Automated analysis device, and method for adjusting automated analysis device
The automatic analysis device addresses the challenge of maintaining an accurate cleaning range by using a control unit to adjust the cleaning liquid flow rate based on capacitance measurements, ensuring effective cleaning and preventing contamination.
Patent Information
- Application Number
- PCT/JP2024/025150
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-09-13
- Filing Date
- 2024-07-11
- Publication Date
- 2025-03-20
AI Technical Summary
Existing automatic analyzers face challenges in maintaining an accurate cleaning range for dispensing probes due to variations in machinery, such as manufacturing errors and flow path arrangements, which can lead to inadequate cleaning and potential contamination.
The automatic analysis device incorporates a dispensing probe, a cleaning nozzle, a flow rate adjuster, a capacitance measuring unit, and a control unit. The control unit calculates the height information of the cleaning liquid's top surface using capacitance data and determines whether the cleaning liquid flow rate needs adjustment to ensure an appropriate cleaning range.
This solution ensures a consistent and guaranteed cleaning range, unaffected by machinery differences, thereby preventing contamination and improving the accuracy of analytical measurements.
Smart Images

Figure JP2024025150_20032025_PF_FP_ABST
Abstract
Description
Automatic analyzer and method for adjusting automatic analyzer
[0001] The present invention relates to an automatic analyzer that performs qualitative and quantitative analysis of biological samples such as blood and urine, and a method for adjusting the automatic analyzer.
[0002] Patent Document 1 discloses that "the ejection state of the cleaning liquid flow is determined at two horizontal positions using the liquid level detection function of the nozzle" (summary).
[0003] International Publication No. 2022 / 255042
[0004] Automated analyzers perform qualitative and quantitative analysis of specific components contained in biological samples such as blood and urine. In general, the analyzer operates by dispensing the sample from a sample container to a reaction container using a dispensing probe, then dispensing the reagent from the reagent container to the reaction container using a dispensing probe, stirring the mixture, allowing it to react for a certain period of time, and calculating the concentration of the target item from information such as absorbance and luminescence obtained from the reaction solution.
[0005] In such an automatic analyzer, in order to perform accurate measurements, the dispensing probe that aspirates the sample and reagent must be washed in an appropriate washing range.
[0006] However, if the performance of the pump that supplies the washing liquid for washing the dispensing probe deteriorates over time, or if the flow path from the pump to the washing liquid outlet becomes clogged, the flow of the washing liquid will change.
[0007] If the washing range is small, the probe cannot be washed sufficiently, which may result in carryover from the dispensing probe to the cell. To address this reduction in the washing range due to a decrease in the amount of washing water, operators generally perform maintenance by periodically adjusting the amount of washing solution, but this reduction in the washing range may go unnoticed, or even if it is noticed, the adjustment must be done manually, which takes time and results in inconsistency.
[0008] A known technique for checking the amount of washing liquid is disclosed in, for example, Patent Document 1. In the technique described in Patent Document 1, a dispensing probe is positioned at two horizontal points to detect changes in the state of liquid flow.
[0009] Here, in a cleaning method in which the cleaning liquid is discharged at an angle from the cleaning nozzle, it is possible to detect changes in the liquid flow. However, it cannot accommodate differences between devices, such as the tilt of the cleaning nozzle. For example, depending on manufacturing errors and the layout of the flow paths, there are devices in which the slope of the cleaning liquid is steep, even though the amount of cleaning water is sufficient and probe cleaning is possible. The technology described in Patent Document 1 may not be able to accommodate the aforementioned manufacturing errors and other differences between devices, and it has become clear that there is room for more appropriate confirmation and adjustment of the water volume.
[0010] The present invention has been made in consideration of the above-mentioned problems, and aims to provide an automatic analyzer and an adjustment method for an automatic analyzer that can ensure a cleaning range without being affected by differences between machines.
[0011] The present invention includes multiple means for solving the above-mentioned problems, and one example thereof is a device comprising a dispensing probe that dispenses liquid, a cleaning nozzle that ejects cleaning liquid onto the outer wall of the dispensing probe, a flow rate adjustment unit that adjusts the amount of cleaning liquid ejected from the cleaning nozzle, a capacitance measurement unit that measures the capacitance of the dispensing probe, and a control unit, wherein the control unit determines height information of the upper surface of the cleaning liquid based on the capacitance data measured by the capacitance measurement unit in a horizontal position at a cleaning position where the dispensing probe is cleaned, determines the cleaning range of the dispensing probe in the horizontal position based on the height information of the upper surface of the cleaning liquid, and determines whether or not the amount of cleaning liquid needs to be adjusted by the flow rate adjustment unit based on the determined cleaning range.
[0012] According to the present invention, it is possible to ensure a cleaning range that is not affected by differences between machines. Objects, configurations, and effects other than those described above will become apparent from the following description of the embodiments.
[0013] FIG. 1 is a schematic configuration diagram of an automatic analyzer of Example 1. FIG. 2 is a diagram showing the configuration of a sample dispensing mechanism of the automatic analyzer of Example 1. FIG. 3 is a diagram showing an example configuration of a cleaning liquid volume adjustment unit for a sample dispensing probe of the automatic analyzer of Example 1. FIG. 4 is a diagram showing the configuration of a control block for probe cleaning and probe cleaning liquid volume adjustment in the automatic analyzer of Example 1. FIG. 5 is a flowchart for acquiring the height of the upper surface of cleaning liquid in the automatic analyzer of Example 1. FIG. 6 is a flowchart showing a method for checking and adjusting a cleaning range in the automatic analyzer of Example 1. FIG. 7 is a diagram showing thresholds before smoothing processing in the automatic analyzer of Example 1. FIG. 8 is a diagram showing thresholds after smoothing processing in the automatic analyzer of Example 1. FIG. 9 is a diagram showing an example height position of a sample dispensing probe in the automatic analyzer of Example 1. FIG. 10 is a diagram showing a cleaning range confirmation height and flow for each operation in the automatic analyzer of Example 2.
