Automatic analysis device
Patent Information
- Application Number
- JP2024572993
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2023-01-23
- Filing Date
- 2024-01-16
- Publication Date
- 2026-09-09
- Estimated Expiration
- 2044-01-16
AI Technical Summary
【0007】 本発明によれば、試薬等の分注を繰り返しても、試薬等の薄まりを抑制できる自動分析装置を提供することが可能となる。
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Figure 0007918291000003
Abstract
Description
[Technical Field]
[0001] The present invention relates to an automatic analyzer. [Background Art]
[0002] An automatic analyzer for analyzing biological samples such as blood and urine includes a dispensing mechanism for dispensing a sample or reagent into a reaction container. The dispensing mechanism sucks and discharges samples or reagents by operating a syringe connected to a nozzle. However, due to mechanical characteristics, there is a slight backlash accompanied by idle rotation between the suction operation and the discharge operation of the syringe. Therefore, in order to accurately dispense samples and reagents, it is necessary to eliminate backlash before discharge. For example, Patent Document 1 describes a technique for optimizing the backlash avoidance operation by measuring the backlash amount that varies for each device. [Prior Art Literature] [Patent Literature]
[0003] [Patent Document 1] Japanese Unexamined Patent Publication No. 2020-143927 [Summary of the Invention] [Problem to be Solved by the Invention]
[0004] However, even in the automatic analyzer described in Patent Document 1, when the nozzle is immersed in the liquid surface of a liquid such as a reagent, not only suction but also discharge (discharge for backlash avoidance) is performed. Here, since the inside of the nozzle is filled with system water for propagating the pressure of the syringe, the sucked reagent or the like will be diluted by the water remaining on the inner wall of the nozzle. When the diluted reagent or the like is discharged back into the reagent container or the like for backlash avoidance, the reagent or the like in the container is also diluted. When the number of dispensing operations increases (for example, to thousands of times) and discharge back is repeated, the amount of water carried into the container cannot be ignored, and the dilution of the concentration of reagents and the like may also affect measurement accuracy.
[0005] This invention has been made in view of these problems, and its purpose is to provide an automated analyzer that can suppress the dilution of reagents even when reagents are dispensed repeatedly. [Means for solving the problem]
[0006] To solve the aforementioned problems, the present invention provides an automatic analyzer equipped with a dispensing mechanism that dispenses a reagent or sample into a reaction vessel by operating a syringe connected to a nozzle, wherein, with the nozzle immersed in the liquid surface in the reagent container or sample container, the syringe performs an operation to aspirate a predetermined amount of the reagent or sample, and while the nozzle moves from the reagent container or sample container to the reaction vessel, the syringe performs an air aspiration operation to aspirate air and an air discharge operation to discharge a portion of the aspirated air, and after the nozzle has moved to the reaction vessel, the syringe performs an operation to discharge the remaining aspirated air and a predetermined amount of the reagent or sample into the reaction vessel. [Effects of the Invention]
[0007] According to the present invention, it is possible to provide an automated analyzer that can suppress the dilution of reagents even when reagents are dispensed repeatedly. [Brief explanation of the drawing]
[0008] [Figure 1] A schematic diagram showing the overall configuration of the automated analyzer. [Figure 2] A schematic diagram showing the flow path configuration and reagent bottles of the reagent dispensing mechanism. [Figure 3] A diagram showing an example of the reagent dispensing operation sequence in an automated analyzer related to a comparative example. [Figure 4] Time chart of reagent dispensing in an automated analyzer related to a comparative example. [Figure 5] A figure showing the trend of measured values obtained by an automated analyzer for the comparative example. [Figure 6] A diagram showing an example of the reagent dispensing operation sequence in the automated analyzer according to Example 1. [Figure 7] A time chart of reagent dispensing in the automated analyzer according to Example 1. [Figure 8] A figure showing the changes in measured values obtained by the automated analyzer according to Example 1. [Figure 9] A diagram showing an example of the reagent dispensing operation sequence in the automated analyzer according to Example 2. [Figure 10] A time chart of reagent dispensing in the automated analyzer according to Example 2. [Modes for carrying out the invention]
[0009] Embodiments of the present invention will be described below with reference to the drawings.
[0010] (Overall configuration of the automated analyzer) The automated analyzer is a device that dispenses a sample such as blood or urine and a reagent into a reaction vessel 2, reacts them, and measures the resulting liquid. Figure 1 is a schematic diagram showing the overall configuration of the automated analyzer according to this embodiment. As shown in Figure 1, the automated analyzer consists of a sample transport mechanism 8, a reagent disk 3, a reaction disk 1, a sample dispensing mechanism 9, reagent dispensing mechanisms 11, 13, stirring mechanisms 17, 18, a spectrophotometer 16 (measurement unit), a washing mechanism 15, a control unit 24, etc.
