Automatic analysis device and dispensing method

Abstract

When dispensing multiple liquids simultaneously, the system minimizes liquid films and residues generated during the aspiration of liquids drawn before the liquid targeted for anomaly detection, enabling high-accuracy detection of anomalies during the dispensing of the liquid targeted for anomaly detection. The automated analysis device includes a container holding fluid, a pressure source, a probe for dispensing fluid into the container, and a flow path connecting the probe and the pressure source. The automated analysis device has multiple levels for aspirating air at different speeds, either when aspirating air into the probe or into a suction head mounted at the tip of the probe, and the level is used based on at least one of the type of fluid or the volume of air aspirated.

Description

Technical Field

[0001] This invention relates to an automatic analysis device and a dispensing method. Background Technology

[0002] Automated analytical devices such as biochemical analysis devices and immunoassay devices include: a dispensing mechanism that draws in a predetermined amount of biological samples or other specimens and reagents and discharges them into a reaction vessel; and an analysis mechanism that analyzes the reaction solution of the specimens and reagents.

[0003] The dispensing mechanism consists of a probe inserted into a liquid such as a 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 sample or reagent container, causing the syringe to aspirate a predetermined amount of liquid. The probe then moves towards the reaction container and dispenses the liquid, thereby dispensing the predetermined amount of liquid. Additionally, to prevent components from being carried over to the next test during dispensing, a disposable pipette tip is sometimes attached to the tip of the probe.

[0004] Depending on the analytical procedure, sometimes multiple reagents, or both reagents and samples, are simultaneously held in a probe or pipette tip (dispensing nozzle) and dispensed into the reaction vessel. By holding multiple liquids simultaneously in the dispensing nozzle, multiple types of liquids are continuously aspirated, and after all liquids are aspirated, they are discharged into the reaction vessel, thus dispensing. By simultaneously dispensing multiple liquids, it is possible to reduce the amount of cleaning water used, the number of pipette tips used, and the dispensing time required.

[0005] During dispensing, abnormalities may occur, such as air bubbles generated during suction through the sample container, blockage of the flow path by high-viscosity samples, or cellulose such as fibrin in the sample. Therefore, by accurately estimating the dispensing state and detecting abnormalities with high precision, the accuracy of analytical results can be improved.

[0006] As a method for detecting abnormalities in the excretion process, Patent Document 1 discloses the following technique: based on the pressure changes during the excretion of the specimen, the integral value of the pressure data in a specific time interval, the difference between the average pressure value calculated at the end of the excretion and the average pressure value calculated during normal excretion are used as indicators, and these are compared with a pre-set threshold to detect abnormalities in the excretion process.

[0007] In addition, Patent Document 2 discloses the following technique: using the ratio of the pressure of a reference liquid used for anomaly detection to the pressure of a predetermined liquid to detect anomalies during the dispensing of the liquid.

[0008] Existing technical documents

[0009] Patent documents

[0010] Patent Document 1: Japanese Patent No. 3633631

[0011] Patent Document 2: Japanese Patent Application Publication No. 11-258244 Summary of the Invention

[0012] The problem that the invention aims to solve

[0013] However, in the structure described in Patent Document 1, when multiple liquids are dispensed simultaneously, if the attraction of the liquid that is the object of anomaly detection is not the beginning, the accuracy of anomaly detection may be reduced due to liquid film, liquid residue, etc. generated during the attraction of the preceding liquid.

[0014] Regarding Patent Document 2, similarly to Patent Document 1, when multiple liquids are dispensed simultaneously, if the attraction of the liquid that is the object of anomaly detection is not the beginning, the accuracy of anomaly detection may be reduced due to liquid film, liquid residue, etc. generated during the attraction of the preceding liquid.

[0015] Therefore, this disclosure provides the following technology: when dispensing multiple liquids simultaneously, it minimizes liquid films, liquid residues, etc. generated during the attraction of liquids attracted before the liquid to be detected as an anomaly, and enables high-accuracy detection of anomalies during the dispensing of the liquid to be detected as an anomaly.

[0016] Methods for solving problems

[0017] An example of the automatic analysis apparatus of the present invention comprises: a container holding a fluid; a pressure source; a probe dispensing the fluid within the container; and a flow path connecting the probe and the pressure source. The automatic analysis apparatus is characterized by having multiple levels for the suction speed of air suction when drawing air to the probe or to a suction head mounted at the tip of the probe, and the levels are used differently depending on at least one of the type of fluid and the volume of air suction.

[0018] In one example of the fluid dispensing method of the present invention using an automatic analysis device, the automatic analysis device includes: a container holding a fluid; a pressure source; a probe dispensing the fluid in the container; and a flow path connecting the probe and the pressure source. The automatic analysis device has multiple levels for the suction rate of the air when drawing air to the probe or to a suction head mounted at the tip of the probe. The dispensing method includes distinguishing the use of the levels based on at least one of the type of fluid and the volume of air drawn.

