Automatic analyzer, and dispensing method
By using multiple suction speed levels for air aspiration in the automatic analyzer, the system effectively minimizes liquid films and residues, enhancing the accuracy of abnormality detection during the dispensing of multiple liquids.
Patent Information
- Application Number
- JP2023204054
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-12-01
- Publication Date
- 2025-06-12
AI Technical Summary
Existing automatic analyzers face challenges in accurately detecting abnormalities during the dispensing of multiple liquids, as liquid films or residues from preceding liquids can interfere with the detection of abnormalities in the liquid being analyzed.
The automatic analyzer employs a dispensing mechanism with multiple levels of suction speed for air aspiration, which are adjusted based on the type of fluid or the suction volume of air, minimizing liquid films and residues and enabling precise abnormality detection.
This approach allows for highly accurate detection of abnormalities during dispensing, improving the reliability of analysis results by reducing the impact of liquid films and residues.
Smart Images

Figure 2025089078000001_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to an automatic analyzer and a dispensing method.
Background Art
[0002] Automatic analyzers such as biochemical analyzers and immunoassay analyzers are equipped with a dispensing mechanism that aspirates a specified amount of a sample such as a biological sample and a reagent and discharges it into a reaction vessel, and an analysis mechanism that analyzes the reaction solution of the sample and the reagent.
[0003] The dispensing mechanism is composed of a probe inserted into a liquid such as a sample or a reagent, a syringe that serves as a pressure source for aspirating and discharging the liquid, and a flow path connecting the probe and the syringe. The dispensing mechanism inserts the probe into the liquid in the sample container or reagent container, operates the syringe to aspirate a specified amount of the liquid, moves the probe to the reaction vessel, and discharges the liquid to dispense a specified amount of the liquid. Note that, at the time of dispensing, in order to prevent the carry-over of components to the next test, a disposable tip may be attached to the tip of the probe.
[0004] Depending on the analysis item, a plurality of reagents or both the reagent and the sample may be simultaneously held in the probe or the tip (dispensing nozzle) and dispensed into the reaction vessel. When holding a plurality of liquids in the dispensing nozzle simultaneously in this way, the dispensing is performed by successively aspirating a plurality of types of liquids and discharging all the liquids into the reaction vessel after aspirating all the liquids. By simultaneously dispensing a plurality of types of liquids, it is possible to reduce the amount of washing water used, reduce the number of tips used, and shorten the time required for dispensing.
[0005] At the time of dispensing, abnormalities such as aspirating bubbles generated by handling the sample container and clogging of the flow path due to high-viscosity samples or fibers such as fibrin in the sample may occur. Therefore, by accurately estimating the dispensing state and detecting with high accuracy that an abnormality has occurred, the accuracy of the analysis result can be improved.
[0006] As a method for detecting abnormalities in dispensing, for example, Patent Document 1 discloses a technique for detecting abnormalities in dispensing by using, as an index, the integrated value of pressure data in a specific time period with respect to pressure fluctuations during specimen ejection, or the difference between the average pressure value calculated at the end of ejection and the average pressure value calculated during normal ejection, and comparing these with preset threshold values.
[0007] Further, Patent Document 2 discloses a technique for detecting an abnormality when dispensing a predetermined liquid by using the ratio of the pressure when dispensing a reference liquid used as a reference for abnormality detection to the pressure when dispensing the predetermined liquid.
Prior Art Documents
Patent Documents
[0008]
Patent Document 1
Patent Document 2
Summary of the Invention
Problems to be Solved by the Invention
[0009] However, in the configuration described in Patent Document 1, when simultaneously dispensing a plurality of types of liquids, if the suction of the liquid to be detected for abnormalities is not at the head, the accuracy of abnormality detection may decrease due to the liquid film or remaining liquid generated during the suction of the preceding liquid.
[0010] Similarly to Patent Document 1, in the case of Patent Document 2, when simultaneously dispensing a plurality of types of liquids, if the suction of the liquid to be detected for abnormalities is not at the head, the accuracy of abnormality detection may decrease due to the liquid film or remaining liquid generated during the suction of the preceding liquid.
[0011] Therefore, the present disclosure provides a technique that minimizes liquid films, liquid residues, etc. generated during suction of a liquid sucked before a liquid to be subjected to abnormality detection when dispensing a plurality of liquids simultaneously, and enables highly accurate detection of abnormalities during dispensing of the liquid to be subjected to abnormality detection.
Means for Solving the Problems
[0012] An example of an automatic analyzer according to the present invention is a container for containing a fluid, a pressure source, a probe for dispensing the fluid in the container, a flow path connecting the probe and the pressure source, and an automatic analyzer comprising wherein the automatic analyzer has a plurality of levels of suction speed for sucking air when sucking air into the probe or when sucking air into a tip attached to the probe tip, and uses the levels properly according to at least one of the type of the fluid or the suction volume of the air.
