Liquid stirring method for automatic analysis device, and automatic analysis device capable of executing same
Patent Information
- Application Number
- JP2025529677
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Filing Date
- 2024-10-18
- Publication Date
- 2025-09-22
AI Technical Summary
Existing liquid stirring methods in automatic analyzers, such as discharge stirring, often fail to provide sufficient stirring force for reagents that tend to aggregate, leading to inadequate analysis results.
A modified discharge stirring method that involves aspirating and discharging liquids above the liquid level in the container, incorporating air suction during the second suction step, and optimizing re-discharge amount, speed, and gas-liquid mixing to enhance shear stress and homogenization, while minimizing air bubble inclusion.
This method achieves a sufficient stirring effect for reagents that aggregate, improving analysis accuracy by effectively breaking down aggregates and maintaining low air bubble interference, thus enhancing the homogenization and refinement of liquids.
Abstract
Description
Liquid stirring method for automatic analyzer and automatic analyzer capable of executing the same
[0001] The present invention relates to a liquid stirring method for an automatic analyzer and an automatic analyzer capable of carrying out the method.
[0002] In the medical field, automated analyzers are used to perform qualitative and quantitative analysis of any substance in a sample, such as blood, serum, or urine, by mixing it with a reagent containing an enzyme or antibody that reacts with a specific biological component or chemical substance contained in the sample.
[0003] In small automated analyzers, in order to avoid increasing the size, instead of installing a stirring mechanism using a dedicated stirring rod, a discharge stirring method is sometimes used, which uses a liquid dispensing mechanism to stir. This is a technique in which the liquid to be stirred is sequentially drawn into the dispensing mechanism and then simultaneously discharged. Because the stirring force is weaker than stirring using a stirring rod, various techniques have been proposed to improve the stirring force.
[0004] For example, Patent Document 1 discloses a technology in which, when aspirating a 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.
[0005] JP 2011-107089 A
[0006] However, depending on the analysis item, there may be cases where a stronger stirring capacity is required than in the method of Patent Document 1. For example, in analysis items using reagents that tend to aggregate, there is a concern that accurate analysis results may not be obtained unless the aggregates can be sufficiently broken down by stirring.
[0007] The technology disclosed in Patent Document 1 is expected to provide a higher mixing effect than conventional dispensing and mixing by incorporating air bubbles into the liquid and vibrating the air bubbles in the liquid, but the mixing effect may be insufficient for the analysis items mentioned above.
[0008] An object of the present invention is to provide a dispensing and stirring method that can achieve a sufficient stirring effect even for analysis items that use reagents that are prone to aggregation, and an automatic analyzer that can perform this method.
[0009] The present invention to achieve the above object is as follows.
[0010] A liquid stirring method for an automatic analyzer equipped with a dispensing probe that aspirates and / or discharges liquid, comprising: a first suction step of aspirating a first stirred liquid using the dispensing probe; a second suction step of aspirating a second stirred liquid while the first stirred liquid is contained in the dispensing probe; and a first stirring step of discharging the first stirred liquid and the second stirred liquid into a container, wherein in the second suction step, air is also aspirated when aspirating the second stirred liquid, and in the first stirring step, the first stirred liquid and the second stirred liquid are discharged into the container above the liquid level of the liquid contained in the container. A liquid stirring method for an automatic analyzer, and an automatic analyzer capable of performing the same.
[0011] According to the present invention, it is possible to provide a dispensing and mixing method that can achieve a sufficient mixing effect even for analysis items that use reagents that are prone to aggregation, and an automatic analyzer that can execute the method.
[0012] 1 is a schematic diagram showing an example of the overall configuration of an automatic analyzer; FIG. 2 is a schematic diagram showing an example of the configuration of a dispensing unit; FIG. 3 is a schematic diagram showing a flow for a user to select a stirring mode; FIG. 4 is a diagram explaining the effects and correlation between a first mode and a second mode; FIG. 5 is a schematic diagram of a two-time stirring operation in a first mode; and FIG. 6 is a schematic diagram of a one-time stirring operation in a second mode.
[0013] A preferred embodiment of the automatic analyzer according to the present invention will now be described with reference to the accompanying drawings.
[0014] 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.
