Automatic analysis device and dispensing method
By employing a combination of dispensing nozzles, pressure sources, flow paths, pressure sensors, and control units in an automated analysis device, the sequence of liquid aspiration and pressure measurement are controlled, solving the accuracy problem of detecting anomalies in the dispensing of various types of liquids, and achieving efficient anomaly detection and reagent conservation.
Patent Information
- Application Number
- CN202080079513.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2019-12-05
- Filing Date
- 2020-10-07
- Publication Date
- 2025-11-11
- Estimated Expiration
- 2040-10-07
AI Technical Summary
When dispensing multiple types of liquids simultaneously, existing technologies struggle to detect dispensing anomalies with high accuracy. In particular, the accuracy of anomaly detection is reduced due to differences in the dispensing volume and physical properties of the liquids, and miniaturization of the device is also difficult.
By employing a combination of injection nozzles, pressure sources, flow paths, pressure sensors, and control units, the injection nozzles and pressure sources are controlled to drive the injection system to draw in the first segment of air, the first segment of liquid, the second segment of air, and the second segment of liquid in a specific sequence. The pressure sensors are used to measure the pressure and store the time-series data, thereby achieving high-precision anomaly detection.
It can detect aberrations with high accuracy, improve the reliability of analytical results, reduce reagent consumption, and meet the needs of different analytical projects.
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Figure CN114729951B_ABST
Abstract
Description
Technical Field
[0001] This disclosure relates to an automatic analysis device and a dispensing method. Background Technology
[0002] Automated analytical devices such as biochemical analysis devices and immunoassay devices are equipped with: a dispensing mechanism that draws a predetermined amount of biological samples or other test subjects and reagents and sprays them into a reaction vessel; and an analytical mechanism that analyzes the reaction solution of the test subjects and reagents.
[0003] The dispensing mechanism consists of a probe inserted into a liquid such as a test sample 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 inserts the probe into the liquid in the test sample or reagent container, causing the syringe to aspirate a predetermined amount of liquid, moving the probe to the reaction container for dispensing, thereby dispensing the predetermined amount of liquid. Additionally, to prevent components from being left for subsequent checks, a disposable tip is sometimes fitted to the tip of the probe during dispensing.
[0004] Depending on the analytical project, sometimes multiple reagents, or both reagents and detectors, are simultaneously held in the probe or nozzle to dispense them into the reaction vessel. By simultaneously holding multiple liquids in the nozzle, various types of liquids are continuously aspirated, and after all liquids have been aspirated, they are sprayed into the reaction vessel, thus dispensing the liquids. By dispensing multiple types of liquids simultaneously, it is possible to reduce the amount of cleaning water used, reduce the number of nozzles used, and shorten the dispensing time.
[0005] During dispensing, anomalies can occur due to the attraction of high-viscosity detector particles (such as those generated during detector container handling) and cellulose fibers (such as fibrin) within the detector particles, leading to blockages in the flow path. Therefore, accurately estimating the dispensing state and detecting anomalies with high precision can improve the accuracy of analytical results.
[0006] As a method for detecting anomalies in injection, for example, Patent Document 1 discloses the following technique: for pressure changes during the ejection of the detection body, the integral value of pressure data in a specific time interval, the difference between the average pressure calculated at the end of ejection and the average pressure calculated during normal ejection are used as indicators, and they are compared with a preset threshold to detect anomalies in injection.
[0007] Furthermore, Patent Document 2 discloses a technique for detecting anomalies when a given liquid is dispensed by comparing the pressure of a reference liquid used as a reference for anomaly detection with the pressure of a given liquid dispensed by the same liquid.
[0008] Existing technical documents
[0009] Patent documents
[0010] Patent Document 1: JP Patent No. 3633631
[0011] Patent Document 2: JP Japanese Patent Application Publication No. 11-258244 Summary of the Invention
[0012] The problem that the invention aims to solve
[0013] However, as described in Patent Document 1, when multiple types of liquids are dispensed simultaneously, the accuracy of anomaly detection may be reduced due to differences in the dispensing volume and physical properties of other liquids that are drawn into the nozzle before the liquid that is the object of detection for dispensing anomalies.
[0014] Regarding Patent Document 2, similarly to Patent Document 1, due to differences in the dispensing volume and physical properties of the reference liquid drawn into the dispensing nozzle before the given liquid that becomes the target of the anomaly, there is a possibility of reduced accuracy in anomaly detection. Furthermore, because a portion of the reference liquid needs to be retained, miniaturization of the device is difficult.
[0015] Therefore, this disclosure provides the following technology: when dispensing multiple liquids simultaneously, it is possible to detect anomalies during the dispensing of a liquid that is the object of anomaly detection with high precision, without relying on the dispensing volume or physical property value of the liquid attracted before the liquid that is the object of anomaly detection.
[0016] Methods for solving problems
[0017] To address the aforementioned issues, the automatic analysis apparatus of this disclosure is characterized by comprising: a dispensing nozzle for dispensing fluid; a pressure source for pressure variations in the fluid dispensed from the dispensing nozzle; a flow path connecting the dispensing nozzle and the pressure source; a pressure sensor for measuring the pressure within the flow path when the fluid is dispensed from the dispensing nozzle; a storage unit for storing time-series data of the pressure measured by the pressure sensor; and a control unit for controlling the driving of the dispensing nozzle and the pressure source, wherein the control unit controls the dispensing nozzle and the pressure source such that suction is performed at the dispensing nozzle in the order of a first segment of air, a first segment of liquid, a second segment of air, and a second segment of liquid, and at least one of the suction amounts of the first segment of air and the second segment of air is determined based on the suction amount of the first liquid.
[0018] Further features relating to this disclosure will become clear from the description and drawings herein. Furthermore, this disclosure is achieved and realized through elements and combinations of various elements, as well as through the detailed description thereafter and the appended claims.
[0019] The description in this specification is merely illustrative and is not intended to limit the claims or applications of this disclosure in any sense.
[0020] The effects of the invention
[0021] According to the automatic analysis device disclosed herein, anomalies during the dispensing of liquids that are the object of anomaly detection can be detected with high accuracy.
[0022] Other issues, structures, and effects not mentioned above will be clarified through the following description of the implementation methods. Attached Figure Description
[0023] Figure 1 This is a schematic structural diagram showing the dispensing mechanism of the automatic analysis device according to the first embodiment.
[0024] Figure 2 This is a flowchart illustrating the dispensing method according to the first embodiment.
[0025] Figure 3 This is a flowchart illustrating the method for determining the presence or absence of an anomaly according to the first embodiment.
[0026] Figure 4 It means Figure 2 A schematic diagram of the probe and the state of the fluid inside the end during the dispensing operation.
[0027] Figure 5 It means Figure 2 A flowchart illustrating the method for calculating the amount of reagent and segmented air drawn during the dispensing process.
[0028] Figure 6 This is a graph showing the relationship between the determination index and the amount of reagent dispensed in the first embodiment.
[0029] Figure 7 This is a schematic structural diagram showing the dispensing mechanism of the automatic analysis device according to the second embodiment.
[0030] Figure 8 This is a flowchart illustrating the dispensing method according to the second embodiment.
[0031] Figure 9 It means Figure 8 A schematic diagram of the fluid state inside the probe during the dispensing operation.
[0032] Figure 10 This is a flowchart illustrating the method for determining the presence or absence of an anomaly according to the third embodiment.
[0033] Figure 11 This is a graph showing the relationship between the judgment index and the reagent dispensing volume in the third embodiment, as well as the judgment threshold.
[0034] Figure 12 This is a schematic structural diagram showing the dispensing mechanism of the automatic analysis device according to the fourth embodiment.
[0035] Figure 13 This is a flowchart illustrating the method for determining the presence or absence of an anomaly as described in the fourth embodiment.