[0011] The reaction disk 1 has reaction vessels 2 arranged in a circular pattern. The reaction vessels 2 are containers for holding a mixture of the sample and reagent, and multiple vessels are arranged on the reaction disk 1. Near the reaction disk 1 is a sample transport mechanism 8 that transports a sample rack 7, which is loaded with multiple sample containers 6 containing the sample to be analyzed. The reaction vessels 2 are immersed in a reaction tank 5 filled with a heat-conductive medium (e.g., constant-temperature water) whose temperature is controlled to 37 degrees Celsius, and the temperature of the reaction vessels 2 is constantly maintained at 37 degrees Celsius by the circulation of the constant-temperature water within the reaction tank 5.
[0012] The reagent disk 3 can carry a plurality of reagent bottles 4 (reagent containers) storing reagents used for analysis on its circumference, and also functions as a cold storage for keeping the reagent bottles 4 cold.
[0013] A sample dispensing mechanism 9 for dispensing a sample from a sample container 6 to a reaction container 2 is disposed between the reaction disk 1 and a sample transport mechanism 8. The sample dispensing mechanism 9 is capable of rotating in the horizontal direction and moving in the vertical direction, and includes a sample nozzle 10 with a tip facing downward. A cleaning tank 19 for cleaning the sample nozzle 10 with cleaning water is disposed within the operating range of the sample dispensing mechanism 9. Furthermore, reagent dispensing mechanisms 11 and 13 for dispensing a reagent from a reagent bottle 4 to a reaction container 2 are installed between the reaction disk 1 and the reagent disk 3. The reagent dispensing mechanisms 11 and 13 are capable of rotating in the horizontal direction and moving in the vertical direction, and respectively include reagent nozzles 12 and 14 with tips facing downward. Cleaning tanks 20 and 21 for respectively cleaning the reagent nozzles 12 and 14 with cleaning water are disposed within the operating ranges of the reagent dispensing mechanisms 11 and 13.
[0014] Around the reaction disk 1, there are disposed stirring mechanisms 17 and 18, a spectrophotometer 16 that measures the absorbance of a reaction solution by measuring transmitted light obtained from a light source (not shown) through the reaction solution in the reaction container 2, a cleaning mechanism 15 that cleans used reaction containers 2, and the like.
[0015] The stirring mechanisms 17 and 18 are capable of rotating in the horizontal direction and moving in the vertical direction, and stir a mixed liquid (reaction solution) of a sample and a reagent by being inserted into the reaction container 2. Cleaning tanks 22 and 23 for cleaning the stirring mechanisms 17 and 18 with cleaning water are disposed within the operating ranges of the stirring mechanisms 17 and 18.
[0016] A control unit 24 is configured of a computer or the like, controls the operations of each mechanism constituting the automatic analyzer, and performs arithmetic processing for obtaining the concentration of a predetermined component in a sample. In FIG. 1, for the sake of simplifying the illustration, the connection relationships between each mechanism constituting the automatic analyzer and the control unit 24 are omitted.
[0017] In the automatic analyzer configured as described above, analysis processing is generally performed in the following flow. First, the control unit 24 dispenses a sample in the sample container 6 on the sample rack 7 conveyed near the reaction disk 1 by the sample conveyance mechanism 8 into the reaction container 2 on the reaction disk 1 by the sample nozzle 10 of the sample dispensing mechanism 9. Thereafter, the control unit 24 cleans the sample nozzle 10 in the cleaning tank 19. Next, the control unit 24 dispenses the reagent in the reagent bottle 4 on the reagent disk 3 into the reaction container 2 into which the sample has been dispensed in advance by the reagent nozzles 12, 14 of the reagent dispensing mechanisms 11, 13. Thereafter, the control unit 24 cleans the reagent nozzles 12, 14 in the cleaning tanks 20, 21. Subsequently, the control unit 24 stirs the mixed liquid of the sample and the reagent in the reaction container 2 by the stirring mechanisms 17, 18. Thereafter, the control unit 24 causes light emitted from a light source to transmit through the reaction container 2 containing the mixed liquid, and measures the luminous intensity of the transmitted light by the spectrophotometer 16. The luminous intensity information measured by the spectrophotometer 16 is transmitted to the control unit 24 via an A / D converter and an interface. Then, the control unit 24 calculates the concentration of a predetermined component of the analysis item based on the received luminous intensity information, and causes the calculation result to be displayed on a display unit (not shown) or the like, or stored in a storage unit (not shown).