[0015] 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 sample / reagent disk (hereinafter simply referred to as disk) 102, a dispensing unit 105, an incubator (reaction disk) 104, a control unit 106, an input / output unit 107, and a memory unit 108. Each unit will be described below.
[0016] The disk 102 stores the specimen container 100 containing the specimen and the reagent bottle 101 containing the reagent, and also transports the specimen container 100 and the reagent bottle 101 to a position accessible to the dispensing unit 105 .
[0017] The dispensing unit 105 dispenses and agitates specimens and reagents from specimen containers 100 or reagent bottles 101 into reaction containers 103 stored in an incubator 104. Detailed parameters for dispensing and agitation are controlled by the control unit 106. The specimens and reagents may be dispensed by a single dispensing unit 105, or two dispensing units, one for specimen and one for reagent, may be provided and each may dispense separately. A more detailed configuration of the dispensing unit 105 will be described later using FIG. 2.
[0018] The incubator 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 by the dispensing unit 105. The mixture in the reaction vessel 103 becomes a reaction liquid to be used in the measurement by storing the reaction vessel 103 within a predetermined temperature range.
[0019] The control unit 106 is a computer that controls the operation of each unit.
[0020] 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.
[0021] 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).
[0022] 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.
[0023] 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.
[0024] 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 attached to its tip.
[0025] Syringe pump 204 draws in and pushes out system water in dispensing probe 203 by driving plunger 207 to draw in and eject specimens, reagents, and air from the lower end of 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.
[0026] 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.
[0027] As an example of the operation of the dispensing unit 105 controlled by the control unit 106, we will explain the case where a reagent is discharged into a reaction vessel 103 into which a reaction liquid has already been discharged, the liquid in the reaction vessel 103 is made into a mixed liquid, and this mixed liquid is stirred by the suction and discharge operations of the probe 203.
[0028] This series of operations is called a dispensing and stirring operation, and the liquid to be dispensed is not limited to a reagent, but may be a specimen or water.
[0029] The discharging and stirring method will be described below.
[0030] Assume that there is liquid A in the reaction vessel 103 beforehand. Discharging a liquid into the reaction vessel 103 is called discharging. After discharging liquid B into the reaction vessel 103, liquid A and liquid B are simultaneously aspirated using the dispensing probe 203 in order to mix the discharged liquid B with liquid A. Next, the aspirated liquid A and liquid B are discharged again into the reaction vessel. This operation is called re-discharging. 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 discharging and mixing.
[0031] The advantage of discharge mixing is that it does not require a dedicated mixing unit to be incorporated into the equipment, thereby saving space and reducing costs. However, compared to general mixing methods using a stirring rod, discharge mixing can have lower mixing efficiency depending on the substance being mixed. In other words, although discharge mixing has sufficient homogenizing ability to mix liquid A and liquid B, if liquid A and liquid B contain bonds of fine molecules (aggregates, etc.), its ability to break down those bonds into fine particles can be inferior to other mixing methods.
[0032] One of the reasons for this difference in mixing ability is the difference in shear force during mixing. In spatula mixing, the spatula rotates in the liquid to be mixed, exerting a shearing force on the aggregates. In contrast, in discharge mixing, the shearing force on the aggregates may be insufficient.
[0033] This embodiment is characterized in that when the mixed liquid C sucked into the dispensing probe is dispensed into a container, it is dispensed from above the liquid surface in the container. When the mixed liquid C collides with the liquid surface, a force that shears the aggregates is applied. When dispensing liquid from a dispensing probe, the liquid is generally dispensed with the tip of the dispensing probe below the liquid surface to prevent the dispensed liquid from splashing onto the inner wall of the container or entraining air bubbles. In the present invention, the liquid is intentionally dispensed from above the liquid surface to apply a shear force to the liquid being stirred.
[0034] In other words, the method includes a first suction step in which the first stirred liquid (Liquid A) is sucked in by the dispensing probe, a second suction step in which the second stirred liquid is sucked in while the first stirred liquid is contained in the dispensing probe, and a first stirring step in which the first stirred liquid and the second stirred liquid are discharged into a container, wherein in the second suction step, air is also sucked in when the second stirred liquid is sucked in, and in the first stirring step, the first stirred liquid and the second stirred liquid are discharged into the container above the liquid level of the liquid contained in the container.
