Automatic analysis device
The automated analyzer addresses carry-over contamination by controlling process order and inserting empty cycles, ensuring accurate analysis results for both low- and high-sensitivity items.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- HITACHI HIGH TECH CORP
- Filing Date
- 2025-08-12
- Publication Date
- 2026-06-25
AI Technical Summary
Existing automated analyzers fail to adequately address carry-over issues when continuously measuring low-sensitivity and high-sensitivity items, leading to potential contamination in high-sensitivity measurements.
The automated analyzer incorporates a dispensing unit, analysis unit, nozzle, and control unit to perform specific processes in a controlled order, including an additional washing step and insertion of empty cycles to minimize carry-over, particularly when switching between low- and high-sensitivity items.
This configuration effectively reduces carry-over contamination, ensuring accurate and reliable analysis results even when measuring items with varying sensitivity levels.
Smart Images
Figure JP2025028548_25062026_PF_FP_ABST
Abstract
Description
Automated analyzer
[0001] The present invention relates to an automated analyzer.
[0002] An automated analyzer performs qualitative and quantitative analysis of specimens such as blood and urine. As a conventional technique, for example, the one described in Patent Document 1 is known. Patent Document 1 discloses an immuno-automated analyzer including a specimen rack for placing a specimen, a reagent disk for storing reagent containers, a specimen dispensing mechanism for dispensing and aliquoting a specimen, a reagent dispensing mechanism for dispensing and aliquoting a reagent, a magnetic particle stirring mechanism for stirring a magnetic particle solution among the reagents, and a reaction vessel for containing the aliquoted specimen and reagent and performing a reaction.
[0003] International Publication No. 2014 / 115591
[0004] In Patent Document 1, regarding the measurement of low-sensitivity items (high signals) and high-sensitivity items (low signals), no consideration is given to the case where these are continuously measured. When continuously measuring low-sensitivity items and high-sensitivity items, the cleaning operation of the immuno-cell flow path or the like in one cycle becomes insufficient, and there is a concern about the occurrence of carry-over in high-sensitivity items.
[0005] Therefore, an object of the present invention is to provide an automated analyzer capable of reducing carry-over even when continuously measuring low-sensitivity items and high-sensitivity items.
[0006] An automated analyzer according to one aspect of the present invention comprises a dispensing unit for dispensing a sample and reagents into a first container, an analysis unit for analyzing the components of a sample using a mixed solution consisting of the sample and reagents, a nozzle for aspirating the mixed solution from the first container and sending it to the analysis unit, and a control unit for controlling the dispensing unit, the analysis unit, and the nozzle. The analyzer is configured to perform at least an analysis step in the order of a first process of dispensing the sample and reagents into the first container, a second process of sending the mixed solution from the first container to the analysis unit, and a third process of analyzing the components of the sample using the mixed solution in the analysis unit, and at least a fourth process of sending a washing solution from a second container to the analysis unit via the nozzle. The control unit controls the analyzer to assign the analysis step for the third item instead of the washing step when the analysis step for the third item is interrupted in the schedule and the second item is determined to be an item of a sample for which the carryover effect is low.
[0007] According to the present invention, carryover can be reduced even when measuring low-sensitivity and high-sensitivity items in succession.
[0008] A plan view showing the overall configuration of the automated analyzer. A diagram showing the flow of sample measurement processing. A flowchart showing the process of determining whether to interrupt an interrupt request into an available cycle. A flowchart showing the process of setting the cleaning process in response to an interrupt request. A diagram showing the flow of sample measurement processing.
[0009] Embodiments of the present invention will be described below with reference to the drawings. In this embodiment, one automated analyzer will be described as an example, but the present invention can also be applied to an integrated automated analyzer system that includes two or more automated analyzers.
[0010] <First Embodiment> The first embodiment will be described with reference to Figures 1 to 3.
[0011] Figure 1 is a schematic plan view showing the overall configuration of the automated analyzer.
[0012] The automated analyzer 1 is configured by connecting the analyzer 2 and the control device 3 with a communication line or the like.