[0018] (Configuration of Dispensing Mechanism) Next, the configuration of the dispensing mechanism will be specifically described with reference to FIG. 2. In the following description, the reagent dispensing mechanisms 11 and 13 are taken as an example, but the same configuration can also be applied to the sample dispensing mechanism 9.
[0019] FIG. 2 is a diagram schematically showing the flow path configuration of the reagent dispensing mechanism and the reagent bottle. The reagent dispensing mechanisms 11 and 13 mainly include the reagent nozzles 12, 14 and a syringe 25, and dispense the reagent in the reagent bottle 4 into the reaction container by operating the syringe 25 connected to the reagent nozzles 12 and 14. Here, the syringe 25 is provided with a plunger 30, and a motor 31 is connected to the plunger 30. The motor 31 drives the plunger 30, thereby sucking and discharging the reagent to be dispensed from the reagent nozzles 12 and 14.
[0020] Furthermore, a flow path from the reagent nozzles 12 and 14 to the water supply pump 29 via the syringe 25, solenoid valve 27, and liquid delivery pump 28 is formed by a tube 26, and the flow path is filled with system water. System water is water used for pressure propagation, etc., and is generally purified water such as ion-exchanged water. When the inside of the reagent nozzles 12 and 14 is to be cleaned, the solenoid valve 27 opens, and system water (cleaning water) supplied from the water supply pump 29 is discharged from the tip of the reagent nozzles 12 and 14.
[0021] When the reagent dispensing mechanisms 11 and 13 dispense reagents, first, while maintaining the closed state of the solenoid valve 27, the reagent nozzles 12 and 14 move to a position for drawing reagents from the reagent bottle 4 (reagent suction position). Next, when the tips of the reagent nozzles 12 and 14 reach the liquid surface of the reagent, the plunger 40 is driven in the suction direction, drawing the reagent into the reagent nozzles 12 and 14. After that, the reagent nozzles 12 and 14 move to a position for discharging the reagent into the reaction vessel 2 (reagent discharge position), and in this state, the plunger 40 is driven in the discharge direction, discharging the reagent into the reaction vessel 2. After the reagent dispensing mechanisms 11 and 13 have dispensed the reagents, the reagent nozzles 12 and 14 move to the washing tanks 20 and 21, where the inside and outside of the reagent nozzles 12 and 14 are washed.
[0022] Furthermore, reagent bottle 4 is filled with a specified amount of reagent. The specified amount is the sum of the dispensing volume (defined as an analytical parameter) multiplied by the number of analyzable tests, plus the dead volume, i.e., the reagent remaining at the bottom of the bottle that cannot be used for analysis. Figure 2 shows an example of a reagent bottle containing two types of reagents, with each reagent having a different number of analyzable tests.
[0023] Next, we will explain in detail how the reagent dispensing mechanism works.
[0024] (Comparative example) First, as a comparative example, we will explain the case of dispensing reagents using a conventional automated analyzer, based on Figures 3 to 5. Figure 3 is a diagram showing an example of the operation sequence of reagent dispensing in the automated analyzer related to the comparative example, and Figure 4 is a time chart of reagent dispensing in the automated analyzer related to the comparative example.
[0025] First, in the cleaning step 3-1, the cleaning water supplied from the aforementioned liquid delivery pump 28 is used to clean the inside and outside of the reagent nozzles 12 and 14 in the cleaning tanks 20 and 21. While the inside of the reagent nozzles 12 and 14 is being cleaned, the syringe 25 is used to perform aspiration, ensuring the amount of system water to be discharged in the system water discharge step 3-3 and the reagent discharge step 3-8 described later. The set operating amount of the syringe 25 in the cleaning step 3-1 is an operating amount (suction amount) equivalent to a μL. However, there are gaps between the various mechanisms that make up the syringe 25, and when the syringe 25 performs an operation in the opposite direction to the previous operation, backlash occurs as a small amount of free rotation. Although not shown in Figure 3, there is a return to home operation, which is an operation in the discharge direction, before the cleaning step 3-1. Therefore, if the amount of backlash that actually occurs in the comparative example syringe 25 (hereinafter sometimes simply referred to as "actual backlash amount") is X', then the actual suction amount in the cleaning step 3-1 is a-X'. Note that the actual backlash amount X' varies from syringe to syringe.
[0026] Next, in drying step 3-2, water droplets adhering to the outside of reagent nozzles 12 and 14 are removed. Note that in the case of automated analyzers that do not have a drying function, this drying step 3-2 is omitted.
