Liquid stirring method for automatic analysis device and automatic analysis device capable of performing method

By adopting a liquid stirring method using a dispensing probe in an automated analyzer, spraying liquid from above the container's liquid surface and adjusting parameters, the problem of insufficient stirring of easily agglutinating reagents was resolved, achieving more accurate analysis results.

CN120660002APending Publication Date: 2025-09-16HITACHI HIGH TECH CORP
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Patent Information

Application Number
CN202480009912.7
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2023-06-30
Filing Date
2024-06-19
Publication Date
2025-09-16

AI Technical Summary

Technical Problem

When processing reagents that are prone to agglutination, existing automatic analysis devices have insufficient stirring effect, resulting in inaccurate analysis results.

Method used

A liquid stirring method using a dispensing probe includes a first suction step, a second suction step, and a first stirring step. By sucking and spraying the liquid from above the liquid surface in the container, shear force is increased to promote homogenization, and the re-dispensing amount, speed, and number of gas-liquid mixing times are adjusted according to the analysis items.

Benefits of technology

The stirring effect of the easily agglutinated reagent is improved, the accuracy and reliability of the analysis results are ensured, and the interference of bubbles on the analysis results is avoided.

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Abstract

In order to provide a discharge stirring method that achieves a sufficient stirring effect even with respect to an analysis item using a reagent that is likely to agglutinate, and an automatic analysis device using the method, the following configuration is adopted. A liquid stirring method of an automatic analysis device having a dispensing probe that sucks and / or discharges a liquid, and an automatic analysis device capable of performing the method, the liquid stirring method including: a first suction step of sucking a first stirred liquid through the dispensing probe; a second suction step of sucking a second stirred liquid in a state where the first stirred liquid is accommodated in the dispensing probe; and a first stirring step for discharging the first liquid to be stirred and the second liquid to be stirred into the container, a second suction step for sucking air while sucking the second liquid to be stirred, and a first stirring step for discharging the first liquid to be stirred and the second liquid to be stirred into the container above the liquid surface of the liquid contained in the container.
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Description

Technical Field

[0001] The present invention relates to a liquid stirring method for an automatic analyzing device and an automatic analyzing device capable of executing the method. Background Art

[0002] In the medical field, automated analyzers are used that perform qualitative and quantitative analysis of arbitrary substances in samples such as blood, serum, and urine by mixing reagents containing enzymes and antibodies that react with specific biological components and chemical substances contained in the samples.

[0003] To avoid large-scale development, small automated analyzers sometimes use ejection stirring, which utilizes a liquid dispensing mechanism, instead of a stirring mechanism using a dedicated stirring rod. This technique involves sequentially drawing the stirred liquid into the dispensing mechanism and then simultaneously ejecting it. The stirring force is smaller than that achieved with a stirring rod, and various techniques have been proposed to increase this force.

[0004] For example, Patent Document 1 discloses the following technology: when sucking the stirred liquid into a dispensing probe (pipette), not all of the liquid is sucked in. Instead, segmented air is introduced into the front end of the pipette head during suction, and then the stirred liquid is repeatedly sucked and ejected, thereby improving the stirring effect.

[0005] Prior art literature

[0006] Patent Literature

[0007] Patent Document 1: Japanese Patent Application Laid-Open No. 2011-107089 Summary of the Invention

[0008] Problems to be solved by the invention

[0009] However, some analysis items may require stronger stirring capabilities than the method of Patent Document 1. For example, in analysis items using reagents that easily aggregate, accurate analysis results may not be obtained unless the aggregates are sufficiently fined by stirring.

[0010] The technology disclosed in Patent Document 1 includes bubbles in the liquid and causes the bubbles in the liquid to oscillate, thereby expecting a higher stirring effect than conventional dispensing stirring. However, for the above-mentioned analysis items, the stirring effect may be insufficient.

[0011] An object of the present invention is to provide a jet stirring method capable of obtaining a sufficient stirring effect even for analysis items using a reagent that easily agglutinates, and an automatic analyzer capable of executing the method.

[0012] Means for solving problems

[0013] The present invention for achieving the above-mentioned object is as follows.