[0035] However, depending on the analysis item, the presence of bubbles in the mixed solution (reaction solution) may cause problems in the analysis. Therefore, a second feature of this embodiment is that, for analysis items in which aggregates are present in the mixed solution and need to be broken down into smaller particles, the above-mentioned discharge and stirring method is performed, and for analysis items in which aggregates are not present and it is not necessary to apply shear force to the mixed solution, the liquid is discharged with the tip of the dispensing probe below the liquid surface as in the conventional method, thereby avoiding the entrainment of bubbles and also avoiding adverse effects such as splashing of the liquid.
[0036] Furthermore, a third feature of this embodiment is that in order to improve the mixing efficiency during discharge and mixing, the following methods can be selected appropriately depending on the analysis item: 1. Increasing the re-discharge amount, 2. Accelerating the re-discharge speed, and 3. Gas-liquid mixing. 1. The movement of the liquid becomes more dynamic, promoting homogenization of the liquids. 2. The Reynolds number of the liquid increases, forming turbulence, improving not only the homogenization of the liquids but also the ability to atomize. 3. By mixing minute gas particles into the liquid to create a gas-liquid mixture, the shear stress of the turbulence increases compared to when there is only liquid, improving the atomization force on the molecules in the liquid. It is preferable to store in advance which of these methods to implement for each analysis item.
[0037] In other words, the parameters of re-discharge volume, re-discharge speed, and number of gas-liquid mixings (number of times of dispensing and stirring) can be expected to have the following effects: Increasing re-discharge volume: Promotes homogenization of the liquids Increasing re-discharge speed: Promotes homogenization and increases shear stress Increasing number of gas-liquid mixings: Increases shear stress on the aggregates There is a trade-off between shear stress and air bubble incorporation. In other words, if you want to increase shear stress, air bubbles will be incorpo- rated. If you want to suppress air bubble incorporation, the shear transverse stress will decrease. If you only have two choices, whether to entrain air bubbles or not, there is a possibility that the necessary shear stress and air bubble incorporation will not be met when measuring a given analysis item. For this reason, it is preferable to determine the optimal combination of the above parameters for each analysis item based on the properties of the reagent, etc., and set them in advance for each analysis item.
[0038] The user can select any stirring method depending on the type of analysis item. The flow for selecting a discharge stirring method depending on the characteristics of the target item and the expected analytical accuracy will be described using Figure 3.
[0039] In flow 302, if the user determines that the efficiency of stirring the reaction liquid needs to be prioritized over suppressing the impact of air bubbles entering the reaction liquid on the analysis results, the user can select the first stirring mode. In flow 303, the first mode is a two-stage stirring operation in which liquid is discharged into a reaction vessel, the liquid in the reaction vessel is aspirated, the liquid is re-discharged, the liquid is again aspirated, and the liquid is again discharged. Details of the operation of the first mode will be described later using Figure 5.
[0040] On the other hand, if the user determines in flow 302 that the inclusion of bubbles in the reaction liquid has a significant impact on the analysis results and prioritizes bubble suppression over stirring efficiency, the user can select the second stirring mode. In flow 304, the second mode is a one-time stirring operation in which liquid is discharged into a reaction vessel, the liquid in the reaction vessel is aspirated, the liquid is re-discharged, and then the liquid is not re-aspirated. Details of the operation of the second mode will be described later using Figure 6.
[0041] After prioritizing stirring efficiency by selecting the first mode, prevention of bubble generation and dilution is selected in flow 305. If bubble generation and dilution are not prevented and stirring efficiency is prioritized, the re-discharge amount, re-discharge speed, third-re-discharge amount, and third-re-discharge speed can be set arbitrarily in flows 306 to 309. This makes it possible to realize a stirring pattern according to the stirring difficulty of the analysis item. Note that increasing the re-discharge amount and third-re-discharge amount improves stirring efficiency, but conversely, increases the frequency of bubble generation. Increasing the re-discharge speed and third-re-discharge speed improves stirring efficiency, but conversely, increases the frequency of bubble generation.