[0027] Here, at the end of the cleaning process 3-1, when the solenoid valve 27 is closed and the pressure from the liquid delivery pump 28 is shut off, some of the system water is discharged from the tips of the reagent nozzles 12 and 14 due to the residual pressure inside the reagent nozzles 12 and 14. At this time, air is drawn into the reagent nozzles 12 and 14 instead of the discharged system water. As a result, the tips of the reagent nozzles 12 and 14 may become unstable, such as by the generation of air bubbles. To resolve this, in the system water discharge process 3-3, the system water present at the tips of the reagent nozzles 12 and 14 is discharged. The operating setting amount of the syringe 25 in the system water discharge process 3-3 is less than the operating setting amount a μL in the cleaning process 3-1, and corresponds to an operating amount (discharge amount) of b μL. However, in the system water discharge process 3-3, the syringe 25 moves in the opposite direction to the previous suction operation, resulting in an actual backlash amount X', and the actual discharge amount becomes b-X'.
[0028] Next, while the reagent nozzles 12 and 14 move horizontally toward the reagent aspiration position, the segmented air aspiration process 3-4 is performed in which the syringe 25 aspirates segmented air. Segmented air is air that separates the system water from the reagent, and it serves as an air layer to prevent the reagent from coming into contact with the system water and becoming diluted during reagent aspiration. The set operating amount of the syringe 25 in the segmented air aspiration process 3-4 is an operating amount (aspiration amount) equivalent to cμL. However, in the segmented air aspiration process 3-4, the syringe 25 moves in the opposite direction to the previous dispensing operation, so an actual backlash amount X' occurs, and the actual aspiration amount becomes c-X'.
[0029] Here, when determining the operating volume cμL of syringe 25, the maximum backlash amount (hereinafter sometimes simply referred to as "backlash operating volume") X that is assumed in the design of the comparative example syringe 25 is taken into consideration. Specifically, it is determined such that the relationship c ≥ backlash operating volume X holds. Note that the backlash operating volume X is set to a value that includes a margin of safety over the theoretically estimated backlash amount, and is therefore larger than the actual backlash amount X'.
[0030] Next, in the air discharge step 3-5, syringe 25 discharges a portion of the segmented air to cancel the backlash generated in the segmented air suction step 3-4. The set operating amount of syringe 25 in the air discharge step 3-5 is an operating amount (discharge amount) equivalent to dμL, but the actual discharge amount is d-X', as it is subtracted by the actual backlash amount X'. When determining the set operating amount dμL, the backlash set operating amount X is also taken into consideration, and the relationship is set operating amount d ≥ backlash set operating amount X. The amount of segmented air remaining in reagent nozzles 12 and 14 when the air discharge step 3-5 is completed is (c-X')-(d-X')=c-dμL.
[0031] Next, the reagent nozzles 12 and 14 descend to the reagent aspiration position, and in the reagent aspiration step 3-6, with the reagent nozzles 12 and 14 immersed in the liquid surface of the reagent bottle 4, the syringe 25 aspirates a predetermined amount of reagent. The operating setting amount of the syringe 25 in the reagent aspiration step 3-6 is the operating amount (aspiration amount) corresponding to eμL, but the actual aspiration amount is reduced by the actual backlash amount X', so it becomes e-X'. The operating setting amount eμL is set by adding the backlash operating setting amount X to the amount of reagent required for analysis.
[0032] Next, in the reagent dispensing (backlash dispensing) step 3-7, the syringe 25 dispenses a portion of the reagent while the reagent nozzles 12 and 14 are immersed in the liquid surface inside the reagent bottle 4. The reagent dispensing (backlash dispensing) step 3-7 is a step to cancel the amount of backlash generated in the reagent aspiration step 3-6. The operating setting amount for the syringe 25 in the reagent dispensing (backlash dispensing) step 3-7 is an operating amount (dispensing amount) equivalent to f μL, but the actual dispensing amount is reduced by the actual backlash amount X', so it becomes f-X'. When determining the operating setting amount f μL, the backlash operating setting amount X is also taken into consideration, and the relationship is operating setting amount f ≥ backlash operating setting amount X.
[0033] Next, the reagent nozzles 12 and 14 rise, then move horizontally to the reagent dispensing position and descend again. Subsequently, in reagent dispensing step 3-8, syringe 25 dispenses the reagent, segmented air, and system water into reaction vessel 2. The set operating amount of syringe 25 in reagent dispensing step 3-8 is the operating amount (dispensing amount) corresponding to gμL. In reagent dispensing step 3-8, since syringe 25 operates in the same direction as the previous dispensing operation, there is no need to consider backlash. Furthermore, the amount of change of the syringe immediately before reagent dispensing step 3-8 in the comparative example (the final operating amount in the suction direction obtained by adding and subtracting the suction amount and dispensing amount of the series of syringe operations performed from step 3-1 to step 3-7), M1, can be expressed by the following equation 1. M1=(a-X')-(b-X')+(c-X')-(d-X')+(e-X')-(f-X')=a-b+c-d+ef...(Formula 1) In other words, the actual backlash amount X', which varies from syringe to syringe, is ultimately canceled out, thus ensuring dispensing accuracy.