[0014] A liquid stirring method for an automatic analyzer and an automatic analyzer capable of executing the method, wherein the automatic analyzer has a dispensing probe for sucking and / or ejecting liquid, wherein the liquid stirring method includes: a first sucking step, sucking a first stirred liquid by the dispensing probe; a second sucking step, sucking a second stirred liquid while the first stirred liquid is contained in the dispensing probe; a first stirring step, ejecting the first stirred liquid and the second stirred liquid into a container, and in the second sucking step, sucking air while sucking the second stirred liquid, and in the first stirring step, ejecting the first stirred liquid and the second stirred liquid into the container above the liquid level of the liquid contained in the container.

[0015] Effects of the Invention

[0016] According to the present invention, a dispensing and stirring method capable of achieving a sufficient stirring effect even for analysis items using a reagent that easily agglutinates, and an automatic analyzer capable of executing the method can be provided. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a schematic diagram showing an example of the overall configuration of an automatic analyzer.

[0018] Figure 2 This is a schematic diagram of an example of the structure of a dispensing component.

[0019] Figure 3 This is a schematic diagram showing the flow of the user selecting the stirring mode.

[0020] Figure 4 This is a diagram explaining the effects and correlation between the first mode and the second mode.

[0021] Figure 5 This is a schematic diagram of two stirring operations in the first mode.

[0022] Figure 6 This is a schematic diagram of one stirring operation in the second mode. DETAILED DESCRIPTION

[0023] Hereinafter, preferred embodiments of the automatic analyzer of the present invention will be described with reference to the accompanying drawings.

[0024] In the following description and drawings, components having the same functional configuration are denoted by the same reference numerals, and redundant description is omitted.

[0025] Example

[0026] use Figure 1 An example of the overall structure of an automatic analyzer will be described. This device analyzes specific components contained in samples such as blood and urine provided by a patient. It includes a sample / reagent disk (hereinafter referred to as a disk) 102, a dispensing unit 105, an incubator (reaction disk) 104, a control unit 106, an input / output unit 107, and a storage unit 108. Each component is described below.

[0027] The tray 102 stores sample containers 100 containing samples and reagent bottles 101 containing reagents, and transports the sample containers 100 and reagent bottles 101 to positions accessible to the dispensing unit 105 .

[0028] The dispensing unit 105 dispenses the specimen and reagent from the specimen container 100 and the reagent bottle 101 to the reaction container 103 stored in the incubator 104 and stirs the mixture. The detailed parameters of the dispensing and stirring are controlled by the control unit 106. In addition, the specimen and reagent can be dispensed by a single dispensing unit 105, or two dispensing units, namely the specimen dispensing unit and the reagent dispensing unit, can be provided to dispense the specimen and reagent separately. Figure 2 This will be described later.

[0029] The incubator 104 stores a reaction vessel 103 containing a mixed solution of a specimen and a reagent within a temperature range that allows the mixed solution to react, and transports the reaction vessel 103 to a location accessible to the dispensing unit 105. By storing the reaction vessel 103 within a predetermined temperature range, the mixed solution in the reaction vessel 103 becomes a reaction solution for measurement.

[0030] The control unit 106 is a computer that controls the operation of each unit.

[0031] The input / output unit 107 is a device that accepts input of data required for analysis or displays analysis results, and is, for example, a keyboard, a mouse, a touch panel, a liquid crystal display, or the like.

[0032] The storage unit 108 is a device that stores data required for analysis and analysis results, and is, for example, a HDD (Hard Disk Drive) or an SSD (Solid State Drive).

[0033] use Figure 2 A configuration example of the dispensing unit 105 will be described. The dispensing unit 105 includes a shaft 201 , an arm 202 , a dispensing probe 203 , a syringe pump 204 , a tube 205 , and a solenoid valve 206 .

[0034] The shaft 201 is a hollow member extending vertically and moves up and down. The arm 202 is a hollow member extending horizontally. One end is connected to the upper end of the shaft 201, and the other end is attached to the dispensing probe 203, which rotates about the shaft 201. The rotation of the arm 202 moves the dispensing probe 203 to directly above the specimen container 100 and reagent bottle 101.

