Automatic analysis device and dispensing method
By utilizing multiple suction speed levels for air aspiration in the automatic analyzer's dispensing mechanism, the analyzer effectively minimizes liquid film and residue issues, enhancing abnormality detection accuracy and improving analysis results.
Patent Information
- Application Number
- PCT/JP2024/038041
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-12-01
- Filing Date
- 2024-10-25
- Publication Date
- 2025-06-05
AI Technical Summary
Existing automated analyzers face challenges in accurately detecting abnormalities during the dispensing of multiple liquids, particularly due to liquid film and residue issues, which can reduce the accuracy of abnormality detection.
The automatic analyzer employs a dispensing mechanism with multiple levels of suction speed for air aspiration, selectively using these levels based on the type of fluid or suction volume of air, to minimize liquid film and residue generation and enhance abnormality detection accuracy.
This approach allows for highly accurate detection of abnormalities during dispensing, improving the accuracy of analysis results while minimizing the generation of liquid films and residues.
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Figure JP2024038041_05062025_PF_FP_ABST
Abstract
Description
Automated analyzer and dispensing method
[0001] The present invention relates to an automatic analyzer and a dispensing method.
[0002] BACKGROUND ART Automated analyzers such as biochemical analyzers and immunoanalyzers are equipped with a dispensing mechanism that aspirates a specified amount of specimen, such as a biological sample, and reagent and dispenses it into a reaction vessel, and an analyzing mechanism that analyzes the reaction liquid between the specimen and reagent.
[0003] The dispensing mechanism is composed of a probe inserted into a liquid such as a specimen or reagent, a syringe that serves as a pressure source for aspirating and dispensing the liquid, and a flow path connecting the probe and the syringe. The dispensing mechanism dispenses a specified amount of liquid by inserting the probe into the liquid in a specimen container or reagent container, operating the syringe to aspirate a specified amount of liquid, moving the probe to a reaction container, and dispensing it. When dispensing, a disposable tip may be attached to the tip of the probe to prevent components from being carried over to the next test.
[0004] Depending on the analysis item, multiple reagents, or both reagents and samples, may be held simultaneously in a probe or tip (dispensing nozzle) and dispensed into a reaction vessel. When multiple liquids are held simultaneously in the dispensing nozzle, multiple types of liquids are successively aspirated and dispensed into a reaction vessel after all liquids have been aspirated. Dispensing multiple types of liquids simultaneously can reduce the amount of wash water used, the number of tips used, and the time required for dispensing.
[0005] During dispensing, abnormalities can occur, such as the suction of air bubbles generated by handling the sample container, or clogging of the flow path due to a highly viscous sample or fibrin or other fibrous material in the sample. Therefore, by accurately estimating the dispensing status and detecting the occurrence of an abnormality with high accuracy, the accuracy of the analysis results can be improved.
[0006] As a method for detecting abnormalities in dispensing, for example, Patent Document 1 discloses a technology that uses the integral value of pressure data over a specific time interval in response to pressure fluctuations during sample ejection, or the difference between the average pressure value calculated at the end of ejection and the average pressure value calculated during normal ejection, as indicators, and compares these with a preset threshold value to detect abnormalities in dispensing.
[0007] Furthermore, Patent Document 2 discloses a technology for detecting abnormalities when a specified liquid is dispensed, using the ratio between the pressure when a reference liquid, which is used as a standard for detecting abnormalities, is dispensed and the pressure when a specified liquid is dispensed.
[0008] Patent No. 3633631 Publication JP 11-258244 Publication
[0009] However, in the configuration described in Patent Document 1, when dispensing multiple types of liquid simultaneously, if the liquid that is the target of abnormality detection is not the first to be aspirated, the accuracy of abnormality detection may be reduced due to liquid films or residual liquid that occur when the preceding liquid is aspirated.
[0010] As with Patent Document 1, in Patent Document 2, when dispensing multiple types of liquid simultaneously, if the liquid that is the target of abnormality detection is not aspirated first, the accuracy of abnormality detection may be reduced due to liquid films or residual liquid that occur when aspirating the preceding liquid.
[0011] Therefore, the present disclosure provides a technology that minimizes the liquid film and residual liquid that occur when aspirating the liquid that is aspirated before the liquid that is the target of abnormality detection when dispensing multiple liquids simultaneously, and enables highly accurate detection of abnormalities when dispensing the liquid that is the target of abnormality detection.
[0012] An example of an automatic analyzer according to the present invention is an automatic analyzer comprising: a container for containing a fluid; a pressure source; a probe for dispensing the fluid in the container; and a flow path connecting the probe and the pressure source, wherein the automatic analyzer has a plurality of levels of aspiration speed for aspirating air when aspirating the air into the probe or when aspirating air into a tip attached to the tip of the probe, and the levels are used depending on at least one of the type of fluid or the volume of air aspirated.
[0013] In one example of the method for dispensing a fluid using an automatic analyzer according to the present invention, the automatic analyzer comprises: a container for storing a fluid; a pressure source; a probe for dispensing the fluid in the container; and a flow path connecting the probe and the pressure source; the automatic analyzer has a plurality of levels of suction speed for aspirating air into the probe or into a tip attached to the tip of the probe; and the dispensing method includes selectively using the levels depending on at least one of the type of fluid or the volume of air aspirated.