[0036] Figure 14 This is a graph showing the relationship between the judgment index and the viscosity of the reagent, as well as the judgment threshold, in the fourth embodiment. Detailed Implementation
[0037] [First Implementation]
[0038] <Structure of the dispensing mechanism of the automatic analysis device>
[0039] In the dispensing mechanism of the automatic analysis device according to the first embodiment, a detachable end is installed at the front end of the probe. In this embodiment, the dispensing mechanism sequentially draws in the reagent and the detector and simultaneously dispenses them into the reaction vessel, thereby detecting the attraction (hereinafter referred to as "air suction") or blockage of air bubbles when the detector is drawn in a state in which the reagent is pre-drawn and held in the end.
[0040] Figure 1 This is a schematic structural diagram showing the dispensing mechanism 100 of the automatic analysis device according to the first embodiment. (See diagram below.) Figure 1 As shown, the dispensing mechanism 100 includes a tip 101, a probe 102, a flow path 103, a syringe 104, a syringe drive unit 106, a probe drive unit 107, a control unit 108, a water supply pump 109, a water supply tank 110 for containing cleaning water 105, a solenoid valve 111, a reagent container 112 for containing reagents 113 (first liquid) corresponding to the analysis items, a detector container 114 for containing detectors 115 (second liquid), 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, a display unit 125, and a tip waste unit 126.
[0041] The tip 101 (dispensing nozzle) allows for attachment and detachment of the front end of the probe 102. A probe drive unit 107, including a motor and actuator (not shown), is connected to the probe 102, enabling the probe 102 to move horizontally and vertically to a given position. The tip 101 is held, for example, in an end-cap holder (not shown). The probe drive unit 107 moves the probe 102 above the end-cap holder and then lowers it, allowing the tip 101 to be mounted on the probe 102. Alternatively, the tip 101 can be mounted to the probe 102 via an end-cap buffer that temporarily holds the tip 101.
[0042] 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 barrel 104a and a plunger 104b, with a syringe drive 106 connected to the plunger 104b. The syringe drive 106 drives the plunger 104b relative to the barrel 104a in the vertical direction, thereby drawing in and ejecting fluid (liquid and gas) from the end 101 connected to the probe 102.
[0043] The syringe 104 has a flow path communicating with a water supply tank 110, through which a solenoid valve 111 and a water supply pump 109 are installed. Cleaning water 105 is contained in the water supply tank 110, and the water supply pump 109 drives the cleaning water 105 to be sprayed from the probe 102, thereby cleaning the interior of the probe 102. Cleaning of the probe 102 is performed, for example, before the dispensing of the reagent 113 and the detection body 115.
[0044] Although not illustrated, the automated analyzer includes a reagent magazine for holding reagent container 112, a detector container rack for holding detector container 114, and a reaction tray for holding reaction container 116. The holding units for reagent container 112, detector container 114, and reaction container 116 are not limited to the aforementioned holding units. Reagent 113 and detector 115, drawn to end 101, are dispensed into reaction container 116.
[0045] The dispensing of reagent 113 and detector 115 into reaction vessel 116 is completed at the waste disposal section 126 at the end 101.
[0046] The control unit 108 controls the operation 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 is configured to control not only the individual components of the dispensing mechanism 100, but also the operation of the entire automatic analysis device.
[0047] Pressure sensor 117 is connected to a branch block 118 located midway through flow path 103 to measure the pressure within flow path 103. Pressure sensor 117 outputs the pressure detection signal to signal amplifier 119. The position of pressure sensor 117 can be as follows: Figure 1 As shown, it is located on the syringe 104 side, but by connecting the pressure sensor 117 as close as possible to the probe 102, pressure changes at the opening of the tip 101 can be measured with good sensitivity.
[0048] Signal amplifier 119 amplifies the detection signal from pressure sensor 117 and outputs the amplified signal to A / D converter 120. A / D converter 120 converts the amplified signal into a digital signal, which is then output as a pressure value to determination unit 121.
[0049] The determination unit 121 is a circuit used to determine whether there is an abnormality during the dispensing operation of the dispensing mechanism 100. The determination unit 121 includes: a sampling unit 122 that receives pressure value input from the A / D converter 120; a storage unit 123 that stores data such as pressure value input to the sampling unit 122; and a calculation unit 124 that performs processing on the data stored in the storage unit 123.
[0050] The determination unit 121 is configured to communicate with the control unit 108, and when it determines that a stop action needs to be performed based on the data processing result in the calculation unit 124, it sends the action content to the control unit 108.
[0051] The determination unit 121 can be configured as a dedicated circuit board within the automatic analysis device, or it can function as the determination unit 121 by reading and executing a program recorded in the storage unit 123 via a processor. Alternatively, it can function as the determination unit 121 by reading and executing a program within a server that can communicate with the automatic analysis device wirelessly or via a wired connection.
[0052] 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, etc.
[0053] <Dispensing method>
[0054] Figure 2 This is a flowchart illustrating the distribution method according to the first embodiment. The distribution method of this embodiment actually uses... Figure 1 The control unit 108 shown controls the operation of each component of the dispensing mechanism 100 (syringe drive unit 106, probe drive unit 107, water pump 109, and solenoid valve 111, etc.). Hereinafter, we will describe each component of the dispensing mechanism 100 as the main body of the operation.
[0055] In step S201, the control unit 108 sets the solenoid valve 111 to the open state and drives the water supply pump 109 to spray cleaning water 105 from the water supply tank 110 from the probe 102. As a result, the inside of the probe 102 is cleaned.
[0056] In step S202, the syringe drive unit 106 drives the syringe 104 to draw in the first segment of air within the probe 102. This is to prevent the cleaning water 105 filling the probe 102 from mixing with the reagent 113 drawn in the next step.
[0057] In step S203, the probe drive unit 107 moves the probe 102 above the end holder or end buffer and then lowers it, thereby equipping the end 101 at the front end of the probe 102.
[0058] In step S204, the probe drive unit 107 moves the probe 102 above the reagent container 112, causing it to descend until the tip of the end 101 is immersed in the reagent 113.
[0059] In step S205, the syringe drive unit 106 drives the syringe 104 to draw reagent 113 into the tip 101.
[0060] In step S206, the probe drive unit 107 raises the probe 102 until the tip of the end 101 emerges from the reagent 113. Then, the syringe drive unit 106 drives the syringe 104 to draw in a second segment of air within the end 101. This is to prevent the reagent 113 previously drawn into the end 101 from mixing with the liquid drawn in the next step.
[0061] In this embodiment, only one type of reagent 113 is aspirated, but depending on the analytical item, there may be cases where multiple reagents are dispensed. In the case of dispensing multiple reagents, steps S204 to S206 are repeated as needed to aspirate all the reagents to be dispensed and the second segment of air separating them within the end 101.
[0062] In step S207, the probe drive unit 107 moves the probe 102 above the detection body container 114, causing it to descend until the tip of the end 101 is immersed in the detection body 115.
[0063] In step S208, the syringe drive unit 106 drives the syringe 104 to aspirate the detector 115 within the tip 101. Here, the sampling unit 122 of the determination unit 121 receives the pressure value input during the aspiration action of the detector 115 and stores the pressure value during the aspiration action of the detector 115 as time series data (hereinafter referred to as "pressure history record") in the storage unit 123.
[0064] In step S209, the probe drive unit 107 raises the probe 102 until the tip of the end 101 comes out of the detection body 115, and moves the probe 102 so that the tip of the end 101 is located inside the reaction vessel 116.
[0065] In step S210, the syringe drive unit 106 drives the syringe 104 to spray the reagent 113 and the detector 115 held in the tip 101 into the reaction container 116. At this time, if multiple reagents are attracted, all the reagents attracted in the tip 101 will be sprayed into the reaction container 116 simultaneously.