[0014] Hereinafter, an embodiment of the automatic analyzer and the method for adjusting the automatic analyzer of the present invention will be described with reference to the drawings. In the drawings used in this specification, identical or corresponding components are designated by the same or similar reference numerals, and repeated description of these components may be omitted.
[0015] First Embodiment A first embodiment of the automatic analyzer and the method for adjusting the automatic analyzer of the present invention will be described with reference to FIGS. 1 to 9. FIG.
[0016] First, the overall configuration of the automatic analyzer and the details of the configuration of each part will be described with reference to Fig. 1. Fig. 1 is a schematic diagram of the automatic analyzer of Example 1.
[0017] The automatic analyzer 100 shown in FIG. 1 is an apparatus for measuring a reaction liquid that has undergone a chemical reaction in a reaction vessel 102 and analyzing its components.
[0018] This automatic analyzer 100 has, as its main components, a reaction disk 101, a cleaning mechanism 103, a spectrophotometer 104, a stirring mechanism 105, a cleaning tank 106, a first reagent dispensing mechanism 107, a second reagent dispensing mechanism 107a, a cleaning tank 108, a reagent disk 109, a first sample dispensing mechanism 111, a second sample dispensing mechanism 111a, a cleaning tank 113, a sample transport mechanism 117, and a controller 118.
[0019] Of these components, the first reagent dispensing mechanism 107, the second reagent dispensing mechanism 107a, the first sample dispensing mechanism 111, and the second sample dispensing mechanism 111a each have a liquid level detector 210 (see FIG. 3, etc., and will be described in detail later).
[0020] Reaction vessels 102 are arranged circumferentially on the reaction disk 101. The reaction vessels 102 are containers for containing a mixed liquid obtained by mixing a sample and a reagent, and a plurality of reaction vessels 102 are arranged on the reaction disk 101. A sample transport mechanism 117 is arranged near the reaction disk 101 to transport a sample rack 116 loaded with sample vessels 115.
[0021] A first sample dispensing mechanism 111 and a second sample dispensing mechanism 111a, which are rotatable and movable up and down, are disposed between the reaction disk 101 and the sample transport mechanism 117, and each mechanism is equipped with a sample dispensing probe 111b. A sample syringe 122 is connected to each of the sample dispensing probes 111b. The sample dispensing probe 111b moves horizontally while tracing an arc around the rotation axis, and moves up and down to dispense a sample from a sample container 115 to a reaction container 102.
[0022] The reagent disk 109 is a storage cabinet on which a plurality of reagent bottles 110 containing reagents, detergent bottles 112, etc. can be placed on the circumference. The reagent disk 109 is kept cold.
[0023] Between the reaction disk 101 and the reagent disk 109, a first reagent dispensing mechanism 107 and a second reagent dispensing mechanism 107a, which are rotatable and movable up and down, are installed, and each of them is equipped with a reagent dispensing probe 120.
[0024] The reagent dispensing probe 120 is moved vertically and horizontally by the first reagent dispensing mechanism 107 or the second reagent dispensing mechanism 107a. A reagent syringe 121 is connected to each reagent dispensing probe 120. The reagent syringe 121 dispenses the reagent, detergent, diluent, pretreatment reagent, etc., aspirated from the reagent bottle 110, detergent bottle 112, diluent bottle, pretreatment reagent bottle, etc., via the reagent dispensing probe 120 into the reaction vessel 102.
[0025] Around the reaction disk 101, there are arranged a cleaning mechanism 103 for cleaning the inside of the reaction vessel 102, a spectrophotometer 104 for measuring the absorbance of light that passes through the mixed liquid in the reaction vessel 102, a stirring mechanism 105 for mixing the sample and reagent dispensed into the reaction vessel 102, and the like.
[0026] Additionally, a washing tank 108 for the reagent dispensing probe 120 is located within the operating range of the first reagent dispensing mechanism 107 and the second reagent dispensing mechanism 107a, a washing tank 113 for the sample dispensing probe 111b is located within the operating range of the first sample dispensing mechanism 111 and the second sample dispensing mechanism 111a, and a washing tank 106 for the stirring mechanism 105 is located within the operating range of the stirring mechanism 105. The sample dispensing probe 111b is washed at the washing position of the washing tank 113 for the sample dispensing probe 111b. The washing position in this invention refers to the position where the washing operation of the dispensing probe in the washing tank is actually performed during the analysis operation of the automated analyzer. In this embodiment, a case where both internal and external washing of the dispensing probe are performed will be described as an example of the washing position. The water volume is checked and adjusted at the horizontal position of the washing position.
[0027] Each mechanism is connected to a controller 118, and its operation is controlled by the controller 118. The controller 118, which serves as a control section, is composed of a computer or the like, and controls the operation of each mechanism described above within the automatic analyzer, as well as performing calculations to determine the concentration of a predetermined component in a liquid sample such as blood or urine.
[0028] The analysis process of the test sample by the above-described automatic analyzer 100 is performed in the following order.
[0029] First, a sample in a sample container 115 placed on a sample rack 116 transported near the reaction disk 101 by a sample transport mechanism 117 is dispensed into a reaction container 102 on the reaction disk 101 by the sample dispensing probes 111b of the first sample dispensing mechanism 111 and the second sample dispensing mechanism 111a.
