Automatic analysis device and liquid stirring method for automatic analysis device

The automated analyzer maintains consistent stirring efficiency by controlling the probe tip's immersion and separation based on liquid discharge amounts, addressing inefficiencies in existing systems and enhancing mixing quality.

WO2025142477A1PCT designated stage expired Publication Date: 2025-07-03HITACHI HIGH TECH CORP
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Patent Information

Application Number
PCT/JP2024/043748
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-12-29
Filing Date
2024-12-11
Publication Date
2025-07-03

AI Technical Summary

Technical Problem

Existing automated analyzers face challenges in maintaining consistent stirring efficiency during discharge stirring, which is affected by the varying amounts of liquid discharged from the dispensing probe depending on the analysis item.

Method used

An automated analyzer and method that controls the immersion and separation of the dispensing probe tip based on the amount of liquid discharged, ensuring consistent stirring efficiency by adjusting the tip's position relative to the liquid surface during suction and discharge operations.

Benefits of technology

Achieves constant stirring efficiency regardless of the liquid amount discharged, minimizing contamination and ensuring thorough mixing even with viscous solutions.

✦ Generated by Eureka AI based on patent content.

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Abstract

The following configuration provides: an automatic analysis device, which can ensure constant stirring efficiency regardless of the amount of liquid discharged from a dispensing probe by discharge agitation; and a liquid stirring method for the automatic analysis device. Provided is the automatic analysis device and the liquid stirring method for the automatic analysis device, the device comprises: a probe for suctioning and discharging a liquid; a placement part for placing a container for storing the liquid; a syringe for feeding the liquid to the probe through a flow passage; and a control unit for controlling the operation of the probe and the syringe. The control unit executes controls so that: if the amount of liquid discharged from a distal end of the probe into the container is more than or equal to a predetermined value, the distal end is separated from a liquid surface of the container at the end of operation of the syringe; and if the amount of liquid discharged from the probe into the container is less than the predetermined value, the distal end is immersed in the liquid of the container at the end of operation of the syringe.
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Description

Automatic analyzer and liquid stirring method for automatic analyzer

[0001] The present invention relates to an automatic analyzer and a liquid stirring method for an automatic analyzer.

[0002] In automated analyzers used in the medical field, samples and reagents must be thoroughly stirred. Stirring methods include using a stirring rod and dispensing / mixing using a liquid dispensing mechanism.

[0003] Here, Patent Document 1 discloses a technology in which, when aspirating the liquid to be stirred into a dispensing probe (pipette), the entire amount of liquid is not aspirated, but segmented air is introduced into the tip of the pipette tip during aspirating, and then the aspirating and dispensing of the liquid to be stirred is repeated, thereby improving the stirring effect.

[0004] JP 2011-107089 A

[0005] Automated analyzers perform analyses using a wide variety of reagents corresponding to many analysis items, but the amount of reagent used per analysis and the amount of sample mixed with the reagent vary depending on the analysis item. While investigating ways to improve the mixing efficiency of dispensing and stirring, the inventors discovered that mixing efficiency varies depending on the amount of liquid dispensed from the dispensing probe during dispensing and stirring, and invented a method that achieves consistent mixing efficiency regardless of the amount of liquid. Patent Document 1 does not describe changing the mixing method depending on the amount of liquid dispensed. An object of the present invention is to provide an automated analyzer and a liquid mixing method for an automated analyzer that achieve consistent mixing efficiency regardless of the amount of liquid dispensed from the dispensing probe during dispensing and stirring.

[0006] The present invention, which achieves the above object, is as follows: An automatic analyzer and a liquid stirring method for an automatic analyzer, comprising: a probe that aspirates and dispenses liquid, a mounting unit on which a container that contains the liquid is placed, a syringe that delivers the liquid to the probe via a flow path, and a control unit that controls the operation of the probe and the syringe, wherein the control unit controls the syringe so that the tip is separated from the liquid surface in the container when the operation of the syringe ends if the amount of liquid dispensed from the tip of the probe into the container is equal to or greater than a predetermined amount, and controls the syringe so that the tip is immersed in the liquid in the container when the operation of the syringe ends if the amount of liquid dispensed from the probe into the container is less than the predetermined amount.