[0066] In step S211, the probe drive unit 107 moves the probe 102 to the end discarding part 126, and removes the probe 102 by discarding the end 101 into the end discarding part 126.
[0067] In step S212, the calculation unit 124 of the determination unit 121 determines whether there are any abnormalities (detection abnormalities) such as blockage or cavitation during the suction of the detector 115, based on the pressure history records stored in the storage unit 123 during the suction of the detector 115. Furthermore, the pressure history records for cases where abnormalities such as cavitation or blockage occurred during the suction of the detector 115 differ from the pressure history records for cases where normal dispensing was performed. Therefore, by referring to the pressure history records, the presence or absence of abnormalities can be determined. The method for determining the presence or absence of abnormalities using the pressure history records will be described later.
[0068] In this step, the determination unit 121 sends the determination result of the presence or absence of an anomaly to the display unit 125 and the control unit 108. In addition, the display unit 125 displays the determination result.
[0069] If no abnormality is determined in step S212 (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 betting distribution has ended normally, and terminates the betting distribution operation. The control unit 108 repeats steps S201 to S213 corresponding to the analysis item.
[0070] If an abnormality is determined in step S212 (Yes), the process proceeds to step S214. In step S214, the control unit 108 determines, based on the determination result received from the determination unit 121, that an abnormality has occurred during the aspiration of the detector 115. At this time, the display unit 125 displays an alarm, and the dispensing operation of the corresponding detector 115 is terminated. Furthermore, the detector 115 is returned to the user. In this way, by stopping the dispensing of the abnormal detector 115, the consumption of reagents used in subsequent analyses can be reduced.
[0071] Alternatively, the order of steps S212-S214 and steps S209-S211 can be interchanged. In this case, step S212 is executed after step S208. If an abnormality is detected in step S212 and the process moves to step S214, the control unit 108 does not move to step S209 and ends the dispensing operation. As a result, since the abnormal detection object 115 is not ejected into the reaction container 11 and the process ends, the consumption or cleaning time of the reaction container 116 can be reduced.
[0072] <Methods for determining the presence or absence of anomalies>
[0073] Figure 3 It means Figure 2 The flowchart shows the method for determining the presence or absence of an abnormality in the determination unit 121 in step S212.
[0074] In step S301, the calculation unit 124 reads the pressure history record of the detection body aspiration stored in the storage unit 123. In this specification, the "pressure history record of the detection body aspiration" refers to the pressure value within a given time range that includes the action time (absorption action time) of the syringe 104 when aspirating the detection body 115 in step S208.
[0075] In step S302, the calculation unit 124 calculates the determination index used to determine the presence or absence of an anomaly based on the pressure history record during the attraction of the detector body. The "determination index" can include, for example, the average pressure value during the attraction action of the detector body 115, the average pressure value before or after the attraction action of the detector body 115, the maximum or minimum pressure value, the pressure pulsation period or amplitude of the pressure history record, and statistical distances such as the Euclidean distance between a pre-set reference pressure history record and the pressure history record obtained in this step. The "reference pressure history record" can be set based on a large number of pressure values obtained in the past; it can be the pressure value when the detector body is judged to be attracting normally, or the pressure value when an anomaly is judged during the attraction of the detector body. The similarity or dissimilarity between the reference pressure history record and the determination index can also be used. Furthermore, multiple combinations of the above-mentioned indices can be used as determination indices.
[0076] In this embodiment, the difference between the average pressure value during the suction action of the detection body 115 and the average pressure value before the suction action is calculated as a determination criterion, and this difference is used to determine whether it is normal dispensing or empty suction. As for the causes of empty suction, considerations include unforeseen air bubbles generated during the handling of the detection body container 114, leading to false detection of the liquid level. Additionally, air bubbles may be generated when the blood detection body 115 is shaken during delivery.
[0077] In step S303, the calculation unit 124 determines whether there is an abnormality in the attraction of the detector 115 based on the determination index. Methods for determining the presence or absence of an abnormality include comparing the determination index with a given determination threshold, or determining an abnormality when a combination of multiple determination indices meets a certain condition. In this embodiment, an algorithm that compares the determination index with a fixed determination threshold is used to determine the presence or absence of an abnormality. The determination threshold used in determining the presence or absence of an abnormality is pre-stored in the storage unit 123.
[0078] In order to detect anomalies during the attraction of the detector 115 with high accuracy, the inventors of this invention have conducted in-depth research and found that reducing the amount (volume) of reagent 113 (first liquid) attracted before the attraction of the detector 115 (second liquid) has an effect on the aforementioned pressure history record.
[0079] The dispensing volume of reagent 113 varies depending on the analytical procedure. As an example of a physical formula characterizing the pressure loss caused by friction in the flow within a pipeline, the following Hagen-Poiseuille formula (1) can be cited.
[0080] P loss 128μLQ / (πd 4 (1)
[0081] Here, P loss μ represents pressure loss, μ represents fluid viscosity, L represents the length of the pipe occupied by the fluid, π represents pi, d represents pipe diameter, and Q represents flow rate in the pipe.
[0082] When multiple types of fluids are present in the pipeline, the pressure loss P loss Calculations are made for each fluid component. If the dispensing volume of reagent 113 is different, the length L of the tubing occupied by the fluid at end 101 and probe 102 will change. Consequently, the pressure loss P... loss Changes in reagent 113 can affect the pressure history record used to determine the presence or absence of anomalies. Furthermore, the pressure history record is also affected by differences in fluid configuration within the tubing due to variations in the dispensing volume of reagent 113, caused by pressure wave reflections from the boundaries of fluid components within the tubing. Therefore, by reducing the impact of reagent 113 dispensing volume on the pressure history record, highly accurate anomaly detection can be achieved. Therefore, the dispensing procedure for reducing the impact of reagent 113 dispensing volume variations on the pressure history record will be explained below.
[0083] Figure 4 It means Figure 2 A schematic diagram showing the state of the fluid within probe 102 and end cap 101 during the dispensing operation. Figure 4 (a) indicates the state of probe 102 immediately after being cleaned with cleaning water 105 in step S201. For example... Figure 4 As shown in (a), the interior of probe 102 is filled with cleaning water 105.
[0084] Figure 4 (b) represents the state after the first segment of air 401 is attracted in step S202 and the end head 101 is equipped in step S203.
[0085] Figure 4 (c) indicates the state after the reagent 113 is attracted in step S205. The reagent 113 is located at the front end of the end 101.
[0086] Figure 4(d) indicates the state in step S206 where the second segment of air 402 was attracted. That is, it indicates the state before the detector 115 was attracted. The second segment of air 402 is located at the front end of the end 101, and the reagent 113 is located above it. In addition, in Figure 4 In (d), the state when only one type of reagent 113 and detector 115 are attracted is shown, but in the case of multiple reagents being dispensed, the amount of reagent attracted is alternately configured by reagent 113 and the second segment of air 402.
[0087] Figure 4 (e) indicates the state in step S208 where the detector 115 is attracted. The detector 115 is located at the front end of the end 101, the second segment air 402 is located above it, and the reagent 113 is located on the second segment air 402.
[0088] As described above, the pressure history during suction of the detector 115 is used to determine the presence or absence of abnormalities. The state before suction of the detector 115 ( Figure 4 In (d) of the test, the position of the boundary 403 between the cleaning water 105 and the first segment air 401 varies depending on the dispensing volume of the reagent 113. By fixing the position of this boundary 403, the influence of the dispensing volume of the reagent 113 on the pressure history record during the attraction of the detection body 115 can be reduced.