[0014] Further features related to the present disclosure will become apparent from the description and accompanying drawings of this specification, and aspects of the present disclosure may be realized and realized by the elements and combinations of various elements and aspects set forth in the following detailed description and the appended claims.
[0015] The descriptions in this specification are exemplary and illustrative only and are not intended to limit the scope or application of the present disclosure in any way.
[0016] According to the automatic analyzer of the present disclosure, it is possible to detect with high accuracy any abnormality that occurs when dispensing a liquid that is the target of abnormality detection.
[0017] Problems, configurations, and effects other than those described above will become apparent from the following description of the embodiments.
[0018] FIG. 1 is a schematic diagram showing the configuration of a dispensing mechanism of an automatic analyzer according to a first embodiment. FIG. 2 is a flowchart showing a dispensing method according to the first embodiment. FIG. 3 is a flowchart showing a method for determining the presence or absence of an abnormality according to the first embodiment. FIG. 4 is a schematic diagram showing the state of fluid in a probe and a tip during the dispensing operation of FIG. 2. FIG. 5 is a flowchart showing a method for calculating the intake rate of segmented air during the dispensing operation of FIG. 2. FIG. 6 is a schematic diagram showing the configuration of a dispensing mechanism of an automatic analyzer according to a modified example of the first embodiment. FIG. 7 is a flowchart showing a method for calculating the intake rate of segmented air according to a second embodiment. FIG. 8 is a flowchart showing a method for calculating the intake rate of segmented air according to a third embodiment. FIG. 9 is a schematic diagram showing the state of fluid in a probe according to a fourth embodiment.
[0019] [First embodiment] <Configuration of dispensing mechanism of automatic analyzer> The dispensing mechanism of the automatic analyzer according to the first embodiment employs a configuration in which a detachable tip is attached to the tip of a probe. The dispensing mechanism of this embodiment sequentially aspirates a reagent and a specimen into the tip and dispenses them simultaneously into a reaction vessel, and detects the aspiration of air bubbles (hereinafter referred to as "empty aspiration") or clogging when aspirating the specimen while the reagent has already been aspirated and held in the tip.
[0020] 1 is a schematic diagram showing a dispensing mechanism 100 of an automated analyzer according to a first embodiment. As shown in Fig. 1 , the dispensing mechanism 100 includes a tip 101, a probe 102, a flow path 103, a syringe 104 (pressure source), a syringe driver 106, a probe driver 107, a controller 108, a water supply pump 109, a water supply tank 110 containing cleaning water 105, an electromagnetic valve 111, a reagent container 112 (container) containing a reagent 113 (fluid) corresponding to an analysis item, a specimen container 114 (container) containing a specimen 115 (fluid), a reaction vessel 116, a pressure sensor 117, a branching block 118, a signal amplifier 119, an A / D converter 120, a determination unit 121 (including a sampling unit 122, a memory unit 123, and a calculation unit 124), a display unit 125, a tip disposal unit 126, a washing tank 127, and a solenoid valve 128.
[0021] The tip 101 (dispensing nozzle) is detachable from the tip of the probe 102. A probe driver 107 such as a motor or actuator (not shown) is connected to the probe 102, which allows the probe 102 to be moved horizontally and vertically to a predetermined position. The tip 101 is held, for example, in a tip rack (not shown), and the probe driver 107 moves the probe 102 above the tip rack and then lowers it, thereby attaching the tip 101 to the probe 102. The tip 101 may be attached to the probe 102 in a tip buffer that temporarily holds the tip 101.
[0022] The probe 102 is connected to a syringe 104 via a flow path 103, and the interior thereof is filled with cleaning water 105. The syringe 104 has a cylinder 104a and a plunger 104b, and a syringe drive unit 106 is connected to the plunger 104b. The syringe drive unit 106 drives the plunger 104b vertically relative to the cylinder 104a, thereby aspirating and discharging fluid (liquid and gas) at the tip 101 connected to the probe 102. In particular, the probe 102 can dispense a reagent 113 in a reagent container 112 and a specimen 115 in a specimen container 114.
[0023] The syringe 104 has a flow path that communicates with a water supply tank 110, and the flow path is provided with an electromagnetic valve 111 and a water supply pump 109. The water supply tank 110 contains cleaning water 105, and the cleaning water 105 is discharged from the probe 102 by driving the water supply pump 109, thereby cleaning the inside of the probe 102. The cleaning of the probe 102 is performed, for example, before dispensing the reagent 113 and the specimen 115.
[0024] Although not shown, the automated analyzer has a reagent storage container for holding reagent containers 112, a sample container rack for holding sample containers 114, and a reaction disk for holding reaction containers 116. The means for holding the reagent containers 112, sample containers 114, and reaction containers 116 are not limited to those described above. Reagent 113 and sample 115 aspirated into tip 101 are dispensed into reaction container 116.