[0035] The dispensing probe 203 is a thin tube that is inserted into the specimen container 100 or reagent bottle 101 by the vertical movement of the shaft 201. The upper end is connected to the tube 205. The tube 205 passes through the arm 202 and the shaft 201, connecting the dispensing probe 203 and the syringe pump 204. The dispensing probe 203 can be a hollow metal tube or have a disposable dispensing tip at the front end.

[0036] The syringe pump 204 draws in and pushes out system water in the dispensing probe 203 by driving the plunger 207 to aspirate and eject specimens, reagents, and air from the lower end of the dispensing probe 203. The introduction of system water creates a negative pressure inside the dispensing probe for suction, while the pushing out of system water creates a positive pressure inside the dispensing probe for ejection, thereby dispensing liquids such as specimens and reagents.

[0037] The solenoid valve 206 is provided between the system water container 208 containing system water and the syringe pump 204 and is closed during specimen dispensing, etc. When dispensing is completed, the solenoid valve 206 opens, and the system water supplied from the system water container 208 cleans the inner wall of the dispensing probe 203, and the tube 205 is filled with system water. In other words, the tube 205 is filled with system water before dispensing.

[0038] As an example of the operation of the dispensing unit 105 controlled by the control unit 106 , the following case is described: a reagent is ejected into the reaction container 103 from which the reaction liquid has been ejected, and the liquid in the reaction container 103 is made into a mixed liquid, which is stirred by the suction / ejection operation of the probe 203 .

[0039] Note that this series of operations is referred to as a discharge and stirring operation, and the liquid discharged is not limited to a reagent, but may also be a specimen or water.

[0040] The spray stirring method will be described below.

[0041] Assume that liquid A is already in the reaction container 103. Discharging liquid into the reaction container 103 is called discharging. After discharging liquid B into the reaction container 103, liquid A and liquid B are simultaneously aspirated using the dispensing probe 203 to mix the discharged liquid B with liquid A.

[0042] Next, the sucked liquid A and liquid B are ejected again into the reaction container. This operation is called re-ejection.

[0043] Thus, the liquid A and the liquid B are mixed to form a mixed liquid C. The series of operations of mixing the liquid A and the liquid B to form the mixed liquid C is called ejection stirring.

[0044] The advantage of jet stirring is that it does not require a dedicated stirring unit to be assembled in the device, thus achieving space and cost savings. However, compared to conventional stirring methods using a stirring rod, jet stirring sometimes has lower stirring efficiency depending on the stirring object. Specifically, this is because, although jet stirring has sufficient homogenization ability to mix Liquid A and Liquid B, when Liquid A and Liquid B contain micromolecules (agglomerates, etc.), the ability to dissociate these bonds is sometimes inferior to other stirring methods.

[0045] One reason for this difference in stirring ability is the difference in shear force during stirring. In blade stirring, the blade rotates in the stirred liquid, which in turn exerts a shear force on the aggregates. In contrast, this is because the shear force on the aggregates is sometimes insufficient in jet stirring.

[0046] This embodiment is characterized in that when the mixed liquid C drawn into the dispensing probe is ejected into the container, it is ejected 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 exerted. When the liquid is ejected from the dispensing probe, generally, the liquid is ejected with the tip of the dispensing probe below the liquid surface to prevent the liquid from scattering toward the inner wall of the container or from being entrained in bubbles. In the present invention, the liquid is intentionally ejected from above the liquid surface to apply shear force to the stirred liquid.

[0047] In other words, it is characterized in that it includes: a first suction step, sucking the first stirred liquid of liquid A through the dispensing probe; a second suction step, sucking the second stirred liquid when the first stirred liquid is contained in the dispensing probe; and a first stirring step, spraying the first stirred liquid and the second stirred liquid into the container, in the second suction step, sucking air when sucking the second stirred liquid, and in the first stirring step, spraying the first stirred liquid and the second stirred liquid into the container above the liquid level of the liquid contained in the container.