[0013] The analyzer 2 is a device that analyzes a sample by measuring the luminescence and color change that occur when the sample is reacted with an analytical reagent, and comprises a sample transport path 4, a reagent refrigerator 16, an incubator (reaction disk) 21, and an analysis unit 13.
[0014] The control device 3 is a device that controls various parts of the analysis device 2, and is, for example, a computer. The operator inputs the desired analysis content from the input unit of the control device 3, such as a keyboard, mouse, or touch panel, and confirms the analysis results on the output unit, such as an LCD display or touch panel.
[0015] The sample transport path 4 is a mechanism that transports a sample rack 5, which is loaded with multiple sample containers 6 for containing samples such as blood and urine, to the dispensing position 22 of the sample dispensing unit 7. The sample dispensing unit 7 aspirates samples from the transported sample containers 6 and discharges the samples into the reaction vessel 12 installed in the incubator 21.
[0016] In the sample dispensing unit 7, the dispensing tip 10, which is transported from the mounting rack 11 to the dispensing tip attachment / detachment unit 8 by the transport unit 9, is attached. To prevent contamination during sample dispensing, the dispensing tip 10 is replaced each time a sample is dispensed.
[0017] The reagent refrigerator 16 is a mechanism for storing reagent containers 18 containing analytical reagents at a low temperature, and includes a reagent disc 17 and a reagent jacket 19. The internal temperature of the reagent refrigerator 16 is maintained at, for example, 5 to 10 degrees Celsius. The reagent disc 17 holds the reagent containers 18 and rotates around a vertical axis as its pivot point, moving the reagent containers 18 to a predetermined position, for example, the dispensing position of the reagent dispensing unit 15. The reagent jacket 19 is a covering located on the outside of the reagent disc 17 and remains stationary even when the reagent disc 17 rotates.
[0018] The incubator 21 is a mechanism that maintains a constant temperature to promote the reaction of the mixed solution of the sample dispensed by the sample dispensing unit 7 and the reagent dispensed by the reagent dispensing unit 15. Prior to the dispensing of the sample and reagent into the incubator 21, the reaction vessel 12 is transported from the mounting rack 11 by the transport unit 9.
[0019] The analysis unit 13 analyzes the components of a sample by measuring the color change, luminescence, etc., of the reaction solution dispensed from the reaction vessel 12 located in the incubator 21 by the reaction solution dispensing unit 14. The analysis unit 13 has two detection units, a first detection unit 13a and a second detection unit 13b, which perform detection and measurement for the analysis of the components of the sample, respectively. These detection units correspond to flow cells (immunocells) in an automated immunoassay analyzer. In this embodiment, the case in which the analysis unit 13 has two detection units is described as an example, but it is not limited to this, and the embodiment can be applied similarly even when there are three or more detection units.
[0020] The measurement results from the analysis unit 13 are displayed on the output unit of the control device 3, such as a liquid crystal display or touch panel. The reaction vessels 12 into which the reaction solution has been dispensed are removed by being transported from the incubator 21 to the mounting rack 11 by the transport unit 9.
[0021] The measurement procedure is set up as follows: an analysis step in which the sample and reagents are dispensed into a first container, a second step in which the nozzle mixture of the reaction solution dispensing unit 14 is sent from the first container to the analysis unit 13, and a third step in which the components of the sample are analyzed using the mixture in the analysis unit 13; and a fourth step in which a washing step is performed in which washing solution is sent from the second container to the analysis unit 13 via the nozzle of the reaction solution dispensing unit 14.
[0022] More specifically, the analysis process involves dispensing the sample and reagents (first process), B / F separation (a process performed in the B / F separation unit 23 to physically separate the sample bound to magnetic particles from the unbound sample) and delivery of the sample to the analysis unit 13 through the nozzle of the reaction solution dispensing unit 14 (second process), and measurement of the sample in the analysis unit 13 (first detection unit 13a, second detection unit 13b) (third process). Here, the B / F separation unit 23 has a suction / discharge nozzle (not shown), and during B / F separation, only the tip of the suction nozzle enters the sample container 6. Therefore, the possibility of carry-over (CO) is considered low.