[0042] On the other hand, if it is desired to suppress bubble generation while increasing the stirring efficiency, the third re-discharge amount in the first mode is set to 0 in flow 310. This selects an operation that does not involve re-suction or third re-discharge, even though it is the first mode. However, the first mode without third re-discharge is inferior in stirring efficiency compared to the first mode with third re-discharge, and is inferior in bubble suppression compared to the second mode.
[0043] In the second mode in flow 304, the re-discharge amount and re-discharge speed cannot be set arbitrarily, but are set automatically according to the total liquid volume. This makes it possible to realize a discharge and stirring operation specialized for bubble suppression. If it is desired to improve the stirring efficiency while enhancing bubble suppression in flow 311, the total liquid volume of the reaction liquid is increased in flow 312. Increasing the total liquid volume improves the stirring efficiency, and furthermore, because the bubble suppression operation is selected according to the total liquid volume, the bubble suppression effect is also maintained.
[0044] FIG. 4 shows an example of the relationship between the stirring efficiency and the bubble suppression effect in the first and second modes.
[0045] The first mode is shown in cases A to G. The advantage of the first mode is its high mixing efficiency. Two consecutive discharge and mixing operations generate gas-liquid mixing in the reaction liquid. Molecules that tend to aggregate in the liquid are effectively broken down into smaller particles by the flow where shear stress is increased by the gas-liquid mixing, and the effective concentration of molecules that are important in enzyme reactions and antigen-antibody reactions increases, promoting the reaction.
[0046] The shear stress of gas-liquid mixing tends to increase as the second discharge speed increases. However, the first mode has two weaknesses. One is that it inevitably introduces air bubbles into the liquid. Depending on the analysis item, air bubbles in the liquid can promote oxidation and inhibit the reaction. Furthermore, in analyses involving absorbance measurement, air bubbles can obstruct the light path, potentially preventing accurate absorbance measurements. The other weakness is that because the discharge and stirring operation is repeated twice, the amount of contact with the inner wall of the probe increases compared to when the discharge and stirring is performed only once, which can accelerate contamination of the reaction liquid.
[0047] For example, in the case of an automatic analyzer whose probe is filled with water, repeated dispensing and stirring operations increase the frequency with which the reaction solution becomes contaminated by water remaining on the inner wall of the probe, diluting the reaction solution. There is a trade-off between improving stirring efficiency and the two weaknesses. This relationship is shown in the graph in Figure 4.
[0048] Case A shows a case in which the total volume of the reaction liquid in the first mode is 100 μL, the re-ejection volume is 30 μL, the re-ejection speed is 100 μL / s, the third re-ejection volume is 30 μL, and the third re-ejection speed is 100 μL / s. Using this case as a reference point, other cases will be explained.
[0049] Case B shows the case in which the total volume of the reaction liquid in the first mode is 100 μL, the re-discharge volume is 80 μL, the re-discharge speed is 100 μL / s, the third re-discharge volume is 80 μL, and the third re-discharge speed is 100 μL / s. In case B, the re-discharge volume and third re-discharge volume are larger than in case A, so the stirring efficiency is higher and at the same time the frequency of bubble generation increases.
[0050] Case C shows the case in which the total volume of the reaction liquid in the first mode is 100 μL, the re-discharge volume is 80 μL, the re-discharge speed is 200 μL / s, the third re-discharge volume is 80 μL, and the third re-discharge speed is 200 μL / s. In case C, the re-discharge speed and the third re-discharge speed are faster than in case B, so the stirring efficiency is higher and at the same time the frequency of bubble generation increases.
[0051] Case D shows the case in which the total volume of the reaction liquid in the first mode is 100 μL, the re-discharge volume is 80 μL, the re-discharge speed is 300 μL / s, the third re-discharge volume is 80 μL, and the third re-discharge speed is 300 μL / s. In case D, the re-discharge speed and the third re-discharge speed are faster than in case C, so the stirring efficiency is higher and at the same time the frequency of bubble generation increases.
[0052] Case E shows the case in which the total volume of the reaction liquid in the first mode is 100 μL, the re-discharge volume is 80 μL, the re-discharge speed is 300 μL / s, the third re-discharge volume is 0 μL, and the third re-discharge speed is 0 μL / s. In case E, the second discharge and stirring operation is not performed, so the stirring efficiency is lower than in case D, but the generation of bubbles can be suppressed and contamination of the reaction liquid is reduced.