[0013] In an example of a method for dispensing a fluid using an automatic analyzer according to the present invention, the automatic analyzer has a container for containing a fluid, a pressure source, a probe for dispensing the fluid in the container, a flow path connecting the probe and the pressure source, and comprises wherein the automatic analyzer has a plurality of levels of suction speed for sucking air when sucking air into the probe or when sucking air into a tip attached to the probe tip, and the dispensing method includes properly using the levels according to at least one of the type of the fluid or the suction volume of the air.
[0014] Further features related to the present disclosure will become apparent from the description herein and the accompanying drawings. Also, aspects of the present disclosure are achieved and realized by elements and combinations of various elements and the aspects of the following detailed description and the appended claims.
[0015] The description herein is merely exemplary and does not limit the scope or application examples of the present disclosure in any sense.
Advantages of the Invention
[0016] According to the automatic analyzer of the present disclosure, it is possible to highly accurately detect an abnormality during dispensing of a liquid to be subjected to abnormality detection.
[0017] Problems, configurations, and effects other than those described above will be clarified by the description of the following embodiments.
Brief Description of the Drawings
[0018]
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Mode for Carrying Out the Invention
[0019] [First Embodiment] <Configuration of the Dispensing Mechanism of the Automatic Analyzer> In the dispensing mechanism of the automatic analyzer according to the first embodiment, a form in which a detachable chip is attached to the tip of the probe is adopted. The dispensing mechanism of this embodiment sucks the reagent and the sample into the chip in order and simultaneously dispenses them into the reaction vessel, and detects the suction of air bubbles (hereinafter referred to as "air suction") or clogging when sucking the sample while sucking and holding the reagent in the chip in advance.
[0020] FIG. 1 is a schematic configuration diagram showing a dispensing mechanism 100 of an automatic analyzer according to the first embodiment. As shown in FIG. 1, the dispensing mechanism 100 includes a chip 101, a probe 102, a flow path 103, a syringe 104 (pressure source), a syringe drive unit 106, a probe drive unit 107, a control unit 108, a water supply pump 109, a water supply tank 110 that stores washing water 105, a solenoid valve 111, a reagent container 112 (container) that stores a reagent 113 (fluid) according to the analysis item, a sample container 114 (container) that stores a sample 115 (fluid), a reaction vessel 116, a pressure sensor 117, a branch block 118, a signal amplifier 119, an A / D converter 120, a determination unit 121 (including a sampling unit 122, a storage unit 123, and a calculation unit 124), a display unit 125, a chip disposal unit 126, a washing tank 127, and a solenoid valve 128.
[0021] The chip 101 (dispensing nozzle) is detachable from the tip of the probe 102. A probe driving unit 107 such as a motor and an actuator (not shown) is connected to the probe 102, and by this, the probe 102 can be moved in the horizontal and vertical directions and moved to a predetermined position. The chip 101 is held, for example, in a chip rack (not shown), and the chip 101 can be attached to the probe 102 by the probe driving unit 107 moving the probe 102 above the chip rack and lowering it. Note that the chip 101 may be attached to the probe 102 in a chip buffer that temporarily holds the chip 101.
[0022] The probe 102 is connected to the syringe 104 via the flow path 103, and their interiors are filled with cleaning water 105. The syringe 104 has a cylinder 104a and a plunger 104b, and a syringe driving unit 106 is connected to the plunger 104b. The syringe driving unit 106 drives the plunger 104b in the vertical direction with respect to the cylinder 104a, and thereby sucks and discharges fluids (liquids and gases) with the chip 101 connected to the probe 102. In particular, the probe 102 can dispense the reagent 113 in the reagent container 112 and the specimen 115 in the specimen container 114.
[0023] The syringe 104 has a flow path communicating with the water supply tank 110, and a solenoid valve 111 and a water supply pump 109 are provided in the flow path. The cleaning water 105 is stored in the water supply tank 110, and by driving the water supply pump 109 to discharge the cleaning water 105 from the probe 102, the inside of the probe 102 can be cleaned. The cleaning of the probe 102 is performed, for example, before dispensing the reagent 113 and the specimen 115.
[0024] Although not shown in the figure, the automatic analyzer has a reagent storage that holds the reagent container 112, a specimen container rack that holds the specimen container 114, and a reaction disk that holds the reaction container 116. The holding means for the reagent container 112, the specimen container 114, and the reaction container 116 are not limited to the above. The reagent 113 and the specimen 115 sucked by the chip 101 are dispensed into the reaction container 116.
[0025] The control unit 108 controls the operations of the syringe drive unit 106, the probe drive unit 107, the water supply pump 109, and the solenoid valve 111. The control unit 108 may be configured to control not only each component of the dispensing mechanism 100 but also the operations of the entire automatic analyzer.