[0019] Further features relating to this disclosure will become clear from the description and drawings in this specification. Furthermore, this disclosure is implemented and carried out by means of elements and combinations thereof, as well as the detailed description thereafter and the appended scope of the claimed patent protection.

[0020] The description in this specification is merely a typical example and does not limit the scope of the patent protection sought or the application of this disclosure in any sense.

[0021] Invention Effects

[0022] According to the automatic analysis device disclosed herein, anomalies during the dispensing of liquids, which are the objects of anomaly detection, can be detected with high accuracy.

[0023] Other issues, structures, and effects not mentioned above will be clarified through the following description of the implementation methods. Attached Figure Description

[0024] Figure 1 This is a schematic structural diagram showing the dispensing mechanism of the automatic analysis device according to the first embodiment.

[0025] Figure 2 This is a flowchart illustrating the sub-annotation method of the first embodiment.

[0026] Figure 3 This is a flowchart illustrating the method for determining whether an abnormality exists in the first embodiment.

[0027] Figure 4 It means Figure 2 A schematic diagram of the fluid state inside the probe and suction head during the dispensing operation.

[0028] Figure 5 It means Figure 2 A flowchart illustrating the calculation method for the suction velocity of segmented air during the injection process.

[0029] Figure 6 This is a schematic structural diagram of the dispensing mechanism of the automatic analysis device, which represents a variation of the first embodiment.

[0030] Figure 7 This is a flowchart illustrating the method for calculating the suction velocity of segmented air in the second embodiment.

[0031] Figure 8 This is a flowchart illustrating the method for calculating the suction velocity of segmented air in the third embodiment.

[0032] Figure 9 This is a schematic diagram showing the state of the fluid in the probe according to the fourth embodiment. Detailed Implementation

[0033] [First Implementation Method]

[0034] <Structure of the dispensing mechanism of the automatic analysis device>

[0035] In the dispensing mechanism of the automatic analysis apparatus of the first embodiment, a detachable pipette tip is mounted on the tip of the probe. In this embodiment, the dispensing mechanism sequentially draws reagent and sample into the pipette tip and simultaneously dispenses them into the reaction container. It detects the aspiration of air bubbles (hereinafter referred to as "empty aspiration") or blockage when aspirating the sample while the reagent is pre-drawn into and held in the pipette tip.

[0036] 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 pipette tip 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 for holding cleaning water 105, a solenoid valve 111, a reagent container 112 (container) for holding reagents 113 (fluid) corresponding to the analysis items, a sample container 114 (container) for holding samples 115 (fluid), a reaction container 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 pipette tip waste unit 126, a cleaning tank 127, and a solenoid valve 128.

[0037] The suction tip 101 (dispensing nozzle) can be attached and detached relative to 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, thereby allowing the probe 102 to move to a predetermined position in both the horizontal and vertical directions. The suction tip 101 is held, for example, in a suction tip holder (not shown), and the probe drive unit 107 moves the probe 102 above the suction tip holder and lowers it, thereby allowing the suction tip 101 to be mounted onto the probe 102. Alternatively, the suction tip 101 can also be mounted on the probe 102 in a suction tip buffer that temporarily holds the suction tip 101.

[0038] 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 drive 106 is connected to the plunger 104b. The syringe drive 106 drives the plunger 104b relative to the cylinder 104a in a vertical direction, thereby drawing in and discharging fluid (liquid and gas) from the suction tip 101 connected to the probe 102. In particular, the probe 102 is capable of dispensing reagent 113 in reagent container 112 and specimen 115 in specimen container 114.

[0039] The syringe 104 has a flow path communicating with a water supply tank 110, in which a solenoid valve 111 and a water supply pump 109 are provided. The water supply tank 110 contains cleaning water 105, which is discharged from the probe 102 by the drive of the water supply pump 109, 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 sample 115.

[0040] Although the illustration is omitted, the automated analyzer includes a reagent magazine for holding reagent container 112, a sample container rack for holding sample container 114, and a reaction tray for holding reaction container 116. The holding units for reagent container 112, sample container 114, and reaction container 116 are not limited to the components described above. Reagent 113 and sample 115, drawn onto pipette tip 101, are dispensed into reaction container 116.

[0041] 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 can also be configured to control not only the components of the dispensing mechanism 100, but also the operation of the entire automatic analysis device.

[0042] Pressure sensor 117 is connected to a branch block 118 located midway through flow path 103, and measures time-series pressure data within flow path 103. Pressure sensor 117 outputs the detected pressure signal to signal amplifier 119. For example... Figure 1 As shown, the pressure sensor 117 can be located on the side of the syringe 104, but by connecting the pressure sensor 117 as close as possible to the probe 102, pressure changes at the opening of the suction tip 101 can be measured with high sensitivity.