[0053] Case F shows the case in which the total volume of the reaction liquid in the first mode is 200 μL, the re-discharge volume is 160 μL, the re-discharge speed is 300 μL / s, the third re-discharge volume is 160 μL, and the third re-discharge speed is 300 μL / s. Because the total volume of the reaction liquid in Case F is greater than in Case D, the stirring efficiency is higher, and at the same time, the frequency of bubble generation increases. Because the re-discharge volume and the third re-discharge volume are also increased, the reaction liquid is more contaminated than in Case D.
[0054] Case G shows the case in which the total volume of the reaction liquid in the first mode is 200 μL, the re-discharge volume is 160 μL, the re-discharge speed is 300 μL / s, the third re-discharge volume is 0 μL, and the third re-discharge speed is 0 μL / s. In case E, the second discharge and stirring operation is not performed, so the stirring efficiency is lower than in case F, but the generation of bubbles can be suppressed and contamination of the reaction liquid is reduced. In addition, the total volume of the liquid is increased compared to case E, so the stirring efficiency is improved.
[0055] The second mode is shown in Case H and Case I. The advantage of the second mode is that it can suppress the generation of bubbles in the reaction liquid. By performing a predetermined dispensing and stirring operation once for the total liquid volume, it is possible to dispense and stir the reaction liquid without generating bubbles in the reaction liquid.
[0056] Due to the operational characteristics of the dispensing and stirring process, which involves aspirating and dispensing the reaction solution, bubbles are likely to be trapped in the reaction solution due to the liquid being drawn in or the air being expelled from the probe. However, as mentioned above, there is a risk that bubbles in the reaction solution may adversely affect the analysis results depending on the analysis item.
[0057] To solve this problem, this embodiment provides a second mode that prioritizes bubble suppression in addition to a first mode that prioritizes mixing efficiency. This allows for an appropriate dispensing and mixing operation to be performed for analysis items that require bubble suppression. However, since the second mode cannot be used to perform two mixing operations to improve mixing efficiency, the only way to improve mixing efficiency is to increase the total liquid volume. Since an increase in the total liquid volume leads to an increase in the amount of reagent used, this has the disadvantage of being poor cost-effective.
[0058] Case H shows the case in the second mode where the total volume of the reaction liquid is 100 μL, the re-discharge volume is 50 μL, and the re-discharge speed is 200 μL / s. In case H, although the stirring efficiency is low, the effect of suppressing air bubbles is high and contamination of the reaction liquid is also low.
[0059] Case I shows the case in which the total volume of the reaction liquid is 100 μL, the re-discharge volume is 50 μL, and the re-discharge speed is 200 μL / s in the second mode. Case I can improve the stirring efficiency compared to Case H while maintaining the bubble suppression effect of the second mode.
[0060] The detailed operation of the second stirring in the first mode will be described with reference to FIG.
[0061] 5A: A liquid 501 is previously placed in the reaction vessel 103. A reagent 502 held in the probe 203 is ejected into the reaction vessel 103. The force of the ejection causes the reagent 502 and the liquid 501 to partially mix.
[0062] FIG. 5(b): As the probe 203 is lowered, the partially mixed liquid 501 and reagent 502 are sucked into the probe.
[0063] 5(c): While the probe 203 is being raised, the mixed liquid 503 is re-discharged into the reaction vessel 103. At this time, the mixed liquid 503 rises along the inner wall of the reaction vessel 103 and then descends due to gravity, causing air to be entrained. As a result, multiple air bubbles 504 are generated in the mixed liquid 503.
[0064] 5(d): During the dispensing of the mixed liquid 503, the probe 203 rises while maintaining a constant distance from the liquid surface. The rising of the mixed liquid 503 along the inner wall of the reaction vessel 103 settles down over time. Meanwhile, the bubbles 504 generated in the liquid by the entrainment in FIG. 5(c) rise to the liquid surface.
[0065] 5( e ): After re-discharge, the bubbles 504 in the mixed liquid 503 rise vertically upward, forming a bubble layer on the liquid surface. After re-discharge, the tip of the probe 203 is immersed in the mixed liquid 503 .