[0007] In this case, when a highly viscous solution is to be stirred, it is preferable to control the syringe so that the tip is immersed in the liquid in the container when the syringe operation is completed, regardless of the amount of liquid.

[0008] It is possible to provide an automatic analyzer and a liquid stirring method for an automatic analyzer that can obtain a constant stirring efficiency regardless of the amount of liquid discharged from the dispensing probe during dispensing and stirring.

[0009] Schematic diagram of an automatic analyzer. Schematic diagram showing an example of the configuration of a dispensing unit. Schematic diagram showing a flow for automatically selecting a stirring mode. Schematic diagram of stirring mode operation A. Schematic diagram of stirring mode operation B. Diagram showing the relationship between liquid surface height and tip height. Diagram explaining the discharge speed and the rising of liquid in a reaction vessel. Diagram explaining the force relationship of droplets.

[0010] Hereinafter, preferred embodiments of the automatic analyzer according to the present invention will be described with reference to the drawings.

[0011] In the following description and accompanying drawings, components having the same functional configuration are denoted by the same reference numerals to avoid repetitive explanations. The technical scope of the present invention is not limited to these embodiments.

[0012] An example of the overall configuration of an automatic analyzer will be described using Figure 1. The automatic analyzer is a device that analyzes specific components contained in samples such as blood and urine provided by patients, and includes a mounting unit 102 on which containers are mounted, a dispensing unit 105, a cell disk (incubator) 104, a control unit 106, an input / output unit 107, and a memory unit 108. Each unit will be described below.

[0013] The mounting unit 102 stores the specimen containers 100 containing specimens and the reagent bottles 101 containing reagents, and transports the specimen containers 100 and the reagent bottles 101 to positions accessible by the dispensing unit 105 .

[0014] The dispensing unit 105 dispenses and agitates specimens and reagents from specimen containers 100 or reagent bottles 101 into reaction containers 103 stored on a cell disk 104. Detailed parameters for dispensing and agitation are controlled by the control unit 106. Operations can also be automatically selected based on registered liquid information for the solutions. Note that specimens and reagents may be dispensed by a single dispensing unit 105, or two dispensing units, one for specimens and one for reagents, may be provided and each may be dispensed separately. A more detailed configuration of the dispensing unit 105 will be described later using FIG. 2.

[0015] The cell disk 104 stores the reaction vessel 103, which contains a mixture of a specimen and a reagent, within a temperature range that allows the mixture to react, and transports the reaction vessel 103 to a position accessible to the dispensing unit 105. The mixture in the reaction vessel 103 becomes a reaction liquid to be used in measurement by storing the reaction vessel 103 within a predetermined temperature range.

[0016] The control unit 106 is a computer that controls the operation of each unit, and is responsible for controlling the operation in this embodiment.

[0017] The input / output unit 107 is a device that receives input of data necessary for analysis and displays the results of the analysis, and is, for example, a keyboard, a mouse, a touch panel, a liquid crystal display, or the like.

[0018] The storage unit 108 is a device that stores data necessary for analysis and analysis results, and is, for example, a hard disk drive (HDD) or a solid state drive (SSD).

[0019] An example of the configuration of the dispensing unit 105 will be described with reference to Fig. 2. The dispensing unit 105 has a shaft 201, an arm 202, a dispensing probe 203, a syringe pump 204, a tube 205, and an electromagnetic valve 206.

[0020] The shaft 201 is a hollow member extending vertically and can be moved up and down. The arm 202 is a hollow member extending horizontally, with one end connected to the upper end of the shaft 201 and the other end to which a dispensing probe 203 is attached, and is rotated around the shaft 201 as a rotation axis. By rotating the arm 202, the dispensing probe 203 is moved to directly above the sample container 100 or the reagent bottle 101.

[0021] The dispensing probe 203 is a thin tube that is inserted into the sample container 100 or the reagent bottle 101 by the up and down movement of the shaft 201, and its upper end is connected to a tube 205. The tube 205 connects the dispensing probe 203 to the syringe pump 204 through the arm 202 and the shaft 201. The dispensing probe 203 may be a hollow metal tube, or may have a disposable dispensing tip 209 attached to its tip.