[0026] The pressure sensor 117 is connected to a branch block 118 provided in the middle of the flow path 103 and measures time-series data on the pressure in the flow path 103. The pressure sensor 117 outputs a detection signal of the pressure to the signal amplifier 119. The position of the pressure sensor 117 may be on the syringe 104 side as shown in FIG. 1, but by connecting the pressure sensor 117 at a position as close as possible to the probe 102, pressure fluctuations at the opening of the 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] The determination unit 121 is a circuit for determining the presence or absence of an abnormality during the dispensing operation of the dispensing mechanism 100. The determination unit 121 includes a sampling unit 122 that receives the input of the pressure value from the A / D converter 120, a storage unit 123 that stores data such as the pressure value input to the sampling unit 122, and a calculation unit 124 that executes processing on the data stored in the storage unit 123.
[0029] The determination unit 121 is configured to be communicable with the control unit 108, and when it is determined from the result of data processing in the calculation unit 124 that it is desirable to abort the operation, the determination unit 121 transmits the content of the abort operation to the control unit 108.
[0030] The determination unit 121 may be configured as hardware within 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 within a server connected communicably to the automatic analyzer wirelessly or by wire may read and execute a program and 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 result of data processing in the determination unit 121, information regarding the result, and the like.
[0032] The chip disposal unit 126 disposes of the chip 101 in which the dispensing of the reagent 113 and the specimen 115 into the reaction vessel 116 has been completed.
[0033] The cleaning tank 127 is composed of a cleaning nozzle 127a and a drain cup 127b, and the outer wall of the chip 101 can be cleaned by the cleaning nozzle 127a. The cleaning water 105 when cleaning the outer wall of the chip 101 is discharged from the cleaning nozzle 127a through the solenoid valve 128.
[0034] <Dispensing method> FIG. 2 is a flowchart showing the dispensing method according to the first embodiment, and particularly shows a method for dispensing a fluid using an automatic analyzer. The dispensing method of the present embodiment is executed by the automatic analyzer. Actually, the control unit 108 shown in FIG. 1 controls the operations of the respective components of the dispensing mechanism 100 (the syringe drive unit 106, the probe drive unit 107, the water supply pump 109, the solenoid valve 111, etc.) to implement it. However, in the following, there may be cases where the respective components of the dispensing mechanism 100 are described with the operation as the main subject.
[0035] In step S201, the control unit 108 opens the solenoid 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. Thereby, the inside of the probe 102 is cleaned.
[0036] In step S202, the syringe drive unit 106 drives the syringe 104 to suck 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 sucked in the next step.
[0037] In step S203, the probe drive unit 107 moves the probe 102 above the chip rack or chip buffer and then lowers it to attach the chip 101 to the tip of the probe 102.
[0038] In step S204, it is determined whether there is a reagent that needs to be dispensed. If there is a reagent that needs to be dispensed (Yes), steps S205 to S208, which are the steps of sucking the reagent, are performed, and then the process returns to step S204. That is, the steps from S205 to S208 are repeatedly executed until the suction of all the reagents that need to be dispensed is completed. For example, if there are two types of reagents that need to be dispensed and suction is required, the steps from S205 to S208 are repeated twice. If there is no reagent that needs to be dispensed (No), the steps from S205 to S208 are not performed.
[0039] In step S205, the probe drive unit 107 moves the probe 102 above the reagent container 112 and lowers it until the tip of the chip 101 is immersed in the reagent 113.
[0040] In step S206, the syringe drive unit 106 drives the syringe 104 to suck the reagent 113 into the chip 101. Then, the probe drive unit 107 raises the probe 102 until the tip of the chip 101 comes out of the reagent 113.
[0041] In step S207, the syringe drive unit 106 drives the syringe 104 to suck segmented air into the chip 101. This is to prevent the reagent 113 previously sucked into the chip 101 from mixing with the liquid to be sucked in the next step.
[0042] In step S208, the control unit 108 opens the solenoid 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, the outer wall of the chip 101 is cleaned. This is to prevent the reagent 113 previously aspirated into the chip 101 from mixing into the liquid aspirated in the next step.
[0043] As described above, the steps from S205 to S208 may be repeated multiple times. The dispensing mechanism 100 can perform the step of aspirating air (step S207) multiple times between aspirating and discharging the fluid (reagent 113 and / or sample 115) into the probe 102. This can prevent many types of fluids from mixing.
[0044] In step S209, it is determined whether there is a sample that needs to be dispensed. If there is a sample that needs to be dispensed (Yes), steps S210 to S214, which are the steps of aspirating the sample, are performed. If there is no sample that needs to be dispensed (No), the steps from S210 to S214 are not performed.
[0045] In step S210, the probe driving unit 107 moves the probe 102 above the sample container 114 and lowers it until the tip of the chip 101 is immersed in the sample 115.
[0046] In step S211, the syringe driving unit 106 drives the syringe 104 to aspirate the sample 115 into the chip 101. Here, the sampling unit 122 of the determination unit 121 receives the input of the pressure value during the aspiration operation of the sample 115 and transmits the pressure value related to the aspiration operation of the sample 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 in the time period before the start of the suction operation, during the suction operation, and after the end of the suction operation. In each time period, the pressure may be measured at multiple time points. Thereafter, the probe drive unit 107 raises the probe 102 until the tip of the chip 101 exits the specimen 115.