[0025] The control unit 108 controls the operations of the syringe driving unit 106, the probe driving unit 107, the water supply pump 109, and the solenoid valve 111. The control unit 108 may be configured to control not only the operations of the components of the dispensing mechanism 100, but also the operations of the entire automatic analyzer.
[0026] Pressure sensor 117 is connected to branch block 118 provided midway through flow channel 103, and measures time-series data on the pressure within flow channel 103. Pressure sensor 117 outputs a pressure detection signal to signal amplifier 119. The position of pressure sensor 117 may be on the syringe 104 side as shown in FIG. 1 , but by connecting pressure sensor 117 to a position as close as possible to probe 102, pressure fluctuations at the opening of chip 101 can be measured with high sensitivity.
[0027] The signal amplifier 119 amplifies the detection signal of the pressure sensor 117 and outputs the amplified signal to the A / D converter 120. The A / D converter 120 converts the amplified signal into a digital signal and outputs it to the determination unit 121 as a pressure value.
[0028] Determination unit 121 is a circuit for determining whether or not an abnormality occurs during the dispensing operation of dispensing mechanism 100. Determination unit 121 has a sampling unit 122 that receives pressure value input from A / D converter 120, a memory unit 123 that stores data such as the pressure value input to sampling unit 122, and a calculation unit 124 that executes processing on the data stored in memory unit 123.
[0029] The determination unit 121 is configured to be able to communicate with the control unit 108, and when it is determined from the results of data processing in the calculation unit 124 that it is desirable to stop the operation, it transmits the details of the stop operation to the control unit 108.
[0030] The determination unit 121 may be configured as hardware in the automatic analyzer as a dedicated circuit board, or may function as the determination unit 121 by a processor reading and executing a program recorded in the storage unit 123. Furthermore, a processor in a server connected to the automatic analyzer wirelessly or via a wire so as to be able to communicate with the automatic analyzer may read and execute a program to function as the determination unit 121.
[0031] The display unit 125 is connected to the control unit 108 and the determination unit 121, and displays the results of data processing in the determination unit 121, information related to the results, and the like.
[0032] The tip disposal unit 126 discards the tip 101 after the reagent 113 and the specimen 115 have been dispensed into the reaction vessel 116 .
[0033] The cleaning tank 127 is composed of a cleaning nozzle 127a and a drain cup 127b, and the cleaning nozzle 127a can clean the outer wall of the chip 101. Cleaning water 105 used to clean the outer wall of the chip 101 is discharged from the cleaning nozzle 127a through an electromagnetic valve 128.
[0034] 2 is a flowchart showing a dispensing method according to the first embodiment, and in particular shows a method of dispensing a fluid using an automatic analyzer. The dispensing method of this embodiment is executed by the automatic analyzer, and is actually implemented by the control unit 108 shown in FIG. 1 controlling the operation of each component of the dispensing mechanism 100 (such as the syringe driver 106, the probe driver 107, the water supply pump 109, and the solenoid valve 111). However, in the following description, each component of the dispensing mechanism 100 may be described as the subject of the operation.
[0035] In step S201, the control unit 108 opens the electromagnetic valve 111 and drives the water supply pump 109 to discharge the cleaning water 105 in the water supply tank 110 from the probe 102. In this way, the inside of the probe 102 is cleaned.
[0036] In step S202, the syringe driving unit 106 drives the syringe 104 to aspirate segmented air into the probe 102. This is to prevent the cleaning water 105 filled in the probe 102 from mixing with the reagent 113 to be aspirated in the next step.
[0037] In step S203, the probe driver 107 moves the probe 102 above the tip rack or tip buffer, and then lowers it, thereby attaching the tip 101 to the tip of the probe 102.
[0038] In step S204, it is determined whether or not there is any reagent that requires dispensing. If there is any reagent that requires dispensing (Yes), steps S205 to S208, which are steps for aspirating the reagent, are performed, and then the process returns to step S204. That is, steps S205 to S208 are repeatedly executed until all reagents that require dispensing have been aspirated. For example, if there are two types of reagents that require aspirating and dispensing, steps S205 to S208 are repeated twice. If there is no reagent that requires dispensing (No), steps S205 to S208 are not executed.
[0039] In step S205, the probe driver 107 moves the probe 102 above the reagent container 112 and lowers the probe 102 until the tip of the tip 101 is immersed in the reagent 113.
[0040] In step S206, the syringe driving unit 106 drives the syringe 104 to aspirate the reagent 113 into the tip 101. Thereafter, the probe driving unit 107 raises the probe 102 until the tip of the tip 101 emerges from the reagent 113.
[0041] In step S207, the syringe driving unit 106 drives the syringe 104 to aspirate segmented air into the tip 101. This is to prevent the reagent 113 previously aspirated into the tip 101 from mixing with the liquid to be aspirated in the next step.
[0042] In step S208, the control unit 108 opens the electromagnetic valve 128 and drives the water supply pump 109 to discharge the cleaning water 105 in the water supply tank 110 from the cleaning nozzle 127a, thereby cleaning the outer wall of the tip 101. This is to prevent the reagent 113 previously aspirated into the tip 101 from mixing with the liquid to be aspirated in the next step.