[0022] The syringe pump 204 draws in and pushes out system water in the dispensing probe 203 by driving a syringe 207 in order to draw in and eject specimens, reagents, and air from the lower end of the dispensing probe 203. Liquids such as specimens and reagents are dispensed by drawing in system water to create negative pressure inside the dispensing probe, and by pushing out system water to create positive pressure inside the dispensing probe.

[0023] The solenoid valve 206 is provided between the syringe pump 204 and a system water container 208 that stores system water, and is closed while the specimen or the like is being dispensed. When dispensing is complete, the solenoid valve 206 is opened, and the inner wall of the dispensing probe 203 is washed with the system water supplied from the system water container 208, and the inside of the tube 205 is filled with the system water. In other words, the tube 205 is filled with system water before dispensing.

[0024] As an example of the operation of the dispensing unit 105 controlled by the control unit 106, a case will be described in which liquid a, segmented air, and liquid b are aspirated into the dispensing tip 209, and then liquid a, segmented air, and liquid b are simultaneously discharged into the reaction vessel 103, the liquid in the reaction vessel 103 becomes mixed liquid c, and this mixed liquid c is stirred by the re-aspirating and re-discharging operations of the dispensing probe 203. This series of operations is called a dispensing and stirring operation, and the discharged liquid a and liquid b are not limited to reagents and may be specimens or water.

[0025] The dispensing and mixing operation will be described below. In this example, it is assumed that a single dispensing probe with a tip attached to its tip is a multi-shot that dispenses multiple types of liquid simultaneously, and that the same tip is used to perform dispensing and mixing.

[0026] Discharging liquid into the reaction vessel 103 is called discharging. After simultaneously discharging liquid a and liquid b into the reaction vessel 103, the tip is used to simultaneously aspirate liquid a and liquid b from the reaction vessel 103 in order to mix the discharged liquid a and liquid b. This is called re-aspiration. Next, the re-aspirated liquid a and liquid b are discharged again into the reaction vessel 103. This operation is called re-discharge. As a result, liquid a and liquid b mix together to form mixed liquid c. The series of operations that mix liquid a and liquid b to form mixed liquid c is called discharge mixing.

[0027] Furthermore, to prevent the solutions a and b from mixing in the tip during aspiration, an air layer called segmented air is sucked in to create an air layer, and the segmented air is also expelled along with liquid a and liquid b during ejection. As a result, the ejected mixed liquid c contains air bubbles. These air bubbles are sucked back into the tip when aspiration is resumed, and are expelled simultaneously with mixed liquid c when ejection is resumed. The air bubbles in mixed liquid c form an air-liquid mixed state, enhancing the stirring effect.

[0028] The flow of selecting an operation in this embodiment will be described with reference to Fig. 3. In the discharge stirring operation, the stirring operation is automatically selected according to the total amount of liquid a and liquid b stored in the storage unit 108.

[0029] The amounts of liquid a and liquid b are uniquely determined for each measurement item. The re-aspiration and re-discharge amounts during dispensing and stirring are defined by the following formula (S302): Re-aspiration amount = amount of liquid a + amount of liquid b - 16 μL Re-discharge amount = amount of liquid a + amount of liquid b - 8 μL When re-aspiration is performed, an amount 16 μL less than the sum of the amounts of liquid a and liquid b is aspirated. This is to ensure that at least 16 μL of liquid ultimately remains in the reaction solution. 16 μL is the amount that results in a liquid level height of approximately 1.5 mm from the bottom of the reaction vessel used in this example. If a clearance of 1.5 mm is not maintained between the tip end and the bottom of the vessel at the end of re-aspiration, the tip end may become clogged, resulting in insufficient re-aspiration. Therefore, this is defined as the amount of liquid a + amount of liquid b - 16 μL. When re-dispensing, an amount 8 μL less than the sum of the amounts of liquid a and liquid b is dispensed. In other words, an amount 8 μL more than the amount of re-aspiration is dispensed. 8 μL is the surplus volume required to re-eject the entire re-aspirated liquid without leaving any liquid remaining in the tip, thereby allowing the series of re-aspirated and re-ejected dispensing and stirring steps to be completed without any loss of reaction liquid.