[0048] However, depending on the analysis, the presence of bubbles in the mixed liquid (reaction solution) can hinder analysis. Therefore, as a second feature of this embodiment, the aforementioned jet stirring method is used, depending on the analysis. For analysis where aggregates are present in the mixed liquid and their miniaturization is required, the aforementioned jet stirring method is used. For analysis where aggregates are absent and shearing forces are not required, the liquid is jetted with the tip of the dispensing probe below the liquid surface, as in the conventional method. This method switches the jet stirring method to avoid the entrapment of bubbles and the adverse effects of liquid scattering.

[0049] Furthermore, as the third feature of this embodiment, in order to improve the stirring efficiency during the spray stirring, methods such as 1. increasing the re-spraying amount, 2. accelerating the re-spraying speed, and 3. performing gas-liquid mixing are appropriately selected according to the analysis items. According to 1., the activity of the liquid becomes dynamic, promoting the homogenization of the liquids. According to 2., the Reynolds number of the liquid increases, forming turbulence, thereby improving the miniaturization ability in addition to the homogenization of the liquids. 3. Gas-liquid mixing is performed by mixing tiny gases into the liquid. Compared with the case of only liquid, the shear stress of the turbulent flow increases, and the miniaturization force on the molecules in the liquid is improved. Preferably, one of these is pre-stored and executed according to the analysis item.

[0050] In other words, the following effects can be expected for the parameters of the re-discharge amount, the re-discharge speed, and the number of gas-liquid mixing times (the number of times of discharge and stirring), respectively.

[0051] Increased re-discharge volume: Promotes homogenization of liquids

[0052] Increased ejection speed: promotes homogenization and increases shear stress

[0053] Increased gas-liquid mixing times: Increased shear stress on aggregates

[0054] Shear stress and bubble incorporation are in a trade-off relationship. That is, if you want to increase shear stress, you incorporate bubbles. If you want to suppress bubble incorporation, you reduce the shear stress.

[0055] If there are only two options, either bubble entrainment or non-entrainment, shear stress and bubble entrainment may not be sufficient for measuring any analysis item. Therefore, it is preferable to determine the optimal value of the 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.

[0056] Users can select any stirring method according to the type of analysis items. Figure 3 , the process for selecting the jet stirring method according to the characteristics of the target item and the expected analysis accuracy is described.

[0057] In process 302, if the user determines that the stirring efficiency of the reaction liquid should be prioritized over suppressing the influence of bubbles mixed into the reaction liquid on the analysis results, the user can select the first stirring mode. In process 303, the first mode is a stirring action of spraying liquid into the reaction container, sucking the liquid in the reaction container, spraying the liquid again, sucking the liquid again, and spraying the liquid again. The details of the action of the first mode are described in detail in the following table. Figure 5 This will be described later.

[0058] On the other hand, in process 302, the user determines that the mixing of bubbles into the reaction liquid has a great impact on the analysis results, and the user prioritizes bubble suppression over stirring efficiency. In this case, the user can select the second stirring mode. In process 304, the second mode is a stirring action in which the liquid in the reaction container is sucked after the liquid is sprayed into the reaction container, and the liquid is sprayed again without re-sucking the liquid. The details of the second mode operation are described in detail in the following table. Figure 6 This will be described later.

[0059] After prioritizing stirring efficiency by selecting the first mode, preventing the generation and dilution of bubbles is selected in process 305. When prioritizing stirring efficiency without preventing the generation and dilution of bubbles, the re-ejection amount, re-ejection speed, re-re-ejection amount, and re-re-ejection speed can be arbitrarily set in processes 306 to 309. Thus, a stirring mode corresponding to the stirring difficulty of the analysis item can be implemented. In addition, by increasing the re-ejection amount and re-re-ejection amount, stirring efficiency is improved, while the frequency of bubble generation is increased. By speeding up the re-ejection speed and re-re-ejection speed, stirring efficiency is improved, while the frequency of bubble generation is increased.

[0060] On the other hand, if you want to improve stirring efficiency while also suppressing bubble generation, the re-discharge amount in the first mode is set to 0 in process 310. This selects the first mode, but without re-suction and re-discharge. However, the first mode without re-discharge has lower stirring efficiency than the first mode with re-discharge, and has lower bubble suppression than the second mode.