[0030] Next, the reagent to be used for analysis is dispensed from the reagent bottle 110 on the reagent disk 109 by the first reagent dispensing mechanism 107 or the second reagent dispensing mechanism 107a into the reaction vessel 102 into which the sample has been previously dispensed. Subsequently, the mixing mechanism 105 mixes the mixture of the sample and the reagent in the reaction vessel 102.
[0031] Thereafter, light generated from a light source is transmitted through a reaction vessel 102 containing the mixed liquid, and the luminous intensity of the transmitted light is measured by a spectrophotometer 104. The luminous intensity measured by the spectrophotometer 104 is sent to a controller 118 via an A / D converter and an interface (both of which are omitted for convenience of illustration). The controller 118 then performs calculations to determine the concentration of a predetermined component in a liquid sample such as blood or urine, and displays the result on a display unit (not shown) or the like.
[0032] While an automatic analyzer that determines the concentration of a predetermined component using the spectrophotometer 104 will be described as an example, the present invention is not limited to a biochemical analyzer, and may be an analyzer that performs analysis of other analysis items, such as an immunoanalyzer that performs analysis of immune analysis items. The biochemical analyzer is also not limited to the form shown in Fig. 1, and may be one that is separately equipped with an analyzer that measures other analysis items, such as electrolytes.
[0033] Furthermore, the automated analyzer 100 is not limited to a single analysis module configuration as shown in FIG. 1, but can be configured to connect two or more analysis modules capable of measuring various identical or different analysis items and preprocessing modules that perform preprocessing via a transport device.
[0034] Next, the configuration of the sample dispensing mechanism will be described using Fig. 2. Note that Fig. 2 shows the configuration of the first sample dispensing mechanism 111, but the second sample dispensing mechanism 111a has a similar configuration, so details thereof will be omitted. Furthermore, this is not limited to the sample dispensing mechanism, and the first reagent dispensing mechanism 107 or the second reagent dispensing mechanism 107a also have a similar mechanism, so details thereof will be omitted.
[0035] As shown in Figure 2, the sample dispensing mechanism is composed of a sample dispensing arm 111c having a sample dispensing probe 111b at its tip, a horizontal movement mechanism 111d that moves the sample dispensing arm 111c horizontally, a vertical movement mechanism 111e that moves the sample dispensing arm 111c vertically (Z direction), and a rotational movement mechanism (not shown) that rotates the sample dispensing arm 111c.
[0036] The sample dispensing mechanism uses these moving mechanisms to move the sample dispensing probe 111b to an aspirating position where the sample is aspirated from the sample container 115, an ejection position where the aspirated sample is ejected into the reaction container 102, and a washing position where the tip of the sample dispensing probe 111b is washed in the washing tank 113.
[0037] Furthermore, the sample dispensing mechanism lowers (in the Z direction) the sample dispensing probe 111b to match the heights of the sample container 115, reaction container 102, and washing tank 113 at the suction position, discharge position, and washing position.
[0038] In this embodiment, the cleaning of the sample dispensing probe 111b is described as an example, but the cleaning of the reagent dispensing probe 120, which has a similar mechanism, can also be applied in the same way. The cleaning of the reagent dispensing probe 120 can also be applied to an automatic analyzer equipped with a mechanism for dispensing a sample and a reagent with a single probe.
[0039] 3 is a diagram showing an example of the configuration of the cleaning liquid volume adjustment unit of the sample dispensing probe 111b. As shown in Fig. 3, the cleaning liquid volume adjustment unit is composed of a cleaning liquid supply pump 208 that supplies cleaning liquid from a pure water facility (not shown), an electromagnetic valve 217 that turns on / off the liquid supply by opening / closing control, an adjustment valve 216 that can change the open / close state by a control current, a cleaning nozzle 202 that discharges cleaning liquid, a waste liquid tank 219 that stores waste liquid discharged from the cleaning tank 113, and a flow path 218 that connects each component.
[0040] Furthermore, a liquid level detector 210, which is configured by, for example, a capacitance sensor, is mounted in the sample dispensing arm 111c of the sample dispensing mechanism and is electrically connected to the controller 118 that executes the smoothing process.
[0041] When cleaning the sample dispensing probe 111b, the solenoid valve 217 is opened and the cleaning liquid supplied from the cleaning liquid supply pump 208 is ejected from the cleaning nozzle 202. The liquid flow from the cleaning nozzle 202 comes into contact with the outer surface of the sample dispensing probe 111b, removing dirt adhering to the outer surface of the sample dispensing probe 111b.
[0042] In this embodiment, the flow rate adjusting unit capable of adjusting the amount of cleaning liquid is the adjustment valve 216, and an example is shown in which one adjustment valve 216 adjusts the amount of cleaning liquid from one cleaning nozzle 202, but it is also possible to adjust the amount of liquid from two or more cleaning nozzles with one adjustment valve 216. When adjusting the amount of liquid from multiple cleaning nozzles, it is desirable to adjust in advance so that the amount of liquid discharged from each cleaning nozzle is approximately the same by making the flow path configuration from the cleaning liquid supply pump 208 to the cleaning nozzles the same or by providing an adjustment valve in each flow path.
[0043] Next, the configuration of the mechanism related to cleaning and its control system will be described with reference to Fig. 4. Fig. 4 is a diagram showing an example of the configuration of a control block for probe cleaning and adjusting the amount of probe cleaning liquid.