[0030] It is desirable to select appropriate values ​​for the above 16 μL and 8 μL values ​​depending on the shape of the reaction vessel being used. In this example, the clearance between the tip end and the bottom of the vessel at the end of re-aspiration was set to 1.5 mm, but depending on the shape of the tip end and the bottom of the vessel being used, a value greater than or less than 1.5 mm may be better. If the appropriate value for the clearance between the tip end and the bottom of the vessel at the end of re-aspiration changes, the value of 16 μL will also change. The 8 μL surplus volume required to re-eject the entire amount of re-aspirated liquid without any residual liquid in the tip can also be changed as appropriate within the range that allows the entire amount of re-aspirated liquid to be re-ejected without any residual liquid in the tip.

[0031] Next, the liquid is assigned to either operation A or operation B depending on whether the re-discharge volume is equal to or greater than a predetermined value (predetermined value) or less (S303). In this embodiment, when the re-discharge volume is 42 μL or greater, operation A is selected as the stirring operation (S304), and when the re-discharge volume is less than 42 μL, operation B is selected as the stirring operation (S307). If the conditions for operation B are met, it is determined whether the liquid properties of mixed liquid c are special (S308). If they are special, operation C is selected (S311). Criteria for determining whether a liquid is special are registered in advance. For example, "high viscosity" or "strong surface tension" are typical examples. The determination may be made based on the liquid properties of liquids a and b registered in advance, or the user may select each time.

[0032] The re-ejection speeds in each of operation A, operation B, and operation C are A>B≧C, and the nozzle lift speed during re-ejection is A>B>C (see S314). The reason for this will be described later.

[0033] In this example, the predetermined volume is set to 42 μL. The main reason for this is that, because the reaction vessel is a combination of a portion of a sphere and a cylinder, if the liquid volume is less than the predetermined volume, the liquid flow is highly random within the hemisphere, resulting in high stirring efficiency, while if the liquid volume is greater than the predetermined volume, the liquid flow is less random near the cylindrical shape of the reaction vessel, resulting in low stirring efficiency. If the discharge volume is greater than the predetermined volume, the decrease in stirring efficiency can be suppressed by increasing the discharge speed.

[0034] As a secondary effect, by increasing the re-ejection speed when the ejection amount is large, it is possible to suppress a decrease in the throughput of the entire apparatus.

[0035] Operation A will be described in detail with reference to Figure 4. After liquids a and b are aspirated into the dispensing tip 209, the dispensing probe 203 and the dispensing tip 209 at the tip of the probe are moved to the top of the reaction vessel 103 by the rotation of the shaft 201.

[0036] In S401, the dispensing probe 203 descends, and after dispensing is complete, the tip of the dispensing tip 209 stops at a position where it is immersed 3 mm into the mixed liquid c. In S402, the syringe 207 starts operating, and the mixed liquid c in the dispensing tip 209 is dispensed into the reaction vessel 103. During this time, the dispensing probe 203 continues to stop at the dispensing start position.

[0037] The dispensing probe 203 does not move up and down between the end of dispensing and the start of re-aspiration. When the syringe 207 starts to drive and re-aspiration begins in S403, the solution begins to be drawn into the dispensing tip 209, and at the same time, the dispensing probe 203 begins to descend. The immersion amount is gradually reduced from 3 mm, and mixed liquid c is aspirated into the tip. As described above, the amount of mixed liquid c aspirated into the tip is defined as liquid a + liquid b - 16 μL.

[0038] In S404, the operation of the syringe 207 stops when only 16 μL of liquid a + liquid b has been aspirated into the tip. When the re-aspirating is complete, the tip of the dispensing tip 209 is controlled to be immersed approximately 1 mm into the mixed liquid c. By minimizing the immersion area, the contamination area is reduced, and the risk of liquid being carried away is also reduced.

[0039] Before the pulsation of the liquid in the dispensing tip 209 caused by inertia settles, the syringe 207 is driven in the reverse direction to start re-dispensing. As described above, the re-dispensing amount is defined as liquid a + liquid b - 8 μL. By discharging 8 μL more than the re-suction amount, it is possible to discharge all of the liquid in the dispensing tip 209.