[0061] In the second mode in process 304, the re-ejection volume and re-ejection speed cannot be set arbitrarily; instead, they are automatically set based on the total liquid volume. This enables a spraying and stirring action specifically designed for bubble suppression. To improve both bubble suppression and stirring efficiency in process 311, the total liquid volume of the reaction solution is increased in process 312. Increasing the total liquid volume improves stirring efficiency, while selecting a bubble suppression action appropriate to the total liquid volume maintains the bubble suppression effect.

[0062] use Figure 4 An example of the relationship between the stirring efficiency and the bubble suppression effect in the first mode and the second mode is shown.

[0063] The first mode is shown as Cases A to G. The advantage of the first mode lies in its high stirring efficiency. Two consecutive jet stirring actions create gas-liquid mixing within the reaction liquid. Molecules that tend to aggregate within the liquid are effectively miniaturized by the increased shear stress generated by the gas-liquid mixing. This increases the effective concentration of molecules important in enzyme reactions and antigen-antibody reactions, promoting the reactions.

[0064] In addition, the shear stress of the gas-liquid mixture tends to be enhanced by increasing the re-ejection speed. However, the first mode has two weaknesses. One is that bubbles must be mixed into the liquid. Depending on the analysis item, the bubbles in the liquid promote oxidation and inhibit the reaction. In addition, in the case of analysis accompanied by absorbance measurement, the bubbles obstruct the light path, and thus the absorbance may not be measured correctly. Another weakness is that since the ejection and stirring action is repeated twice, the number of contacts with the inner wall of the probe increases compared to the case where only one ejection and stirring is performed, which promotes the contamination of the reaction liquid.

[0065] For example, in the case of an automatic analyzer in which a probe is filled with water, repeated ejection and stirring operations increase the number of times the reaction solution is contaminated by water remaining on the inner wall of the probe, thereby diluting the reaction solution.

[0066] The improvement of stirring efficiency is in a trade-off relationship with these two weaknesses. Figure 4 as shown in the chart.

[0067] Case A shows a case in which the total volume of the reaction solution is 100 μL, the re-discharge volume is 30 μL, the re-discharge rate is 100 μL / s, the re-re-discharge volume is 30 μL, and the re-re-discharge rate is 100 μL / s in the first mode. This case is used as a reference point for the description of other cases.

[0068] Case B shows the case in the first mode where the total reaction liquid volume is 100 μL, the re-discharge volume is 80 μL, the re-discharge rate is 100 μL / s, the re-re-discharge volume is 80 μL, and the re-re-re-discharge rate is 100 μL / s. Case B has a larger re-discharge volume and re-re-re-discharge volume than Case A, resulting in higher stirring efficiency and a higher frequency of bubble generation.

[0069] Case C shows the case in the first mode where the total reaction liquid volume is 100 μL, the re-ejection volume is 80 μL, the re-ejection rate is 200 μL / s, the re-re-ejection volume is 80 μL, and the re-re-ejection rate is 200 μL / s. Case C has faster re-ejection and re-re-re-ejection speeds than Case B, resulting in higher stirring efficiency and a higher frequency of bubble generation.

[0070] Case D shows the case in the first mode where the total reaction liquid volume is 100 μL, the re-ejection volume is 80 μL, the re-ejection rate is 300 μL / s, the re-re-ejection volume is 80 μL, and the re-re-ejection rate is 300 μL / s. Case D has faster re-ejection and re-re-re-ejection speeds than Case C, resulting in higher stirring efficiency and a higher frequency of bubble generation.

[0071] Case E shows a situation in which, in the first mode, the total reaction liquid volume is 100 μL, the re-discharge volume is 80 μL, the re-discharge rate is 300 μL / s, the re-re-discharge volume is 0 μL, and the re-re-discharge rate is 0 μL / s. Case E does not perform a second discharging and stirring operation, so the stirring efficiency is lower than that of Case D. However, the generation of bubbles is suppressed, and contamination of the reaction liquid is reduced.