[0048] In step S212, the calculation unit 124 of the determination unit 121 determines (detects an abnormality) whether there is an abnormality such as clogging or air aspiration during the suction of the specimen 115 based on the pressure history during specimen suction stored in the storage unit 123. That is, based on the pressure history, it is determined whether the dispensing of the specimen to be analyzed was performed normally.
[0049] Note that the pressure history when an abnormality such as air aspiration or clogging occurs during the suction of the specimen 115 is significantly different from the pressure history when normal dispensing is performed. Therefore, by referring to the pressure history, it is possible to determine the presence or absence of an abnormality. 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 of the presence or absence of an abnormality to the display unit 125 and the control unit 108. Further, the display unit 125 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 that the specimen 115 was suctioned normally based on the determination result received from the determination unit 121.
[0052] If it is determined in step S212 that there is an abnormality (Yes), the process proceeds to step S214. In step S214, the control unit 108 determines that there was an abnormality during the suction of the specimen 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 specimen 115 is terminated. Also, the specimen 115 is returned to the user. In this way, by aborting the dispensing of the specimen 115 with an abnormality, the consumption of the reagent used in subsequent analysis can be reduced.
[0053] In the example of FIG. 2, the process proceeds to step S215 after step S214. However, as a modification, predetermined error processing or the like may be executed after step S214. In that case, other processing may be executed thereafter instead of step S215 and subsequent steps.
[0054] In step S215, the probe 102 is moved so that the tip of the chip 101 is positioned inside the reaction vessel 116.
[0055] In step S216, the syringe drive unit 106 drives the syringe 104 to discharge the liquid held in the chip 101 into the reaction vessel 116. At this time, all the reagents and specimens sucked into the chip 101 are simultaneously discharged into the reaction vessel 116.
[0056] In step S217, the probe drive unit 107 moves the probe 102 to the chip disposal unit 126 and removes the chip 101 from the probe 102 by disposing of the chip 101 in the chip disposal unit 126.
[0057] <Method for determining presence or absence of abnormality> FIG. 3 is a flowchart showing a method for determining the presence or absence of an abnormality by the determination unit 121 in step S212 of FIG. 2.
[0058] In step S301, the calculation unit 124 reads out the pressure history at the time of specimen aspiration stored in the storage unit 123. In this specification, the "pressure history at the time of specimen aspiration" refers to the pressure values in a predetermined time range including the operation time (aspiration operation time) of the syringe 104 when aspirating the specimen 115 in step S211.
[0059] In step S302, the calculation unit 124 calculates a determination index used for determining the presence or absence of an abnormality based on the pressure history at the time of specimen aspiration. The "determination index" includes, for example, at least one of the following values: - The average value of the pressure values during the aspiration operation of the specimen 115. - The average value of the pressure values at a predetermined time immediately before the start of the aspiration operation of the specimen 115. - The average value of the pressure values at a predetermined time immediately after the end of the aspiration operation of the specimen 115. - The maximum value of the pressure values during the aspiration operation of the specimen 115. - The minimum value of the pressure values during the aspiration operation of the specimen 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 the preset reference pressure history and the pressure history obtained in this step. The distance may be a statistical distance, and for example, it may be the Euclidean distance. The Euclidean distance between the pressure history {a 1 , a 2 , a 3 , …, a n} and the pressure history {b 1 , b 2 , b 3 , …, b n} can be expressed as √{Σ(a i - b i ) 2} (where 1 ≤ i ≤ n).
[0060] The "reference pressure history" is, for example, set based on a large number of pressure values obtained in the past, and may be the pressure value when it is determined that the specimen has been aspirated normally (in this case, for example, when the statistical distance is greater than the determination 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 specimen aspiration (in this case, for example, when the statistical distance is less than the determination threshold, it is determined that there is an abnormality).
[0061] Also, the reference pressure history may be determined based on the pressure measured during the segmented air aspiration immediately before aspirating the specimen and using the pressure value during the segmented air aspiration. That is, the pressure history when aspirating air may be used to determine whether the dispensing of the specimen to be analyzed has been performed normally (in this case, for example, when the statistical distance is less than the determination threshold, it is determined that there is an abnormality). In this way, it is possible to make a determination that is less affected by the temporal change in the state of the flow path.
[0062] The statistical distance (i.e., similarity or dissimilarity) from this reference pressure history can also be used as a determination index. When measuring the pressure during the segmented air suction immediately before aspirating the specimen and determining the presence or absence of an abnormality based on the pressure value during the segmented air suction, it is preferable to set the suction speed during the segmented air suction immediately before to be the same as the suction speed during the specimen aspiration. Also, a plurality of the above-described indexes may be combined and used as a determination index.