[0043] The signal amplifier 119 amplifies the detection signal from 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 as a pressure value to the determination unit 121.

[0044] The determination unit 121 is a circuit used to determine whether there is any 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.

[0045] The determination unit 121 is configured to communicate with the control unit 108. If the determination is based on the data processing result in the calculation unit 124, and it is determined that an operation should be stopped, the determination unit 121 sends the content of the stop operation to the control unit 108.

[0046] 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 having a processor read and execute a program recorded in the storage unit 123. Alternatively, it can function as the determination unit 121 by having a processor in a server that is wirelessly or wiredly connected to the automatic analysis device read and execute the program.

[0047] 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.

[0048] After the pipette tip 101 has dispensed reagent 113 and sample 115 into reaction vessel 116, it is discarded into pipette tip disposal section 126.

[0049] The cleaning tank 127 consists of a cleaning nozzle 127a and a drain cup 127b, and can clean the outer wall of the suction head 101 through the cleaning nozzle 127a. The cleaning water 105 used to clean the outer wall of the suction head 101 is discharged from the cleaning nozzle 127a through the solenoid valve 128.

[0050] <Dispensing method>

[0051] Figure 2 This is a flowchart illustrating the dispensing method of the first embodiment, and more particularly, the dispensing method for fluids using an automatic analysis device. The dispensing method of this embodiment is performed by an automatic analysis device; in practice, it is achieved through… 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.), but the components of the dispensing mechanism 100 will sometimes be described as the main body of the operation below.

[0052] In step S201, the control unit 108 sets the solenoid valve 111 to the open state and drives the water supply pump 109 to discharge cleaning water 105 from the water supply tank 110 from the probe 102. As a result, the inside of the probe 102 is cleaned.

[0053] In step S202, the syringe drive unit 106 drives the syringe 104 to draw segmented air into 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.

[0054] In step S203, the probe drive unit 107 moves the probe 102 above the tip holder or tip buffer and then lowers it, thereby mounting the tip 101 onto the front end of the probe 102.

[0055] In step S204, it is determined whether there is any reagent that needs to be dispensed. If there is a reagent that needs to be dispensed (yes), steps S205 to S208 are performed to aspirate the reagent, and then the process returns to step S204. That is, steps S205 to S208 are repeatedly performed until all the reagents that need to be dispensed have been aspirated. For example, if there are two types of reagents that need to be aspirated, steps S205 to S208 are repeated twice. If there is no reagent that needs to be dispensed (no), steps S205 to S208 are not performed.

[0056] 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 pipette tip 101 is immersed in the reagent 113.

[0057] In step S206, the syringe drive unit 106 drives the syringe 104 to draw the reagent 113 into the pipette tip 101. Then, the probe drive unit 107 causes the probe 102 to rise until the tip of the pipette tip 101 leaves the reagent 113.

[0058] In step S207, the syringe drive unit 106 drives the syringe 104 to draw segmented air into the pipette tip 101. This is to prevent the reagent 113 drawn into the pipette tip 101 first from mixing with the liquid drawn in the next step.

[0059] In step S208, the control unit 108 opens the solenoid valve 128 and drives the water supply pump 109 to discharge cleaning water 105 from the water supply tank 110 through the cleaning nozzle 127a. This cleans the outer wall of the suction head 101. This is to prevent the reagent 113 initially drawn onto the suction head 101 from mixing with the liquid drawn in the next step.

[0060] As described above, by repeating steps S205 to S208 multiple times, the dispensing mechanism 100 can perform the air aspiration step (step S207) multiple times from the time the fluid (reagent 113 and / or sample 115) is drawn into the probe 102 until it is discharged. As a result, multiple fluids can be kept from mixing.

[0061] In step S209, it is determined whether there is a sample that needs to be aspirated. If there is a sample that needs to be aspirated (yes), steps S210 to S214 are performed to aspirate the sample. If there is no sample that needs to be aspirated (no), steps S210 to S214 are not performed.

[0062] In step S210, the probe drive unit 107 moves the probe 102 above the sample container 114 and lowers the probe 102 until the tip of the suction tip 101 is immersed in the sample 115.

[0063] In step S211, the syringe drive unit 106 drives the syringe 104 to draw the sample 115 into the suction head 101. Here, the sampling unit 122 of the determination unit 121 receives the input of the pressure value during the suction action of the sample 115 and sends the pressure value involved in the suction action of the sample 115 as time-series data (hereinafter, sometimes referred to as "pressure history") to the storage unit 123. The storage unit 123 stores this data.

[0064] For example, pressure values ​​are measured during the time periods before the suction action begins, during the suction action, and after the suction action ends. Pressure can also be measured at multiple time points within each time period. Afterwards, the probe drive unit 107 raises the probe 102 until the tip of the suction head 101 leaves the sample 115.

