Automatic analysis device
The automatic analyzer addresses residual liquid issues in multi-liquid dispensing by adjusting excess aspiration volumes based on liquid order, ensuring accurate and efficient liquid delivery into reaction vessels.
Patent Information
- Application Number
- JP2022097049
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2022-06-16
- Publication Date
- 2026-01-07
- Estimated Expiration
- 2042-06-16
AI Technical Summary
Existing automated analyzers face challenges in accurately dispensing multiple types of liquids into reaction vessels due to residual liquid remaining in the dispensing mechanism, leading to inefficiencies and reduced analytical accuracy.
The automatic analyzer employs a dispensing mechanism controlled by a control unit that adjusts the excess aspirated volume based on the order of liquid aspiration to ensure accurate dispensing of target volumes, accounting for residual liquid retention in the mechanism.
This approach enables precise dispensing of multiple liquids into reaction vessels, enhancing analytical accuracy and efficiency by minimizing residual liquid in the dispensing mechanism.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to an automatic analyzer. [Background technology]
[0002] In recent years, automated analyzers that perform biochemical analysis, immunoassay, and genetic analysis in a fully or semi-automated manner have been widely used in fields such as clinical testing. In automated analyzers, reagents and test samples are generally aspirated from containers using a dispensing mechanism and dispensed into reaction containers in an incubator. Components contained in the mixture of reagents and samples in the reaction container are then detected by a detection unit.
[0003] As a technique for improving analytical accuracy, Patent Document 1 discloses an automatic analyzer that increases or decreases the amount of surplus at the front end and the amount of surplus at the rear end depending on the total amount of specimen to be dispensed. [Prior art documents] [Patent documents]
[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2009-243969 Summary of the Invention [Problem to be solved by the invention]
[0005] Depending on the analysis item, in order to reduce the number of washings and shorten the dispensing time, the dispensing mechanism may successively aspirate multiple types of liquid (multiple reagents, or a reagent and a sample) in one dispensing and continuously discharge the aspirated liquid into a reaction vessel. In such cases, the liquid aspirated first is held deep inside the dispensing mechanism and is therefore likely to remain in the dispensing mechanism when discharged, while the liquid aspirated later leaves relatively little liquid remaining.
[0006] An object of the present invention is to provide an automatic analyzer that supplies a target dispensing amount of liquid to a reaction vessel and has high analytical accuracy, even when a dispensing mechanism continuously aspirates and dispenses multiple types of liquid. [Means for solving the problem]
[0007] In order to solve the above problem, the automatic analyzer of the present invention comprises a dispensing mechanism that aspirates liquid from a specimen container or a reagent container and dispenses it into a reaction container, and a control unit that controls the operation of the dispensing mechanism so that a target dispensing volume is obtained, and the dispensing mechanism aspirates an excess aspirated volume of liquid in addition to the target dispensing volume of liquid during dispensing, and when the dispensing mechanism aspirates multiple types of liquid continuously and dispenses the aspirated multiple types of liquid continuously, the control unit changes the excess aspirated volume of liquid aspirated by the dispensing mechanism depending on the order in which the liquids are aspirated. [Effects of the Invention]
[0008] According to the present invention, it is possible to provide an automatic analyzer that supplies a target amount of liquid to a reaction vessel and has high analytical accuracy, even when a dispensing mechanism continuously aspirates and dispenses multiple types of liquid. The detailed problems, configurations, and effects will become clear from the description of the following embodiments. [Brief explanation of the drawings]
[0009] [Figure 1] FIG. 1 is a schematic diagram illustrating the configuration of an automatic analyzer according to a first embodiment. [Figure 2] FIG. [Figure 3] A diagram showing the internal structure of the probe and tip when dispensing three different liquids simultaneously. [Figure 4] 10 is a flowchart showing the operation procedure of the dispensing mechanism when dispensing three types of liquids simultaneously. [Figure 5] A diagram showing the internal structure of the probe and tip when dispensing two liquids simultaneously. [Figure 6] 10 is a flowchart showing the operation procedure of the dispensing mechanism when dispensing two types of liquid simultaneously. [Figure 7] A diagram showing the internal appearance of the probe and tip when dispensing one type of liquid. [Figure 8] 10 is a flowchart showing the operation procedure of the dispensing mechanism when dispensing one type of liquid. [Figure 9] 10 is a table for setting a dispensing pattern for each analysis item in the first embodiment. [Figure 10] FIG. 4 is a block diagram showing the flow of information when the control unit controls the dispensing mechanism according to the analysis item. [Figure 11] 10 is a table for setting a dispensing pattern for each analysis item in Example 2. [Figure 12] 10 is a table for setting a dispensing pattern for each analysis item in the third embodiment. DETAILED DESCRIPTION OF THE INVENTION
[0010] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. [Example]
[0011] The automated analyzer according to Example 1 aspirates reagents and specimens into a tip attached to the tip of a probe of a dispensing mechanism and dispenses them into a reaction vessel. In this example, an example will be described in which the dispensing mechanism continuously aspirates up to three types of liquid (reagents or specimens) and continuously dispenses these liquids into a reaction vessel.
[0012] 1 is a schematic diagram of an automatic analyzer according to Example 1. The automatic analyzer 1 mainly includes a reagent disk 102, a sample disk 104, an incubator 106, a detection unit 109, a dispensing mechanism 111, a cleaning mechanism 116, and a control unit 207 (see FIG. 2).
[0013] Reagent bottles 101 (reagent containers) containing reagents used in analysis are held on a reagent disk 102, and specimen containers 103 containing specimens are held on a specimen disk 104. Reaction vessels 105 in which specimens react with reagents are held in an incubator 106 whose temperature is regulated to a constant value.
[0014] The reaction vessel 105 is loaded onto the automatic analyzer while supported by a reaction vessel tray 107, and is then transported onto the incubator 106 via a gripper 108. The components of the solution in which the reaction has progressed in the reaction vessel 105 are detected by a detection unit 109. After the detection is completed, the used reaction vessel 105 is discarded via the gripper 108 into a reaction vessel disposal port 110.