[0063] In this specification, the "suction speed" can be represented by, for example, the moving speed of a specific member (for example, the plunger 104b of the syringe 104) with the unit being m / s or the moving speed in a specific flow path of the fluid being aspirated. Alternatively, the suction speed can be represented by, for example, m 3 / s and can also be represented by the flow rate of the fluid being aspirated. It can also be represented by other flow velocities, flow rates, etc. The conversion of these physical quantities can be appropriately performed by, for example, the control unit 108.
[0064] In this embodiment, as a determination index, the difference between the average value of the pressure values during the aspiration operation of the specimen 115 and the average value of the pressure values for a predetermined time before the start of the aspiration operation is calculated, and this is used to determine whether it was a normal dispensing or an air aspiration. For example, when the difference is smaller than a predetermined threshold value, it is determined that an air aspiration occurred. As a cause of the air aspiration, misdetection of the liquid level due to bubbles unintentionally generated by handling of the specimen container 114 can be considered. Note that bubbles are generated when the blood specimen 115 is shaken during conveyance.
[0065] In step S303, the calculation unit 124 determines the presence or absence of an abnormality during the aspiration of the specimen 115 based on the determination index. As methods for determining the presence or absence of an abnormality, in addition to the above-described specific methods, for example, there are a method of comparing the determination index with a predetermined determination threshold value, a method of determining an abnormality when a condition in which a combination of a plurality of determination indexes is satisfied, and the like. In the present embodiment, an algorithm will be used in which the presence or absence of an abnormality is determined by comparing the determination index with a certain determination threshold value. The determination threshold value used for determining the presence or absence of an abnormality is stored in advance in the storage unit 123.
[0066] FIG. 4 is a schematic diagram showing the state of the fluid in the probe 102 and the chip 101 in the dispensing operation shown in FIG. 2. In FIG. 4, a case where one type of reagent and one type of specimen are dispensed is illustrated. FIG. 4(a) shows the state immediately after the inside of the probe 102 is washed with the washing water 105 in step S201. As shown in FIG. 4(a), the inside of the probe 102 is filled with the washing water 105.
[0067] FIG. 4(b) shows the state after aspirating the segmented air 401 in step S202 and attaching the chip 101 in step S203.
[0068] FIG. 4(c) shows the state after aspirating the reagent 113 in step S206. The reagent 113 is located at the tip of the chip 101.
[0069] FIG. 4(d) shows the state in which the segmented air 402 is aspirated in step S207. The segmented air 402 is located at the tip of the chip 101, and the reagent 113 is located thereon. Although FIG. 4(d) shows one type of reagent 113, when a plurality of reagents are dispensed, the reagent 113 and the segmented air 402 are alternately arranged by the number of aspirated reagents.
[0070] Fig. 4(e) shows the state in which the specimen 115 is aspirated in step S211. The specimen 115 is located at the tip of the chip 101, the segmented air 402 is located thereon, and the reagent 113 is located above the segmented air 402.
[0071] As described above, the presence or absence of an abnormality is determined using the pressure history during aspiration of the specimen 115. Before aspirating the specimen 115, aspiration steps for the reagent 113, the segmented air 401, the segmented air 402, etc. are performed. For example, regarding the boundary 403 between the washing water 105 and the segmented air 401, it has moved upward in all the aspiration steps of the reagent 113, the segmented air 401, and the segmented air 402.
[0072] When the boundary 403 moves, a part of the washing water 105 may adhere to the inner wall of the probe 102 and be left behind, and a liquid film may be generated on the inner wall of the probe 102. By reducing the generation of such a liquid film, it is possible to suppress the occurrence of the remaining liquid of the washing water 105 below the boundary 403 and keep the state before aspirating the specimen 115 (Fig. 4(d)) uniform. Thereby, by enhancing the reproducibility of the pressure history during aspiration of the specimen 115, it becomes possible to accurately determine the presence or absence of an abnormality during aspiration of the specimen 115.
[0073] As an example of a physical formula representing the thickness d of the liquid film generated when the boundary 403 moves, the following formula (1) can be cited. d ∝ D×(μv / σ) 2 / 3 … Formula (1) Here, D represents the flow path diameter, μ represents the viscosity of the fluid, v represents the aspiration speed, σ represents the surface tension of the fluid, and ∝ indicates a proportional relationship. The amount of the remaining liquid of the washing water 105 left at the lower part of the boundary 403 is the value obtained by multiplying the moving distance of the boundary 403 by the formula (1).
[0074] In order to reduce the amount of the remaining liquid of the washing water 105, it is effective to decrease the aspiration speed. Specifically, it is effective to decrease the aspiration speed in the aspiration steps of the reagent 113, the segmented air 401, and the segmented air 402. However, decreasing the aspiration speed in the aspiration steps will increase the time required for dispensing.
[0075] In this embodiment, step S202, which is the step of aspirating segmented air, is taken as an example, and a method for reducing the aspiration speed in this step is shown. FIG. 5 is a flowchart showing the method for setting the aspiration speed in step S202.