[0065] In step S212, the calculation unit 124 of the determination unit 121 determines whether there are any abnormalities (detection abnormalities) such as blockage or empty suction when aspirating the sample 115, based on the pressure history stored in the storage unit 123 during sample aspiration. That is, based on the pressure history, it determines whether the dispensing of the sample of the analysis object is proceeding normally.

[0066] Furthermore, the pressure history under abnormal conditions such as air suction or blockage during sample aspiration 115 differs significantly from the pressure history under normal dispensing conditions. Therefore, by referring to the pressure history, it is possible to determine whether any abnormalities have occurred. The method for determining whether any abnormalities have occurred will be described later.

[0067] In this step, the determination unit 121 sends the determination result of whether there is an abnormality to the display unit 125 and the control unit 108. In addition, the display unit 125 displays the determination result.

[0068] 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 sample 115 has been attracted normally.

[0069] If an abnormality is determined to exist 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 exists during the aspiration of the sample 115. At this time, the display unit 125 displays an alarm, and the dispensing operation of the corresponding sample 115 is terminated. Furthermore, the sample 115 is returned to the user. In this way, by stopping the dispensing of the abnormal sample 115, the consumption of reagents used in subsequent analyses can be reduced.

[0070] In addition, Figure 2In the example, the process proceeds to step S215 after step S214. However, as a variation, predetermined error handling may be performed after step S214. In this case, other processes may be performed instead of step S215.

[0071] In step S215, the probe 102 is moved so that the tip of the pipette 101 is located inside the reaction vessel 116.

[0072] In step S216, the syringe drive unit 106 drives the syringe 104 to discharge the liquid held in the pipette tip 101 into the reaction container 116. At this time, all reagents and samples drawn into the pipette tip 101 are simultaneously discharged into the reaction container 116.

[0073] In step S217, the probe drive unit 107 moves the probe 102 to the tip discarding part 126, discards the tip 101 into the tip discarding part 126, and thereby removes it from the probe 102.

[0074] <Methods for determining the presence or absence of abnormalities>

[0075] Figure 3 It means Figure 2 The flowchart shows the method for determining whether there is an abnormality in step S212, which is determined by the determination unit 121.

[0076] In step S301, the calculation unit 124 reads the pressure history during sample aspiration stored in the storage unit 123. In this specification, "pressure history during sample aspiration" refers to pressure values ​​within a predetermined time range including the action time (absorption action time) of the syringe 104 when aspirating sample 115 in step S211.

[0077] In step S302, the calculation unit 124 calculates the judgment index used in determining the presence or absence of abnormalities based on the pressure history during sample suction. The "judgment index" includes, for example, at least one of the following values:

[0078] - The average pressure value during the suction operation of specimen 115.

[0079] - The average pressure value at the scheduled time before the suction operation of specimen 115 is about to begin.

[0080] - The average pressure value at a predetermined time immediately after the suction operation of specimen 115.

[0081] - The maximum pressure value during the suction operation of specimen 115.

[0082] -Minimum pressure value during suction of specimen 115.

[0083] - The pressure pulsation cycle of multiple attraction operations.

[0084] - Pressure pulsation amplitude in the history of multiple attraction operations.

[0085] - The distance between the pressure history used as a pre-defined baseline and the pressure history obtained in this step. This distance can be a statistical distance, such as the Euclidean distance. Pressure history {a1, a2, a3, ..., a...} n} and stress history {b1, b2, b3, ..., b n The Euclidean distance of} can be expressed as √{Σ(a ) i -b i ) 2} represents (where 1≤i≤n).

[0086] "The pressure history that serves as the baseline" can be set based on a large number of pressure values ​​obtained in the past. It can be the pressure value when the sample was attracted normally (in which case, for example, if the statistical distance is greater than the judgment threshold, it is judged to be abnormal), or the pressure value when the sample was attracted and it was judged to be abnormal (in which case, for example, if the statistical distance is less than the judgment threshold, it is judged to be abnormal).

[0087] Furthermore, the pressure history used as a benchmark can also be determined by measuring the pressure during segmented air aspiration before the sample is aspirated and by basing the determination on the pressure value during segmented air aspiration. That is, the historical pressure history during air aspiration can also be used to determine whether the sample aspiration of the analysis object is proceeding normally (in this case, for example, an abnormality is determined if the statistical distance is less than the determination threshold). In this way, a determination that is not easily affected by changes in the state of the flow path over time can be made.