[0015] The reagent disk 102, the sample disk 104, and the incubator 106 are integrally provided with a reagent disk drive mechanism 102a, a sample disk drive mechanism 104a, and an incubator drive mechanism 106a, which rotate and drive them, respectively. The reagent disk 102, the sample disk 104, and the incubator 106 are moved by the drive mechanisms to positions where the dispensing mechanism 111 can access the liquid. "Access" here does not simply mean approaching the liquid, but also means aspirating the liquid. The same applies hereinafter.
[0016] The dispensing mechanism 111 uses disposable tips 112 to prevent components of the specimen or reagent from being carried over to the next analysis during dispensing. The dispensing mechanism 111 aspirates the required specimen and reagent using tips 112 placed in a tip buffer 113. The tips 112 are supported on a tip tray 114 and loaded into the automatic analyzer, and are transported from the tip tray 114 onto the tip buffer 113 via a gripper 108. After dispensing, the tips 112 are discarded into a tip disposal port 115. The cleaning mechanism 116 cleans the dispensing mechanism 111 to prevent components from being carried over when dispensing different liquids.
[0017] 2 is a schematic diagram of the dispensing mechanism. A tip 112 is attached to the tip of a probe 201 that constitutes the dispensing mechanism 111. The probe 201 is connected via a tube 202 to a syringe 203 for aspirating and dispensing liquid. The syringe 203 is able to aspirate and dispense liquid by moving a plunger 203b relative to a cylinder 203a. The flow path of the dispensing mechanism 111 is filled with cleaning water 204, which serves to improve the efficiency of pressure propagation and to clean away dirt.
[0018] Syringe 203 is operated to suck and discharge by syringe driver 205, and probe 201 is operated to rotate up and down by probe driver 206 (movement mechanism). Controller 207 controls the amount and timing of these operations. Cleaning water 204 contained in cleaning water tank 208 is sent into the flow path via pump 209. When cleaning water 204 is to be sent to probe 201, controller 207 opens and closes solenoid valve 210 to start or stop the sending.
[0019] The tip 112 attached to the tip of the probe 201 in the tip buffer 113 accesses three types of reagents 211a, 211b, and 211c contained in the reagent bottle 101, the sample 212 contained in the sample container 103, the reaction container 105, and the cleaning mechanism 116, and is then discarded through the tip disposal port 115. The cleaning mechanism 116 is composed of a cleaning nozzle 116a and a drain cup 116b, and the outer wall of the tip 112 can be washed with the cleaning nozzle 116a. With the tip detached, cleaning water can be discharged from the probe 201 into the drain cup 116b, thereby cleaning the inner wall of the probe 201. The supply of cleaning water to the cleaning nozzle 116a is started and stopped by opening and closing the solenoid valve 213 using the control unit 207.
[0020] <Example of dispensing three types of liquids simultaneously> Figure 3 shows the internal state of the probe and tip when three types of liquid are successively aspirated and simultaneously dispensed into reaction vessels. Initially, the probe 201 is filled with cleaning water 204 (Figure 3(1)). Next, the control unit 207 drives the syringe 203 to aspirate segmented air 301 into the probe 201, and then causes the probe 201 to access the tip buffer 113 and attach the tip 112 (Figure 3(2)). In this way, by aspirating segmented air 301 into the probe 201 in advance, dripping of the cleaning water 204 can be prevented when attaching the tip 112.
[0021] Next, the control unit 207 drives the probe 201 to immerse the tip 112 in the liquid 302. Here, the liquid 302 is one of the reagents 211a, 211b, and 211c, or the specimen 212. After immersion, the control unit 207 drives the syringe 203 to aspirate the liquid 302 into the tip 112 (FIG. 3(3)). During aspirating, the liquid 302 adheres to the outer wall of the tip 112. Therefore, the control unit 207 accesses the probe 201 to the cleaning mechanism 116, which discharges cleaning water 204 from the cleaning nozzle 116a onto the outer wall of the tip 112, thereby washing away the liquid 302 adhering to the outer wall of the tip 112. Before or after this cleaning, the control unit 207 drives the syringe 203 to aspirate air 303 into the probe 201, thereby preventing the liquid 302 from dripping (FIG. 3(4)).
[0022] Next, the control unit 207 drives the probe 201 to immerse the tip 112 in the liquid 304. Here, the liquid 304 is one of the reagents 211a, 211b, and 211c, or the specimen 212. After immersion, the control unit 207 drives the syringe 203 to aspirate the liquid 304 into the tip 112 (FIG. 3(5)). During aspirating, the liquid 304 adheres to the outer wall of the tip 112. Therefore, the control unit 207 accesses the probe 201 to the cleaning mechanism 116, which discharges cleaning water 204 from the cleaning nozzle 116a onto the outer wall of the tip 112, thereby washing away the liquid 304 adhering to the outer wall of the tip 112. Before or after this cleaning, the control unit 207 drives the syringe 203 to aspirate segmented air 305 into the probe 201, thereby preventing the liquid 304 from dripping (FIG. 3(6)).
[0023] Finally, the control unit 207 drives the probe 201 to immerse the tip 112 in the liquid 306. Here, the liquid 306 is one of the reagents 211a, 211b, and 211c, or the specimen 212. After immersion, the control unit 207 drives the syringe 203 to aspirate the liquid 306 into the tip 112 (FIG. 3(7)). Since all of the liquids to be dispensed have been aspirated through the steps up to this point, the control unit 207 drives the probe 201 to access the reaction vessel 105 and dispense all of the liquid (FIG. 3(8)). This makes it possible to dispense three types of liquid, liquid 302, liquid 304, and liquid 306, using a single tip 112. Note that after the three types of liquids have been dispensed into the reaction vessel 105, the control unit 207 may agitate the liquids by aspirating and dispensing the liquids in the reaction vessel 105 into the tip 112.
[0024] 4 is a flowchart showing the operation procedure of the dispensing mechanism when dispensing three types of liquid simultaneously. First, cleaning water 204 is supplied into the inside of probe 201 to clean the inside of probe 201 (step S401). Next, air 301 is sucked into probe 201 (step S402), and tip 112 is attached to the tip of probe 201 (step S403).