[0076] In step S501, it is determined whether or not to dispense the sample in this dispensing. When dispensing the sample (Yes), in order to determine the abnormality during aspiration of the sample 115 with high accuracy, it is desirable to enhance the reproducibility of the pressure history during aspiration of the sample 115. Therefore, it is desirable to suppress the occurrence of the remaining liquid of the washing water 105. For this reason, it is desirable to reduce the aspiration speed in step S202, and the aspiration speed is set to the low speed v1 (step S502). In this case, steps S210 to S214 are to be executed in the process of FIG. 2.
[0077] On the other hand, when not dispensing the sample (No), since it is not necessary to determine the presence or absence of an abnormality during aspiration of the sample 115, the aspiration speed is set to the high speed v2 (step S503). That is, v2 > v1. In this case, steps S210 to S214 are not executed in the process of FIG. 2.
[0078] As described above, the dispensing mechanism 100 has a plurality of levels, namely v1 (the first level) and v2 (the second level), as the level of the aspiration speed for aspirating air into the probe 102 (or into the tip 101 attached to the tip of the probe 102).
[0079] In the above, the aspiration speed in step S202 is changed according to whether or not to dispense the sample in this dispensing. That is, the dispensing mechanism 100 selectively uses the plurality of levels v1 and v2 according to the type of the fluid to be aspirated, and in particular, selectively uses them according to whether or not the fluid to be aspirated contains the sample to be analyzed. Thereby, when dispensing the sample 115, the presence or absence of an abnormality during aspiration can be accurately determined, and when not dispensing the sample 115, it is possible to prevent the dispensing time from becoming long. Changing the speed of the aspiration process according to the presence or absence of sample dispensing can be applied to any of the aspiration processes of the reagent 113, the segmented air 401, and the segmented air 402.
[0080] <Technical effects> As described above, the automatic analyzer of the present embodiment changes the suction speed in the suction process of segmented air and reagents according to the presence or absence of specimen dispensing. When dispensing a specimen, by reducing the suction speed in the suction process of segmented air and reagents, the generation of a liquid film generated in the flow path before specimen suction is suppressed, and by enhancing the reproducibility of the pressure history during specimen suction, it becomes possible to accurately determine the presence or absence of abnormalities during specimen suction.
[0081] In addition, by reducing the suction speed only when there is specimen dispensing, an increase in the dispensing time required can be minimized, and the number of analyses that can be processed per unit time can be maximized.
[0082] The configuration of this embodiment is particularly effective when multiple suction steps are performed before sucking the specimen, such as sucking segmented air and reagents and then sucking the specimen. When multiple suction steps are performed before specimen suction, by suppressing the generation of a liquid film in all steps, it becomes possible to accurately determine the presence or absence of abnormalities during specimen suction.
[0083] <Modification 1 of the First Embodiment> FIG. 6 is a schematic configuration 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 chip 101 and the probe 102 shown in FIG. 1. Since the configurations other than the probe 601 are the same as those of the dispensing mechanism 100 of the first embodiment, the description thereof is omitted.
[0084] In this modification, in the flowchart of FIG. 2, steps S203 and S217 are omitted, and the chip is replaced with a probe. Further, in FIG. 4, the chip 101 and the probe 102 are combined and replaced with the probe 601.
[0085] <Modification 2 of the First Embodiment> Abnormal determination in the dispensing of the specimen may be omitted. For example, in step S211, pressure measurement may not be performed, and steps S212 to S214 may be omitted. Further, the pressure sensor 117, the signal amplifier 119, the A / D converter 120, the determination unit 121, etc. may also be omitted.
[0086] [Second Embodiment] In the first embodiment, in step S501, the suction speed in step S202 was changed according to whether or not to dispense the specimen in the dispensing. In this embodiment, the suction speed in the suction process of the segmented air is changed according to the suction volume of the segmented air.
[0087] As described in the first embodiment, the remaining liquid amount of the washing water 105 left at the lower part of the boundary 403 is the value obtained by multiplying the moving distance of the boundary 403 by the formula (1). The moving distance of the boundary 403 becomes long in the process with a large suction volume.
[0088] In this embodiment, taking the suction processes of the segmented air 401 and the segmented air 402 as an example, a method of changing the suction speed according to the magnitude of the suction volume of the segmented air is shown. FIG. 7 is a flowchart showing a method of setting the suction speed in the suction processes of the segmented air 401 and the segmented air 402.
[0089] In step S701, the volume of the segmented air 401 and the volume of the segmented air 402 are compared. When the volume of the segmented air 401 is larger (Yes), since the remaining liquid of the washing water 105 is likely to occur in the suction process of the segmented air 401, the suction speed of the segmented air 401 is set to the low speed v1, and the suction speed of the segmented air 402 is set to the high speed v2 (step S702). That is, v2>v1.