[0072] Case F shows a situation in which, in the first mode, the total reaction liquid volume is 200 μL, the re-discharge volume is 160 μL, the re-discharge rate is 300 μL / s, the re-re-discharge volume is 160 μL, and the re-re-discharge rate is 300 μL / s. Case F increases the total liquid volume compared to Case D, resulting in higher stirring efficiency and a higher frequency of bubble generation. The re-discharge and re-re-re-discharge volumes also increase, resulting in greater contamination of the reaction liquid compared to Case D.

[0073] Case G shows the first mode with a total reaction liquid volume of 200 μL, a re-discharge volume of 160 μL, a re-discharge rate of 300 μL / s, a re-discharge volume of 0 μL, and a re-discharge rate of 0 μL / s. Case E does not perform a second discharging and stirring operation, so stirring efficiency is lower than in Case F. However, bubble generation is suppressed, and contamination of the reaction liquid is reduced. Furthermore, compared to Case E, the total liquid volume is increased, resulting in improved stirring efficiency.

[0074] The second mode is shown as 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 single spouting and stirring operation on the total liquid volume, spouting and stirring can be performed without generating bubbles in the reaction liquid.

[0075] Because spray stirring draws and ejects the reaction solution, it is prone to bubbles in the reaction solution due to the entrainment of liquid and the ejection of segmented air within the probe. However, as mentioned above, depending on the analysis, there is a risk that bubbles in the reaction solution may adversely affect the analysis results.

[0076] To address this issue, this embodiment features a second mode that prioritizes bubble suppression, in addition to the first mode, which prioritizes stirring efficiency. This allows for appropriate jet stirring action for analysis items requiring bubble suppression. However, the second mode cannot perform two stirring actions to improve stirring efficiency. Therefore, to improve stirring efficiency, only the total liquid volume is increased.

[0077] The increase in the total liquid volume leads to an increase in the amount of reagents used, and therefore has a disadvantage of poor cost performance.

[0078] Case H shows the case in the second mode where the total reaction liquid volume is 100 μL, the re-discharge volume is 50 μL, and the re-discharge rate is 200 μL / s. Although case H has low stirring efficiency, it has a high bubble suppression effect and reduces contamination of the reaction liquid.

[0079] Case I shows a case in which the total reaction liquid volume is 100 μL, the re-discharge volume is 50 μL, and the re-discharge rate is 200 μL / s in the second mode. Case I improves stirring efficiency compared to Case H while maintaining the bubble suppression effect of the second mode.

[0080] use Figure 5 The detailed operation of the secondary stirring in the first mode will be described.

[0081] Figure 5 (a): The reaction container 103 is previously filled with liquid 501. The reagent 502 held in the probe 203 is ejected into the reaction container 103. The reagent 502 and the liquid 501 are partially mixed due to the momentum of the ejection.

[0082] Figure 5 (b) : While the probe 203 is lowered, the partially mixed liquid 501 and reagent 502 are sucked into the probe.

[0083] Figure 5 (c) The mixed liquid 503 is ejected again into the reaction vessel 103 while the probe 203 is raised. At this point, the mixed liquid 503 rises along the inner wall of the reaction vessel 103 and then descends due to gravity, entraining air. Consequently, a plurality of bubbles 504 are generated within the mixed liquid 503.

[0084] Figure 5 (d) In the process of ejecting the mixed liquid 503, the probe 203 rises while maintaining a certain distance from the liquid surface. The rise of the mixed liquid 503 along the inner wall of the reaction container 103 becomes stable over time. Figure 5 The bubbles 504 generated in the liquid by the entrainment in (c) rise to the liquid surface.

[0085] Figure 5 (e) in the figure: After the re-discharge is completed, the bubbles 504 in the mixed liquid 503 rise vertically upward to form a bubble layer on the liquid surface. In addition, after the re-discharge is completed, the tip of the probe 203 is immersed in the mixed liquid 503.

[0086] Figure 5(f) in the figure: Suction of mixed liquid 503 begins. At this point, probe 203, immersed in mixed liquid 503, is controlled to descend while maintaining the length of its tip. The flow generated by re-suction draws a portion of the layer of bubbles 504 into the probe. Ultimately, mixed liquid 503 and bubbles 504 are randomly drawn into probe 203.