[0044] The automatic analyzer control unit 601 is part of the controller 118, which is a central processing unit for controlling the entire apparatus. The automatic analyzer control unit 601 of this embodiment obtains height information about the top surface of the cleaning liquid based on capacitance data measured by the liquid level detector 210 when the sample dispensing probe 111b is in the horizontal position at the cleaning position where it is cleaned, obtains the cleaning range of the sample dispensing probe 111b in the horizontal position based on the height information about the top surface of the cleaning liquid, and determines whether or not adjustment of the amount of cleaning liquid by the flow rate adjuster is necessary based on the obtained cleaning range. Details of this will be described later. The automatic analyzer control unit 601 preferably executes the steps of obtaining height information about the top surface of the cleaning liquid, obtaining the cleaning range, and determining whether or not adjustment of the amount of cleaning liquid is necessary.
[0045] The automatic analyzer control unit 601 receives commands such as test instructions from the user via a GUI 602. The dispensing mechanism positions the sample dispensing probe 111b based on instructions from a dispensing arm control unit 603 to a dispensing arm horizontal movement unit 604 and a dispensing arm vertical movement unit 605.
[0046] The cleaning liquid upper surface normal height confirmation control unit 606 detects the height of the cleaning liquid upper surface when the cleaning range of the sample dispensing probe 111b is confirmed to be normal, such as at the time of installation, via the cleaning liquid contact determination unit 607, and stores the acquired height information in the liquid flow detection height table 608. For convenience of illustration, two cleaning liquid contact determination units 607 are shown in Figure 4.
[0047] When checking the cleaning liquid top surface height, when obtaining the cleaning liquid surface height (when detecting the top end position of the cleaning liquid by liquid level detection in the horizontal position during cleaning), the sample dispensing probe 111b is lowered at a slower speed than during the cleaning operation, so that the cleaning liquid top surface height can be obtained accurately by liquid level detection.
[0048] During analysis, cleaning is performed by moving the sample dispensing probe 111b to the cleaning position in response to instructions from the probe cleaning control unit 609. If the position of the tip of the sample dispensing probe 111b at this time is set to the cleaning horizontal position height 502, during cleaning range confirmation and adjustment, cleaning range detection is performed by moving the tip of the sample dispensing probe 111b to the cleaning liquid upper surface detection height 503 or a height with a margin 504 stored in the liquid flow detection height table 608 in response to instructions from the cleaning range detection and adjustment control unit 610. Switching between analysis and liquid volume adjustment is performed by the normal cleaning mode / cleaning range detection and adjustment mode switching unit 611.
[0049] The opening and closing of the adjustment valve 216 for discharging the cleaning liquid is controlled by an electromagnetic valve control unit 612, and cleaning water is discharged at any time during probe cleaning or liquid volume detection and adjustment. The detection signal is judged via a cleaning liquid contact judgment unit 607 (processing details are shown in Figures 7 and 8) and a cleaning range detection and adjustment control unit 610.
[0050] The cleaning range detection and adjustment control unit 610 determines whether or not the adjustment valve 216 needs to be controlled (whether or not the amount of cleaning liquid needs to be adjusted by the adjustment valve 216) and the amount of control (the degree of opening of the adjustment valve 216) based on the height information of the upper surface obtained by the cleaning liquid contact determination unit 607. The open / close state of the adjustment valve 216 is controlled by changing the control output from the adjustment valve control unit 613. The control output when the adjustment valve 216 is controlled and the information on the liquid flow height measured at that time are managed in the adjustment valve control table 614, and by referring to this information when the adjustment valve 216 is controlled from the next time onwards, the amount of cleaning liquid can be brought to a target state with fewer operations.
[0051] 5 is a flowchart showing the operation for checking the cleaning liquid upper surface detection height 503 when the cleaning range is normal, which will be described later. In the flowchart, the cleaning liquid upper surface height at the horizontal position for cleaning the probe is acquired as a reference value for checking the cleaning range, at a timing such as during installation when the cleaning range is normal. The sample dispensing probe 111b operates in a state where it is positioned at a horizontal position 501 during cleaning, which will be described later. The main actors that execute each step in the flow of FIG. 5 and each step in the flow of FIG. 6, which will be described later, are the components shown in FIG. 4, i.e., the controller 118.
[0052] First, the solenoid valve 217 is opened (S701) to start discharging the cleaning liquid.
[0053] Thereafter, the liquid level detector 210 is changed to a microcomputer capable of smoothing processing (S702). A number k=a is given so that multiple repetitions are possible (S703).
[0054] Thereafter, the automatic analyzer control unit 601, which is triggered by the falling pulse of the sample dispensing probe 111b ((=using the falling pulse as a trigger)), starts waiting for measurement of the liquid level detection voltage (S704).
[0055] The sample dispensing probe 111b is then lowered at a slower speed than normal movement (S705). Lowering at a slower speed prevents the liquid level detector 210 from falsely detecting a contact detection signal with the cleaning liquid, and the resolution of the lowering pulse is increased, reducing the detection variability of the cleaning liquid upper edge position. During the lowering, a sensor signal is acquired, and a determination is made as to whether the signal value exceeds the liquid detection threshold. When the signal value exceeds the threshold, the lowering pulse is recorded as the detection height (S706).
[0056] Then, the cleaning liquid is raised to the initial height (S707) to prepare for the next operation. The operations of S703 to S707 are repeated multiple times (S708, S709). In this way, it is desirable to obtain height information of the upper surface of the cleaning liquid multiple times and to determine the cleaning range based on the obtained height information of the upper surface of the cleaning liquid multiple times.
[0057] After repeating this operation multiple times, the solenoid valve 217 is closed (S710).Then, the averaged descending pulse is stored as an adjustment value (S711), and the cleaning liquid upper surface height acquisition process is terminated.
[0058] 6 is a flowchart showing the operation of checking the cleaning range and adjusting the amount of cleaning liquid when it is determined that the cleaning range is insufficient. The operation is performed with the sample dispensing probe 111b positioned in the cleaning horizontal position 501.