[0023] Furthermore, as part of the cleaning process, the B / F separation unit 23 is cleaned by washing the suction / discharge nozzle (not shown) that dispenses the sample (reaction solution) from the incubator 21 to the B / F separation unit 23 with system water (pure water), or by replacing the liquid inside the suction / discharge nozzle with a buffer solution for B / F separation.
[0024] Furthermore, as part of the cleaning process, the analysis unit 13 may undergo a process of sending a system buffer solution (e.g., buffer solution) to the analysis unit 13 (fourth process), or a special cleaning operation (fourth process) of sending a larger amount of system cleaning solution (e.g., alkaline detergent) to the analysis unit 13.
[0025] The following describes an example of setting an empty cycle in the sample / reagent dispensing (first process) cycle. In this embodiment, by setting an empty cycle in the sample / reagent dispensing (first process) cycle, an empty cycle can also be set in the B / F separation / liquid delivery (second process) and detection (third process) cycles, and by inserting a washing operation (washing step) into the set empty cycle, the risk of carryover can be reduced.
[0026] Figure 2 shows the flow of the sample measurement process.
[0027] Normally, a washing operation is performed at the end of each cycle: sample / reagent dispensing, B / F separation / transfer, and detection. However, in this embodiment, an additional empty cycle is provided to perform a washing operation separately from the washing operation performed at the end of each cycle. Below, item 1 will be described as a low-sensitivity item (an item with little influence from carryover), and item 2 as a high-sensitivity item (an item with a high influence from carryover).
[0028] First, let's consider an example where an order is created to sequentially perform the following steps in a series of cycles (for example, cycles 1 to 10): analysis of item 1: n=2 measurements, analysis of item 2: n=2 measurements, and analysis of item 1: n=2 measurements. Note that the number of measurements can be n=1 or less, and is not limited to that number. Also, the samples targeted for item 1 and item 2 may be the same or different.
[0029] In the analysis process for item 2, empty cycles are inserted immediately before the B / F separation cycle and immediately before the detection cycle. When empty cycles are present, a cleaning process is executed without consuming tips or other components. In other words, in addition to the cleaning operations in the normal cycle (rinsing the nozzle with pure water and flowing the cleaning solution into the detection unit (flow cell's flow path)), a cleaning process is also performed in the empty cycle to thoroughly clean the components related to the preceding analysis process for item 1, thereby reducing the impact of carryover on the analysis process for item 2. It should be noted that while carryover is explained as occurring when high-sensitivity and low-sensitivity samples are measured alternately, it can also occur when a normal-sensitivity item is measured after a low-sensitivity item (high signal). In that case as well, the impact of carryover can be similarly reduced.
[0030] Next, we will explain the interrupt operation. Although a free cycle is provided to insert a cleaning operation to avoid carryover, there are cases where it does not significantly affect carryover. In such cases, if a measurement is interrupted, assigning that measurement to the free cycle will prevent an increase in analysis time. Hereafter, free cycle 1 and free cycle 2 will be referred to as free 1 and free 2, respectively.
[0031] Here, empty cycle 2 is immediately before item 1, which is less affected by carryover in detection unit (1), and immediately before empty cycle 1 in detection unit (2). In other words, empty cycle 2 is not immediately before the detection cycle of item 2, which is greatly affected by carryover. Also, in detection unit (2), there is empty cycle 1 after empty cycle 2, so a washing step can be inserted into empty cycle 1. Therefore, empty cycle 2 is an interruptible cycle. In addition, although empty cycle 2 comes immediately before item 2 in the B / F separation cycle, it is considered to be less affected by carryover than detection by the detection unit (in B / F separation, only the tip of the nozzle penetrates into the sample container), so it can be interrupted. In this embodiment, in an interruptible cycle, if there is a request to measure an urgent sample (a sample with a short measurement time, etc.), it is possible to allocate the dispensing of the sample and reagents so that B / F separation and detection by the detection unit are performed in empty cycle 2.