[0043] As described above, steps S205 to S208 may be repeated multiple times, and the dispensing mechanism 100 can perform the step of aspirating air (step S207) multiple times between aspirating and dispensing the fluid (reagent 113 and / or specimen 115) into the probe 102. This makes it possible to prevent many types of fluids from mixing together.
[0044] In step S209, it is determined whether or not there is a sample that requires dispensing. If there is a sample that requires dispensing (Yes), steps S210 to S214, which are steps for aspirating the sample, are performed. If there is no sample that requires dispensing (No), steps S210 to S214 are not performed.
[0045] In step S210, the probe driver 107 moves the probe 102 above the sample container 114 and lowers the probe 102 until the tip of the tip 101 is immersed in the sample 115.
[0046] In step S211, the syringe driving unit 106 drives the syringe 104 to aspirate the specimen 115 into the tip 101. Here, the sampling unit 122 of the determination unit 121 receives input of the pressure value during the aspirating operation of the specimen 115, and transmits the pressure value related to the aspirating operation of the specimen 115 to the storage unit 123 as time-series data (hereinafter, sometimes referred to as "pressure history"). The storage unit 123 stores this.
[0047] For example, pressure values are measured before the start of the suction operation, during the suction operation, and after the suction operation is completed. Pressure may be measured at multiple points in each time period. Then, the probe driver 107 raises the probe 102 until the tip of the tip 101 emerges from the specimen 115.
[0048] In step S212, the calculation unit 124 of the determination unit 121 determines (detects) whether or not an abnormality such as clogging or dry suction occurred during the suction of the sample 115, based on the pressure history during the suction of the sample stored in the memory unit 123. In other words, based on the pressure history, it determines whether or not the sample to be analyzed was dispensed normally.
[0049] The pressure history when an abnormality such as dry suction or clogging occurs during the aspirating of the sample 115 is significantly different from the pressure history when normal dispensing is performed. Therefore, the presence or absence of an abnormality can be determined by referring to the pressure history. The method for determining the presence or absence of an abnormality will be described later.
[0050] In this step, the determination unit 121 transmits the determination result as to whether or not there is an abnormality to the display unit 125 and the control unit 108. The display unit 125 also displays the determination result.
[0051] If it is determined in step S212 that there is no abnormality (No), the process proceeds to step S213. In step S213, the control unit 108 determines, based on the determination result received from the determination unit 121, that the sample 115 has been aspirated normally.
[0052] If it is determined in step S212 that an abnormality has occurred (Yes), the process proceeds to step S214. In step S214, the control unit 108 determines that an abnormality has occurred during the aspirating of the sample 115 based on the determination result received from the determination unit 121. At this time, an alert is displayed on the display unit 125, and the dispensing operation of the corresponding sample 115 is terminated. The sample 115 is also returned to the user. In this way, by canceling the dispensing of the sample 115 that has an abnormality, it is possible to reduce the consumption of reagents to be used in subsequent analyses.
[0053] In the example of FIG. 2, the process proceeds to step S215 after step S214. However, as a variant, a predetermined error process or the like may be executed after step S214, and in that case, other processes may be executed thereafter instead of steps S215 and onward.
[0054] In step S215, the probe 102 is moved so that the tip of the tip 101 is positioned inside the reaction vessel 116.
[0055] In step S216, the syringe driving unit 106 drives the syringe 104 to discharge the liquid held in the tip 101 into the reaction vessel 116. At this time, all of the reagent and specimen aspirated into the tip 101 are simultaneously discharged into the reaction vessel 116.
[0056] In step S217, the probe driving unit 107 moves the probe 102 to the tip disposal unit 126 and removes the tip 101 from the probe 102 by discarding it in the tip disposal unit 126.
[0057] <Method of Determining Presence or Absence of Abnormality> FIG. 3 is a flowchart showing a method of determining presence or absence of abnormality by the determination unit 121 in step S212 of FIG.
[0058] In step S301, the calculation unit 124 reads out the pressure history during sample aspiration stored in the storage unit 123. In this specification, the "pressure history during sample aspiration" refers to pressure values in a predetermined time range that includes the operation time (aspiration operation time) of the syringe 104 when aspirating the sample 115 in step S211.
[0059] In step S302, the calculation unit 124 calculates a judgment index used to judge the presence or absence of an abnormality based on the pressure history during sample aspiration. The "judgment index" includes, for example, at least one of the following values: - The average value of the pressure value during the aspiration operation of the sample 115. - The average value of the pressure value for a predetermined time immediately before the start of the aspiration operation of the sample 115. - The average value of the pressure value for a predetermined time immediately after the end of the aspiration operation of the sample 115. - The maximum value of the pressure value during the aspiration operation of the sample 115. - The minimum value of the pressure value during the aspiration operation of the sample 115. - The pressure pulsation period of the pressure history related to multiple aspiration operations. - The pressure pulsation amplitude of the pressure history related to multiple aspiration operations. - The distance between a preset reference pressure history and the pressure history acquired in this step. The distance may be a statistical distance, and as a specific example, may be the Euclidean distance. Pressure history {a 1 , a 2 , a 3 , ..., a n} and pressure history {b 1 , b 2 , b 3 , ..., b n}, the Euclidean distance is i -b i ) 2} (where 1≦i≦n).