[0087] Figure 5 (g) in FIG: At the end of re-suction, the tip of the probe is in the liquid. A portion of the bubble 504 is sucked into the probe, while the remaining portion remains above the liquid surface, forming a bubble layer.

[0088] Figure 5 (h) in the figure: the probe 203 starts to rise.

[0089] Figure 5 (i) In the above, re-discharge is started when the tip of the probe 203 rises above the liquid level by a predetermined amount. At this time, the bubbles drawn into the probe 203 are transformed into microbubbles 505 of 1 mm or less by the turbulence of the discharge flow from the probe 203 .

[0090] The microbubbles 505 are ejected into the reaction container together with the mixed liquid 503. At this time, the mixed liquid 503 is ejected again from the bubble layer formed on the liquid surface of the mixed liquid 503 or from the upper part, thereby forming a stirring flow in which the bubbles 504 and the microbubbles 505 are mixed in the mixed liquid 503.

[0091] Furthermore, the probability of formation of the fine bubbles 505 depends on the inner diameter of the probe 203 and the re-ejection speed.

[0092] The inner diameter of the probe 203 is uniquely determined by the automatic analyzer. Therefore, the user can control the generation of the fine bubbles 505 by selecting the ejection speed within a predetermined range.

[0093] Figure 5 (j) The re-ejected mixed liquid 503 contains microbubbles 505. The microbubbles randomly move within the reaction vessel, causing the mixed liquid 503 to become a gas-liquid mixed state. This gas-liquid mixing increases the shear stress on the molecules within the liquid compared to simply stirring the liquid, resulting in enhanced particle size reduction capabilities achieved through jet stirring.

[0094] Figure 5 (k) in the figure: After the re-discharge is completed, the flow of the mixed liquid 503 converges and the generated micro bubbles begin to stack on the liquid surface.

[0095] use Figure 6 The detailed operation of one stirring in the second mode will be described.

[0096] Figure 6(a) in the figure: Reaction vessel 103 is pre-filled with liquid 601. Reagent 602, held within probe 203, is ejected into reaction vessel 103. The momentum of the ejection causes partial mixing of reagent 602 and liquid 601. To prevent the probabilistic generation of bubbles within the liquid from fragmented air, the distance between the probe tip and the liquid surface is controlled so that bubbles ejected from the probe tip burst before entering the liquid.

[0097] Figure 6 (b) : While lowering the probe 203, the partially mixed liquid 601 and reagent 602 are sucked into the probe. Figure 6 In (a), no bubbles are generated, so there is no risk of bubbles being sucked into the probe.

[0098] Figure 6 (c) in the figure: The probe tip rises above the liquid surface. The distance between the residual liquid in the reaction vessel and the probe tip is controlled to be greater than in the first mode. The ejected mixed liquid expands downward in a fan-shaped pattern, increasing the contact area between the ejected stream and the residual liquid compared to the first mode. This reduces the risk of liquid entrainment during the re-ejection process.

[0099] Figure 6 (d) in the figure: Re-discharge begins. The re-discharge speed is controlled to a flow rate that does not cause liquid entrainment. The user cannot arbitrarily set the re-discharge volume and re-discharge speed. No bubbles are present in the mixed liquid during the re-discharge process.

[0100] Figure 6 (e) in the figure: After the spraying is completed, there are no bubbles in the mixed liquid.

[0101] Description of Reference Numerals

[0102] 100: Specimen container, 101: Reagent bottle, 102: Disk, 103: Reaction container, 104: Incubator, 105: Dispensing unit, 106: Control unit, 107: Input / output unit, 108: Storage unit, 201: Axis, 202: Arm, 203: Dispensing probe, 204: Syringe pump, 205: Tube, 206: Solenoid valve, 207: Plunger, 208: System water container, 501: Pre-ejected liquid, 502: Reagent, 503: Mixed liquid, 504: Bubbles, 505: Microbubbles, 601: Pre-ejected liquid, 602: Reagent, 603: Mixed liquid.