[0059] As shown in FIG. 6, the water level confirmation operation is started by first changing the liquid level detector 210 to a microcomputer capable of smoothing processing (S801).
[0060] Thereafter, the sample dispensing probe 111b is lowered to the cleaning solution upper surface detection height 503, which is previously acquired as an adjustment value (S802). When moving to the cleaning solution upper surface height, a height 504 with a margin for adding a lowering amount can be set, thereby determining the cleaning range to be guaranteed and providing a margin for the range up to which adjustment can be performed. Figure 10, which will be described later, shows an example of a flow for manipulating the ease of starting adjustment by providing a margin for the cleaning range.
[0061] Next, a number k=a is assigned so that the cleaning range can be repeatedly cleaned multiple times (S803). After that, without changing the height, the bp is increased in advance to output a descending pulse that is a trigger for starting to acquire the liquid level detection voltage (S804).
[0062] Thereafter, the automatic analyzer control unit 601, which is triggered by the falling pulse of the sample dispensing probe 111b, starts waiting for measurement of the liquid level detection voltage (S805).
[0063] Thereafter, the bp decreases to output a falling pulse that serves as a trigger to the automatic analyzer control unit 601 (S806). After the decrease, a sensor signal is acquired for a certain period of time. The sensor signal acquisition time at this time ensures the time for the water flow to stabilize after the solenoid valve 217 is opened. Thereafter, the solenoid valve 217 is opened for a certain period of time (S807). After the cleaning solution has been discharged until it is sufficiently stable, the solenoid valve 217 is closed (S808).
[0064] Thereafter, the presence or absence of cleaning liquid is determined by the ON / OFF of the liquid level detection at the cleaning liquid upper surface detection height 503 (S809). Thereafter, in order to reduce the risk of false detection, the above-described processes of S804 to S809 are repeated multiple times (S810, S811). In this way, similar to S708 and S709, it is desirable to obtain information on the height of the upper surface of the cleaning liquid multiple times and determine the cleaning range based on the obtained information on the height of the upper surface of the cleaning liquid multiple times.
[0065] After multiple attempts, the water level rises to the initial height (S812). Then, the cleaning range is determined to see if the multiple liquid level detections are successful (S813). If the cleaning range is successful, the confirmation operation ends. If the cleaning range is unsuccessful, the water volume adjustment operation ends.
[0066] If it is determined that the water volume needs to be adjusted, the sample dispensing probe 111b is lowered to the cleaning liquid upper surface detection height 503, which is acquired in advance as an adjustment value (S814).
[0067] Thereafter, the flow rate is increased by increasing the new voltage regulation value of the regulation valve 216 by a certain amount compared to the voltage regulation value currently being used (S815).
[0068] By increasing the count value from the voltage adjustment value that was used, the time required for adjustment is shortened. Also, the amount of adjustment value to be increased at one time is determined by taking into consideration that if the count number is too small, the flow rate change is small and it takes time to adjust the flow rate, and if the count number is too large, there is a limit to the opening degree of the proportional solenoid valve, making it impossible to adjust the solenoid valve quickly. In this way, it is desirable to increase the opening degree of the adjustment valve 216 in units larger than the set minimum unit.
[0069] Then, a number k=a is assigned so that multiple repetitions are possible (S816). After that, without changing the height, the bp is increased in advance to output a descending pulse that is a trigger for starting to acquire the liquid level detection voltage (S817).
[0070] Thereafter, the automatic analyzer control unit 601, which is triggered by the falling pulse of the sample dispensing probe 111b, starts waiting for measurement of the liquid level detection voltage (S818).
[0071] Thereafter, the bp decreases to output a triggering falling pulse to the automatic analyzer control unit 601 (S819). After the decrease, a sensor signal is acquired for a certain period of time. The sensor signal acquisition time at this time ensures the time for the water flow to stabilize after the solenoid valve 217 is opened. Thereafter, the solenoid valve 217 is opened for a certain period of time (S820). After the cleaning liquid has been discharged until it is sufficiently stable, the solenoid valve 217 is closed (S821).
[0072] Thereafter, the presence or absence of cleaning liquid is determined by the ON / OFF of the liquid level detection at the cleaning liquid upper surface detection height 503 (S822). Thereafter, in order to reduce the risk of false detection, the above-described processes of S817 to S822 are repeated multiple times (S823, S824). In this way, similar to S708, S709, S810, and S811, it is desirable to obtain information on the height of the upper surface of the cleaning liquid multiple times and determine the cleaning range based on the obtained information on the height of the upper surface of the cleaning liquid multiple times.
[0073] Then, the cleaning range is judged to see if the multiple liquid level detections result in a judgment of OK (S825). If the cleaning range judgment is OK multiple times, the water volume adjustment operation is terminated. On the other hand, if the cleaning range judgment is NG, it is checked whether the solenoid valve voltage adjustment value is set to the maximum value (S826).
[0074] If it is determined in S826 that the maximum value has been reached, adjustment is not possible and the device is stopped (S827). On the other hand, if it is determined that the maximum value has not been reached, the solenoid valve adjustment count value is increased again (S828), and the process returns to S815 to increase the voltage adjustment value, and the water volume adjustment operation of S816 to S822 is repeated.
[0075] Here, "n," which is the reference value for the number of repetitions in S708 in Fig. 5, "m" in S810 in Fig. 6, and "l" in S823, can be set to different numbers depending on the state of the apparatus when the cleaning liquid top surface detection process is performed, such as during maintenance or analysis. For example, the number of repetitions can be set to be smaller during analysis than during maintenance, when there is more time, in order to shorten the interruption of analysis.