[0034] However, in the comparative example, there is a problem in the reagent dispensing (backlash dispensing) step 3-7 where diluted reagent is discharged back into the reagent bottle 4. This is because, even if segmented air separates the reagent from the system water, the water remaining on the inner walls of the reagent nozzles 12 and 14 actually dilutes the reagent within the nozzles 12 and 14. The degree of dilution varies depending on the amount of segmented air, the amount of reagent aspirated, the aspiration speed, etc.
[0035] For example, if 3 μL of liquid is dispensed in reagent dispensing (backlash dispensing) step 3-7, 0.3 μL of water is introduced into reagent bottle 4 with a single reagent dispensing operation. If the number of dispensing cycles (number of analytical tests) of reagent bottle 4 is, for example, 2000, the total amount of water introduced will be 2000 × 0.3 = 600 μL. Therefore, when the amount of reagent remaining in reagent bottle 4 reaches near the dead volume, the concentration of the reagent will be approximately 12% diluted compared to the concentration of the reagent before use. Thus, if the original reagent in reagent bottle 4 is considered 100%, the final concentration will generally be diluted to about 90%. In other words, immediately before replacing reagent bottle 4, the liquid dispensed in reagent dispensing (backlash dispensing) step 3-7 will contain not only the reagent but also about 10% water.
[0036] Figure 5 shows the trend of measured values obtained by an automated analyzer for the comparative example. Figure 5 shows the results of measuring the same sample 500 times consecutively using one reagent bottle. According to Figure 5, in the case of the comparative example, it can be seen that the measured values fluctuate in one direction as the number of dispensing cycles increases.
[0037] In the case of reagents containing an excess of the reactant, changes in concentration at the time of discharge into the reaction vessel have little effect on the analytical results. However, in the case of reagents that do not contain an excess of the reactant, changes in concentration can have a significant impact on the analytical results. Furthermore, a small amount of water is introduced into reagent bottle 4 during reagent aspiration steps 3-6 due to water adhering to the outside of reagent nozzles 12 and 14. Therefore, in the case of reagents where concentration stability at the time of discharge into reaction vessel 2 is required, the comparative example may result in a decrease in analytical accuracy.
[0038] Therefore, in the automated analyzer according to the example, reagent dispensing (backlash dispensing) is not performed with the reagent nozzles 12 and 14 immersed in the liquid surface in the reagent bottle 4. Instead, while the reagent nozzles 12 and 14 are moving from the reagent bottle 4 to the reaction vessel 2, the syringe 25 performs an air suction operation to draw in air and an air discharge operation to discharge a portion of the drawn-in air. Examples 1 and 2 will be described in detail below. [Examples]
[0039] The case of dispensing reagents using the automated analyzer of Example 1 will be explained with reference to Figures 6 to 8. Figure 6 is a diagram showing an example of the operation sequence of reagent dispensing in the automated analyzer of Example 1, and Figure 7 is a time chart of reagent dispensing in the automated analyzer of Example 1.
[0040] The washing process 6-1, drying process 6-2, system water discharge process 6-3, and segmented air suction process 6-4 are the same as those in the comparative example: washing process 3-1, drying process 3-2, system water discharge process 3-3, and segmented air suction process 3-4. However, the operating volume of syringe 25 in segmented air suction process 6-4 is different from that in the comparative example, and is an operating volume (suction volume) equivalent to hμL. This is because in Example 1, there is no process corresponding to the air discharge process 3-5 of the comparative example.
[0041] Next, in reagent aspiration step 6-5, similar to reagent aspiration step 3-6 of the comparative example, the syringe 25 draws a predetermined amount of reagent with the reagent nozzles 12 and 14 immersed in the liquid surface of the reagent bottle 4. However, the set operating amount of the syringe 25 in reagent aspiration step 6-5 is different from that of the comparative example, being an operating amount (aspiration amount) equivalent to iμL. This is because in Example 1, there is no step corresponding to the reagent dispensing (backlash dispensing) step 3-7 of the comparative example. Note that in reagent aspiration step 6-5, since the syringe 25 moves in the same direction as the previous aspiration operation, there is no need to consider backlash. That is, the actual aspiration amount in reagent aspiration step 6-5 is an operating amount equivalent to iμL.