[0025] Next, the dispensing mechanism 111 accesses the liquid 302 in the following procedure: the probe 201 is driven to immerse the tip 112 in the liquid 302 (step S404), and the liquid 302 is aspirated into the tip 112 (step S405). After that, the dispensing mechanism 111 accesses the cleaning mechanism 116 to clean the outer wall of the tip 112, and the tip 112 is cleaned and the segmented air 303 is aspirated (step S406).
[0026] Next, the dispensing mechanism 111 accesses the liquid 304 in the following procedure: the probe 201 is driven to immerse the tip 112 in the liquid 304 (step S407), and the liquid 304 is aspirated into the tip 112 (step S408). After that, the dispensing mechanism 111 accesses the cleaning mechanism 116 to clean the outer wall of the tip 112, and the tip 112 is cleaned and the segmented air 305 is aspirated (step S409).
[0027] Next, dispensing mechanism 111 accesses liquid 306 in the following procedure: Probe 201 is driven to immerse tip 112 in liquid 306 (step S410), and liquid 306 is aspirated into tip 112 (step S411).
[0028] Finally, dispensing mechanism 111 accesses incubator 106 and dispenses the aspirated liquid. That is, probe 201 moves to reaction vessel 105 (step S412), and liquids 302, 304, and 306 are dispensed into reaction vessel 105 (step S413). Thereafter, probe 201 moves to tip disposal port 115, and tip 112 is removed (step S414). Note that immediately after the liquid is dispensed into reaction vessel 105 in step S413, dispensing mechanism 111 may agitate the liquid in reaction vessel 105 by aspirating and dispensing it into tip 112.
[0029] 3 and 4, the first, second, and third liquids to be aspirated are liquid 302, liquid 304, and liquid 306, respectively. Liquid 302 is first in the aspirated order, so it reaches the top of chip 112 in FIG. 3. On the other hand, liquid 306 is third in the aspirated order, so it only reaches the bottom of chip 112. Liquid 304 is second in the aspirated order, so it reaches a height midway between liquids 302 and 306.
[0030] In step 413 of Figure 4, when the liquid is discharged into the reaction vessel 105, residual liquid due to the liquid film occurs in the tip 112. The longer the distance the liquid travels in the tip 112, the greater the residual liquid due to the liquid film. For this reason, liquid 302, which reaches the top of the tip 112, has the most residual liquid. On the other hand, liquid 306, which only reaches the bottom of the tip 112, has the least residual liquid. The residual amount of liquid 304 is intermediate between that of liquid 302 and liquid 306.
[0031] In order to accurately dispense the target dispensing amounts of liquid 302, liquid 304, and liquid 306, it is necessary to aspirate excess liquid 302, liquid 304, and liquid 306 by the estimated remaining amount, taking into account the amount of liquid remaining in tip 112 during the dispensing process. Specifically, controller 207 pre-sets not only the target dispensing amounts but also the amount of excess liquid to be aspirated (excess aspirated amount). Then, in steps S405, S408, and S411 of FIG. 4, controller 207 causes dispensing mechanism 111 to aspirate an amount of liquid equivalent to the sum of the target dispensing amount and the excess aspirated amount. Here, controller 207 changes the amount of excess aspirated depending on the aspirating order. Desirably, the excess aspirated amount for liquid 302, which is aspirated first, is set to the largest, the excess aspirated amount for liquid 306, which is aspirated last, is set to the smallest, and the excess aspirated amount for liquid 304 is set to an intermediate amount between liquids 302 and 306.
[0032] Here, the thickness of the liquid film also depends on the physical properties of the liquid, such as viscosity, surface tension, etc. In other words, since the amount of remaining liquid differs depending on the physical properties of the liquid, if the physical properties of the liquid are known before suction, it is desirable to set the excess suction amount according to the physical properties of the liquid.
[0033] <Example of dispensing two types of liquids simultaneously> Figure 5 shows the internal state of the probe and tip when two types of liquid are successively aspirated and simultaneously dispensed into a reaction vessel. Initially, the probe 201 is filled with cleaning water 204 (Figure 5(1)). Next, the control unit 207 drives the syringe 203 to aspirate segmented air 501 into the probe 201, and then causes the probe 201 to access the tip buffer 113 and attach the tip 112 (Figure 5(2)).
[0034] Next, the control unit 207 drives the probe 201 to immerse the tip 112 in the liquid 502. Here, the liquid 502 is one of the reagents 211a, 211b, and 211c, or the specimen 212. After immersion, the control unit 207 drives the syringe 203 to aspirate the liquid 502 into the tip 112 (FIG. 5(3)). During aspirating, the liquid 502 adheres to the outer wall of the tip 112. Therefore, the control unit 207 accesses the probe 201 to the cleaning mechanism 116, which discharges cleaning water 204 from the cleaning nozzle 116a onto the outer wall of the tip 112, thereby washing away the liquid 502 adhering to the outer wall of the tip 112. Before or after this cleaning, the control unit 207 drives the syringe 203 to aspirate air 503 into the probe 201, thereby preventing the liquid 502 from dripping (FIG. 5(4)).
[0035] Finally, the control unit 207 drives the probe 201 to immerse the tip 112 in the liquid 504. Here, the liquid 504 is one of the reagents 211a, 211b, and 211c, or the specimen 212. After immersion, the control unit 207 drives the syringe 203 to aspirate the liquid 504 into the tip 112 (FIG. 5(5)). Since all of the liquid to be dispensed has been aspirated through the steps up to this point, the control unit 207 drives the probe 201 to access the reaction vessel 105 and dispense all of the liquid (FIG. 5(6)). This makes it possible to dispense two types of liquid, liquid 502 and liquid 504, using a single tip 112. Note that after the two types of liquid have been dispensed into the reaction vessel 105, the control unit 207 may agitate the liquid by aspirating and dispensing the liquid in the reaction vessel 105 into the tip 112.
[0036] 6 is a flowchart showing the operation procedure of the dispensing mechanism when dispensing two types of liquid simultaneously. First, cleaning water 204 is supplied into the inside of probe 201 to clean the inside of probe 201 (step S601). Next, air 501 is sucked into probe 201 (step S602), and tip 112 is attached to the tip of probe 201 (step S603).