[0088] Alternatively, the statistical distance (i.e., similarity or dissimilarity) from the pressure history used as the benchmark can be used as a criterion. Furthermore, when measuring the pressure during segmented air aspiration before aspirating the sample, and using the pressure value during segmented air aspiration as a benchmark to determine whether there is an abnormality, it is preferable to set the aspiration rate during the previous segmented air aspiration to be the same as the aspiration rate during sample aspiration. Additionally, multiple of the above-mentioned criteria can be combined as criterions.

[0089] In this specification, "suction speed" can be expressed in units such as m / s, and can be measured by the moving speed of a specific component (e.g., the plunger 104b of syringe 104) or the moving speed of the aspirated fluid in a specific flow path. Alternatively, the suction speed can also be expressed in units such as m. 3 / s is expressed as the flow rate of the attracted fluid. It can also be expressed as other flow rates, such as velocity or flow rate. The conversion of these physical quantities can be performed appropriately by the control unit 108, for example.

[0090] In this embodiment, as a determination criterion, the difference between the average pressure value during the suction operation of the sample 115 and the average pressure value at a predetermined time before the start of the suction operation is calculated, and this difference is used to determine whether it is normal dispensing or empty suction. For example, if the difference is less than a predetermined threshold, it is determined to be empty suction. As a cause of empty suction, considerations include false detection of the liquid level caused by air bubbles accidentally generated during the handling of the sample container 114. In addition, air bubbles may be generated when the blood sample 115 vibrates during transport.

[0091] In step S303, the calculation unit 124 determines whether there is an abnormality during the attraction of the sample 115 based on the determination index. Besides the specific method described above, other methods for determining the presence or absence of an abnormality include comparing the determination index with a predetermined 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 whether there is an abnormality. The determination threshold used to determine whether there is an abnormality is pre-stored in the storage unit 123.

[0092] Figure 4 It means Figure 2 A schematic diagram showing the state of the fluid within the probe 102 and suction tip 101 during the dispensing operation. Additionally, in Figure 4 The example illustrates the situation where one reagent and one sample are dispensed. Figure 4 (a) indicates the state immediately after cleaning the probe 102 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.

[0093] Figure 4 (b) indicates the state after the segmented air 401 is drawn in step S202 and the suction head 101 is installed in step S203.

[0094] Figure 4 (c) indicates the state after reagent 113 was attracted in step S206. Reagent 113 is located at the front end of pipette tip 101.

[0095] Figure 4 (d) indicates the state of aspirated segmented air 402 in step S207. Segmented air 402 is located at the front end of pipette tip 101, with reagent 113 positioned on top of it. Additionally, in Figure 4 (d) represents a reagent 113, but in the case of dispensing multiple reagents, reagent 113 and segmented air 402 are alternately configured to attract the amount of reagent.

[0096] Figure 4(e) indicates the state in step S211 where the sample 115 was attracted. The sample 115 is located at the front end of the pipette tip 101, with segmented air 402 on it and reagent 113 on the segmented air 402.

[0097] As described above, the pressure history during the suction of the sample 115 is used to determine whether there are any abnormalities. Before suctioning the sample 115, suction steps are performed on the reagent 113, segmented air 401, segmented air 402, etc. For example, regarding the boundary 403 between the cleaning water 105 and the segmented air 401, it moves upward in all suction steps of the reagent 113, segmented air 401, and segmented air 402.

[0098] As the boundary 403 moves, sometimes a portion of the cleaning water 105 adheres to and remains on the inner wall of the probe 102, forming a liquid film on the inner wall of the probe 102. By reducing the formation of such a liquid film, it is possible to suppress the formation of residual cleaning water 105 on the underside of the boundary 403, and uniformly maintain the state of the specimen 115 before aspiration. Figure 4 (d) Therefore, by improving the reproducibility of the pressure history during the aspiration of the specimen 115, it is possible to determine with high precision whether there are any abnormalities during the aspiration of the specimen 115.

[0099] 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.

[0100] Where D represents the flow path diameter, μ represents the fluid viscosity, v represents the suction velocity, σ represents the fluid surface tension, and ∝ represents the proportional relationship. The residual amount of cleaning water 105 remaining at the lower part of the boundary 403 is the value obtained by multiplying equation (1) by the moving distance of the boundary 403.

[0101] To reduce the amount of residual liquid in the cleaning water 105, reducing the suction rate is effective. Specifically, reducing the suction rate of the suction steps for reagent 113, segmented air 401, and segmented air 402 is effective. However, reducing the suction rate of the suction steps will prolong the dispensing time.

[0102] In this embodiment, taking step S202, which is a segmented air suction process, as an example, a method for reducing the suction speed in this process is shown. Figure 5 This is a flowchart illustrating the method for setting the suction speed in step S202.