[0060] The "reference pressure history" is set, for example, based on a large number of pressure values obtained in the past, and may be the pressure value when it is determined that the sample has been aspirated normally (in this case, for example, if the statistical distance is greater than the judgment threshold, it is determined that there is an abnormality), or it may be the pressure value when it is determined that there is an abnormality during sample aspirate (in this case, for example, if the statistical distance is less than the judgment threshold, it is determined that there is an abnormality).
[0061] Furthermore, the reference pressure history may be determined based on the pressure measured during segmental air aspiration immediately before aspirating the sample. That is, the pressure history during air aspiration may be used to determine whether the sample to be analyzed was dispensed normally (in this case, for example, an abnormality is determined if the statistical distance is smaller than the determination threshold). This allows for a determination that is less susceptible to changes in the state of the flow path over time.
[0062] The statistical distance (i.e., similarity or dissimilarity) from this reference pressure history can also be used as a judgment index. When measuring the pressure during segmental air aspiration immediately before aspirating a sample and determining the presence or absence of an abnormality based on the pressure value during segmental air aspiration, it is preferable to set the aspiration speed during the immediately preceding segmental air aspiration to the same as the aspiration speed during sample aspiration. Furthermore, a combination of the above-mentioned indices may be used as a judgment index.
[0063] In this specification, the "suction speed" may be expressed in units of, for example, m / s, by the moving speed of a specific member (for example, the plunger 104b of the syringe 104) or the moving speed of the aspirated fluid in a specific flow path. Alternatively, the suction speed may be expressed in units of, for example, m 3 / s, and can be expressed as the flow rate of the fluid being sucked. It can also be expressed as other flow speeds, flow rates, etc. The conversion of these physical quantities can be performed appropriately by the control unit 108, for example.
[0064] In this embodiment, the difference between the average pressure value during the aspirating operation of the sample 115 and the average pressure value for a predetermined time before the start of the aspirating operation is calculated as a judgment index, and this is used to judge whether dispensing was normal or whether it was an empty aspirate. For example, if the difference is smaller than a predetermined threshold, it is determined to be an empty aspirate. Possible causes of an empty aspirate include erroneous detection of the liquid level due to air bubbles unintentionally generated during handling of the sample container 114. Air bubbles are generated when the blood sample 115 is shaken during transportation.
[0065] In step S303, the calculation unit 124 determines the presence or absence of an abnormality during aspiration of the sample 115 based on the determination index. In addition to the specific methods described above, methods for determining the presence or absence of an abnormality include, for example, a method of comparing the determination index with a predetermined determination threshold, and a method of determining an abnormality when a combination of multiple determination indexes satisfies a certain condition. In this embodiment, an algorithm is used that compares the determination index with a certain determination threshold to determine the presence or absence of an abnormality. The determination threshold used to determine the presence or absence of an abnormality is stored in advance in the storage unit 123.
[0066] 4 is a schematic diagram showing the state of the fluid in the probe 102 and the tip 101 during the dispensing operation shown in FIG. 4 illustrates an example in which one type of reagent and one type of sample are dispensed. FIG. 4(a) shows the state immediately after the inside of the probe 102 is washed with washing water 105 in step S201. As shown in FIG. 4(a), the inside of the probe 102 is filled with washing water 105.
[0067] FIG. 4B shows the state after the segmented air 401 is sucked in step S202 and the tip 101 is attached in step S203.
[0068] 4C shows the state after the reagent 113 has been aspirated in step S206. The reagent 113 is located at the tip of the tip 101.
[0069] 4(d) shows the state after the air segments 402 have been aspirated in step S207. The air segments 402 are located at the tip of the tip 101, and the reagent 113 is located above the air segments 402. Note that although one type of reagent 113 is shown in FIG. 4(d), when dispensing multiple reagents, the reagents 113 and the air segments 402 are arranged alternately in the same number as the number of aspirated reagents.
[0070] 4E shows the state after the specimen 115 has been aspirated in step S211. The specimen 115 is located at the tip of the tip 101, with segmented air 402 located above it, and the reagent 113 located above the segmented air 402.
[0071] As described above, the presence or absence of an abnormality is determined using the pressure history during the aspirating of the specimen 115. Before aspirating the specimen 115, the aspirating processes of the reagent 113, the segmented air 401, the segmented air 402, etc. are performed. For example, the boundary 403 between the cleaning water 105 and the segmented air 401 moves upward in all of the aspirating processes of the reagent 113, the segmented air 401, and the segmented air 402.
[0072] When the boundary 403 moves, some of the cleaning water 105 may adhere to and be left behind on the inner wall of the probe 102, forming a liquid film on the inner wall of the probe 102. Reducing the occurrence of such a liquid film can prevent the cleaning water 105 from remaining below the boundary 403, and can maintain a uniform state ( FIG. 4( d )) before the specimen 115 is aspirated. This improves the reproducibility of the pressure history during the aspirating of the specimen 115, making it possible to determine with high accuracy whether or not an abnormality occurs during the aspirating of the specimen 115.