[0037] Next, the dispensing mechanism 111 accesses the liquid 502 in the following procedure: the probe 201 is driven to immerse the tip 112 in the liquid 502 (step S604), and the liquid 502 is aspirated into the tip 112 (step S605). After that, the dispensing mechanism 111 accesses the cleaning mechanism 116 to clean the outer wall of the tip 112, and the cleaning of the tip 112 and the aspirating of the segmented air 503 are performed (step S606).
[0038] Next, dispensing mechanism 111 accesses liquid 504 in the following procedure: Probe 201 is driven to immerse tip 112 in liquid 504 (step S607), and liquid 504 is aspirated into tip 112 (step S608).
[0039] Finally, the dispensing mechanism 111 accesses the incubator 106 and dispenses the aspirated liquid. That is, the probe 201 moves to the reaction vessel 105 (step S609), and the liquids 502 and 504 are dispensed into the reaction vessel 105 (step S610). Thereafter, the probe 201 moves to the tip disposal port 115, and the tip 112 is removed (step S611). Note that immediately after the liquid is dispensed into the reaction vessel 105 in step S610, the dispensing mechanism 111 may agitate the liquid in the reaction vessel 105 by aspirating and dispensing it into the tip 112.
[0040] 5 and 6, the first and second liquids to be aspirated are liquid 502 and liquid 504, respectively. Because liquid 502 is first in the aspirated order, it reaches the top of chip 112 in FIG. 5. On the other hand, because liquid 504 is second in the aspirated order, it only reaches the bottom of chip 112.
[0041] 6, in the process of discharging the liquid into the reaction vessel 105, residual liquid due to the liquid film occurs in the tip 112. The residual liquid due to the liquid film increases as the distance traveled by the liquid in the tip 112 increases. Therefore, a large amount of liquid 502 remains, reaching the upper part of the tip 112. On the other hand, a small amount of liquid 504 remains, reaching only the lower part of the tip 112.
[0042] In order to accurately dispense the target dispensing amounts of liquid 502 and liquid 504, it is necessary to aspirate excess liquid 502 and liquid 504 by the estimated remaining amount, taking into account the amount of liquid remaining in tip 112 during the dispensing process. Specifically, control unit 207 pre-sets not only the target dispensing amounts but also the amount of excess to be aspirated (excess aspirated amount). Then, in steps S605 and S608 in FIG. 6, control unit 207 causes dispensing mechanism 111 to aspirate an amount of liquid equivalent to the sum of the target set amount and the excess aspirated amount. Here, control unit 207 changes the excess aspirated amount depending on the aspirating order. Desirably, a larger excess aspirated amount is set for liquid 502, which is aspirated first, and a smaller excess aspirated amount is set for liquid 504, which is aspirated later.
[0043] Here, the thickness of the liquid film also depends on the physical properties of the liquid, such as viscosity, surface tension, etc. In other words, since the amount of remaining liquid differs depending on the physical properties of the liquid, if the physical properties of the liquid are known before suction, it is desirable to set the excess suction amount according to the physical properties of the liquid.
[0044] <Example of dispensing one type of liquid> 7 shows the internal state of the probe and tip when one type of liquid is dispensed into a reaction vessel. Initially, the probe 201 is filled with cleaning water 204 (FIG. 7(1)). Next, the control unit 207 drives the syringe 203 to aspirate partial air 701 into the probe 201, and then causes the probe 201 to access the tip buffer 113 and attach the tip 112 (FIG. 7(2)).
[0045] Next, the control unit 207 drives the probe 201 to immerse the tip 112 in the liquid 702. Here, the liquid 704 is one of the reagents 211a, 211b, and 211c, or the specimen 212. After immersion, the control unit 207 drives the syringe 203 to aspirate the liquid 702 into the tip 112 (FIG. 7(3)). After the steps up to this point have been completed, the liquid to be dispensed has been aspirated, so the control unit 207 drives the probe 201 to access the reaction vessel 105 and dispense the liquid (FIG. 7(4)). This makes it possible to dispense a single liquid 702 using the tip 112.
[0046] 8 is a flowchart showing the operation procedure of the dispensing mechanism when dispensing one type of liquid. First, cleaning water 204 is supplied into the inside of probe 201 to clean the inside of probe 201 (step S801). Next, air 701 is sucked into probe 201 (step S802), and tip 112 is attached to the tip of probe 201 (step S803).
[0047] Next, dispensing mechanism 111 accesses liquid 702 in the following procedure: probe 201 is driven to immerse tip 112 in liquid 702 (step S804), and liquid 702 is aspirated into tip 112 (S805).
[0048] Finally, the dispensing mechanism 111 accesses the incubator 106 and dispenses the aspirated liquid. That is, the probe 201 moves to the reaction vessel 105 (step S806), and the liquid 702 is dispensed into the reaction vessel 105 (step S807). Thereafter, the probe 201 moves to the tip disposal port 115, and the tip 112 is removed (step S808). Note that immediately after the liquid is dispensed into the reaction vessel 105 in step S807, the dispensing mechanism 111 may agitate the liquid in the reaction vessel 105 by aspirating and dispensing it into the tip 112.
[0049] 7 and 8, only the liquid 702 is to be aspirated. In the step of dispensing the liquid into the reaction vessel 105 in step S807 in FIG. 8, residual liquid occurs in the tip 112 due to a liquid film. In order to accurately dispense the target dispensing amount of the liquid 702, it is necessary to aspirate excess liquid 702 by the estimated amount of residual liquid, taking into account the amount of liquid remaining in the tip 112 during the dispensing step. Specifically, the control unit 207 sets in advance not only the target dispensing amount but also the amount of excess to be aspirated (excess aspirated amount). Then, in step S805 in FIG. 8, the control unit 207 causes the dispensing mechanism 111 to aspirate an amount of liquid equivalent to the sum of the target dispensing amount and the excess aspirated amount.