[0089] The position of the boundary 403 between the cleaning water 105 and the first segment air 401 varies depending on the sum of the amount of the first segment air 401 attracted in step S202, the amount of reagent 113 attracted in step S205, and the amount of the second segment air 402 attracted in step S206 (the total volume of the fluids). Therefore, by controlling the action of the syringe 104 to keep the total volume of fluid attracted before the aspiration of the detection body 115 fixed, the position of the boundary 403 can be fixed. However, the term "fixed" position of the boundary 403 does not mean that the boundary 403 must be precisely located in the same position throughout all dispensing actions of the analysis. It can deviate by, for example, ±10 μL from the sum of the above, depending on the device, probe, and end used. Even if the total volume of the fluids is fixed, it is self-evident that the position of the boundary 403 between the cleaning water 105 and the first segment air 401 will change depending on the inner diameter of the probe and end.
[0090] Figure 5 It means Figure 2 A flowchart illustrating the method for calculating the suction volume of reagent 113, first segment air 401, and second segment air 402 during the dispensing process. This method, for example, is used in... Figure 2The dispensing operation shown is executed by the control unit 108 before it begins, performing the aspiration of reagents and segmented air based on the calculated aspiration volume. Furthermore, before this method is executed, the total volume of reagent 113, first segmented air 401, and second segmented air 402 is pre-stored in the storage unit of the control unit 108. The total volume of these fluids can be set to the same value regardless of the analytical item.
[0091] In step S501, the control unit 108 calculates the amount of reagent 113 attracted in step S205 and the amount of second-segment air 402 attracted in step S206. The amount of reagent 113 attracted can be set according to the analytical item and the type of reagent. Furthermore, when repeating steps S204 to S206 to attract multiple types of reagents within the same end, the control unit 108 calculates the sum of the amounts of reagent attracted in step S205 and the sum of the amounts of second-segment air attracted in step S206, respectively.
[0092] In step S502, the control unit 108 calculates the amount of the first segment of air 401 to be drawn in step S202 based on the amount of reagent 113 and the segmented air volume calculated in step S501. At this time, the amount of the first segment of air 401 is calculated so that the sum of the amount of the first segment of air 401, the amount of reagent 113, and the amount of the second segment of air 402 becomes fixed. Based on the calculated aspiration amounts, the control unit 108 determines the actuation amount of the syringe 104 and issues an instruction to the syringe drive unit 106.
[0093] When the tip 101 has a sufficient volume such that reagent 113 does not flow from the tip 101 into the probe 102, the fluid configuration inside the probe 102 before the aspiration of the detector 115 (the position of the boundary 403 between the cleaning water 105 and the first segment air 401) can be fixed by adjusting the amount of the first segment air 401 as described above. By fixing the fluid configuration inside the probe 102, the influence of differences in the dispensing volume of reagent 113 on the pressure history record during detector aspiration can be reduced.
[0094] As described above, in this embodiment, the following structure is adopted: First, the amount of reagent 113 attracted in step S205 and the amount of the second segment of air 402 attracted in step S206 are calculated, and then the amount of the first segment of air 401 to be attracted is adjusted in step S201. Alternatively, the amount of the first segment of air 401 and the amount of reagent 113 can be calculated first, and then the amount of the second segment of air 402 is adjusted.
[0095] Furthermore, multiple reference values (sums of 20 μL, 50 μL, and 100 μL, etc.) can be pre-stored in the storage unit 123 regarding the total amount of the first segment air 401, the amount of reagent 113, and the amount of the second segment air 402. This allows for the selection of a reference value to be used when the amount of reagent 113 used varies significantly depending on the analytical procedure. For example, if the amount of reagent 113 used is 20 μL, the total can be set to 50 μL; if the amount of reagent 113 used is 50 μL, the total can be set to 100 μL. This prevents a situation where the aspiration volume of segment air 401 and 402 increases despite a small amount of reagent 113. Therefore, it prevents an increase in the driving volume of the syringe 104, thereby extending the lifespan of the syringe 104.
[0096] This demonstrates the improved accuracy of anomaly detection achieved through this implementation method. Figure 6 (a) indicates that the amount of air in segment 401 is kept constant without adjustment (not executed). Figure 5 The relationship between the judgment index (e.g., average pressure value) and the dispensing volume of reagent 113 under the condition of normal dispensing. A ○ indicates a judgment index for normal dispensing of the detector body 115 (normal dispensing group 601). Furthermore, an × indicates a judgment index for cavitation occurring during the aspiration of the detector body 115 (cavitation group 602). For example... Figure 6 As shown in (a), the criteria for determining normal injection group 601 and cavitation group 602 vary significantly depending on the injection volume of reagent 113. Therefore, it is difficult to determine whether cavitation has occurred by comparing the calculated criteria with a fixed threshold.
[0097] In this regard, Figure 6 (b) indicates through Figure 5 The method adjusts the relationship between the judgment index (e.g., average pressure value) and the dispensing volume of reagent 113 when the amount of air 401 in the first segment (total volume of fluid) is adjusted. A circle (○) indicates a judgment index for normal dispensing of the detector 115 (normal dispensing group 603). Furthermore, an × (×) indicates a judgment index for cavitation occurring during the suction of the detector 115 (cavitation group 604). Figure 6 As shown in (b), by adjusting the amount of air 401 in the first segment, the judgment criteria for normal injection group 601 and cavitation group 602 become approximately fixed values, independent of the injection amount of reagent 113. Therefore, by pre-setting a fixed judgment threshold 605 and comparing the calculated judgment criteria with the judgment threshold 605, it is possible to determine whether cavitation has occurred.
[0098] The above describes an example of detecting whether cavitation occurs during the suction of the detector 115. Similarly, the method of this embodiment can be used to determine whether blockage has occurred. That is, by comparing a determination index calculated independently of the dispensing volume of reagent 113 with a fixed determination threshold, it can be determined whether blockage has occurred during suction.
[0099] <Technical Effects>
[0100] As described above, the automatic analysis device of this embodiment performs a dispensing operation to keep the total volume of fluid (segmented air and reagent) aspirated before the aspiration of the detector constant, and to fix the boundary position between the cleaning fluid and segmented air present in the probe. This reduces the impact of reagent dispensing variations on the pressure history record during detector aspiration. More specifically, the judgment index calculated based on the pressure history record of normal dispensing and the judgment index calculated based on the pressure history record of abnormal dispensing can be set to approximately fixed values, independent of the reagent dispensing amount. Therefore, since a fixed judgment threshold value can be set independently of the reagent dispensing amount, i.e., independent of the analytical item, the presence or absence of anomalies can be detected with high accuracy.
[0101] Furthermore, the high accuracy of anomaly detection enhances the reliability of the automated analysis results. Moreover, by terminating the dispensing process upon detecting an anomaly, reagent waste is reduced.
[0102] <Modifications of the first embodiment>
[0103] The above describes a method for detecting abnormalities such as air suction and blockage during the aspiration of the detector 115. The method of this embodiment can also be directly applied to the estimation of the dispensing volume and viscosity of the detector 115.
[0104] Furthermore, in this embodiment, the detector 115 can also be set as the liquid to be detected for dispensing anomalies, and the method of this embodiment can be used in anomaly detection, dispensing volume estimation, and viscosity estimation when reagent 113 is attracted. In this case, "detector 115" can be replaced with "reagent 113" in the above description.
[0105] In this embodiment, as referenced Figure 5As explained, the amount of the first segment of air 401 drawn in step S202 is adjusted so that the sum of the amount of the first segment of air 401 drawn in step S202, the amount of reagent 113 drawn in step S205, and the amount of the second segment of air 402 drawn in step S206 becomes constant. This is because the aim is to reduce the impact of the dispensing volume of reagent 113 on the pressure history record during the aspiration of the detection body 115 by fixing the position of the boundary 403 between the cleaning water 105 and the first segment of air 401 relative to the probe.
[0106] Alternatively, instead of fixing the total amount of fluid attracted before the aspiration of the detector 115, the amount of the first segment air 401 attracted in step S202 can be calculated as a function of the amount of reagent 113 attracted in step S205 and the amount of the second segment air 402 attracted in step S206, corresponding to the structure and configuration of the dispensing mechanism of the automatic analysis device. Furthermore, this function can be determined for each analytical item.