[0066] Figure 5(f): The suction of the mixed liquid 503 begins. At this time, the probe 203 immersed in the mixed liquid 503 is controlled to descend while maintaining the length of the immersed tip. A flow generated by the re-suction causes part of the layer of bubbles 504 to be sucked into the probe. Finally, the mixed liquid 503 and bubbles 504 are randomly sucked into the probe 203.
[0067] 5(g): When the re-suction is completed, the probe tip is in the liquid. Some of the bubbles 504 are sucked into the probe, while the rest remain as a bubble layer on top of the liquid surface.
[0068] FIG. 5(h): The probe 203 starts to rise.
[0069] 5(i): The third ejection starts when the tip of the probe 203 reaches a predetermined height above the liquid surface. At this time, the air bubbles sucked into the probe 203 become microbubbles 505 of 1 mm or less due to the turbulence caused by the ejection flow inside the probe 203.
[0070] The microbubbles 505 are re-ejected into the reaction vessel together with the mixed liquid 503. At this time, the mixed liquid 503 is re-ejected from the middle or upper part of the bubble layer formed on the liquid surface of the mixed liquid 503, so that an agitated flow of the bubbles 504 and the microbubbles 505 mixed together is formed in the mixed liquid 503.
[0071] The probability of forming microbubbles 505 depends on the inner diameter and the second discharge speed of the probe 203. Since the inner diameter of the probe 203 is uniquely determined by the automatic analyzer, the user can control the generation of microbubbles 505 by selecting the second discharge speed within a predetermined range.
[0072] 5(j): The mixed liquid 503 that is ejected again contains microbubbles 505. Because the microbubbles move randomly within the reaction vessel, the mixed liquid 503 becomes a gas-liquid mixed state. This gas-liquid mixture increases the shear stress on the molecules in the liquid compared to when stirring only the liquid, and as a result, the ability to atomize the molecules during ejection and stirring is improved.
[0073] FIG. 5( k ): After the third ejection is completed, the flow of the mixed liquid 503 subsides, and the generated microbubbles begin to accumulate on the liquid surface.
[0074] The detailed operation of the first stirring in the second mode will be described with reference to FIG.
[0075] 6(a): A liquid 601 is placed in advance in the reaction vessel 103. A reagent 602 held in the probe 203 is ejected into the reaction vessel 103. The force of the ejection causes the reagent 602 and the liquid 601 to partially mix. In order to prevent air bubbles from being generated stochastically in the liquid at this time due to segmented air, the distance between the probe tip and the liquid surface is controlled so that the air bubbles ejected from the probe tip burst before penetrating the liquid.
[0076] Fig. 6(b): The probe 203 is lowered while the partially mixed liquid 601 and reagent 602 are sucked into the probe. Since no air bubbles are generated in Fig. 6(a), there is no risk of air bubbles being sucked into the probe.
[0077] Figure 6(c): The probe tip rises above the liquid surface. The distance between the remaining liquid in the reaction vessel and the probe tip is controlled to be greater than in the first mode. The ejected mixed liquid spreads downward in a fan shape, increasing the contact area between the ejected flow and the remaining liquid compared to the first mode. This makes it less likely that liquid will be entrained during re-ejection.
[0078] Figure 6(d): Re-ejection begins. The re-ejection speed is controlled to a flow rate that does not cause liquid entrainment, and the user cannot arbitrarily set the re-ejection amount and re-ejection speed. There are no air bubbles in the mixed liquid during re-ejection.
[0079] FIG. 6(e): After the re-discharge is completed, no air bubbles exist in the mixed liquid.