[0042] Next, the reagent nozzles 12 and 14 rise without dispensing reagent, and then move horizontally toward the reagent dispensing position. In Example 1, the air aspiration process 6-6 is performed during this horizontal movement. The set amount of movement of the syringe 25 in the air aspiration process 6-6 is smaller than the movement amount (aspiration amount) i μL in the reagent aspiration process 6-5, and corresponds to a movement amount (aspiration amount) of j μL. If j ≥ i, the effect of air vibration within the reagent nozzles 12 and 14 will become large, and the state of the reagent and system water within the reagent nozzles 12 and 14 will become unstable. Note that in the air aspiration process 6-6, the syringe 25 moves in the same direction as the previous aspiration operation, so there is no need to consider backlash. That is, the actual aspiration amount in the air aspiration process 6-6 corresponds to a movement amount of j μL.
[0043] Subsequently, syringe 25 performs an air ejection (backlash ejection) process 6-7 while the reagent nozzles 12 and 14 are moving horizontally. The set operating amount of syringe 25 in the air ejection (backlash ejection) process 6-7 is smaller than the operating amount (suction amount) jμL in the air aspiration process 6-6, and is set to kμL. If k≧j, the reagent in the reagent nozzles 12 and 14 would be ejected. However, in the air ejection (backlash ejection) process 6-7, syringe 25 moves in the opposite direction to the previous aspiration operation, so an actual backlash amount X' is generated, and the actual ejection amount is k-X'. Note that when determining the set operating amount kμL, the backlash operating amount X is taken into consideration, and the relationship is set operating amount k≧backlash operating amount X.
[0044] Here, the operating speed of the syringe 25 in the air discharge step 6-7 is slower than the operating speed of the syringe 25 in the reagent aspiration step 6-5, so that vibrations associated with air discharge are suppressed and reagents do not splash out of the reagent nozzles 12 and 14. Furthermore, it is desirable that the operating speed of the syringe 25 in the air aspiration step 6-6 be slower than the operating speed of the syringe 25 in the reagent aspiration step 6-5 in order to suppress vibrations associated with air aspiration.
[0045] Furthermore, the air suction process 6-6 and the air discharge process 6-7 may be performed while the reagent nozzles 12 and 14 are rising or falling, but it is preferable that they be performed during horizontal movement in order to suppress vibration of the liquid inside the reagent nozzles 12 and 14. In addition, it is important to reduce the amount of air remaining at the tips of the reagent nozzles 12 and 14 when the air discharge process 6-7 is completed to less than the amount of segmented air, thereby suppressing the total amount of air drawn into the reagent nozzles 12 and 14, in order to suppress vibration of the liquid.
[0046] Next, when the reagent nozzles 12 and 14 reach the reagent dispensing position, they descend toward the reaction vessel 2. Subsequently, in the reagent dispensing step 6-8, the syringe 25 dispenses air, reagent, segmented air, and system water into the reaction vessel 2. The set operating amount of the syringe 25 in the reagent dispensing step 6-8 is the operating amount (dispensing amount) corresponding to mμL. In the reagent dispensing step 6-8, since the syringe 25 operates in the same direction as the previous dispensing operation, there is no need to consider backlash. Furthermore, the amount of change of the syringe immediately before the reagent dispensing step 6-8 in Example 1, M2 (the final operating amount in the suction direction obtained by adding and subtracting the suction amount and dispensing amount of the series of syringe operations performed from step 6-1 to step 6-7), can be expressed by the following equation 2. M2=(a-X')-(b-X')+(h-X')+i+j-(k-X')=a-b+h+i+jk...(Formula 2) In other words, the actual backlash amount X' is ultimately canceled out, thus ensuring dispensing accuracy.
[0047] Thus, in Example 1, there is no step of discharging the diluted reagent from the reagent nozzles 12 and 14 back into the reagent bottle 4 (reagent backlash dispensing), so the amount of water introduced into the reagent bottle 4 is suppressed. In addition, by eliminating reagent backlash dispensing, the time spent aspirating the reagent can be increased, making it possible to further suppress reagent dilution by slowing down the aspiration speed.
[0048] Figure 8 shows the changes in measured values obtained by the automated analyzer according to Example 1. As with Figure 5, Figure 8 shows the results of measuring the same sample 500 times consecutively using a single reagent bottle. According to Figure 8, unlike the comparative example, the fluctuation in measured values is small in Example 1. [Examples]
[0049] The case of dispensing reagents using the automated analyzer of Example 2 will be explained with reference to Figures 9 and 10. Figure 9 is a diagram showing an example of the operation sequence of reagent dispensing in the automated analyzer of Example 2, and Figure 10 is a time chart of reagent dispensing in the automated analyzer of Example 2.
[0050] In Example 2, after cleaning the reagent nozzles 12 and 14, the syringe 25 draws the reagent without aspirating segmented air. In a water-extrusion type reagent dispensing system where the reagent is a concentrated reagent and is ultimately discharged simultaneously with system water, there is no need to consider the dilution of the reagent within the reagent nozzles 12 and 14 if there is no step of returning the reagent to the reagent bottle 4.