[0107] In addition, in this embodiment, the amount of segmented air is adjusted according to the amount of reagent 113 dispensed, but it is also possible to use a structure such as adjusting the flow rate of the syringe 104 when the detector 115 is aspirated, or adjusting the depth of the tip 101 immersed in the detector 115.
[0108] [Second Implementation]
[0109] In the first embodiment, a dispensing mechanism is described that equips the front end of the probe with a disposable tip and draws in reagents and test subjects within the tip. Figure 1 However, the structure of the betting mechanism is not limited to... Figure 1 The structure shown is as described. Therefore, in the second embodiment, as an example of another dispensing mechanism, an example is proposed where the reagent and the detection body are directly aspirated inside the probe without using a tip. Even though the structure of the dispensing mechanism is different, blockage or cavitation during detection body aspiration can be detected in the same way as in the first embodiment.
[0110] <Structure of the dispensing mechanism>
[0111] Figure 7 This is a schematic structural diagram showing the dispensing mechanism 200 of the automatic analysis device according to the second embodiment. (See diagram for reference.) Figure 7 As shown, the dispensing mechanism 200 replaces Figure 1 The end cap 101 and probe 102 shown are equipped with a probe 701 (dispensing nozzle). The length of the tube of probe 701 can be set to be the same as that of the dispensing nozzle. Figure 1The total length of the conduit is the same when the end 101 is equipped with the probe 102. Regarding the structure other than the probe 701, since it is the same as the dispensing mechanism 100 in the first embodiment, description is omitted.
[0112] In this embodiment, the dispensing mechanism 200 directly attracts the reagent 113 and the detection body 115 through the probe 701. The movement of the probe 701 is controlled by the probe drive unit 107.
[0113] <Dispensing method>
[0114] Figure 8 This is a flowchart illustrating the distribution method according to the second embodiment. The distribution method of this embodiment actually involves... Figure 7 The control unit 108 shown controls the operation of each component of the dispensing mechanism 200, but the following description focuses on each component of the dispensing mechanism 200 as the main body of the operation. Furthermore, regarding the dispensing method of the first embodiment (… Figure 2 The same steps are marked with the same reference numerals. The following only describes the differences from the first embodiment.
[0115] In this embodiment, since header 101 is not used, it is not executed. Figure 2 Steps S203 and S211 in the process.
[0116] First, replacing step S201, in step S801, the control unit 108 sets the solenoid valve 111 to the open state and drives the water supply pump 109 to spray cleaning water 105 from the water supply tank 110 from the probe 701. As a result, the inside of the probe 701 is cleaned.
[0117] After performing step S202, step S802 is performed instead of step S204. In step S802, the probe drive unit 107 moves the probe 701 above the reagent container 112 and lowers it so that the tip of the probe 701 is immersed in the reagent 113.
[0118] After performing steps S205 and S206, step S803 is performed instead of step S207. In step S803, the probe drive unit 107 moves the probe 701 above the detection body container 114 and lowers it so that the tip of the probe 701 is immersed in the detection body 115.
[0119] The subsequent actions are the same as in the first embodiment. Furthermore, the method for determining the presence or absence of an abnormality in step S212 is also the same as... Figure 3 The method shown is the same.
[0120] Figure 9 It means Figure 8 A schematic diagram of the fluid state within probe 701 during the dispensing operation. Figure 9 (a) indicates the state after the probe 701 has been cleaned with cleaning water 105 in step S801. Figure 9 As shown in (a), the interior of probe 701 is filled with cleaning water 105.
[0121] Figure 9 (b) represents the state after the first segment of air 901 is attracted in step S202.
[0122] Figure 9 (c) indicates the state after reagent 113 is attracted in step S205. Reagent 113 is located at the front end of probe 701.
[0123] Figure 9 (d) indicates the state in step S206 where the second segment of air 902 was attracted. That is, it indicates the state before the detector 115 was attracted. The second segment of air 902 is located at the front end of the probe 701, and the reagent 113 is located above it. In addition, in Figure 9 (d) shows the state when only one type of reagent 113 and detector 115 are attracted, but in the case of multiple reagents being dispensed, the number of reagents attracted is achieved by alternately dispensing reagent 113 and second segment air 902.
[0124] Figure 9 (e) indicates the state in step S208 where the detector 115 is attracted. The detector 115 is located at the front end of the probe 701, with the second segment air 902 located above it, and the reagent 113 located on the second segment air 902.
[0125] As described above, the pressure history during suction of the detector 115 is used to determine the presence or absence of abnormalities. The state before suction of the detector 115 ( Figure 9 In (d) of this condition, the position of the boundary 903 between the cleaning water 105 and the first segment air 401 varies depending on the dispensing volume (volume) of the reagent 113. By fixing the position of this boundary 903, the influence of the dispensing volume of the reagent 113 on the pressure history record during the attraction of the detector 115 can be reduced.
[0126] The position of the boundary 903 between the cleaning water 105 and the first segment air 901 varies depending on the sum of the amount of the first segment air 901 drawn in step S202, the amount of reagent 113 drawn in step S205, and the amount of the second segment air 902 drawn in step S206 (the total volume of the fluids). Therefore, by controlling the action of the syringe 104 to keep the total volume of fluid drawn before the aspiration of the detection body 115 fixed, the position of the boundary 903 can be fixed. The amounts of the first segment air 901, reagent 113, and second segment air 902 drawn also vary depending on... Figure 5The same method is used to calculate the same amount of suction. The control unit 108 determines the amount of action of the syringe 104 based on the calculated suction volume and issues an instruction to the syringe drive unit 106.
[0127] <Technical Effects>
[0128] In the second embodiment, similarly to the first embodiment, a dispensing operation is performed to fix the total volume of fluid (segmented air and reagent) aspirated before the detection body is aspirated, thus fixing the boundary position between the cleaning fluid and segmented air present in the probe. This reduces the impact of reagent dispensing variations on the pressure history record during detection body aspiration, enabling high-accuracy detection of anomalies during detection body aspiration. Consequently, the reliability of the analysis results from the automatic analysis device is improved. Furthermore, in this embodiment, since there is no need to equip or disassemble the end cap 101, the dispensing operation can be performed more quickly compared to the first embodiment.
[0129] [Third Implementation]
[0130] In the first and second embodiments, a method was described that by fixing the sum of the amount of segmented air drawn before the detector and the amount of reagent drawn, the influence of the reagent dispensing volume on the pressure history record during detector aspiration was reduced, thereby enabling high-accuracy detection of anomalies during detector aspiration. Therefore, in the third embodiment, a method is proposed to further reduce the influence of the reagent dispensing volume and detect anomalies during detector aspiration with even higher accuracy.
[0131] The dispensing mechanism of the automatic analysis device according to this embodiment can adopt the same structure as that in the first embodiment. Figure 1 Furthermore, regarding the distributing operation, it is also related to the distributing method of the first embodiment (…). Figure 2 The general process is similar. However, in this embodiment, the method for determining the presence or absence of an anomaly in step S212 is different from that in the first embodiment.
[0132] Figure 10 This is a flowchart illustrating the method for determining the presence or absence of an anomaly according to the third embodiment. (Replaces) Figure 3 The determination method of the first embodiment shown is executed by the determination unit 121. Figure 10 The determination method. For... Figure 3 The same steps are labeled with the same reference numerals in the accompanying drawings, and their descriptions are omitted.
[0133] First, steps S301 and S302 are performed in the same manner as in the first embodiment, and a judgment index is calculated based on the historical pressure record when the detection body is attracted.