[0032] The empty slot 1 is immediately before the detection cycle of item 2 in detection unit (1) and detection unit (2), and is considered to have a significant impact on the carryover of item 2; therefore, interrupts are not allowed.
[0033] Figure 3 is a flowchart showing the process for determining whether an interrupt request can be interrupted during an available cycle.
[0034] By managing the flowchart using software and executing it in the control device 3, it is possible to determine whether or not an interrupt can be made for each available cycle of an interrupt request.
[0035] First, when the control device 3 starts measurement on any order, it determines whether or not there is an interruption request such as an urgent sample request (step S100).
[0036] If the result of the determination in step S100 is NO, the process is repeated until the result of the determination becomes YES (until an interrupt request is received).
[0037] Furthermore, if the result of the determination in step S100 is YES, that is, if there is an interrupt request, it is determined whether or not the item of the interrupt request should be inserted into the empty cycle being determined (step S110). In other words, it is determined whether the cycle following the empty cycle is also an empty cycle, or whether the measurement item of the analysis process assigned to the next cycle is a low-sensitivity item (for example, an item with little influence from carryover, like item 1).
[0038] If the result of the determination in step S110 is YES, that is, if the next cycle after the empty cycle being determined is an empty cycle, or if the measurement item of the analysis process assigned to the next cycle is a low-sensitivity item, then the analysis process of the interrupt request is assigned to the empty cycle (step S120), and the process ends.
[0039] Furthermore, if the determination result in step S110 is NO, that is, if the measurement item of the analysis process assigned to the next cycle after the empty cycle being determined is a highly sensitive item (for example, an item that is highly affected by carryover, such as item 2), the analysis process of the interrupt request is assigned to the empty cycle after that analysis item (step S130), and the process ends.
[0040] In this embodiment configured as described above, the device comprises a dispensing unit for dispensing a sample and reagent into a first container, an analysis unit for analyzing the components of the sample using a mixture of the sample and reagent, a nozzle for aspirating the mixture from the first container and sending it to the analysis unit, and a control unit for controlling the dispensing unit, the analysis unit, and the nozzle. The device includes at least an analysis process which is performed in the following order: a first process of dispensing the sample and reagent into the first container, a second process of sending the mixture from the first container to the analysis unit, and a third process in which the analysis unit analyzes the components of the sample using the mixture. It also includes at least a fourth process which is sending a washing solution from the second container to the analysis unit via the nozzle. A washing process is set to perform the analysis, and the control unit is configured such that, when the analysis unit is scheduled to perform the analysis process for the first item, the cleaning process for the analysis unit, and the analysis process for the second item in that order, and the analysis process for the third item is interrupted in the schedule, and the second item is an item related to a sample for which the carryover effect is judged to be low, the control unit will control the system to assign the analysis process for the third item instead of the washing process. This makes it possible to reduce carryover even when measuring low-sensitivity items and high-sensitivity items in succession.
[0041] <Second Embodiment> The second embodiment will be described with reference to Figure 4.
[0042] In this embodiment, when there is a risk that the measurement items of an interrupt request may affect the measurement items of the immediately following cycle, a free cycle is set in the cycle immediately following the interrupt request and the cleaning process is assigned. In this embodiment, the same reference numerals are used for the same components and functional parts as in the first embodiment, and their descriptions are omitted as appropriate.
[0043] Figure 4 is a flowchart showing the process for setting the cleaning process in response to an interruption request.
[0044] By managing the flowchart with software or the like and executing it with the control device 3, an empty cycle can be automatically created, and it is possible to determine whether or not to perform a cleaning operation.
[0045] First, when the control device 3 starts measurement in an arbitrary order, it determines whether there is an interrupt request such as an emergency specimen request (step S200).
[0046] If the determination result in step S100 is YES, the control device dispenses the specimen of the interrupt request (step S210).
[0047] If the determination result in step S200 is NO, the control device dispenses the specimen scheduled in the original order (step S201), and then determines whether there is an interrupt request such as an emergency specimen request at this time (step S202).