[0073] An example of a physical formula expressing the thickness d of the liquid film generated when the boundary 403 moves is the following formula (1): d ∝ D × (μv / σ) 2/3 ...Equation (1) where D is the flow path diameter, μ is the viscosity of the fluid, v is the suction speed, σ is the surface tension of the fluid, and ∝ indicates a proportional relationship. The remaining amount of cleaning water 105 remaining below the boundary 403 is calculated by multiplying equation (1) by the distance traveled by the boundary 403.
[0074] Slowing the aspiration speed is effective in reducing the amount of remaining cleaning water 105. Specifically, it is effective to slow down the aspiration speed in the aspiration steps of reagent 113, segmented air 401, and segmented air 402. However, slowing down the aspiration speed in the aspiration steps increases the time required for dispensing.
[0075] In this embodiment, step S202, which is the step of suctioning segmented air, is taken as an example to show a method for reducing the suction speed in this step. Fig. 5 is a flowchart showing a method for setting the suction speed in step S202.
[0076] In step S501, it is determined whether or not a sample is to be dispensed in the dispensing operation. If a sample is to be dispensed (Yes), it is desirable to increase the reproducibility of the pressure history during the aspiration of the sample 115 in order to accurately determine abnormalities during the aspiration of the sample 115, and therefore it is desirable to prevent residual cleaning water 105. For this reason, it is desirable to reduce the aspiration speed in step S202, and the aspiration speed is set to low speed v1 (step S502). In this case, steps S210 to S214 are executed in the process of FIG. 2.
[0077] On the other hand, if the sample is not to be dispensed (No), there is no need to determine whether or not there is an abnormality during the aspiration of the sample 115, so the aspiration speed is set to high speed v2 (step S503). In other words, v2>v1. In this case, steps S210 to S214 in the process of FIG. 2 are not executed.
[0078] In this way, the dispensing mechanism 100 has multiple levels of aspiration speed, namely v1 (first level) and v2 (second level), when aspirating air into the probe 102 (or into the tip 101 attached to the tip of the probe 102).
[0079] In the above example, the aspiration speed in step S202 is changed depending on whether or not a sample is dispensed during the dispensing process. That is, the dispensing mechanism 100 uses multiple levels v1 and v2 depending on the type of fluid being aspirated, and in particular, depending on whether or not the fluid being aspirated contains the sample to be analyzed. This allows for highly accurate determination of the presence or absence of an abnormality during aspiration when dispensing the sample 115, and prevents the dispensing time from becoming too long when not dispensing the sample 115. Changing the speed of the aspiration process depending on whether or not a sample is dispensed can be applied to the aspiration processes of any of the reagent 113, the segmented air 401, and the segmented air 402.
[0080] <Technical Effects> As described above, the automated analyzer of this embodiment changes the aspiration speed during the aspiration process of segmented air and reagent depending on whether or not a sample is being dispensed. When a sample is being dispensed, slowing down the aspiration speed during the aspiration process of segmented air and reagent suppresses the generation of a liquid film in the flow path before sample aspiration and improves the reproducibility of the pressure history during sample aspiration, making it possible to accurately determine whether or not an abnormality occurs during sample aspiration.
[0081] Furthermore, by slowing down the aspiration speed only when sample dispensing is required, it is possible to minimize the increase in the time required for dispensing and maximize the number of analyses that can be processed per unit time.
[0082] The configuration of this embodiment is particularly effective when multiple aspiration steps are performed before aspirating a sample, such as aspirating segmented air or a reagent before aspirating a sample. When multiple aspiration steps are performed before aspirating a sample, suppressing the generation of a liquid film in all steps makes it possible to accurately determine whether or not there is an abnormality during aspirating the sample.
[0083] <Modification 1 of First Embodiment> Fig. 6 is a schematic diagram showing a dispensing mechanism 200 of an automatic analyzer according to a modification of the first embodiment. As shown in Fig. 6, the dispensing mechanism 200 includes a probe 601 (dispensing nozzle) instead of the tip 101 and probe 102 shown in Fig. 1. The configuration other than the probe 601 is the same as that of the dispensing mechanism 100 of the first embodiment, and therefore a description thereof will be omitted.
[0084] In this modification, steps S203 and S217 are omitted from the flowchart of Fig. 2, and the chip is replaced with a probe. Also, in Fig. 4, the chip 101 and the probe 102 are combined and replaced with a probe 601.
[0085] <Modification 2 of First Embodiment> The abnormality determination during sample dispensing may be omitted. For example, pressure measurement may not be performed in step S211, and steps S212 to S214 may be omitted. Furthermore, the pressure sensor 117, signal amplifier 119, A / D converter 120, determination unit 121, etc. may also be omitted.
[0086] In the first embodiment, the aspiration speed in step S202 is changed depending on whether or not a sample is dispensed in the dispensing operation in step S501. In this embodiment, the aspiration speed in the segmented air aspiration step is changed depending on the aspiration volume of the segmented air.
[0087] As explained in the first embodiment, the amount of cleaning water 105 remaining below the boundary 403 is calculated by multiplying formula (1) by the moving distance of the boundary 403. The moving distance of the boundary 403 becomes longer in processes in which the suction volume is large.