[0134] Next, in step S1001, the determination unit 121 obtains information from the control unit 108 regarding the amount of reagent 113 attracted in step S205. Additionally, in the case of attracting multiple reagents, in step S1001, the determination unit 121 obtains information from the control unit 108 regarding the sum of the amounts of reagents attracted in step S205 and the sum of the amounts of the second segment of air attracted in step S206.
[0135] In step S1002, the calculation unit 124 determines whether there is an abnormality in the aspiration of the detector 115 based on the determination index calculated in step S302 and the information about the aspiration amount of the reagent 113 obtained in step S1001. At this time, similar to the first embodiment, the difference between the average pressure value during the aspiration action of the detector 115 and the average pressure value before the aspiration action is used as the determination index to determine whether it is normal dispensing or empty aspiration.
[0136] In this embodiment, the determination threshold is set as a function that varies with the dispensing volume of reagent 113. The presence or absence of an anomaly is determined by comparing the magnitude of this determination threshold with that of a determination index. The function of the determination threshold is pre-stored in the storage unit 123.
[0137] The determination thresholds involved in this embodiment will be explained. Figure 11 This is a graph showing the relationship between judgment indicators (e.g., average pressure values) and the dispensing volume of reagent 113, as well as the judgment threshold. The ○ symbol indicates a judgment indicator when the test body 115 is dispensed normally (normal dispensing group 1101). Furthermore, the × symbol indicates a judgment indicator when cavitation occurs during the aspiration of the test body 115 (cavitation group 1102). For example... Figure 11 As shown, the decision threshold 1103 is set as a piecewise linear function to minimize the variation caused by the amount of reagent 113 dispensed, for the distances between the normal dispensing group 1101 and the decision threshold 1103, and between the empty dispensing group 1102 and the decision threshold 1103, respectively. The decision threshold 1103 is not limited to a piecewise linear function; for example, it can be a linear function or any polynomial.
[0138] Thus, by setting the judgment threshold used in the anomaly determination as a function that varies according to the dispensing volume of reagent 113, the impact of variations in the dispensing volume of reagent 113 can be reduced for the distances between the normal dispensing group 1101 and the judgment threshold 1103, as well as the distances between the empty aspiration group 1102 and the judgment threshold 1103. Therefore, compared to the case where a fixed judgment threshold is used ( Figure 6 The comparison of (b) can determine the presence or absence of anomalies with higher accuracy.
[0139] Furthermore, in this embodiment, while keeping the total amount of fluid before the aspiration detector 115 fixed, as in the first embodiment, the determination threshold used in determining anomalies is set as a function that varies according to the dispensing volume of reagent 113. However, this embodiment, in which the total amount of fluid before the aspiration detector 115 is not fixed, also sets the determination threshold as a function that varies according to the dispensing volume of reagent 113, is also effective.
[0140] <Technical Effects>
[0141] As described above, the third embodiment employs the following structure: a judgment threshold is set as a function corresponding to the reagent dispensing volume, and a judgment index calculated based on historical pressure records during detector aspiration is compared with the function to determine the presence or absence of an anomaly. Therefore, compared to the first embodiment where the judgment index is compared with a fixed judgment threshold, anomalies can be detected with higher accuracy. Consequently, the reliability of the analysis results from the automated analyzer can be further improved.
[0142] [Fourth Implementation]
[0143] In embodiments 1 to 3, a method was described to detect anomalies during detector aspiration with high accuracy by reducing the influence of the amount of reagent (first liquid) dispensed before the detector (second liquid) aspirates on the pressure history record. However, reducing not only the influence of reagent dispensing volume on the pressure history record but also the influence of physical properties such as reagent viscosity on the pressure history record is effective. Therefore, in embodiment 4, a method is proposed that also considers the influence of reagent physical properties on the pressure history record in order to detect anomalies with higher accuracy.
[0144] If the viscosity of the reagent changes, the viscosity μ of the fluid in the pipeline in the Hagen-Poiseuille equation (1) above will change. Therefore, due to the pressure loss P... loss These variations therefore affect the pressure history records used to determine the presence or absence of anomalies. Furthermore, when reagents pass through tubing of a small diameter, pressure changes within the tubing occur not only due to differences in reagent viscosity but also due to differences in surface tension. In cases where the vertical length of the portion of the tubing occupied by the reagent is long, pressure changes within the tubing also occur due to differences in gravity caused by differences in reagent density.
[0145] <Structure of the dispensing mechanism>
[0146] Figure 12 This is a schematic structural diagram showing the dispensing mechanism 400 of the automatic analysis device according to the fourth embodiment. (See diagram below.) Figure 12 As shown, the dispensing mechanism 400 is the same as the dispensing mechanism of the first embodiment ( Figure 1It is roughly the same, but it also has a reagent property value storage unit 1201.
[0147] The reagent property storage unit 1201 is a database that stores the physical properties of various reagents used in the analysis, such as viscosity, surface tension, and density. The reagent property storage unit 1201 is configured to be connected to or able to communicate with the determination unit 121, and the information stored in the reagent property storage unit 1201 can be read by the determination unit 121.
[0148] <Dispensing method>
[0149] Regarding the distributing actions involved in this embodiment, and the distributing method in the first embodiment ( Figure 2 The general process is similar. However, in this embodiment, the method for determining the presence or absence of an anomaly in step S212 is different from that in the first embodiment.
[0150] Figure 13 This is a flowchart illustrating the method for determining the presence or absence of an anomaly according to the fourth embodiment. (Replaces) Figure 3 The determination method of the first embodiment shown is executed. Figure 13 The determination method. For... Figure 3 The same steps are labeled with the same reference numerals in the accompanying drawings, and their descriptions are omitted.
[0151] First, steps S301 and S302 are performed in the same manner as in the first embodiment, and a judgment index is calculated based on the historical pressure record when the detection body is attracted.
[0152] Next, in step S1301, the determination unit 121 obtains information on the physical properties of reagent 113, such as viscosity, surface tension, and density, from the reagent property value storage unit 1201.
[0153] In step S1302, the determination unit 121 determines whether there is an abnormality during the aspiration of the detector 115 based on the determination index calculated in step S302 and the information on the physical property values of the reagent 113 obtained in step S1301. At this time, similar to the first embodiment, the difference between the average pressure value during the aspiration action of the detector 115 and the average pressure value before the aspiration action is used as the determination index to determine whether it is normal dispensing or empty aspiration.
[0154] Here, as an example of the physical property value of reagent 113, the presence or absence of anomalies is determined based on viscosity. More specifically, the presence or absence of anomalies is determined by setting a determination threshold as a function corresponding to the viscosity of reagent 113, and comparing the magnitude of this determination threshold with a determination index. The function of the determination threshold is pre-stored in the storage unit 123.
[0155] This section explains the determination thresholds involved in this implementation method. Figure 14This is a graph showing the relationship between judgment indicators (e.g., average pressure values) and the viscosity of reagent 113, as well as the judgment threshold. ○ indicates judgment indicators for cases where the test body 115 is normally dispensed (normal dispensing group 1401). Furthermore, × indicates judgment indicators for cases where cavitation occurs during the aspiration of the test body 115 (cavitation group 1402). For example... Figure 14 As shown, the decision threshold 1403 is set as a linear function to minimize the variation caused by the viscosity of reagent 113 for the distances between the normal inhalation group 1401 and the decision threshold 1403, and the distances between the empty inhalation group 1402 and the decision threshold 1403, respectively. The decision threshold 1403 is not limited to a linear function; for example, it can also be a linear function or any polynomial.
[0156] Thus, by setting the judgment threshold used in anomaly determination as a function that varies according to the viscosity of reagent 113, the influence of viscosity differences of reagent 113 can be reduced for the distances between normal inhalation group 1401 and judgment threshold 1403, and between empty inhalation group 1402 and judgment threshold 1403. Therefore, compared to using a fixed judgment threshold value, the presence or absence of anomalies can be determined with higher accuracy.