[0076] 7 and 8 are diagrams showing the smoothing process and threshold value of the capacitance voltage used for detecting the cleaning liquid by turning on / off the liquid level detection in S706, S809, and S822. Fig. 7 shows raw data 400 of the capacitance voltage value when the sensor is slowly brought into contact with the cleaning liquid from the atmosphere, and Fig. 8 shows smoothed data 401 obtained by smoothing the capacitance voltage value when the sensor is slowly brought into contact with the cleaning liquid from the atmosphere. The horizontal axis shows time [ms], and the vertical axis shows capacitance voltage [V].
[0077] In the present invention, "smoothing" refers to finding the average of a certain range of the acquired raw data 400 as one point, and performing this process of finding the average on the raw data 400 within a required range.
[0078] The cleaning liquid has the property of fluctuating due to the influence of gravity and the like, and even splashing of the cleaning liquid affects the capacitance, as shown in raw capacitance voltage data 400 in Fig. 7. As shown in Fig. 7, if the threshold value is set low in raw capacitance voltage data 400, there is a high risk of false detection when the capacitance voltage value temporarily rises, and therefore the threshold value needs to be set significantly higher in order to detect the height at which the probe actually comes into contact with the cleaning liquid.
[0079] The above threshold is determined by smoothing the capacitance voltage value, and when determining the threshold for detecting contact of cleaning liquid with the sample dispensing probe 111b in the raw data 400, it is necessary to set a raw data threshold 403 higher than the smoothed threshold, which is also thought to reduce the risk of false detection due to liquid surface fluctuations.
[0080] 8, it can be seen that the smoothed capacitance voltage values have less influence of fluctuations and splashing of the cleaning liquid in the graph of the smoothed capacitance voltage values than the capacitance voltage values in the raw data 400. By comparing the raw data with the graph after smoothing, it is determined that the cleaning liquid can be detected more accurately by smoothing, and it is desirable to perform the smoothing process.
[0081] Furthermore, when smoothing is performed, the threshold is set to a smoothing threshold 404 that is a fixed amount higher than the reference capacitance voltage value 402. This value is lower than the raw data threshold 403. The smoothing threshold 404 can be set at the rising edge of the graph. By setting it at the rising edge of the graph, the rate of change in capacitance potential during liquid level detection is large relative to the probe falling time for a fixed liquid level detection time, and therefore the variance in the falling pulse used to determine that the liquid level has been detected can be reduced.
[0082] In this way, the controller 118 smooths the capacitance data at predetermined intervals, acquires waveform data, and can detect contact of liquid with the sample dispensing probe 111b based on the acquired waveform data.It can also detect contact of liquid with the sample dispensing probe 111b in a horizontal position based on a comparison of the change in the waveform data within a predetermined time after the sample dispensing probe 111b is positioned at a predetermined height with a predetermined threshold value.
[0083] Furthermore, when checking and adjusting the cleaning range, the sample dispensing probe 111b is kept waiting at the cleaning liquid surface height, and the detection of cleaning liquid is checked multiple times. If cleaning liquid particles remain attached to the sample dispensing probe 111b, the initial value of the capacitance voltage will be high in advance. Even in the above situation, by setting the threshold low, the cleaning liquid capacitance voltage will exceed the threshold when the probe comes into contact with the cleaning liquid, minimizing false detections.
[0084] 9 shows the height of the sample dispensing probe 111b at the horizontal position 501 during washing, which is obtained in FIG. 5 above. The obtained cleaning liquid upper surface height is used to move to the cleaning liquid upper surface height in S802 and S814. Fig. 9(a) shows the cleaning horizontal position height 502 when washing the sample dispensing probe 111b, Fig. 9(b) shows the cleaning liquid upper surface detection height 503 for detecting the cleaning liquid upper surface, and Fig. 9(c) shows the height 504, which is lower by a margin than the cleaning liquid upper surface detection height 503 for detecting the cleaning liquid upper surface.
[0085] Figure 9(a) shows the position of the sample dispensing probe 111b when cleaning the sample dispensing probe 111b, and in this horizontal position, a downward movement is performed to confirm the cleaning range, as shown in (b) and (c) in Figure 9 described below.
[0086] 9(b), when checking the amount of cleaning liquid 500, the automatic analyzer control unit 601 slowly lowers the sample dispensing probe 111b from above the liquid surface, detects the cleaning horizontal position height 502, and acquires height information. Then, using the acquired height information, the height position of the probe is moved to the cleaning liquid flow height. At that position, the liquid level is detected and the presence or absence of cleaning water is determined.
[0087] During automatic adjustment, the cleaning liquid upper surface is detected at a cleaning liquid upper surface detection height 503, and during analysis, the liquid level is detected at a height 504 that is lower than the height at which the cleaning liquid upper surface is detected by a margin that makes it difficult to adjust. In this way, two or more threshold values (cleaning liquid upper surface detection height 503, height with margin 504) can be set as the reference for detecting contact of the sample dispensing probe 111b with the liquid.
[0088] The direction of the cleaning liquid discharged from the cleaning nozzle 202 does not necessarily have to be the same as that shown in FIG. 9, because the liquid flow will draw a parabola due to gravity even when the cleaning liquid is discharged obliquely from bottom to top.
[0089] Here, the cleaning solution tends to fluctuate due to the influence of gravity, etc., which can easily cause splashing (scattering) of the cleaning water. This can result in large variations in the descending distance (detection distance) of the sample dispensing probe 111b. Therefore, in this embodiment, the cleaning unit lowers the sample dispensing probe 111b at a slower speed when checking the height of the cleaning solution top surface (descending detection distance) than when cleaning.
[0090] In this way, by making the descending speed of the sample dispensing probe 111b slower than during cleaning, the resolution of the descending operation becomes finer, and the resolution during smoothing processing also becomes finer, thereby suppressing variation in the detection position and further improving detection accuracy.