[0040] At the same time as re-dispensing begins, the dispensing probe 203 begins to rise. The re-dispensing speed at this time is set to 198 μL / s, and the rising speed of the dispensing probe 203 and dispensing tip 209 is set to 22.5 mm / s. Initially, re-dispensing begins with the dispensing tip 209 immersed in the liquid, and then, as shown in S405, the tip tip is controlled to be positioned above the liquid surface. By dispensing the solution from above the liquid surface, air bubbles can be entrained in the mixed liquid, and a strong stirring effect due to gas-liquid mixing can be expected even when the amount of mixed liquid is large.

[0041] In this embodiment, the re-discharge speed and rising speed during re-discharge are controlled to achieve the above-mentioned effect, and the distance between the liquid surface and the tip is controlled to a maximum of 3 mm to prevent contamination of the inner wall of the reaction vessel and the tip due to liquid splashing. Since contamination reduces the amount of solution ultimately used for analysis and leads to uneven stirring, it is necessary to reduce liquid splashing as much as possible.

[0042] In S406, the rising of the probe is stopped, and then the operation of the syringe 207 is stopped, thereby stopping the rise of the liquid level. Regardless of the amounts of liquid a and liquid b, the tip of the dispensing tip 209 is positioned slightly higher than the liquid level.

[0043] Finally, the dispensing tip 209 rises further and reaches the upper limit, after which the arm is rotated by the shaft, and dispensing and mixing is completed.

[0044] The relationship between the liquid level and tip height during re-dispensing in operation A will be explained using C601 in Figure 6. Immediately after re-dispensing begins, the dispensing tip 209 is immersed 1.3 mm below the liquid level (distance between 601 and 602). The dispensing tip 209 then rises while decreasing its distance from the liquid level, reaching the same height at 110 milliseconds (603). After 110 milliseconds, the dispensing tip 209 continues re-dispensing from a position higher than the liquid level, enabling effective gas-liquid mixing even with a large amount of liquid. The rise during re-dispensing ends at 240 milliseconds, and the dispensing tip 209 waits at a position approximately 1.5 mm above the liquid level (604). Re-dispensing ends at 360 milliseconds, and the rise of the liquid level stops at a position 0.2 mm below the tip of the dispensing tip 209 (605). The liquid level height in C601 is expressed by taking into account the theoretical value determined from the shape of the container and the height of bubbles generated by re-dispensing, as determined by observation.

[0045] In Figure 6, the solution is dripped at a constant rate, but the time change in the liquid level is nonlinear between sections 601 and 603. This is because the bottom of the reaction vessel is hemispherical, as mentioned above. While liquid is being dispensed into a hemispherical reaction vessel, the liquid flow is highly random within the hemisphere, resulting in high mixing efficiency. On the other hand, the time change in the liquid level is linear between sections 603 and 605. This is because droplets are being dispensed into the cylindrical reaction vessel. Within the cylinder, the liquid flow is less random, resulting in low mixing efficiency. It is preferable to increase the dispensing speed above the liquid volume that results in the liquid level reaching 603 to improve mixing efficiency. In the reaction vessel used in this example, the liquid volume that results in the liquid level reaching 603 was 42 μL. The liquid volume at which the dispensing speed is switched depends on the shape of the reaction vessel.

[0046] Operation B will be described in detail using Figure 5. After liquids a and b are aspirated into the tip, the dispensing probe 203 and the dispensing tip 209 at the tip of the probe are moved to the top of the reaction vessel. The dispensing probe 203 descends, and after dispensing is complete, it stops at a position where the tip is immersed 3 mm into the mixed liquid. In S501, the syringe 207 begins to operate, and the mixed liquid in the dispensing tip 209 is dispensed into the reaction vessel. During this time, the dispensing probe 203 remains stopped at the dispensing start position.

[0047] The dispensing probe 203 does not move up and down between the end of dispensing and the start of re-aspiration. After the end of dispensing in S502, the syringe 207 begins to operate, and re-aspiration begins. At the same time that the solution begins to be drawn into the dispensing tip 209, the dispensing tip 209 begins to descend. In S503, the immersion amount is gradually reduced from 3 mm, and the mixed liquid is aspirated into the dispensing tip 209. The amount of mixed liquid c aspirated into the dispensing tip 209 is defined as liquid a + liquid b - 16 μL, as described above.