[0157] Furthermore, while this embodiment uses the viscosity of reagent 113 as a function, in cases where the surface tension and density of reagent 113 have a significant impact on the pressure history record due to the characteristics of the dispensing mechanism, setting the judgment threshold as a function of the surface tension and density of reagent 113 allows for high-precision detection of anomalies. Thus, for example, it is possible to consider which property value—the diameter of the end cap or probe used—has a greater impact on the pressure history record when detecting anomalies.
[0158] Furthermore, in this embodiment, similar to the first embodiment, the total amount of fluid before the aspiration detector 115 is fixed, and the determination threshold used in determining anomalies is set as a function that varies according to the physical properties of the reagent 113. However, this embodiment, in which the total amount of fluid before the aspiration detector 115 is not fixed, also sets the determination threshold as a function that varies according to the physical properties of the reagent 113, is also effective.
[0159] <Technical Effects>
[0160] As described above, the fourth embodiment employs the following structure: a judgment threshold is set as a function corresponding to the physical property value of the reagent, and the presence or absence of an anomaly is determined by comparing this function with a judgment index based on the historical pressure record during the attraction of the detector. Therefore, compared to the first embodiment which compares a fixed judgment threshold and judgment index, anomalies can be detected with higher accuracy. Furthermore, since the influence of the reagent's physical property value on the historical pressure record during the attraction of the detector is reduced, anomaly detection based on the historical pressure record can be performed with higher accuracy, independent of the reagent's physical property value. Thus, the reliability of the analysis results from the automated analysis device can be further improved.
[0161] [Fifth Implementation]
[0162] In the fourth embodiment, an example was described to determine the presence or absence of anomalies by considering the influence of the reagent's physical properties such as viscosity, surface tension, and density on the pressure history record. However, when there are many types of reagents, it is difficult to measure the physical properties of all types of reagents and maintain them in the database (reagent physical property storage unit). Therefore, in the fifth embodiment, a method is proposed to estimate the physical property value of reagent 113 before the detection body is attracted.
[0163] <Structure of the dispensing mechanism>
[0164] The dispensing mechanism of the automatic analysis device involved in this embodiment adopts the same structure as that in the fourth embodiment. Figure 12 Therefore, the explanation is omitted.
[0165] <Dispensing method>
[0166] The dispensing method of this embodiment is the same as Figure 2 The dispensing method shown is roughly the same, but in step S205, the sampling unit 122 receives the pressure value input during the aspiration action of the reagent 113 from the pressure sensor 117, and stores the pressure value during the aspiration action of the reagent 113 as time series data (pressure history record during reagent aspiration) in the storage unit 123. The so-called "pressure history record during reagent aspiration" refers to the pressure value within a given time range that includes the action time (aspiration action time) of the syringe 104 when aspirating the reagent 113 in step S205.
[0167] Since the pressure history record of reagent 113 during attraction reflects the viscosity of reagent 113 as shown in equation (1), the viscosity of reagent 113 can be estimated based on this pressure history record. The calculation unit 124 calculates the viscosity of reagent 113 based on the pressure history record of reagent 113 during attraction stored in the storage unit 123, and saves it to the reagent property value storage unit 1201. Figure 12 ).
[0168] In step S212, the determination of the presence or absence of an abnormality during the attraction of the detector 115 is performed in conjunction with... Figure 13 The determination method of the fourth embodiment shown follows the same steps.
[0169] The above illustrates an example of estimating viscosity as one of the physical properties of reagent 113, but the density of reagent 113 can also be estimated and used in determining the presence or absence of anomalies. In this case, the density can be calculated based on the gravitational head of the pressure value after the attraction of reagent 113 in step S205.
[0170] <Technical Effects>
[0171] The fifth embodiment estimates the physical properties of the reagent based on the historical pressure record during reagent aspiration, and sets the determination threshold used in determining the presence or absence of anomalies as a function corresponding to the estimated physical properties of the reagent. Therefore, in addition to achieving the same effect as the fourth embodiment, anomalies can be detected with high accuracy even without storing information related to the physical properties of the reagents used in the analysis in the reagent property storage unit.
[0172] [Sixth Implementation]
[0173] In the fifth embodiment, a method for estimating reagent properties using historical pressure records during reagent aspiration is described. However, when multiple reagents are to be dispensed simultaneously, repetition is necessary. Figure 2 Steps S204 to S206 are used to estimate the physical property value for each attracted reagent, which makes the process cumbersome. In addition, if the physical property value is estimated for multiple reagents separately, the error will accumulate repeatedly, and there is a possibility that the accuracy of abnormal detection will decrease.
[0174] Therefore, in the sixth embodiment, when multiple reagents are dispensed, a method is proposed that takes into account the influence of multiple reagents attracted before the detection body is attracted on the pressure history record during the attraction of the detection body.
[0175] <Dispensing method>
[0176] The dispensing method of this embodiment is the same as Figure 2 The dispensing method shown is largely the same, but differs in the following aspects. Specifically, in step S206, the last step among steps S204 to S206 of repeating the required number of reagents, the suction flow rate of syringe 104 when aspirating the second segment of air is set to be the same as the suction flow rate of syringe 104 when aspirating the detector 115 in step S208. Therefore, the influence of the multiple reagents held in the tip 101 on the pressure history record during detector aspiration can be estimated.
[0177] More specifically, in step S206, the sampling unit 122 receives the pressure value input during the suction operation of the second segment of air from the pressure sensor 117, and stores the pressure value during the suction operation of the second segment of air as a time series (pressure history record) in the storage unit 123. The calculation unit 124 obtains the pressure history record of the suction of the segment of air in step S206, and estimates the average (representative value) viscosity of the plurality of reagents 113 based on the pressure history record and the above formula (1). The other steps can be performed in the same way as in the fifth embodiment.
[0178] <Technical Effects>
[0179] In the sixth embodiment, when multiple reagents are dispensed simultaneously, representative values of the physical properties of the multiple reagents are estimated, and the determination threshold used in determining the presence or absence of an anomaly is set as a function corresponding to the estimated physical property values of the reagents. Therefore, since it is not necessary to estimate all physical property values for multiple reagents, the process is not only simple, but errors also do not accumulate. Thus, anomalies can be detected with high accuracy without relying on the physical property values of multiple reagents attracted before the attraction of the detection body.
[0180] Furthermore, by setting the suction flow rate of syringe 104 when aspirating the second segment of air in step S206 (the last of steps S204 to S206) and the suction flow rate of syringe 104 when aspirating the detector 115 in step S208 to be the same, the influence of the viscosity of reagent 113 on the pressure history record when aspirating the detector 115 can be more accurately estimated.
[0181] <Modifications of the 6th Embodiment>
[0182] As described above, it can also replace the representative values of the estimated physical properties of multiple reagents as a judgment index, thus eliminating the influence of reagent physical properties and dispensing volume. Specifically, in Figure 3 In the method for determining the presence or absence of an anomaly, the difference between the historical pressure record during the second segment of air aspiration in step S206 and the historical pressure record during the aspiration of the detector 115 in step S208 is calculated as the determination index. Since this determination index is precisely the difference between the historical pressure record before and after the aspiration of the detector, the influence of the physical properties and dispensing volume of multiple reagents aspirated before the aspiration of the detector is offset. By using such a determination index, the presence or absence of an anomaly can be determined with high accuracy, regardless of the dispensing volume or physical properties of the reagents.
[0183] [Variation Example]
[0184] This disclosure is not limited to the embodiments described above, and includes various modifications. For example, the embodiments described above have been explained in detail for ease of understanding of this disclosure, but are not necessarily required to have all the described structures. Furthermore, a part of an embodiment can be replaced with the structure of another embodiment. Furthermore, the structure of another embodiment can be added to the structure of an embodiment. Furthermore, a part of the structure of each embodiment can be added to, deleted from, or replaced with a part of the structure of another embodiment.