[0103] In step S501, it is determined whether a sample is dispensed into the dispenser. If a sample is dispensed (yes), in order to accurately determine any abnormalities during the suction of sample 115, it is desirable to improve the reproducibility of the pressure history during the suction of sample 115, and therefore it is desirable to suppress the generation of residual cleaning water 105. Therefore, it is preferable to reduce the suction speed in step S202, setting the suction speed to a low speed v1 (step S502). In this case, Figure 2 The process involves steps S210 to S214.

[0104] On the other hand, if the sample is not separated (no), it is not necessary to determine whether there is any abnormality during the aspiration of sample 115, so the aspiration speed is set to high speed v2 (step S503). That is, v2 > v1. In this case, Figure 2 Steps S210 to S214 are not executed during the processing.

[0105] Thus, the dispensing mechanism 100 has multiple levels, namely v1 (first level) and v2 (second level), as levels for the suction speed of air when drawing air to the probe 102 (or to the suction head 101 mounted on the front end of the probe 102).

[0106] In the above, the aspiration rate in step S202 is adjusted based on whether a sample is aspirated during the dispensing process. That is, the dispensing mechanism 100 uses multiple levels v1 and v2 depending on the type of fluid being aspirated, and specifically, depending on whether the aspirated fluid contains a sample of the analyte. Therefore, when a sample 115 is aspirated, it is possible to accurately determine whether there are any abnormalities during aspiration, and when a sample 115 is not aspirated, it is possible to prevent the dispensing time from becoming excessive. Adjusting the aspiration rate based on the presence or absence of a sample can be applied to the aspiration processes of reagent 113, segmented air 401, and segmented air 402.

[0107] <Technical Effects>

[0108] As described above, the automatic analysis device of this embodiment adjusts the aspiration rate in the aspiration process of segmented air and reagent based on whether or not a sample is dispensed. In the case of sample dispensing, by slowing down the aspiration rate in the aspiration process of segmented air and reagent, the formation of a liquid film generated in the flow path before sample aspiration is suppressed, improving the reproducibility of pressure history during sample aspiration, thereby enabling highly accurate determination of whether there are any abnormalities during sample aspiration.

[0109] Furthermore, by slowing down the aspiration rate only when there is sample aspiration, the increase in aspiration time can be minimized, maximizing the number of analyses that can be processed per unit time.

[0110] The structure of this embodiment is particularly effective when multiple aspiration steps occur before aspiration of the sample, such as after aspiration of segmented air or reagents. By suppressing the formation of liquid films in all steps during multiple aspiration steps before the sample is aspirated, it is possible to determine with high accuracy whether there are any abnormalities during sample aspiration.

[0111] <Modification 1 of the first embodiment>

[0112] Figure 6 This is a schematic structural diagram of the dispensing mechanism 200 of the automatic analysis device, which represents a variation of the first embodiment. (See diagram for reference.) Figure 6 As shown, the dispensing mechanism 200 has a probe 601 (dispensing nozzle) instead of... Figure 1 The suction tip 101 and probe 102 are shown. The structure other than probe 601 is the same as the dispensing mechanism 100 of the first embodiment, so the description is omitted.

[0113] In this variation, Figure 2 Steps S203 and S217 are omitted in the flowchart, where the pipette tip is replaced with a probe. Additionally, in Figure 4 The pipette tip 101 and probe 102 are replaced with probe 601.

[0114] <Modification 2 of the first embodiment>

[0115] The abnormality determination in the sample dispensing process can also be omitted. For example, pressure measurement can be omitted in step S211, and steps S212 to S214 can be omitted. In addition, pressure sensor 117, signal amplifier 119, A / D converter 120, determination unit 121, etc. can be further omitted.

[0116] [Second Implementation]

[0117] In the first embodiment, in step S501, the suction speed in step S202 is changed depending on whether a sample is dispensed in the dispensing process. In this embodiment, the suction speed in the dispensing process of the segmented air is changed according to the volume of segmented air being dispensed.

[0118] As described in the first embodiment, the amount of residual cleaning water 105 at the lower part of the boundary 403 is the value obtained by multiplying equation (1) by the moving distance of the boundary 403. The process with a larger suction volume is one in which the moving distance of the boundary 403 increases.

[0119] In this embodiment, taking the suction process of segmented air 401 and segmented air 402 as an example, a method for changing the suction speed according to the size of the suction volume of the segmented air is shown. Figure 7 This is a flowchart illustrating the method for setting the suction speed in the suction process of segmented air 401 and segmented air 402.

[0120] In step S701, the volumes of segmented air 401 and segmented air 402 are compared. If the volume of segmented air 401 is larger, liquid residue of cleaning water 105 is more likely to be generated during the suction process of segmented air 401. Therefore, the suction speed of segmented air 401 is set to a low speed v1, and the suction speed of segmented air 402 is set to a high speed v2 (step S702). That is, v2 > v1.