[0051] Washing step 9-1 is the same as washing step 3-1 in the comparative example and washing step 6-1 in Example 1. However, in Example 2, there is no step corresponding to system water discharge step 3-3 in the comparative example or system water discharge step 6-3 in Example 1. Therefore, if bubbles are generated at the tips of reagent nozzles 12 and 14 at the end of washing step 9-1, it becomes impossible to remove the bubbles. For this reason, in Example 2, the liquid washing stop step 9-2 is performed.
[0052] The liquid-based washing stop step 9-2 is a step in which the system water (washing water) used for the internal washing of the reagent nozzles 12 and 14 in washing step 9-1 is stored in the washing tanks 20 and 21, and the solenoid valve 27 is stopped while the tips of the reagent nozzles 12 and 14 are immersed in the system water. At this time, the residual pressure inside the reagent nozzles 12 and 14 draws the system water into the reagent nozzles 12 and 14, but no air is drawn in, so no bubbles are generated. If it is possible to draw in system water instead of air, the solenoid valve 27 may be stopped while the system water used for external washing is being sprayed onto the tips of the reagent nozzles 12 and 14, without storing the system water in the washing tanks 20 and 21. Note that if the dispensing mechanism is capable of gradually reducing the pressure inside the reagent nozzles 12 and 14 at the end of washing, the liquid-based washing stop step 9-2 may be omitted.
[0053] Drying step 9-3 is the same as drying step 3-2 in the comparative example and drying step 6-2 in Example 1. However, in Example 2, after drying step 9-3, reagent aspiration step 9-4 is performed without discharging system water or aspirating segmented air.
[0054] In reagent aspiration step 9-4, similar to reagent aspiration step 3-6 in the comparative example and reagent aspiration step 6-5 in Example 1, the syringe 25 draws a predetermined amount of reagent with the reagent nozzles 12 and 14 immersed in the liquid surface of the reagent bottle 4. However, the operating amount of the syringe 25 in reagent aspiration step 9-4 is set to an operating amount (aspiration amount) equivalent to i'μL. In reagent aspiration step 9-4, since the syringe 25 moves in the same direction as the previous aspiration operation, there is no need to consider backlash. That is, the actual aspiration amount in reagent aspiration step 9-4 is an operating amount equivalent to i'μL.
[0055] Subsequently, similar to Example 1, the reagent nozzles 12 and 14 rise without dispensing reagent, and while the reagent nozzles 12 and 14 move horizontally toward the reagent dispensing position, the air aspiration step 9-5 is performed. The set amount of movement of the syringe 25 in the air aspiration step 9-5 is smaller than the movement amount (aspiration amount) i'μL in the reagent aspiration step 9-4, and corresponds to a movement amount (aspiration amount) of j'μL. In addition, in the air aspiration step 9-5, the syringe 25 moves in the same direction as the previous aspiration operation, so there is no need to consider backlash. That is, the actual aspiration amount in the air aspiration step 9-5 corresponds to a movement amount of j'μL.
[0056] Subsequently, the syringe 25 performs an air ejection (backlash ejection) step 9-6 while the reagent nozzles 12 and 14 are moving horizontally. The set volume of the syringe 25's operation in the air ejection (backlash ejection) step 9-6 is smaller than the operation volume (aspiration volume) j'μL in the air aspiration step 9-5, and is k'μL. However, in the air ejection (backlash ejection) step 9-6, the syringe 25 moves in the opposite direction to the previous aspiration operation, so an actual backlash amount X' is generated, and the actual ejection volume is k'-X'. Note that when determining the set volume k'μL, the backlash set volume X is taken into consideration, and the relationship is set volume k' ≥ backlash set volume X.
[0057] Next, when the reagent nozzles 12 and 14 reach the reagent dispensing position, they descend toward the reaction vessel 2. Subsequently, in the reagent dispensing step 9-7, the syringe 25 dispenses air, reagent, and system water into the reaction vessel 2. The set operating amount of the syringe 25 in the reagent dispensing step 9-7 is an operating amount (dispensing amount) corresponding to m'μL. In the reagent dispensing step 9-7, since the syringe 25 operates in the same direction as the previous dispensing operation, there is no need to consider backlash. Furthermore, the amount of change of the syringe immediately before the reagent dispensing step 9-7 in Example 2, M3 (the final operating amount in the suction direction obtained by adding and subtracting the suction amount and dispensing amount of the series of syringe operations performed from step 9-1 to step 9-6), can be expressed by the following equation 3. M3=(a-X')+i'+j'-(k'-X')=a+i'+j'-k' (Formula 3) In other words, the actual backlash amount X' is ultimately canceled out, thus ensuring dispensing accuracy.