[0048] In S504, the operation of the syringe 207 stops when only liquid a + liquid b - 16 μL has been aspirated into the dispensing tip 209. At the end of this re-suction, the tip of the dispensing tip 209 is immersed approximately 1 mm into the mixed liquid c. Before the pulsation of the liquid in the dispensing tip 209 caused by inertia settles, the syringe 207 is driven in the reverse direction and begins re-discharge. As described above, the re-discharge volume is defined as liquid a + liquid b - 8 μL. By discharging 8 μL more than the re-suction volume, all of the liquid in the dispensing tip 209 can be expelled.

[0049] In S505, the dispensing probe 203 begins to rise simultaneously with the start of re-dispensing. The re-dispensing speed at this time is set to 139 μL / s, and the rising speed of the dispensing probe 203 is set to 15 mm / s. The re-dispensing speed and the rising speed are controlled so that operation A is always greater than operation B. The reasons why both speeds are controlled to be slower than operation A are (1) to improve the mixing effect, and (2) to suppress carry-out of the mixed liquid. These details will be described later using Figures 7 and 8. For the above reasons, operation B is controlled so that the tip of the dispensing tip 209 is always immersed in the mixed liquid, even while reducing the distance between the liquid surface and the tip of the dispensing tip 209 during re-dispensing.

[0050] In this example, the discharge speed and rising speed are controlled to achieve the above-mentioned effects and to prevent the spread of tip contamination due to liquid wetting, so that the immersion distance between the liquid surface and the tip is at most 2 mm. Contamination must be minimized as much as possible because it randomly reduces the amount of solution ultimately used in analysis and poses the risk of uneven mixing.

[0051] After the syringe operation is completed in S506, the re-discharge upward movement continues for a while. After the tip of the dispensing tip 209 separates from the stationary liquid surface, the dispensing probe 203 rises so that the tip of the dispensing tip 209 is slightly above the liquid surface. As the tip of the dispensing tip 209 separates from the liquid surface, the liquid adhering to the tip surface is pulled toward the liquid surface, minimizing the amount of remaining liquid.

[0052] In S507, the dispensing probe 203 and the dispensing tip 209 further rise to reach the upper limit point. After that, the arm 202 is rotated by the shaft 201, and the discharge stirring is completed.

[0053] The relationship between the liquid level and tip height during re-dispensing in operation B will be explained using 602 in Figure 6C. Immediately after re-dispensing begins, the dispensing tip 209 is immersed 1.3 mm below the liquid surface (distance between 606 and 607). Thereafter, the dispensing tip 209 rises while gradually decreasing its distance from the liquid surface. However, unlike operation A, it is controlled to remain submerged at all times. Re-dispensing ends at 100 milliseconds, causing the liquid level to stop rising (608). The tip then separates from the liquid surface over approximately 30 milliseconds (609). The dispensing tip 209 separates after the liquid surface, allowing the liquid adhering to the tip surface to be removed by the liquid surface, thereby reducing the final amount of liquid carried away. Because the tension of the liquid on the dispensing tip 209 is compared with the gravity acting on the amount of solution dispensed per unit time, this comparison is independent of the shape or material of the container bottom. After the dispensing tip 209 separates from the liquid surface, the dispensing tip 209 stops at a position 0.2 mm below the liquid surface (610). The liquid level in C602 is expressed taking into consideration the theoretical value determined from the shape of the container and the height of bubbles generated by re-discharge, which is obtained by observation.

[0054] The reason why the discharge speed and rising speed of operation B are controlled to be slower than those of operation A is "(1) improvement in stirring effect," which will be described with reference to FIG.

[0055] In S701, the tip holds the solution inside. In S702, the solution inside the tip is discharged into the reaction vessel. Since operation B uses a smaller amount of liquid than operation A, if the discharge speed is too fast, discharge ends in a state (701) where the mixed liquid rises due to contact with the bottom of the reaction vessel. 702 shows the solution that has not risen, and inside 702, the solution is mixed as shown in 703. After discharge is complete, the liquid level settles, but some of the risen solution (704) remains on the inner wall of the vessel and is not involved in forming turbulence during discharge, resulting in insufficient mixing. Ultimately, the reaction proceeds while an insufficiently stirred solution is retained, resulting in a deterioration in analytical performance.