[0090] On the other hand, when the volume of the segmented air 401 is smaller (No), since the remaining liquid of the washing water 105 is likely to occur in the suction process of the segmented air 402, the suction speed of the segmented air 401 is set to the high speed v2, and the suction speed of the segmented air 402 is set to the low speed v1 (step S703).
[0091] In this way, the dispensing mechanism 100 selectively uses a plurality of levels v1 and v2 according to the volume of aspirated air. In particular, level v1 with a low aspiration speed is used when the volume of aspirated air is large, and level v2 with a high aspiration speed is used when the volume of aspirated air is small.
[0092] More specifically, in the process flow of aspirating the first volume of air and the second volume of air, when the first volume is larger than the second volume, a low speed v1 is used for aspirating the first volume of air and a high speed v2 is used for aspirating the second volume of air. When the second volume is larger than the first volume, a low speed v1 is used for aspirating the second volume of air and a high speed v2 is used for aspirating the first volume of air.
[0093] In the above, by changing the aspiration speed in the aspiration process of the segmented air 401 and the segmented air 402 according to the aspiration volume of each analyzed air, the presence or absence of an abnormality during the aspiration of the specimen 115 is determined with high accuracy. By only slowing down the process with a large aspiration volume, an increase in the dispensing time required can be minimized, and the number of analyses that can be processed per unit time can be maximized.
[0094] In this embodiment, the segmented air is exemplified and the aspiration speed is set according to the aspiration volume. As a modification, the configuration can also be changed to set the aspiration speed according to the aspiration volume of the reagent.
[0095] Regarding the selective use of levels, the first embodiment and the second embodiment may be combined. For example, a plurality of levels may be selectively used according to both the type of fluid and the volume of aspirated air.
[0096] [Third Embodiment] In this embodiment, the aspiration speed in the aspiration process of the segmented air is changed according to the purpose of aspirating the segmented air.
[0097] In this embodiment, a method of changing the aspiration speed according to whether the pressure in the aspiration process of the segmented air serves as a criterion for abnormal judgment of specimen aspiration is shown. FIG. 8 is a flowchart showing a method of setting the aspiration speed in the aspiration process of the segmented air.
[0098] In this embodiment, the dispensing mechanism 100 has a plurality of levels, namely v1 and v3, as the level of the suction speed of air when sucking air into the probe 102 (or into the chip 101 attached to the tip of the probe 102). v3 > v1, and v3 is the same as the suction speed during specimen suction. The magnitude relationship between v2 and v3 is arbitrary, and v2 = v3 may be satisfied.
[0099] In step S801, it is determined whether the pressure during the suction of the segmented air serves as a criterion for abnormal determination of specimen suction. This can be determined, for example, based on the operation parameters of a preset automatic analyzer.
[0100] When the pressure during the suction of the segmented air does not serve as a criterion for abnormal determination of specimen suction (No), the suction speed of the segmented air 401 is set to the low speed v1 in order to prevent the occurrence of liquid residue of the washing water 105 (step S802). That is, when using the pressure history during air suction to determine whether the dispensing of the specimen to be analyzed is performed normally, v1 among the plurality of levels v1 and v3 is used.
[0101] On the other hand, when the pressure during the suction of the segmented air serves as a criterion for abnormal determination of specimen suction (Yes), since it is a preferable criterion that the suction speed of the segmented air is set to be the same as the suction speed during specimen suction, the suction speed of the segmented air is set to the high speed v3 (step S803).
[0102] In this way, when the time-series data during air suction is not used to determine whether the dispensing of the specimen to be analyzed is performed normally, v3 among the plurality of levels v1 and v3 is used.
[0103] As described above, the presence or absence of an abnormality during aspiration of the specimen 115 is determined with high accuracy by changing the aspiration speed according to whether the pressure in the segmented air aspiration process serves as a criterion for determining an abnormality in specimen aspiration. By setting the aspiration speed of the segmented air aspiration, which serves as a criterion for determining an abnormality in specimen aspiration, to be the same as the aspiration speed of the specimen, a criterion suitable for abnormality determination can be adopted. Furthermore, by reducing the speed of other segmented air aspiration processes, the generation of a liquid film is suppressed, enabling the presence or absence of an abnormality during specimen aspiration to be determined with high accuracy.
[0104] [Fourth Embodiment] In this embodiment, the value of the low speed v1 in Embodiments 1 to 3 is changed according to the diameter and material of the flow path. In particular, the value of the low speed v1 in FIGS. 5, 7, and 8 is changed according to the diameter and material of the flow path where the boundary 403 is located.
[0105] FIG. 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 flow path 901 with a small diameter, a tapered portion 902, a flow path 903 with a large diameter, and a flow path 904 with a different flow path material from the flow paths 901 to 903.
[0106] When the boundary 403 is located in the flow path 901 with a small diameter, the flow velocity v in the pipeline becomes large and liquid residue is likely to occur. Therefore, it is desirable to make the value of the low speed v1 smaller than when the boundary 403 is located in the tapered portion 902 or the flow path 903. On the other hand, when the boundary 403 is located in the flow path 903 with a large diameter, the flow velocity v in the pipeline becomes small and it becomes difficult for liquid residue to occur. Therefore, it is desirable to make the value of the low speed v1 larger than when the boundary 403 is located in the flow path 901 or the tapered portion 902 (however, within the range where v1 < v2).