[0050] Here, the thickness of the liquid film also depends on the physical properties of the liquid, such as viscosity, surface tension, etc. In other words, since the amount of remaining liquid differs depending on the physical properties of the liquid, if the physical properties of the liquid are known before suction, it is desirable to set the excess suction amount according to the physical properties of the liquid.
[0051] FIG. 9 is a table for setting dispensing patterns for each analysis item in Example 1. Analysis examples 1 to 4 set in FIG. 9 correspond to different analysis items, and each analysis pattern is partially different. That is, each analysis example has in common that three types of reagents, reagent 211a, reagent 211b, and reagent 211c, and sample 212 are supplied in two aliquots to a common reaction vessel 105, but differs in the number of types of liquid dispensed each time, the target dispensing amount, or the aspirating order. The amount of excess aspirated for each liquid is determined according to the aspirating order and the target dispensing amount.
[0052] (Analysis example 1) First, in the first dispensing, which is the first dispensing, the dispensing mechanism 111 simultaneously dispenses the reagent 211a and the specimen 212. Specifically, the probe 201 first aspirates the reagent 211a (aspirating order 1), then aspirates the specimen 212 (aspirating order 2), and then discharges these liquids together into the reaction vessel 105. Thereafter, the used tip 112 is discarded, and a new tip 112 is attached to the probe 201.
[0053] Next, in the second dispensing, which is the second dispensing, the dispensing mechanism 111 simultaneously dispenses reagent 211b and reagent 211c. Specifically, the probe 201 first aspirates reagent 211b (aspirating order 1), then aspirates reagent 211c (aspirating order 2), and then discharges these liquids together into the reaction vessel 105. Thereafter, the tip 112 that was being used is discarded, and the dispensing operation of analysis example 1 is completed.
[0054] As described above, in the first dispensing, the reagent 211a is aspirated first, and the sample 212 is aspirated second. Therefore, the reagent 211a corresponds to the liquid 502 in FIGS. 5 and 6, and the sample 212 corresponds to the liquid 504 in FIGS. 5 and 6. Therefore, when the reagent 211a and the sample 212 are dispensed, the remaining liquid volume of the reagent 211a is greater than that of the sample 212. Therefore, the excess aspirated volume of the reagent 211a is set to 1.1 μL, and together with the target dispensing volume of 30 μL, 31.1 μL is aspirated by the probe 201. On the other hand, the excess aspirated volume of the sample 212 is set to 0.7 μL, and together with the target dispensing volume of 30 μL, 30.7 μL is aspirated by the probe 201.
[0055] As described above, in the second dispensing, reagent 211b is aspirated first, and reagent 211c is aspirated second. Therefore, reagent 211b corresponds to liquid 502 in FIGS. 5 and 6, and reagent 211c corresponds to liquid 504 in FIGS. 5 and 6. Therefore, when dispensing reagents 211b and 211c, a larger amount of residual liquid remains in reagent 211b than in reagent 211c. Therefore, the excess aspirated amount of reagent 211b is set to 1.0 μL, and together with the target dispensing amount of 30 μL, a total of 31.0 μL is aspirated by probe 201. On the other hand, the excess aspirated amount of reagent 211c is set to 0.5 μL, and together with the target dispensing amount of 30 μL, a total of 30.5 μL is aspirated by probe 201.
[0056] Furthermore, the excess aspirate volumes of reagent 211a and specimen 212 in the first dispensing are set to be larger than the excess aspirate volumes of reagent 211b and reagent 211c in the second dispensing. This is because, after reagent 211a and specimen 212 are discharged into reaction vessel 105 in the first dispensing, when reagent 211b and reagent 211c are discharged into the same reaction vessel 105 in the second dispensing, components of reagent 211a and specimen 212 (already discharged into reaction vessel 105) adhere to tip 112. Taking into account carryover of components of reagent 211a and specimen 212 due to this adhesion, different excess aspirate volumes are set for the first dispensing and the second dispensing.
[0057] (Analysis example 2) First, in the first dispensing, which is the first dispensing, the dispensing mechanism 111 simultaneously dispenses the reagent 211a and the specimen 212. Specifically, the probe 201 first aspirates the reagent 211a (aspirating order 1), then aspirates the specimen 212 (aspirating order 2), and then discharges these liquids together into the reaction vessel 105. Thereafter, the used tip 112 is discarded, and a new tip 112 is attached to the probe 201.
[0058] Next, in the second dispensing, which is the second dispensing, the dispensing mechanism 111 simultaneously dispenses reagent 211b and reagent 211c. Specifically, the probe 201 first aspirates reagent 211c (aspirating order 1), then aspirates reagent 211b (aspirating order 2), and then discharges these liquids together into the reaction vessel 105. Thereafter, the tip 112 that was being used is discarded, and the dispensing operation of analysis example 2 is completed.
[0059] As described above, in the first dispensing, the reagent 211a is aspirated first, and the sample 212 is aspirated second. Therefore, the reagent 211a corresponds to the liquid 502 in FIGS. 5 and 6, and the sample 212 corresponds to the liquid 504 in FIGS. 5 and 6. Therefore, when the reagent 211a and the sample 212 are dispensed, the remaining liquid volume of the reagent 211a is greater than that of the sample 212. Therefore, the excess aspirated volume of the reagent 211a is set to 1.6 μL, and together with the target dispensing volume of 60 μL, a total of 61.6 μL is aspirated by the probe 201. On the other hand, the excess aspirated volume of the sample 212 is set to 0.4 μL, and together with the target dispensing volume of 30 μL, a total of 30.4 μL is aspirated by the probe 201.
[0060] As described above, in the second dispensing, reagent 211c is aspirated first, and reagent 211b is aspirated second. Therefore, reagent 211c corresponds to liquid 502 in FIGS. 5 and 6, and reagent 211b corresponds to liquid 504 in FIGS. 5 and 6. Therefore, when dispensing reagents 211b and 211c, a larger amount of reagent 211c remains than reagent 211b. Therefore, the excess aspirated amount of reagent 211b is set to 0.6 μL, and together with the target dispensing amount of 30 μL, a total of 30.6 μL is aspirated by probe 201. On the other hand, the excess aspirated amount of reagent 211c is set to 0.8 μL, and together with the target dispensing amount of 30 μL, a total of 30.8 μL is aspirated by probe 201.