[0121] On the other hand, if the volume of segmented air 401 is small (no), liquid residue of cleaning water 105 is easily generated during the suction process of segmented air 402. Therefore, the suction speed of segmented air 401 is set to high speed v2, and the suction speed of segmented air 402 is set to low speed v1 (step S703).

[0122] In this way, the dispensing mechanism 100 uses multiple levels v1 and v2 separately according to the air suction volume. In particular, level v1 with a small suction speed is used when the air suction volume is large, and level v2 with a large suction speed is used when the air suction volume is small.

[0123] More specifically, in the process of drawing in a first volume of air and a second volume of air, when the first volume is larger than the second volume, the first volume of air is drawn in at a low speed v1 and the second volume of air is drawn in at a high speed v2; when the second volume is larger than the first volume, the second volume of air is drawn in at a low speed v1 and the first volume of air is drawn in at a high speed v2.

[0124] In the above, the suction speed in the suction process of segmented air 401 and segmented air 402 is adjusted according to the suction volume of each analytical air sample, thereby accurately determining whether there are any abnormalities during the suction of the sample 115. By slowing down the process with a large suction volume, the increase in the time required for dispensing can be minimized, maximizing the number of analyses that can be processed per unit time.

[0125] In this embodiment, segmented air is used, and the suction speed is set according to the suction volume. As a variation, the structure can also be modified to set the suction speed according to the suction volume of the reagent.

[0126] Regarding the distinction between levels, the first and second embodiments can also be combined. For example, multiple levels can be used separately based on the type of fluid and the volume of air drawn in.

[0127] [Third Implementation Method]

[0128] In this embodiment, the suction speed in the segmented air suction process is changed according to the purpose of the segmented air suction.

[0129] In this embodiment, a method is shown for changing the suction speed based on whether the pressure in the segmented air suction process becomes a criterion for judging the abnormality of the suction sample. Figure 8 This is a flowchart illustrating the method for setting the suction speed in the segmented air suction process.

[0130] In this embodiment, the dispensing mechanism 100 has multiple levels, namely v1 and v3, which are levels representing the suction speed of air when suctioning air to the probe 102 (or to the suction head 101 mounted on the front end of the probe 102). v3 > v1, and v3 is the same as the suction speed when suctioning the sample. The relationship between v2 and v3 is arbitrary, and it can also be that v2 = v3.

[0131] In step S801, it is determined whether the pressure during the suction of the segmented air becomes a criterion for judging the abnormality of the suction sample. This can be determined, for example, based on the pre-set operating parameters of the automatic analysis device.

[0132] If the pressure during the aspiration of the segmented air is not used as a criterion for judging the abnormality of the aspirated specimen (No), in order to prevent the generation of liquid residue of the cleaning water 105, the aspiration speed of the segmented air 401 is set to a low speed v1 (step S802). That is, when the pressure history during aspiration of air is used to judge whether the aspiration of the specimen of the analysis object is performed normally, multiple levels v1 and v3 are used.

[0133] On the other hand, if the pressure during the suction of the segmented air becomes the benchmark for judging the abnormality of the suction sample (yes), and the suction speed of the segmented air is set to be the same as the suction speed during the suction of the sample, then it becomes an appropriate benchmark, so the suction speed of the segmented air is set to high speed v3 (step S803).

[0134] Thus, when the time series data during air intake is not used to determine whether the analysis of the specimens of the target is proceeding normally, multiple levels v1 and v3 are used.

[0135] In the above, the suction speed is adjusted based on whether the pressure in the segmented air suction process becomes a criterion for judging abnormalities in the suctioned sample, thereby accurately determining the presence or absence of abnormalities during the suction of sample 115. By setting the suction speed of the segmented air suction, which becomes the criterion for judging abnormalities in the suctioned sample, to be the same as the suction speed of the sample, a suitable criterion for judging abnormalities can be adopted. Furthermore, by slowing down the suction speed of other segmented air processes, the formation of a liquid film can be suppressed, and the presence or absence of abnormalities during the suction of the sample can be judged with high accuracy.

[0136] [Fourth Implementation Method]

[0137] 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. Specifically, the value is changed according to the diameter and material of the flow path where boundary 403 is located. Figure 5 , Figure 7 , Figure 8 The value of v1 at low speed.

[0138] Figure 9 This is a schematic diagram showing the state of the fluid inside the probe 102. In this embodiment, the flow path inside the probe 102 consists of a small-diameter flow path 901, a tapered portion 902, a large-diameter flow path 903, and a flow path 904 made of a different material than flow paths 901 to 903.

[0139] When boundary 403 is located in the small-diameter flow path 901, the flow velocity v in the pipe increases, making it easier for liquid residue to form. Therefore, it is preferable to make the value of the low velocity v1 smaller than when boundary 403 is located in the conical section 902 and flow path 903. On the other hand, when boundary 403 is located in the large-diameter flow path 903, the flow velocity v in the pipe decreases, making it difficult for liquid residue to form. Therefore, compared to when boundary 403 is located in the flow path 901 and conical section 902, it is preferable to increase the value of the low velocity v1 (where v1 < v2).