[0107] Also, when the flow path 903 and the flow path 904 have the same shape and liquid residue is likely to occur in the flow path 904, it is desirable to make the value of the low speed v1 smaller when the boundary 403 is located in the flow path 904 than when the boundary 403 is located in the flow path 903.
[0108] [Modification Example] The present disclosure is not limited to the above-described embodiments and includes various modifications. For example, by combining the configurations of the first to fourth embodiments and their modifications, it is possible to more effectively increase the accuracy of detecting the presence or absence of abnormalities during specimen aspiration.
[0109] In addition, the above-described embodiments have been described in detail for the purpose of clearly explaining the present disclosure, and it is not necessarily required to include all the configurations described. Also, a part of one embodiment can be replaced with the configuration of another embodiment. Also, the configuration of one embodiment can be added to the configuration of another embodiment. Also, for a part of the configuration of each embodiment, a part of the configuration of another embodiment can be added, deleted, or replaced.
[0110] The dispensing method of each of the above-described embodiments can also be executed not only in an automatic analyzer but also in other devices having a fluid dispensing mechanism. For example, the techniques of each embodiment can also be applied to pharmaceutical manufacturing devices, microreactors, and the like.
Explanation of Reference Numerals
[0111] 100... Dispensing mechanism 101... Chip 102... Probe 103... Flow path 104... Syringe (pressure source) 104a... Cylinder 104b... Plunger 105... Washing water 106... Syringe drive unit 107... Probe drive unit 108... Control unit 109... Water supply pump 110... Water supply tank 111... Electromagnetic valve 112... Reagent container 113... Reagent (fluid) 114... Specimen container (container) 115... Specimen (fluid) 116... Reaction container (container) 117... Pressure sensor 118... Branch block 119... Signal amplifier 120... A / D converter 121... Judgment unit 122... Sampling unit 123... Memory unit 124... Calculation unit 125... Display unit 126... Chip disposal unit 127... Cleaning tank 127a... Cleaning nozzle 127b... Drain cup 128... Electromagnetic valve 200... Dispensing mechanism 401... Sectioned air 402... Sectioned air 403... Boundary 601... Probe 901... Flow path 902... Tapered section 903... Flow path 904... Flow path
Claims
1. A container for containing a fluid, A pressure source, A probe for dispensing the fluid in the container, A flow path connecting the probe and the pressure source, An automatic analyzer comprising: The automatic analyzer, Has a plurality of levels of suction speed for sucking air when sucking air into the probe or when sucking air into a chip attached to the tip of the probe, The levels are selectively used according to at least one of the type of the fluid or the suction volume of the air, An automatic analyzer characterized by the above.
2. In the automatic analyzer according to Claim 1, The automatic analyzer, A pressure sensor for measuring time-series data on the pressure in the flow path, A storage unit for storing the time-series data, Further comprising: The automatic analyzer is characterized by determining whether or not the dispensing of the specimen to be analyzed is normally performed based on the time-series data.
3. In the automatic analyzer according to Claim 1, the levels are selectively used according to whether or not the fluid contains the specimen to be analyzed. An automatic analyzer characterized by the above.
4. In the automatic analyzer according to Claim 1, when the suction volume of the air is large, a level of a small suction speed is used. An automatic analyzer characterized by the above.
5. In the automatic analyzer according to Claim 2, the time-series data when sucking the air is used for the determination of whether or not the dispensing of the specimen to be analyzed is normally performed. An automatic analyzer characterized by the above.
6. In the automatic analyzer according to Claim 5, When the time-series data when sucking the air is used for the determination of whether or not the dispensing of the specimen to be analyzed is normally performed, the first level among the levels is used, When the time-series data when sucking the air is not used for the determination of whether or not the dispensing of the specimen to be analyzed is normally performed, a second level different from the first level among the levels is used, An automatic analyzer characterized by the above.
7. In the automatic analyzer according to Claim 1, a plurality of steps of sucking the air are performed between sucking the fluid into the probe and discharging it. An automatic analyzer characterized by the above.
8. A method for dispensing a fluid using an automatic analyzer, The automatic analyzer, A container for containing a fluid, A pressure source, A probe for dispensing the fluid in the container, A flow path connecting the probe and the pressure source, Comprising: The automatic analysis device has a plurality of levels of the suction speed for sucking air when sucking air into the probe or when sucking air into a chip attached to the tip of the probe. The dispensing method is characterized by including selectively using the levels according to at least one of the type of the fluid or the suction volume of the air.
Citation Information
Patent Citations
Method and apparatus for detecting abnormality of dispenser apparatus
JP1999258244A
Fluid handler and method for processing fluid
JP3633631B2