[0048] If the determination result in step S202 is YES, the process proceeds to step S210, and the control device dispenses the specimen of the interrupt request.
[0049] After the process of step S210 ends, or if the determination result in step S202 is NO, the control device performs B / F separation (step S220), and then performs signal measurement (detection by the detection unit) (step S230).
[0050] Thus, when an interrupt request such as an emergency specimen request is made at the timing of step S200 or step S202, the control device executes specimen dispensing (see step S210) so that B / F separation (see step S220) and signal measurement (see step S230) are performed in the empty cycle.
[0051] Following the process of step S230, the control device determines whether the result S of the signal measurement in step S230 is smaller than a predetermined threshold value (step S240).
[0052] If the result of the judgment in step S240 is NO, that is, if the measurement item for which an interrupt request was made has a high signal and there is a risk that it will affect the measurement item in the following cycle, a cleaning process is assigned to automatically create an empty cycle and perform a cleaning operation immediately before the measurement of the next measurement item (step S241), after which the measurement of the next sample is performed (step S250), and the process is terminated.
[0053] Furthermore, if the determination result in step S240 is YES, that is, if the measurement item for the interrupt request has a low signal and is unlikely to affect the measurement item in the following cycle, the process proceeds to step S250 to measure the next sample and terminates the process.
[0054] The other configurations are the same as in the first embodiment.
[0055] In this embodiment configured as described above, the same effects as in the first embodiment can be obtained.
[0056] <Third Embodiment> The third embodiment will be described with reference to Figure 5.
[0057] This embodiment shows a case where the analysis unit has only one detection unit. In this embodiment, the same reference numerals are used for the same components and functional parts as in the first embodiment, and their descriptions are omitted.
[0058] Figure 5 shows the flow of the sample measurement process in this embodiment.
[0059] In this embodiment as well, an idle cycle is provided to allow for the addition of a cleaning process that performs a cleaning operation.
[0060] First, let's consider an example where an order is created in which, in a certain series of cycles (for example, cycles 1 to 8), the analysis process for item 1: n=2 measurements, the analysis process for item 2: n=2 measurements, and the analysis process for item 1: n=2 measurements are performed sequentially.
[0061] In the analysis process for item 2, empty cycles are inserted immediately before the B / F separation cycle and immediately before the detection cycle. When empty cycles are present, a cleaning process is executed without consuming tips or other components. In other words, in addition to the cleaning operations in the normal cycle (rinsing the nozzle with pure water and flowing cleaning solution to the detection unit), a cleaning process is also performed in the empty cycle to perform thorough cleaning and sufficiently wash away components related to the preceding analysis process for item 1, thereby reducing the impact of carryover on the analysis process for item 2.
[0062] The other configurations are the same as in the first embodiment.
[0063] In this embodiment configured as described above, the same effects as in the first embodiment can be obtained.
[0064] <Note> The present invention is not limited to the embodiments described above, and includes various modifications and combinations that do not depart from the spirit of the invention. Furthermore, the present invention is not limited to having all the configurations described in the embodiments described above, and includes those in which some of the configurations have been omitted.
[0065] For example, in the first and second embodiments, even if an interrupt request occurs and the system automatically determines whether or not to allocate the interrupt request to an available cycle, the final decision on whether or not the interrupt is possible may be made by the operator, who operates the control unit to measure the interrupted sample.
[0066] Furthermore, in the second embodiment, if the measurement item immediately following an interruption request is not highly sensitive or the measurement is no longer necessary, the set free cycle (see step S241 in Figure 4) can be used as an interruption cycle for other emergency samples or other interruptions.
[0067] Furthermore, each of the above configurations and functions may be implemented, in whole or in part, by designing them, for example, using integrated circuits. Alternatively, each of the above configurations and functions may be implemented in software by having the processor interpret and execute programs that realize each function.
