stirring mechanism 19, 20, 21, 22, 23... Cleaning tank 24... Operation unit 24-1... Overall control unit 24-2... Memory unit 24-3... Display unit 24-4... Input unit 26... Opening 27... Information medium reading mechanism (inside of reagent disk)
28... Information medium reading mechanism (outside of reagent disk)
29...information medium 100...analysis unit 200...automatic analyzer 241a...medium reading judgement section 241b...bottle suitability judgement section 241c...judgment section 241c1...judgment section 241c2...liquid property judgement section 241c3...absorbance judgement section 242a...bottle information storage section 242a1...position information storage section 242b...bottle code storage section 601...actually measured absorbance 602...in-apparatus absorbance information 603, 604, 605, 606...difference 607, 609...calculation results 608, 610...deviation rate 611...final judgement

Claims (9)

An automated analyzer for analyzing a sample, comprising:
a reagent holding mechanism capable of accommodating a plurality of reagent container sets each including a plurality of reagent containers each containing one type of reagent;
an information medium reading mechanism for reading first reagent information recorded on an information medium attached to the reagent container set;
an information acquisition unit that measures, by at least two or more different methods, different second reagent information for identifying an installation orientation of the reagent container set when the reagent container set is installed in the reagent holding mechanism,
an installation orientation of the reagent container set is determined based on the first reagent information read by the information medium reading mechanism and the second reagent information actually measured by the information acquisition unit. 2. The automated analyzer according to claim 1,
The automatic analyzer further comprises a storage unit that stores information regarding which of two or more actual measurement methods of the second reagent information is to be used. 2. The automated analyzer according to claim 1,
a reagent dispensing mechanism including a reagent nozzle for dispensing a reagent from the reagent container of the reagent container set;
The automatic analyzer according to claim 1, wherein the second reagent information is actually measured by the reagent dispensing mechanism. 4. The automatic analyzer according to claim 3,
the second reagent information being a reagent liquid level actually measured by a liquid level sensor provided in the reagent dispensing mechanism. 4. The automatic analyzer according to claim 3,
the second reagent information is pressure waveform data actually measured by a pressure sensor provided in the reagent dispensing mechanism when the reagent is aspirated. 2. The automated analyzer according to claim 1,
A light source that irradiates the reagent with light;
and a spectrophotometer that measures optical characteristics of light irradiated from the light source and transmitted through the reagent,
an absorbance actually measured by the spectrophotometer as one of the second reagent information items. 7. The automated analyzer according to claim 6,
The automatic analyzer according to claim 1, wherein the second reagent information is at least one of a relative comparison of absorbance between reagents filled in the same reagent container set and an absolute comparison that evaluates the discrepancy between absorbance information stored in the device and an actually measured absorbance. 3. The automated analyzer according to claim 2,
an automatic analyzer characterized in that, when the actual measurement methods for the second reagent information are detection of the reagent liquid level, pressure waveform data when the reagent is aspirated, and absorbance of the reagent, the method given the highest priority is detection of the reagent liquid level, followed by the pressure waveform data. A method for registering a reagent in an automatic analyzer for analyzing a sample, comprising:
an installation step of installing a reagent container set, which is a collection of multiple reagent containers containing one type of reagent, in a reagent holding mechanism;
an information medium reading step of reading first reagent information recorded on an information medium attached to the reagent container set;
an information acquiring step of actually measuring, by at least two or more different methods, different second reagent information for identifying an installation orientation of the reagent container set when the reagent container set is installed in the reagent holding mechanism;
a determination process for determining an installation orientation of the reagent container set from the first reagent information read in the information medium reading process and the second reagent information actually measured in the information acquisition process.

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