[0061] Furthermore, in the first dispensing of Analysis Example 2, the aspirating order of the reagent 211a and the specimen 212 is the same as the aspirating order in the first dispensing of Analysis Example 1. However, the target dispensing volume of the reagent 211a is 60 μL in Analysis Example 2, compared to 30 μL in Analysis Example 1. As the target dispensing volume increases, the liquid reaches a higher position in the tip 112 in FIG. 5 , and the amount of remaining liquid also increases. Therefore, the excess aspirated volume of the reagent 211a in the first dispensing of Analysis Example 2 is set to be larger than the excess aspirated volume of the reagent 211a in the first dispensing of Analysis Example 1. On the other hand, because the dispensing volume of the reagent 211a in the first dispensing of Analysis Example 2 is larger than that in Analysis Example 1, the specimen 212 is washed away by the reagent 211a during dispensing, and is less likely to remain in the tip 112. Therefore, the excess aspirated volume of the specimen 212 in the first dispensing of Analysis Example 2 is set to be smaller than the excess aspirated volume of the specimen 212 in the first dispensing of Analysis Example 1.
[0062] Furthermore, in the second dispensing of Analysis Example 2, the order in which reagents 211b and 211c are aspirated is reversed from that in the second dispensing of Analysis Example 1. Therefore, the remaining liquid amount of reagent 211b is smaller and the remaining liquid amount of reagent 211c is larger in the second dispensing of Analysis Example 2 compared to Analysis Example 1. Therefore, the amount of excess aspirated of reagent 211b in the second dispensing of Analysis Example 2 is set to be smaller than the amount of excess aspirated of reagent 211b in Analysis Example 1, and the amount of excess aspirated of reagent 211c in the second dispensing of Analysis Example 2 is set to be larger than the amount of excess aspirated of reagent 211c in Analysis Example 1.
[0063] Thus, when comparing Analysis Example 2 with Analysis Example 1, it can be seen that the aspirating order of the liquids dispensed simultaneously and the target dispensing amounts are partially different, and therefore the amount of excess aspirated is also different.
[0064] (Analysis example 3) First, in the first dispensing, which is the first dispensing, the dispensing mechanism 111 simultaneously dispenses the reagent 211a and the specimen 212. Specifically, the probe 201 first aspirates the reagent 211a (aspirating order 1), then aspirates the specimen 212 (aspirating order 2), and then discharges these liquids together into the reaction vessel 105. Thereafter, the used tip 112 is discarded, and a new tip 112 is attached to the probe 201.
[0065] Next, in the second dispensing, which is the second dispensing, the dispensing mechanism 111 simultaneously dispenses reagent 211b and reagent 211c. Specifically, the probe 201 first aspirates reagent 211b (aspirating order 1), then aspirates reagent 211c (aspirating order 2), and then discharges these liquids together into the reaction vessel 105. Thereafter, the tip 112 that was being used is discarded, and the dispensing operation of analysis example 3 is completed.
[0066] As described above, in the first dispensing, the reagent 211a is aspirated first, and the sample 212 is aspirated second. Therefore, the reagent 211a corresponds to the liquid 502 in FIGS. 5 and 6, and the sample 212 corresponds to the liquid 504 in FIGS. 5 and 6. Therefore, when the reagent 211a and the sample 212 are dispensed, the remaining liquid volume of the reagent 211a is greater than that of the sample 212. Therefore, the excess aspirated volume of the reagent 211a is set to 1.5 μL, and together with the target dispensing volume of 30 μL, a total of 31.5 μL is aspirated by the probe 201. On the other hand, the excess aspirated volume of the sample 212 is set to 1.0 μL, and together with the target dispensing volume of 60 μL, a total of 61.0 μL is aspirated by the probe 201.
[0067] As described above, in the second dispensing, reagent 211b is aspirated first, and reagent 211c is aspirated second. Therefore, reagent 211b corresponds to liquid 502 in FIGS. 5 and 6, and reagent 211c corresponds to liquid 504 in FIGS. 5 and 6. Therefore, when dispensing reagents 211b and 211c, a larger amount of residual liquid remains in reagent 211b than in reagent 211c. Therefore, the excess aspirated amount of reagent 211b is set to 1.0 μL, and together with the target dispensing amount of 30 μL, a total of 31.0 μL is aspirated by probe 201. On the other hand, the excess aspirated amount of reagent 211c is set to 0.5 μL, and together with the target dispensing amount of 30 μL, a total of 30.5 μL is aspirated by probe 201.
[0068] Furthermore, in the first dispensing of Analysis Example 3, the target dispensing volume of the sample 212 is larger than that of Analysis Example 1, and liquid is more likely to remain. Therefore, the excess dispensing volume of the sample 212 in Analysis Example 3 is set larger than the excess dispensing volume of the sample 212 in Analysis Example 1. Furthermore, because the target dispensing volume of the sample 212 is larger than that of Analysis Example 1, the reagent 211a, which is first in the aspirating order, reaches the upper part of the tip 112 than in Analysis Example 1, and a larger amount of liquid remains. Therefore, the excess aspirating volume of the reagent 211a in Analysis Example 3 is set larger than the excess aspirating volume of the reagent 211a in Analysis Example 1.
[0069] Thus, when comparing Analysis Example 3 with Analysis Example 1, it can be seen that, particularly in the first dispensing, the target dispensing amounts of the liquids dispensed simultaneously are partially different, and therefore the excess aspirated amounts are also different. Note that in the second dispensing, the aspirating order and target dispensing amounts of the liquids dispensed simultaneously are the same in Analysis Example 1 and Analysis Example 3, and therefore the excess aspirated amounts are the same in each Analysis Example.
[0070] (Analysis example 4) First, in the first dispensing, which is the first dispensing, the dispensing mechanism 111 simultaneously dispenses the reagent 211a, the reagent 211b, and the specimen 212. Specifically, the probe 201 first aspirates the reagent 211a (aspirating order 1), then aspirates the reagent 211b (aspirating order 2), and finally aspirates the specimen 212 (aspirating order 3), and then discharges these liquids together into the reaction vessel 105. Thereafter, the used tip 112 is discarded, and a new tip 112 is attached to the probe 201.