[0056] By slowing down the discharge speed, rising 701 can be prevented, turbulence can be formed throughout the mixed liquid, and effective mixing can be achieved. However, the discharge speed must be set to a necessary and sufficient speed to achieve both the stirring effect and the prevention of rising, taking into consideration the inner diameter of the reaction vessel, the discharge amount, and the typical properties of the liquid to be discharged.

[0057] The reason why the discharge speed and rising speed of operation B are controlled to be slower than those of operation A, "(2) Suppression of carry-out of mixed liquid", will be described with reference to FIG.

[0058] When discharging liquid from a tip, it is necessary to consider the risk that droplets of liquid will form at the tip end when discharging is complete, and the discharged liquid will adhere to the tip due to surface tension.

[0059] C801 shows an example of operation A. In operation A, the re-ejection speed is fast, so a large liquid droplet 801 forms at the tip end when ejection is complete. Since the gravity acting on the large liquid droplet is greater than the surface tension of the tip, the liquid droplet falls.

[0060] C802 shows an example where the tip end is above the liquid surface at the re-discharge speed of operation B. Because operation B has a slower re-discharge speed than operation A, the amount of liquid at the tip end is small, and a small liquid droplet 802 is formed. The surface tension acting upward on the tip is stronger than the resultant force of gravity and inertia acting downward on the small liquid droplet 802, so the liquid droplet remains attached to the tip.

[0061] C803 shows an example of operation B. When re-dispensing is complete, the tip of the tip is immersed in the liquid, so no liquid droplets are formed. Therefore, when the syringe stops driving and the tip rises, the liquid adhering to the tip surface is pulled by the downward surface tension on the liquid surface and the upward surface tension on the tip. The strength of the downward tension is correlated with the surface area of ​​the reaction vessel with which the mixed liquid is in contact. Because the area of ​​the liquid in contact with the reaction vessel is larger than the surface area of ​​the liquid in contact with the tip, the downward surface tension overcomes the upward surface tension, and as the tip rises, all of the liquid is pulled to the liquid surface. As a result, all of the mixed liquid is dispensed into the reaction vessel, and analytical performance does not deteriorate.

[0062] Operation C, like operation B, is controlled so that the tip end is immersed in the liquid surface at the end of re-dispensing. Operation C is intended for liquids with high viscosity or strong surface tension, so there is a high risk of liquid adhesion to the tip end. For this reason, re-dispensing speed C is set to be equal to or lower than re-dispensing speed B, and rising speed during re-dispensing C is set to be lower than rising speed during re-dispensing speed B. Although the slower the re-dispensing speed and rising speed during re-dispensing are, the more improved the dispensing accuracy, there are cases where the re-dispensing speed cannot be set to be lower than re-dispensing speed B from the perspective of stirring effect.

[0063] In this embodiment, the liquid level height is calculated from the liquid level calculation formula h(V) stored in the memory unit 108. The liquid level height h(V) is expressed as h(V) = f(V) + g(V) using the liquid level formula (f(V)) simulated from the CAD data of the reaction vessel and the estimated thickness of the bubble layer (g(V)). V is the reaction liquid volume. By designing the re-discharge speed and the rising speed during re-discharge based on h(V), precise height control is possible.

[0064] 100: Sample container, 101: Reagent bottle, 102: Mounting section, 103: Reaction vessel, 104: Cell disk, 105: Dispensing section, 106: Control section, 107: Input / output section, 108: Memory section 201: Shaft, 202: Arm, 203: Dispensing probe, 204: Syringe pump, 205: Tube, 206: Solenoid valve, 207: Syringe, 208: System water container, 209: Chip.

Claims

1. An automatic analyzer comprising: a probe for sucking and discharging a liquid; a placement unit for placing a container for storing the liquid; a syringe for feeding the liquid to the probe via a flow path; and a control unit for controlling operations of the probe and the syringe, wherein when the amount of the liquid discharged from the tip of the probe into the container is equal to or more than a predetermined amount, the control unit controls such that the tip is separated from the liquid surface of the container at the end of the operation of the syringe, and when the amount of the liquid discharged from the probe into the container is less than the predetermined amount, the control unit controls such that the tip is immersed in the liquid in the container at the end of the operation of the syringe.