[0080] 100: specimen container, 101: reagent bottle, 102: disk, 103: reaction vessel, 104: incubator, 105: dispensing unit, 106: control unit, 107: input / output unit, 108: memory unit, 201: shaft, 202: arm, 203: dispensing probe, 204: syringe pump, 205: tube, 206: solenoid valve, 207: plunger, 208: system water container, 501: pre-discharged liquid, 502: reagent, 503: mixed liquid, 504: bubbles, 505: microbubbles, 601: pre-discharged liquid, 602: reagent, 603: mixed liquid
Claims
1. (delete)
2. (delete)
3. A liquid stirring method for an automatic analyzer equipped with a dispensing probe that aspirates and / or dispenses liquid, comprising: a first suction step of aspirating a first liquid to be stirred by the dispensing probe; a second suction step of aspirating a second liquid to be stirred while the first liquid to be stirred is contained in the dispensing probe; a first stirring step of discharging the first stirred liquid and the second stirred liquid into a container; In the second suction step, air is also sucked when the second liquid to be stirred is sucked, In the first stirring step, the first liquid to be stirred and the second liquid to be stirred are discharged into the container above the liquid level of the liquid contained in the container; a re-aspiration step in which the mixed liquid of the first liquid to be stirred and the second liquid to be stirred, which have been discharged into the container in the first agitation step, are aspirated again by the dispensing probe so as to include any air bubbles in the mixed liquid; a second stirring step of discharging a mixture of the first liquid to be stirred and the second liquid to be stirred contained in the dispensing probe into the container above the liquid level of the liquid contained in the container; A liquid stirring method for an automatic analyzer, comprising:
4. 4. The liquid stirring method for an automatic analyzer according to claim 3, A liquid agitation method for an automatic analyzer, characterized in that the second agitation step is not performed depending on the analysis items assigned to the mixed liquid.
5. 4. The liquid stirring method for an automatic analyzer according to claim 3, A liquid stirring method for an automatic analyzer, characterized in that, depending on the analysis item assigned to the mixed liquid, the amount of aspirated mixture of the first stirred liquid and the second stirred liquid in the re-aspiration step is set to zero.
6. 5. The liquid stirring method for an automatic analyzer according to claim 4, When the second stirring step is not performed, in the first stirring step, In the first suction step, when the second liquid to be stirred is aspirated, the dispensing probe is configured to aspirate the second liquid to be stirred below the liquid surface of the second liquid to be stirred; A liquid stirring method for an automatic analyzer, characterized in that in the first stirring step, the first stirred liquid and the second stirred liquid are ejected into the container below the liquid level of the liquid contained in the container.
7. 4. The liquid stirring method for an automatic analyzer according to claim 3, The total liquid volume of the first stirred liquid and the second stirred liquid, the discharge volume of the first stirred liquid and the second stirred liquid to be simultaneously discharged into the container in the first stirring step, and the discharge speed at that time, A plurality of patterns of the relationship between A liquid agitation method for an automatic analyzer, comprising selecting one of the stored patterns for agitation in accordance with an analysis item assigned to the first liquid to be agitated.
8. 8. The liquid stirring method for an automatic analyzer according to claim 7, Furthermore, a re-aspiration step of re-aspiration of the mixed liquid of the first liquid to be stirred and the second liquid to be stirred contained in the container by the dispensing probe; a second stirring step of discharging a mixture of the first liquid to be stirred and the second liquid to be stirred contained in the dispensing probe into the container; The amounts of the first and second agitated liquids to be simultaneously discharged into the container in the second agitation step, and the discharge speeds at that time; The relationship between the above and the pattern in the first stirring step is also stored, A liquid agitation method for an automatic analyzer, comprising selecting one of the stored patterns for agitation in accordance with an analysis item assigned to the first liquid to be agitated.
9. 9. The liquid stirring method for an automatic analyzer according to claim 7 or 8, Furthermore, In the step of discharging a mixed liquid of the first liquid to be stirred and the second liquid to be stirred contained in the dispensing probe into the container, A liquid stirring method for an automatic analyzer, characterized in that the height of the dispenser probe from the liquid surface of the accommodated mixed liquid when the mixed liquid is discharged into the container is also stored in the stored pattern.
10. (delete)
11. 4. The liquid stirring method for an automatic analyzer according to claim 3, A liquid stirring method for an automatic analyzer, characterized in that it includes a segmented air suction step between the first suction step and the second suction step, in which an air phase is suctioned to prevent the first stirred liquid and the second stirred liquid from mixing.
12. An automatic analyzer characterized by comprising a control device for controlling each mechanism including the dispensing probe so that the liquid stirring method for the automatic analyzer described in any one of claims 3 to 8 and 11 is performed.