[0091] Next, the effects of this embodiment will be described.
[0092] The automated analyzer 100 of the first embodiment of the present invention described above comprises a sample dispensing probe 111b that dispenses samples or a reagent dispensing probe 120 that dispenses reagents, a cleaning nozzle 202 that ejects cleaning liquid onto the outer walls of the sample dispensing probe 111b and the reagent dispensing probe 120, a flow rate adjustment unit that adjusts the amount of cleaning liquid ejected from the cleaning nozzle 202, a liquid level detector 210 that measures the capacitance of the sample dispensing probe 111b and the reagent dispensing probe 120, and a controller 118. The controller 118 determines height information of the upper surface of the cleaning liquid based on capacitance data measured by the liquid level detector 210 at the horizontal position in the cleaning position where the sample dispensing probe 111b and the reagent dispensing probe 120 are cleaned, determines the cleaning range of the sample dispensing probe 111b and the reagent dispensing probe 120 at the horizontal position based on the height information of the upper surface of the cleaning liquid, and determines whether or not the flow rate adjustment unit needs to adjust the amount of cleaning liquid based on the determined cleaning range.
[0093] This makes it possible to determine whether the height of the cleaning liquid dispensed, i.e., the cleaning range, is appropriate at the horizontal position where the actual cleaning operation is performed, eliminating the effects of factors such as the tilt of the cleaning liquid. This means that even if there are differences between machines, such as the manufacturing errors mentioned above, it is possible to determine whether the cleaning range is appropriate, and it becomes possible to guarantee the cleaning range without being affected by differences between machines. As a result, adjustments to maintain the appropriate cleaning range can be made automatically.
[0094] In addition, the controller 118 smooths the capacitance data at predetermined intervals, acquires waveform data, and detects contact of the sample dispensing probe 111b with the liquid based on the acquired waveform data. This reduces the effect of variations in the acquired data, allowing for more accurate determination of whether or not the cleaning liquid has come into contact with the sample dispensing probe 111b, thereby improving the detection accuracy of the cleaning range and making the cleaning range more appropriate.
[0095] Furthermore, the controller 118 detects contact of the sample dispensing probe 111b with the liquid based on a comparison of the change in waveform data within a predetermined time after the sample dispensing probe 111b is positioned at a predetermined height in the horizontal position with a preset threshold value. This allows the threshold value to be set at a lower position than in the case of the raw data 400, and at the rising point of the graph, thereby increasing the rate of change in the liquid level detection potential with respect to the probe lowering time and reducing height detection errors. In other words, the detection accuracy of the cleaning range can be further improved.
[0096] In addition, when acquiring height information of the upper surface, the controller 118 can further subdivide the height information by lowering the sample dispensing probe 111b at a slower speed than during the cleaning operation, thereby further improving the accuracy of confirmation of the cleaning range.
[0097] Furthermore, by setting two or more thresholds, the ease of adjustment can be controlled, so that the cleaning range confirmation operation can be performed according to the situation at the time of confirmation, thereby avoiding any impact on the start of analysis, etc.
[0098] The flow rate adjusting unit is an adjusting valve 216 that can adjust the amount of cleaning liquid, and the controller 118 can easily adjust the flow rate by adjusting the opening degree of the adjusting valve 216 based on the height information of the upper surface.
[0099] Furthermore, by increasing the degree of opening of the adjusting valve 216 in units larger than the minimum unit that has been set, the time required to adjust the flow rate of the cleaning liquid can be shortened.
[0100] In addition, the controller 118 acquires height information of the upper surface of the cleaning liquid multiple times and determines the cleaning range based on the acquired height information of the upper surface of the cleaning liquid multiple times, thereby reducing detection errors of the cleaning range due to false detection and contributing to the realization of more appropriate cleaning.
[0101] Furthermore, by acquiring height information of the upper surface of the cleaning liquid multiple times at different times depending on the timing at which the height information of the upper surface of the cleaning liquid is obtained, the cleaning range confirmation operation can be performed according to the situation at the time of confirmation.
[0102] Second Embodiment An automatic analyzer and an adjustment method for the automatic analyzer according to a second embodiment of the present invention will be described with reference to Fig. 10. Fig. 10 is a diagram showing the cleaning range confirmation height and flow for each operation.
[0103] FIG. 10 shows the height positions at which the sample dispensing probe 111b checks the cleaning liquid 500 during each operation.
[0104] 10, when automatic adjustment is performed as part of periodic maintenance (S901), the cleaning liquid is checked at the cleaning liquid upper surface (cleaning liquid upper surface detection height 503 in FIG. 9), whereas when performed for each analysis (S902), the cleaning liquid is checked at a position lowered by a margin from the cleaning liquid upper surface height (height 504 with a margin in FIG. 9). This is a means for manipulating the guaranteed cleaning range.
[0105] In the automated analyzer 100, if the analyzer stops during analysis, testing will also stop, so adjustments are made in advance during automatic adjustments during maintenance whenever possible. However, if the cleaning range is not cleaned according to specifications, analytical performance will be affected, so the cleaning range is also checked during analysis preparation. Furthermore, when it is determined that the cleaning judgment is inappropriate and adjustment operations are initiated, the cleaning liquid is checked on the surface of the cleaning liquid (S903). The above operation is to return the cleaning range to its initial state.
[0106] The other configurations and operations are substantially the same as those of the automatic analyzer and the method for adjusting the automatic analyzer of the first embodiment, and details thereof will be omitted.
[0107] The automatic analyzer and the method for adjusting an automatic analyzer according to the second embodiment of the present invention also provide substantially the same effects as those of the automatic analyzer and the method for adjusting an automatic analyzer according to the first embodiment described above.