2. The automatic analyzer according to claim 1, wherein the predetermined amount is determined based on an amount of liquid at which the liquid level rise rate in the container can be linearly approximated.

3. The automatic analyzer according to claim 1, wherein the predetermined amount is determined based on an amount of liquid that fills a height at which the inner diameter of the container is constant at that height or more.

4. The automatic analyzer according to claim 1, wherein the control unit controls such that the discharge rate when the amount of the liquid discharged from the tip of the probe into the container is equal to or more than the predetermined amount is higher than the discharge rate when the amount of the liquid discharged from the probe into the container is less than the predetermined amount.

5. The automatic analyzer according to claim 1, wherein the control unit controls such that the rising rate during discharge of the probe when the amount of the liquid discharged from the tip of the probe into the container is equal to or more than the predetermined amount is higher than the rising rate during discharge of the probe when the amount of the liquid discharged from the probe into the container is less than the predetermined amount.

6. The automatic analyzer according to claim 1, wherein a chip is attached to the tip of the probe.

7. The automatic analyzer according to claim 1, wherein the control unit controls such that the probe sequentially sucks a first liquid from a first container, sucks air, and then sucks a second liquid from a second container, and then discharges a mixed liquid of the first liquid and the second liquid into a third container.

8. In the automatic analyzer according to claim 7, after the control unit discharges the air into the third container together with the mixed solution, the control unit re-sucks the mixed solution and the air from the third container, and controls to re-discharge the mixed solution and the air into the third container. An automatic analyzer characterized by this.

9. In the automatic analyzer according to claim 8, when the viscosity of the mixed solution at the time of re-discharge is equal to or greater than the predetermined amount, the control unit controls so that the tip of the probe is immersed in the liquid in the third container at the end of the operation of the syringe. An automatic analyzer characterized by this.

10. In the automatic analyzer according to claim 9, the control unit controls so that the tip of the probe is immersed in the liquid in the third container from the start of re-discharge to the end of the operation of the syringe. An automatic analyzer characterized by this.

11. A method for stirring a liquid in an automatic analyzer, comprising a probe for sucking and discharging a liquid, a placement unit for placing a container for storing the liquid, and a syringe for feeding the liquid to the probe through a flow path. When the amount of liquid discharged from the tip of the probe into the container is equal to or greater than a predetermined amount, the tip is separated from the liquid surface of the container at the end of the operation of the syringe. When the amount of liquid discharged from the probe into the container is less than the predetermined amount, the tip is immersed in the liquid in the container at the end of the operation of the syringe. A method for stirring a liquid in an automatic analyzer.

12. In the method for stirring a liquid in an automatic analyzer according to claim 11, the predetermined amount is determined based on the amount of liquid at which the rising speed of the liquid surface in the container can be linearly approximated. A method for stirring a liquid in an automatic analyzer characterized by this.

13. In the method for stirring a liquid in an automatic analyzer according to claim 11, the discharge speed when the amount of liquid discharged from the tip of the probe into the container is equal to or greater than the predetermined amount is made faster than the discharge speed when the amount of liquid discharged from the probe into the container is less than the predetermined amount. A method for stirring a liquid in an automatic analyzer characterized by this.

14. In the method for stirring a liquid in an automatic analyzer according to claim 11, the rising speed during discharge of the probe when the amount of liquid discharged from the tip of the probe into the container is equal to or greater than the predetermined amount is made faster than the rising speed during discharge of the probe when the amount of liquid discharged from the probe into the container is less than the predetermined amount. A method for stirring a liquid in an automatic analyzer characterized by this.

15. In the liquid stirring method of the automatic analyzer according to claim 11, after the probe sequentially sucks the first liquid from the first container, sucks air, and sucks the second liquid from the second container, the probe discharges the mixed liquid in which the first liquid and the second liquid are mixed into the third container. A liquid stirring method for an automatic analyzer, characterized in that.

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