[0140] Furthermore, when flow path 903 and flow path 904 have the same shape, and liquid residue is easily generated in flow path 904, it is preferable to reduce the value of low speed v1 when boundary 403 is located in flow path 904 compared to when boundary 403 is located in flow path 903.

[0141] [Variation Example]

[0142] This disclosure is not limited to the embodiments described above, but includes various modifications. For example, by combining the structures of the first to fourth embodiments and their modifications, it is possible to more effectively and accurately determine the presence or absence of abnormalities during sample aspiration.

[0143] Furthermore, the embodiments described above are for the purpose of easily understanding and illustrating this disclosure, and it is not necessary to possess all the structures described. Additionally, a portion of one embodiment can be replaced with the structure of another embodiment. Furthermore, the structure of another embodiment can be added to the structure of one embodiment. Moreover, regarding a portion of the structure of each embodiment, a portion of the structure of another embodiment can be added, deleted, or replaced.

[0144] The dispensing methods described above can be performed not only in automated analysis devices but also in other devices with fluid dispensing mechanisms. For example, the methods of each embodiment can also be applied to pharmaceutical manufacturing apparatuses, microreactors, etc.

[0145] Explanation of reference numerals in the attached figures

[0146] 100… betting institutions

[0147] 101… suction head

[0148] 102… probe

[0149] 103…Flow path

[0150] 104… Syringe (pressure source)

[0151] 104a…Cylinder Block

[0152] 104b…plunger

[0153] 105…washing water

[0154] 106…Injector drive unit

[0155] 107…Probe Drive Section

[0156] 108…Control Department

[0157] 109…water supply pump

[0158] 110…water supply tank

[0159] 111…Solenoid valve

[0160] 112…Reagent Container

[0161] 113…Reagent (Fluid)

[0162] 114…Specimen container (container)

[0163] 115… Specimen (fluid)

[0164] 116…Reaction Vessel (Container)

[0165] 117… Pressure Sensor

[0166] 118…branch block

[0167] 119…signal amplifier

[0168] 120…A / D converter

[0169] 121… Judgment Department

[0170] 122…Sampling Department

[0171] 123… Storage Department

[0172] 124…Computing Department

[0173] 125… Display Section

[0174] 126…Sucking head waste section

[0175] 127…washing tank

[0176] 127a… Cleaning nozzle

[0177] 127b…drainage cup

[0178] 128…Solenoid valve

[0179] 200… betting institutions

[0180] 401…Sectional Air

[0181] 402…Sectional Air

[0182] 403…boundary

[0183] 601…probe

[0184] 901…Flow path

[0185] 902…conical part

[0186] 903…Flow path

[0187] 904...Flow path.

Claims

1. An automatic analysis device, comprising: A container that holds fluid; Pressure source; A probe that dispenses fluid into the container; and The flow path connects the probe and the pressure source. Its features are, The automatic analysis device has multiple levels of suction speed for drawing air into the probe or into a suction head mounted at the tip of the probe. The level is used according to at least one of the type of fluid and the volume of air drawn in.

2. The automatic analysis device according to claim 1, characterized in that, The automatic analysis device also includes: A pressure sensor that measures time-series data of pressure within the flow path; and The storage unit stores the time-series data. The automatic analysis device uses the time series data to determine whether the analysis of the sample has been performed correctly.

3. The automatic analysis device according to claim 1, characterized in that, The level is used based on whether the fluid contains a sample of the analyte.

4. The automatic analysis device according to claim 1, characterized in that, When the volume of air being drawn is large, a low suction velocity is used.

5. The automatic analysis device according to claim 2, characterized in that, The time-series data during the aspiration of air is used to determine whether the analysis of the sample is proceeding normally.

6. The automatic analysis device according to claim 5, characterized in that, When using the time-series data of the air intake process to determine whether the analysis of the sample is proceeding normally, the first level among the levels is used. Without using the time-series data of the air intake for determining whether the analysis of the specimen is being performed normally, a second level, which is different from the first level, is used.

7. The automatic analysis device according to claim 1, characterized in that, The process of drawing air is performed multiple times from the time the fluid is drawn into the probe until it is discharged.

8. A method for dispensing fluid using an automatic analysis device, characterized in that, The automatic analysis device includes: A container that holds fluid; Pressure source; A probe that dispenses fluid into the container; as well as The flow path connects the probe and the pressure source. The automatic analysis device has multiple levels of suction speed for drawing air into the probe or into a suction head mounted at the tip of the probe. The dispensing method includes distinguishing the use of the level based on at least one of the type of fluid and the volume of air drawn in.

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