[0185] The dispensing methods described above can be implemented not only in automated analysis devices but also in other devices with fluid dispensing mechanisms. For example, the methods described in these embodiments can also be used in pharmaceutical manufacturing equipment, microreactors, and the like.
[0186] Explanation of reference numerals in the attached figures
[0187] 100, 200, 400... betting agencies
[0188] 101...end
[0189] 102... probe
[0190] 103…Flow path
[0191] 104... Syringe
[0192] 104a... cylinder
[0193] 104b...plunger
[0194] 105…washing water
[0195] 106... Syringe drive unit
[0196] 107...Probe drive unit
[0197] 108…Control Department
[0198] 109...water supply pump
[0199] 110...water supply tank
[0200] 111…Solenoid valve
[0201] 112…Reagent Container
[0202] 113…Reagent
[0203] 114… Detection container
[0204] 115… Detection body
[0205] 116…Reaction Vessel
[0206] 117... Pressure Sensor
[0207] 118... branch block
[0208] 119…signal amplifier
[0209] 120…A / D converter
[0210] 121… Judgment Department
[0211] 122...Sampling Section
[0212] 123… Storage Department
[0213] 124…Computing Department
[0214] 125… Display Section
[0215] 126...End-end waste section
[0216] 401… Segment 1 Air
[0217] 402…Segment 2 Air
[0218] 403…boundary
[0219] 601, 603...normal injection group
[0220] 602, 604... air suction group
[0221] 605… Decision threshold
[0222] 701... probe
[0223] 901…Segment 1 Air
[0224] 902…Segment 2 Air
[0225] 903…Boundary
[0226] 1101...normal bet group
[0227] 1102…Air Suction Group
[0228] 1103… Judgment Threshold
[0229] 1201…Reagent Property Value Storage Department
[0230] 1401...normal bet group
[0231] 1402…Air Suction Group
[0232] 1403…Determination threshold.
Claims
1. An automatic analysis device, characterized in that, have: A dispensing nozzle that dispenses fluid; A pressure source, which is used to generate pressure variations from the dispensing of the fluid via the dispensing nozzle; A flow path that connects the dispensing nozzle to the pressure source; A pressure sensor that measures the pressure within the flow path when the dispensing nozzle dispenses the fluid; The storage unit stores time-series data of the pressure measured by the pressure sensor; and The control unit controls the driving of the dispensing nozzle and the pressure source. The control unit controls the dispensing nozzle and the pressure source to draw air into the dispensing nozzle in the order of first segment air, first liquid, second segment air, and second liquid, and determines at least one of the following based on the amount of first liquid drawn: the amount of first segment air drawn and the amount of second segment air drawn. The control unit determines at least one of the suction amount of the first segment air and the suction amount of the second segment air, such that the total volume of all fluid previously drawn into the dispensing nozzle is fixed.
2. The automatic analysis device according to claim 1, characterized in that, The automatic analysis device also includes: The determination unit detects anomalies during the dispensing of the second liquid based on the time series data.
3. The automatic analysis device according to claim 1, characterized in that, The control unit determines the amount of air drawn in the first segment so that the total volume of all fluid previously drawn in at the dispensing nozzle is fixed.
4. The automatic analysis device according to claim 2, characterized in that, The time-series data includes historical pressure records during the attraction of the second liquid. The determination unit calculates a determination index based on the historical pressure record, and detects anomalies during the dispensing of the second liquid by comparing a preset determination threshold with the determination index.
5. The automatic analysis device according to claim 4, characterized in that, The determination unit calculates the difference between the pressure value before the second liquid is attracted and the pressure value during the process of attracting the second liquid, and uses this difference as the determination index.
6. The automatic analysis device according to claim 1, characterized in that, The control unit controls the pressure source so that the amount of air drawn in the second segment and the amount of liquid drawn in the second segment are the same.
7. The automatic analysis device according to claim 6, characterized in that, The automatic analysis device also includes: The determination unit detects anomalies during the dispensing of the second liquid based on the time series data. The determination unit calculates the difference between the pressure value when the second segment of air is attracted and the pressure value when the second liquid is attracted, and uses this difference as a determination index. The unit then detects the anomaly by comparing a preset determination threshold with the determination index.
8. The automatic analysis device according to claim 2, characterized in that, The time-series data includes historical pressure records during the attraction of the second liquid. The determination unit performs the following operations: An assessment index is calculated based on the historical pressure data. The anomaly is detected by comparing the assessment index with a pre-set threshold. The determination threshold is a function that varies based on the amount of the first liquid attracted. The control unit obtains the aspiration volume of the first liquid and compares the determination threshold and the determination index in the obtained aspiration volume of the first liquid.
9. The automatic analysis device according to claim 2, characterized in that, The time-series data includes historical pressure records during the attraction of the second liquid. The determination unit performs the following operations: An assessment index is calculated based on the historical pressure data. The anomaly is detected by comparing the assessment index with a pre-set threshold. The determination threshold is a function that varies based on the physical property values of the first liquid. The control unit obtains the physical property value of the first liquid and compares the determination threshold and the determination index in the obtained physical property value of the first liquid.
10. The automatic analysis device according to claim 1, characterized in that, The control unit controls the dispensing nozzle and the pressure source to alternately draw the first liquid and the second liquid through the dispensing nozzle multiple times.
11. An automatic analysis device, characterized in that, have: A dispensing nozzle that dispenses fluid; A pressure source, which is used to generate pressure variations from the dispensing of the fluid via the dispensing nozzle; A flow path that connects the dispensing nozzle to the pressure source; A pressure sensor that measures the pressure within the flow path when the dispensing nozzle dispenses the fluid; The storage unit stores time-series data of the pressure measured by the pressure sensor; The control unit controls the driving of the dispensing nozzle and the pressure source; and The determination unit detects anomalies in the dispensing of fluid that is considered an anomaly based on the time-series data. The control unit controls the dispensing nozzle and the pressure source to draw air into the dispensing nozzle in the order of first segment air, first liquid, second segment air, and second liquid. The determination unit uses a determination threshold set based on the attraction amount or physical property value of the first liquid to detect the anomaly when the second liquid is attracted. The time-series data includes historical pressure records during the attraction of the second liquid. The determination unit performs the following operations: An assessment index is calculated based on the historical pressure records. The anomaly is detected by comparing the assessment index with a pre-set assessment threshold. The determination threshold is a function that varies based on the attraction amount or physical property value of the first liquid. The control unit obtains the aspiration amount or physical property value of the first liquid, and compares the determination threshold and the determination index in the obtained aspiration amount or physical property value of the first liquid.
12. A fluid distribution method utilizing an automatic analysis device, characterized in that... The automatic analysis device includes: Dispensing nozzle, which dispenses the fluid; A pressure source, which is used to generate pressure variations from the dispensing of the fluid via the dispensing nozzle; and The control unit controls the driving of the dispensing nozzle and the pressure source. The betting method includes: This is performed by driving the pressure source through the control unit: The first segment of air is drawn in through the injection nozzle; After the first segment of air is drawn in, the first liquid is drawn in through the dispensing nozzle; After the first liquid is drawn in, the second segment of air is drawn in through the dispensing nozzle; After the second segment of air is drawn in, the second liquid is drawn in through the dispensing nozzle; as well as The control unit determines at least one of the suction amounts of the first segment of air and the second segment of air based on the suction amount of the first liquid. The control unit determines at least one of the suction amount of the first segment air and the suction amount of the second segment air, such that the total volume of all fluid previously drawn into the dispensing nozzle is fixed.
Citation Information
Patent Citations
Method and apparatus for detecting abnormality of dispenser apparatus
JP1999258244A
Automatic analytical apparatus
CN105917239A