[0068] 1...Automatic analyzer, 2...Analyzer, 3...Control device, 4...Sample transport path, 5...Sample rack, 6...Sample container, 7...Sample dispensing unit, 8...Dispensing tip attachment / detachment unit, 9...Transport unit, 10...Dispensing tip, 11...Mounting rack, 12...Reaction vessel, 13...Analysis unit, 13a...First detection unit, 13b...Second detection unit, 14...Reaction solution dispensing unit, 15...Reagent dispensing unit, 16...Reagent refrigerator, 17...Reagent disc, 18...Reagent container, 19...Reagent jacket, 21...Incubator (reaction disc), 22...Dispensing position, 23...B / F separation unit
Claims
1. The apparatus comprises: a dispensing unit for dispensing a sample and reagents into a first container; an analysis unit for analyzing the components of the sample using a mixture of the sample and reagents; a nozzle for aspirating the mixture from the first container and sending it to the analysis unit; and a control unit for controlling the dispensing unit, the analysis unit, and the nozzle. The apparatus includes at least an analysis step which is performed in the order of a first process of dispensing the sample and reagents into the first container, a second process of sending the mixture from the first container to the analysis unit, and a third process in which the analysis unit analyzes the components of the sample using the mixture. The apparatus also includes at least a washing step which is performed by sending a washing solution from a second container to the analysis unit via the nozzle. The control unit is characterized in that, when the analysis unit is scheduled to execute in the order of analysis step for a first item, a first washing step for the analysis unit, and an analysis step for a second item, and an analysis step for a third item is interrupted in the schedule, and the second item is an item relating to a sample for which the carryover effect is judged to be low, or there is a second washing step other than the first washing step between the first washing step and the analysis step for the second item, the control unit controls to assign the analysis step for the third item in place of the washing step.
2. An automated analyzer according to claim 1, wherein the control unit controls the analysis process to schedule the analysis process for the third item after the analysis process for the second item if the second item is determined to be an item related to a sample in which carryover is highly likely.
3. An automated analyzer according to claim 1, wherein the analysis unit has a first detection unit and a second detection unit, each performing detection for the analysis of components of the sample, and the control unit controls the system so that, when at least one of the first detection unit and the second detection unit is scheduled to perform an analysis step for a first item, a washing step, and an analysis step for a second item in that order, an analysis step for a third item is interrupted in the schedule of at least one of the first detection unit and the second detection unit, and the second item in the schedule in which the analysis step for the third item is interrupted is an item of a sample for which the carryover effect is judged to be low, the system controls the system to assign the analysis step for the third item in place of the washing step in the schedule in which the analysis step for the third item is interrupted.
4. An automated analyzer according to claim 3, wherein the control unit controls the process so that, when the third item is determined to be an item of a sample for which the carryover effect on the second item is high, a washing step is inserted between the analysis step for the third item and the analysis step for the second item, in which a washing step is performed in which washing solution is sent from the second container to the analysis unit via the nozzle.
5. An automated analyzer according to claim 1, comprising a separation unit that performs a separation step of separating a sample bound to the reagent from an unbound sample in a mixed solution generated by the first process, wherein the washing step further includes a fifth process of sending a washing solution from a third container to the separation unit, and the control unit schedules the washing step to be performed between a plurality of analysis steps that are sequentially executed in the separation unit.
6. The apparatus comprises: a dispensing unit for dispensing a sample and reagents into a first container; an analysis unit for analyzing the components of the sample using a mixture of the sample and reagents; a nozzle for aspirating the mixture from the first container and sending it to the analysis unit; and a control unit for controlling the dispensing unit, the analysis unit, and the nozzle. The apparatus is configured to include at least an analysis step which is performed in the order of a first step which is dispensing the sample and reagents into the first container; a second step which is sending the mixture from the first container to the analysis unit; and a fourth step which is performing at least a washing step which is sending a washing solution from a second container to the analysis unit via the nozzle. The control unit is characterized in that, when the analysis unit is scheduled to execute the analysis process for the first item, the analysis process for the second item, and the analysis process for the third item is interrupted in the schedule, and the second item is an item relating to a sample for which the carryover effect is judged to be low, the control unit controls the washing process to be interrupted between the analysis process for the first item and the analysis process for the second item.