[0088] In this embodiment, a method of changing the suction speed depending on the size of the suction volume of the segmented air is shown, taking the suction process of segmented air 401 and segmented air 402 as an example. Fig. 7 is a flowchart showing a method of setting the suction speed in the suction process of segmented air 401 and segmented air 402.
[0089] In step S701, the volume of the segmented air 401 is compared with the volume of the segmented air 402. If the volume of the segmented air 401 is larger (Yes), the suction speed of the segmented air 401 is set to a low speed v1, and the suction speed of the segmented air 402 is set to a high speed v2 (step S702), since the cleaning water 105 is likely to remain in the suction process of the segmented air 401. In other words, v2 > v1.
[0090] On the other hand, if the volume of the segmented air 401 is smaller (No), residual cleaning water 105 is likely to occur during the suction process of the segmented air 402, so the suction speed of the segmented air 401 is set to high speed v2 and the suction speed of the segmented air 402 is set to low speed v1 (step S703).
[0091] In this way, the dispensing mechanism 100 uses the multiple levels v1 and v2 depending on the volume of air being aspirated. In particular, when the volume of air being aspirated is large, the level v1 of the slow aspirating speed is used, and when the volume of air being aspirated is small, the level v2 of the fast aspirating speed is used.
[0092] More specifically, in the process flow for sucking in a first volume of air and a second volume of air, if the first volume is larger than the second volume, a low speed v1 is used to suck in the first volume of air and a high speed v2 is used to suck in the second volume of air, and if the second volume is larger than the first volume, a low speed v1 is used to suck in the second volume of air and a high speed v2 is used to suck in the first volume of air.
[0093] In the above, the aspiration speed in the aspiration steps of the segmented air 401 and the segmented air 402 is changed according to the aspiration volume of each analysis air, thereby accurately determining whether or not there is an abnormality during aspiration of the specimen 115. By slowing down only the steps in which a large aspiration volume is involved, it is possible to minimize the increase in the time required for dispensing and maximize the number of analyses that can be processed per unit time.
[0094] In this embodiment, the aspiration speed is set according to the aspiration volume using segmented air as an example, but as a modified example, the aspiration speed can be set according to the aspiration volume of the reagent.
[0095] The different levels may be used in a combination of the first and second embodiments. For example, a plurality of levels may be used depending on both the type of fluid and the volume of air suction.
[0096] [Third Embodiment] In this embodiment, the suction speed in the suction process of the segmented air is changed depending on the purpose of suctioning the segmented air.
[0097] In this embodiment, a method of changing the aspiration speed depending on whether the pressure in the segmented air aspiration step is a criterion for determining whether the sample aspiration is abnormal or not is shown. Fig. 8 is a flowchart showing a method of setting the aspiration speed in the segmented air aspiration step.
[0098] In this embodiment, the dispensing mechanism 100 has multiple levels of aspiration speed, namely v1 and v3, when aspirating air into the probe 102 (or into the tip 101 attached to the tip of the probe 102). v3 > v1, and v3 is the same as the aspiration speed when aspirating a sample. The magnitude relationship between v2 and v3 is arbitrary, and v2 = v3 may also be satisfied.
[0099] In step S801, it is determined whether the pressure during the aspiration of the segmented air serves as a criterion for determining whether the sample aspiration is abnormal. This determination can be made based on, for example, preset operating parameters of the automatic analyzer.
[0100] If the pressure during the aspirating of the segmented air does not meet the criteria for determining whether the sample is being aspirated abnormally (No), the aspirating speed of the segmented air 401 is set to a low speed v1 (step S802) to prevent residual cleaning water 105. That is, when the pressure history during aspirating air is used to determine whether the sample to be analyzed has been dispensed normally, v1 of the multiple levels v1 and v3 is used.
[0101] On the other hand, if the pressure during aspirating the segmented air is the criterion for determining abnormalities in sample aspirating (Yes), then setting the aspirating speed of the segmented air to the same as the aspirating speed during sample aspirating is an appropriate criterion, and therefore the aspirating speed of the segmented air is set to high speed v3 (step S803).
[0102] In this way, when the time series data when aspirating air is not used to determine whether the sample to be analyzed has been dispensed normally, v3 out of the multiple levels v1 and v3 is used.
[0103] In the above, the presence or absence of an abnormality during the aspiration of the sample 115 is determined with high accuracy by changing the aspiration speed depending on whether the pressure during the aspiration process of the segmented air serves as the criterion for determining an abnormality in the sample aspiration. By setting the aspiration speed of the segmented air, which serves as the criterion for determining an abnormality in the sample aspiration, to the same as the aspiration speed of the sample, it is possible to adopt an appropriate criterion for determining an abnormality. Furthermore, by slowing down the aspiration process of other segmented air, the generation of a liquid film is suppressed, making it possible to determine with high accuracy whether or not an abnormality occurs during the aspiration of the sample.
[0104] In this embodiment, the value of the low speed v1 in the first to third embodiments is changed depending on the diameter and material of the flow path. In particular, the value of the low speed v1 in Figures 5, 7, and 8 is changed depending on the diameter and material of the flow path where the boundary 403 is located.