[0058] Thus, in Example 2, there is no process for discharging system water or sucking in segmented air, resulting in a simpler overall operation sequence.
[0059] (Note) As described above, in each embodiment, the backflow of reagent into reagent bottle 4 is eliminated, thus suppressing the dilution of the reagent. As a result, the number of tests that can be analyzed in the reagent bottle increases, reducing the frequency of reagent bottle replacement. Furthermore, fluctuations in measured values are suppressed, improving the reliability of measurement results, thus reducing the risk of remeasurement and the frequency of periodic calibration. In other words, it becomes possible to significantly reduce the workload for the user.
[0060] Furthermore, in each embodiment, a characteristic feature is that the syringe 25 performs suction two or more times consecutively while the reagent nozzles 12 and 14 move from the washing tanks 20 and 21 through the reagent bottle 4 (reagent suction position) to the reaction vessel 2 (reagent discharge position). For example, in Example 1, suction is performed three times consecutively from segmented air suction step 6-4 to air suction step 6-6, and in Example 2, suction is performed twice consecutively in reagent suction step 9-4 and air suction step 9-5.
[0061] It should be noted that the present invention is not limited to the embodiments described above, and includes various modifications and combinations. For example, although the embodiments described a water-extrusion type reagent dispensing method in which the reagent and system water are discharged together, the present invention can also be applied to other types of reagent dispensing, such as a method in which a portion of the aspirated reagent is discharged (dummy dispensing). [Explanation of symbols]
[0062] 1...Reaction disc, 2...Reaction vessel, 3...Reagent disc, 4...Reagent bottle, 5...Reaction tank, 6...Sample container, 7...Sample rack, 8...Sample transport mechanism, 9...Sample dispensing mechanism, 10...Sample nozzle, 11,13...Reagent dispensing mechanism, 12,14...Reagent nozzle, 15...Washing mechanism, 16...Spectrophotometer, 17,18...Agitation mechanism, 19...Washing tank, 20,21...Washing tank, 22,23...Washing tank, 24...Control unit, 25...Syringe, 26...Tubing, 27...Solenoid valve, 28...Liquid delivery pump, 29...Water supply pump, 30...Plunger, 31...Motor.
Claims
1. In an automated analyzer equipped with a dispensing mechanism that dispenses reagents or samples into a reaction vessel by operating a syringe connected to a nozzle, With the nozzle immersed in the liquid surface inside the reagent container or sample container, the syringe performs an operation to draw up a predetermined amount of the reagent or sample, While the nozzle moves from the reagent container or sample container to the reaction vessel, the syringe performs an air suction operation to draw in air and an air discharge operation to discharge a portion of the drawn-in air. An automated analyzer characterized in that, after the nozzle moves to the reaction vessel, the syringe performs an operation to discharge the remaining air that was aspirated and a predetermined amount of the reagent or sample into the reaction vessel.
2. In the automated analyzer described in claim 1, An automated analyzer characterized in that the amount of the air discharge operation is greater than or equal to the backlash operation setting amount of the dispensing mechanism.
3. In the automated analyzer described in claim 2, An automated analyzer characterized in that the amount of motion of the air suction operation is smaller than the amount of motion of the operation to aspirate the reagent or the sample.
4. In the automated analyzer described in claim 1, The automated analyzer is characterized in that the syringe performs the air aspiration operation without performing the dispensing operation after performing the aspiration operation of the reagent or the sample.
5. In the automated analyzer according to claim 4, The system further comprises a cleaning tank for cleaning the nozzle with cleaning water, An automated analyzer characterized in that, after cleaning the nozzle, the syringe performs an operation to aspirate segmented air separating the reagent or sample from the system water, and then performs an operation to aspirate the reagent or sample without performing a dispensing operation.
6. In the automated analyzer according to claim 4, The system further comprises a cleaning tank for cleaning the nozzle with cleaning water, An automated analyzer characterized in that, after cleaning the nozzle, the syringe aspirates the reagent or sample without aspirating air.
7. In the automated analyzer described in claim 1, The system further comprises a cleaning tank for cleaning the nozzle with cleaning water, An automated analyzer characterized in that, after cleaning the nozzle, the syringe performs aspiration two or more times consecutively while the nozzle moves from the cleaning tank through the reagent container or sample container to the reaction vessel.
8. In the automated analyzer described in claim 1, An automated analyzer characterized in that the operating speed of the air discharge operation is slower than the operating speed of the reagent or sample aspiration operation.
Citation Information
Patent Citations
Liquid sample dispensing device and driving method
JP2009210354A
Dispensing device and dispensing method
JP2019174318A
autoanalyzer
JP2020143927A