[0108] <Others> The present invention is not limited to the above-described examples, and includes various modifications. The above-described examples have been described in detail to clearly explain the present invention, and the present invention is not necessarily limited to those having all of the described configurations.
[0109] It is also possible to replace part of the configuration of one embodiment with the configuration of another embodiment, or to add the configuration of one embodiment to the configuration of another embodiment.It is also possible to add, delete, or replace part of the configuration of each embodiment with the configuration of another embodiment.
[0110] DESCRIPTION OF SYMBOLS 100...Automatic analyzer 101...Reaction disk 102...Reaction container 103...Cleaning mechanism 104...Spectrophotometer 105...Agitation mechanism 106...Cleaning tank 107...First reagent dispensing mechanism 107a...Second reagent dispensing mechanism 108...Cleaning tank (for reagent dispensing mechanism) 109...Reagent disk 110...Reagent bottle 111...First sample dispensing mechanism 111a...Second sample dispensing mechanism 111b...Sample dispensing probe (dispensing probe) 111c...Sample dispensing arm 111d...Horizontal movement mechanism 111e...Vertical movement mechanism 112...Detergent bottle 113...Cleaning tank (for sample dispensing mechanism) 115...Sample container 116...Sample rack 117...Sample transport mechanism 118...Controller 120...Reagent dispensing probe (dispensing probe) 121...Reagent syringe 122...Sample syringe 202...Cleaning nozzle 208...Cleaning liquid supply pump 210...Liquid level detector (capacitance measurement unit) 216...Adjusting valve (flow rate adjustment unit) 217...Solenoid valve 218...Flow path 219...Waste liquid tank 400...Raw data of capacitance voltage value 401...Smoothed data of capacitance voltage value 402...Reference capacitance voltage value 403...Raw data threshold 404...Smoothing process threshold 500...Cleaning liquid 501...Horizontal position during cleaning 502...Cleaning horizontal position height 503...Cleaning liquid upper surface detection height 504...Height with tolerance 601...Automated analyzer control unit 602...GUI 603...Dispensing arm control unit 604...Dispensing arm horizontal movement unit (X-θ) 605...Dispensing arm up / down movement unit (Z) 606...Cleaning liquid upper surface normal height confirmation control unit 607: Cleaning liquid contact determination unit 608: Liquid flow detection height table 609: Probe cleaning control unit 610: Cleaning range detection and adjustment control unit 611: Normal cleaning mode / cleaning range detection and adjustment mode switching unit 612: Solenoid valve control unit 613: Adjusting valve control unit 614: Adjusting valve control table
Claims
1. An automated analyzer comprising: a dispensing probe for dispensing liquid; a cleaning nozzle for ejecting cleaning liquid onto an outer wall of the dispensing probe; a flow rate adjustment unit for adjusting the amount of cleaning liquid ejected from the cleaning nozzle; a capacitance measurement unit for measuring the capacitance of the dispensing probe; and a control unit, wherein the control unit determines height information of an upper surface of the cleaning liquid based on capacitance data measured by the capacitance measurement unit in a horizontal position at a cleaning position where the dispensing probe is cleaned, determines a cleaning range of the dispensing probe in the horizontal position based on the height information of the upper surface of the cleaning liquid, and determines whether or not adjustment of the amount of cleaning liquid by the flow rate adjustment unit is required based on the determined cleaning range.
2. An automatic analyzer according to claim 1, wherein the control unit smoothes the capacitance data at predetermined intervals, acquires waveform data, and detects contact of the dispensing probe with liquid based on the acquired waveform data.
3. An automatic analyzer according to claim 2, wherein the control unit detects contact of liquid with the dispensing probe based on a comparison of a change in the waveform data within a specified time after the dispensing probe is positioned at a specified height in the horizontal position with a preset threshold value.
4. The automatic analyzer according to claim 3, wherein the control unit, when acquiring the height information of the upper surface, lowers the dispensing probe at a slower speed than during a cleaning operation.
5. The automatic analyzer according to claim 3, wherein two or more threshold values are provided.
6. An automatic analyzer according to claim 3, wherein the flow rate adjustment unit is an adjustment valve capable of adjusting the amount of the cleaning liquid, and the control unit adjusts the degree of opening of the adjustment valve based on information about the height of the upper surface.
7. The automatic analyzer according to claim 6, wherein the degree of opening of the regulating valve is increased in units larger than a set minimum unit.
8. An automatic analyzer according to claim 1, wherein the control unit acquires height information of the upper surface of the cleaning liquid a plurality of times, and determines the cleaning range based on the acquired height information of the upper surface of the cleaning liquid a plurality of times.
9. An automatic analyzer according to claim 8, wherein the number of times that the height information of the upper surface of the cleaning liquid is obtained varies depending on the timing at which the height information of the upper surface of the cleaning liquid is obtained.
10. A method for adjusting an automatic analyzer equipped with a dispensing probe for dispensing liquid, a cleaning nozzle for ejecting cleaning liquid onto the outer wall of the dispensing probe, a flow rate adjustment unit for adjusting the amount of cleaning liquid ejected from the cleaning nozzle, and a capacitance measurement unit for measuring the capacitance of the dispensing probe, comprising the steps of: determining height information of an upper surface of the cleaning liquid based on capacitance data measured by the capacitance measurement unit at a horizontal position in a cleaning position where the dispensing probe is cleaned; determining a cleaning range of the dispensing probe at the horizontal position based on the height information of the upper surface of the cleaning liquid; and determining whether or not adjustment of the amount of cleaning liquid by the flow rate adjustment unit is necessary based on the cleaning range determined.
Citation Information
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