[0105] 9 is a schematic diagram showing the state of the fluid in the probe 102. In this embodiment, the flow path in the probe 102 is composed of a small-diameter flow path 901, a tapered portion 902, a large-diameter flow path 903, and a flow path 904 made of a different material from the flow paths 901 to 903.
[0106] When the boundary 403 is located in the small-diameter flow path 901, the flow velocity v in the pipeline increases, making it easier for residual liquid to remain, so it is desirable to set the value of the low velocity v1 smaller than when the boundary 403 is located in the tapered section 902 or flow path 903. On the other hand, when the boundary 403 is located in the large-diameter flow path 903, the flow velocity v in the pipeline decreases, making it harder for residual liquid to remain, so it is desirable to set the value of the low velocity v1 larger than when the boundary 403 is located in the flow path 901 or tapered section 902 (however, within the range of v1<v2).
[0107] Furthermore, when flow paths 903 and 904 have the same shape and liquid is likely to remain in flow path 904, it is desirable to make the value of the low speed v1 smaller when boundary 403 is located in flow path 904 than when boundary 403 is located in flow path 903.
[0108] [Modifications] The present disclosure is not limited to the above-described embodiments and includes various modifications. For example, the configurations of the first to fourth embodiments and their modifications can be used in combination with each other to more effectively increase the accuracy of determining whether or not an abnormality occurs during sample aspiration.
[0109] Furthermore, the above-described embodiments have been described in detail to clearly explain the present disclosure, and it is not necessary to include all of the configurations described. Furthermore, a part of one embodiment can be replaced with a configuration of another embodiment. Furthermore, a configuration of another embodiment can be added to a configuration of one embodiment. Furthermore, a part of the configuration of each embodiment can be added to, deleted from, or replaced with a part of the configuration of another embodiment.
[0110] The dispensing method of each of the above-described embodiments can be implemented not only in an automatic analyzer but also in other devices having a fluid dispensing mechanism. For example, the techniques of each of the embodiments can be applied to pharmaceutical manufacturing devices, microreactors, etc.
[0111] DESCRIPTION OF SYMBOLS 100... Dispensing mechanism 101... Tip 102... Probe 103... Flow path 104... Syringe (pressure source) 104a... Cylinder 104b... Plunger 105... Cleaning water 106... Syringe drive unit 107... Probe drive unit 108... Control unit 109... Water supply pump 110... Water supply tank 111... Solenoid valve 112... Reagent container 113... Reagent (fluid) 114... Specimen container (container) 115... Specimen (fluid) 116... Reaction vessel (container) 117... Pressure sensor 118... Branching block 119... Signal amplifier 120... A / D converter 121... Determination unit 122... Sampling unit 123... Memory unit 124... Calculation unit 125... Display unit 126... Tip disposal unit 127... Cleaning tank 127a... Cleaning nozzle 127b: Drainage cup 128: Solenoid valve 200: Dispensing mechanism 401: Segmented air 402: Segmented air 403: Boundary 601: Probe 901: Flow path 902: Tapered portion 903: Flow path 904: Flow path
Claims
1. An automatic analyzer comprising: a container for storing a fluid; a pressure source; a probe for dispensing the fluid in the container; and a flow path connecting the probe and the pressure source, wherein the automatic analyzer has a plurality of levels of aspiration speed for aspirating air into the probe or into a tip attached to the tip of the probe, and uses different levels depending on at least one of the type of fluid or the volume of the air aspirated.
2. The automatic analyzer according to claim 1, further comprising a pressure sensor that measures time series data regarding the pressure in the flow path, and a memory unit that stores the time series data, and the automatic analyzer determines whether or not the sample to be analyzed has been dispensed normally based on the time series data.
3. An automatic analyzer according to claim 1, wherein said level is selected depending on whether or not said fluid contains a specimen to be analyzed.
4. An automatic analyzer according to claim 1, characterized in that a low level of suction speed is used when the volume of the air suctioned is large.
5. An automatic analyzer as claimed in claim 2, characterized in that the time series data obtained when the air is aspirated is used to determine whether the sample to be analysed has been dispensed normally.
6. An automatic analyzer as described in claim 5, wherein a first level among the levels is used when the time series data when the air is aspirated is used to determine whether the sample to be analyzed has been dispensed normally or not, and a second level among the levels, different from the first level, is used when the time series data when the air is aspirated is not used to determine whether the sample to be analyzed has been dispensed normally or not.
7. An automatic analyzer according to claim 1, characterized in that the step of aspirating air is carried out a plurality of times between the time when the fluid is aspirated into the probe and the time when the fluid is discharged.
8. A method of dispensing a fluid using an automatic analyzer, the automatic analyzer comprising: a container for storing a fluid; a pressure source; a probe for dispensing the fluid in the container; and a flow path connecting the probe and the pressure source, the automatic analyzer having a plurality of levels of aspiration speed for aspirating air into the probe or into a tip attached to the tip of the probe, the dispensing method including selectively using the levels depending on at least one of the type of fluid or the volume of air aspirated.
Citation Information
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