Claims

1. A liquid stirring method for an automatic analyzer having a dispensing probe for sucking and / or ejecting liquid, characterized in that: The liquid stirring method comprises: a first suction step of sucking a first stirred liquid through the dispensing probe; a second suction step of sucking a second stirred liquid while the first stirred liquid is contained in the dispensing probe; In the first stirring step, the first stirred liquid and the second stirred liquid are sprayed into the container, and in the second suction step, air is sucked in while sucking the second stirred liquid. In the first stirring step, the first stirred liquid and the second stirred liquid are ejected into the container above the liquid level of the liquid contained in the container.

2. The liquid stirring method of the automatic analyzer according to claim 1, characterized in that: The liquid stirring method includes a segmented air suction step, wherein an air phase for suppressing mixing of the first stirred liquid and the second stirred liquid is sucked between the first suction step and the second suction step.

3. The liquid stirring method of the automatic analyzer according to claim 1, characterized in that: The liquid stirring method further comprises: a re-suction step of re-suctioning the mixed liquid of the first stirred liquid and the second stirred liquid ejected into the container in the first stirring step by the dispensing probe so as to contain bubbles in the mixed liquid; In the second stirring step, a mixed liquid of the first liquid to be stirred and the second liquid to be stirred contained in the dispensing probe is ejected into the container above the liquid level of the liquid contained in the container.

4. The liquid stirring method of the automatic analyzer according to claim 3, characterized in that: Depending on the analysis item assigned to the mixed solution, the second stirring step is not performed.

5. The liquid stirring method of the automatic analyzer according to claim 3, characterized in that: The amount of the mixed liquid of the first stirred liquid and the second stirred liquid sucked in the re-sucking step is set to zero according to the analysis item assigned to the mixed liquid.

6. The liquid stirring method of the automatic analyzer according to claim 4, characterized in that: Without performing the second stirring step, in the first stirring step, In the first suction step, when sucking the second stirred liquid, the dispensing probe sucks the second stirred liquid below the liquid surface of the second stirred liquid. 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. A liquid stirring method for an automatic analyzer having a dispensing probe for sucking and / or ejecting liquid, characterized in that: The liquid stirring method comprises: a first suction step of sucking a first stirred liquid through the dispensing probe; a second suction step of sucking a second stirred liquid while the first stirred liquid is contained in the dispensing probe; a first stirring step of spraying the first stirred liquid and the second stirred liquid into the container; a re-suction step of re-suctioning the mixed liquid of the first stirred liquid and the second stirred liquid contained in the container by the dispensing probe; In the second stirring step, a mixed liquid of the first stirred liquid and the second stirred liquid contained in the dispensing probe is ejected into the container. The relationship between the total amount of the first stirred liquid and the second stirred liquid, the ejection amount of the first stirred liquid and the second stirred liquid ejected simultaneously into the container in the first stirring step, and the ejection speed at that time is stored in advance as a plurality of patterns. Which of the stored modes is to be used for stirring is selected according to the analysis item assigned to the first stirred liquid.

8. The liquid stirring method of the automatic analyzer according to claim 7, characterized in that: The liquid stirring method further comprises: a re-suction step of re-suctioning the mixed liquid of the first stirred liquid and the second stirred liquid contained in the container by the dispensing probe; In the second stirring step, a mixed liquid of the first stirred liquid and the second stirred liquid contained in the dispensing probe is ejected into the container. The relationship between the ejection amount of the first stirred liquid and the second stirred liquid ejected into the container simultaneously in the second stirring step and the ejection speed at that time is also stored together with the pattern in the first stirring step. Which of the stored modes is to be used for stirring is selected according to the analysis item assigned to the first stirred liquid.

9. The liquid stirring method of the automatic analyzer according to claim 7 or 8, characterized in that: In the step of ejecting the mixed liquid of the first stirred liquid and the second stirred liquid contained in the dispensing probe into the container, the height of the dispensing probe from the liquid level of the contained mixed liquid when ejecting the mixed liquid into the container is also stored in the stored pattern.

10. An automatic analysis device, characterized in that have: A control device for controlling various mechanisms including the dispensing probe so as to execute the liquid stirring method of the automatic analyzer according to any one of claims 1 to 8.

Citation Information

Patent Citations

  • Liquid mixing method and dispensing apparatus

    JP2011107089A