[0071] Next, in the second dispensing, which is the second dispensing, the dispensing mechanism 111 dispenses only the reagent 211c. Specifically, the probe 201 aspirates only the reagent 211c (aspiration order 1) and then dispenses it into the reaction vessel 105. Thereafter, the tip 112 that was being used is discarded, and the dispensing operation of analysis example 4 is completed.
[0072] As described above, in the first dispensing, reagent 211a is aspirated first, reagent 211b is aspirated second, and sample 212 is aspirated third. Therefore, reagent 211a corresponds to liquid 302 in FIGS. 3 and 4, reagent 211b corresponds to liquid 304 in FIGS. 3 and 4, and sample 212 corresponds to liquid 306 in FIGS. 3 and 4. Therefore, when dispensing reagent 211a, reagent 211b, and sample 212, the remaining liquid amounts increase in the order of reagent 211a, reagent 211b, and sample 212. Therefore, the excess aspirated amount of reagent 211a is set to 1.6 μL, and together with the target dispensing amount of 30 μL, 31.6 μL is aspirated by probe 201. Next, the excess aspirated amount of reagent 211b is set to 0.9 μL, and together with the target dispensing amount of 30 μL, 30.9 μL is aspirated by probe 201. The amount of excess sample 212 aspirated is set to 0.5 μL, and together with the target dispensing amount of 30 μL, a total of 30.5 μL is aspirated by probe 201.
[0073] As described above, in the second dispensing, only reagent 211c is dispensed. Therefore, reagent 211c corresponds to liquid 702 in Figures 7 and 8. The excess aspirated amount of reagent 211c is set to 0.6 µL, and together with the target dispensing amount of 30 µL, a total of 30.6 µL is aspirated by probe 201.
[0074] Furthermore, in the first dispensing in Analysis Example 4, three types of liquid are aspirated consecutively. Therefore, compared to Analysis Example 1, in which two types of liquid are aspirated consecutively, reagent 211a, which is aspirated first, reaches a higher position in tip 112, resulting in a larger amount of remaining liquid. Therefore, even though the aspirating order and target dispensing volume for reagent 211a in Analysis Example 4 are the same as those for Analysis Example 1, the amount of excess aspirated is set to be larger than that for Analysis Example 1. Similarly, in the second dispensing in Analysis Example 4, only reagent 211c is aspirated, resulting in a smaller amount of remaining liquid for reagent 211c, compared to Analysis Example 2, in which two types of liquid are aspirated consecutively. Therefore, even though the aspirating order and target liquid volume for reagent 211c in Analysis Example 4 are the same as those for Analysis Example 2, the amount of excess aspirated is set to be smaller than that for Analysis Example 2. On the other hand, when comparing reagent 211c in analysis example 4 with reagent 211c in analysis example 1, reagent 211c in analysis example 1 is washed away by reagent 211b when discharged, but reagent 211c in analysis example 4 is not washed away. For this reason, the excess aspirate amount of reagent 211c in analysis example 4 is set to be larger than the excess aspirate amount of reagent 211c in analysis example 1.
[0075] Thus, when comparing Analysis Example 4 with the other Analysis Examples, it can be seen that the number of types of liquids dispensed simultaneously is different, and therefore the amount of excess aspirated is also different.
[0076] FIG. 10 is a block diagram showing the flow of information when the control unit controls the dispensing mechanism according to the analysis items. The analysis items are input via the input unit 1001 and stored in the analysis item storage unit 1002. After the analysis begins, the control unit 207 sets the types of liquids to be dispensed simultaneously, the target dispensing amounts for each liquid, the aspirating order, and other information based on the dispensing information previously stored in the dispensing information storage unit 1003. Next, the control unit 207 determines the excess aspirate amount for each liquid and calculates the total aspirate amount for each liquid, which is the sum of the target dispensing amount and the excess aspirate amount. Furthermore, the control unit 207 controls the aspirating operation of the probe 201 via the dispensing control means 1005 (such as the syringe drive unit 205 in FIG. 2) based on the calculated total aspirate amount.
[0077] In addition to the analysis items, information on priority (urgency) may also be input from the input unit 1001. In this case, if the priorities differ, the control unit 207 determines different dispensing patterns, such as the number of types of liquids to be dispensed simultaneously, even if the analysis items are the same. For example, for a normal sample, analysis example 1 is adopted, and reagent 211a and sample 212 are reacted in the first dispensing, and then the second dispensing is performed after a predetermined time has passed. On the other hand, for an urgent sample, analysis example 4 is adopted, and reagent 211a, reagent 211b, and sample 212 are dispensed in the first dispensing, and then the second dispensing is performed immediately. In this way, even if the analysis items are the same, the combination of liquids to be dispensed simultaneously and the aspirating order differ depending on whether the sample is urgent or not, and therefore the amount of excess aspirated also differs.
[0078] According to this embodiment, the excess suction volume is set according to the number of types of liquid to be dispensed simultaneously and the suction order, and the target dispensing volume of liquid can be supplied to the reaction vessel with high accuracy, which not only reduces the number of washings and the dispensing time, but also enables highly reliable analysis for many analysis items. [Example]
[0079] Example 2 will be described with reference to FIG. 11. FIG. 11 is a table for setting dispensing patterns for each analysis item in Example 2. Example 2 changes the amount of excess suction depending on the liquid discharge speed. Only the differences from Example 1 will be described below.
[0080] The (liquid) ejection speed in steps S413, S611, and S807 described in Example 1 can be set to different values depending on the analysis item. For example, as shown in Figure 11, the analysis item corresponding to Analysis Example 6 has a faster ejection speed and higher processing efficiency than the analysis item corresponding to Analysis Example 5.
[0081] Here, the faster the liquid discharge speed, the thicker the liquid film and the greater the amount of remaining liquid. Therefore, in Analysis Example 6, the excess aspirate volume of all liquids is set to be larger than in Analysis Example 5. Note that information regarding the discharge speed for each analysis item is stored in the dispensing information storage unit 1003 in FIG. 10, and the control unit 207 determines the excess aspirate volume of each liquid based on this information.
[0082] According to this embodiment, the target amount of liquid to be dispensed can be supplied to the reaction vessel with higher accuracy, thereby further improving the analytical accuracy. [Example]
[0083] Example 3 will be described with reference to FIG. 12. FIG. 12 is a table for setting dispensing patterns for each analysis item in Example 3. Example 3 changes the amount of excess suction depending on the viscosity of the liquid. Only the differences from Example 1 will be described below.
[0084] The viscosity of the dispensed liquid varies depending on the analysis item. For example, as shown in Figure 12, the analysis item corresponding to Analysis Example 8 has a higher viscosity than the analysis item corresponding to Analysis Example 7.
[0085] Here, the greater the viscosity of the liquid, the thicker the liquid film and the greater the amount of remaining liquid. Therefore, in Analysis Example 8, the excess aspirate volume of all liquids is set to be larger than in Analysis Example 7. Note that information regarding the viscosity for each analysis item is stored in the dispensing information storage unit 1003 in FIG. 10, and the control unit 207 determines the excess aspirate volume of each liquid based on this information.
[0086] According to this embodiment, the target amount of liquid to be dispensed can be supplied to the reaction vessel with higher accuracy, thereby further improving the analytical accuracy.
[0087] The present invention is not limited to the above-described embodiments, and includes various modifications. For example, in the above-described embodiments, the dispensing mechanism 111 that dispenses using a tip 112 has been described, but the same concepts as those in the above-described embodiments can be applied to a dispensing mechanism in which liquid is directly aspirated into the probe 201 without using a tip. Furthermore, in the above-described embodiments, the case where one to three types of liquid are dispensed at once has been described, but four or more types of liquid may be dispensed at once. Furthermore, in the above-described embodiments, the case where two dispensings (first dispensing and second dispensing) are performed into a common reaction vessel has been described, but the number of dispensings into a common reaction vessel may be one, or three or more.
[0088] Furthermore, in Examples 2 and 3, the amount of excess suction was changed according to the liquid's discharge speed and viscosity, but the amount of excess suction may also be changed according to other physical properties of the liquid. For example, the greater the surface tension of the liquid, the thinner the liquid film and the less residual liquid there will be. Therefore, when the surface tension of the liquid is high, the amount of excess suction may be set to be smaller than when the surface tension of the liquid is low. Furthermore, the greater the density of the liquid, the thicker the liquid film and the more residual liquid there will be. Therefore, when the density of the liquid is high, the amount of excess suction may be set to be larger than when the density of the liquid is low. [Explanation of symbols]
[0089] 1...automatic analyzer, 101...reagent bottle, 102...reagent disk, 103...sample container, 104...sample disk, 105...reaction container, 106...incubator, 107...reaction container tray, 108...gripper, 109...detection unit, 110...reaction container waste port, 111...dispensing mechanism, 112...tip, 113...tip buffer, 114...tip tray, 115...tip waste port, 116...cleaning mechanism, 116a...cleaning nozzle, 116b...drainage cup, 201...probe, 202...tube, 203...syringe, 203a...cylinder, 203b...plan 204...cleaning water, 205...syringe driving unit, 206...probe driving unit, 207...control unit, 208...cleaning water tank, 209...pump, 210...solenoid valve, 211a...reagent, 211b...reagent, 212...specimen, 213...solenoid valve, 301...segmented air, 302...liquid, 303...segmented air, 304...liquid, 305...segmented air, 306...liquid, 501...segmented air, 502...liquid, 503...segmented air, 504...liquid, 701...segmented air, 702...liquid, 1001...input unit, 1002...analysis item memory unit, 1003...dispensing information memory unit, 1005...dispensing control means
Claims
1. a dispensing mechanism that aspirates liquid from a specimen container or a reagent container and dispenses it into a reaction container; a control unit that controls the operation of the dispensing mechanism so as to achieve a target dispensing amount, The dispensing mechanism is an automatic analyzer that aspirates an excess aspirated amount of liquid in addition to the target dispensing amount of liquid during dispensing, When the dispensing mechanism continuously aspirates a plurality of types of liquid and continuously discharges the aspirated plurality of types of liquid, The automatic analyzer is characterized in that the control unit controls the dispensing mechanism so that the amount of excess liquid aspirated first is greater than the amount of excess liquid aspirated later.
2. The automatic analyzer according to claim 1, An automatic analyzer characterized in that the number of types of liquids aspirated by the dispensing mechanism varies depending on the analysis item.
3. The automatic analyzer according to claim 1, An automatic analyzer characterized in that the order in which the liquids are aspirated by the dispensing mechanism varies depending on the analysis item.
4. The automatic analyzer according to claim 1, The automatic analyzer is characterized in that the control unit controls the dispensing mechanism so that when the target dispensing amount of liquid is large, the amount of excess aspirated is larger than when the target dispensing amount of liquid is small.
5. The automatic analyzer according to claim 1, When the dispensing mechanism dispenses into a common reaction vessel two or more times, The automatic analyzer is characterized in that the control unit controls the dispensing mechanism so that the amount of excess liquid aspirated the first time is greater than the amount of excess liquid aspirated the second time.
6. The automatic analyzer according to claim 1, When the dispensing mechanism dispenses into a common reaction vessel two or more times, An automatic analyzer characterized in that, even if the analysis items are the same, the number of types of liquid dispensed in the first dispense is different when the priorities are different.
7. The automatic analyzer according to claim 1, The automatic analyzer is characterized in that the control unit controls the dispensing mechanism so that when the liquid suction speed is high, the amount of excess suction is larger than when the liquid suction speed is low.
8. The automatic analyzer according to claim 1, The automatic analyzer is characterized in that the control unit controls the dispensing mechanism so that the amount of excess aspirated is greater when the viscosity of the liquid is high than when the viscosity of the liquid is low.
9. The automatic analyzer according to claim 1, The automatic analyzer is characterized in that the control unit controls the dispensing mechanism so that the amount of excess aspirated is smaller when the surface tension of the liquid is high than when the surface tension of the liquid is low.
Citation Information
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