Dispensing device, automatic analyzer and dispensing method

Abstract

To provide a technology that assesses with high accuracy abnormality that occurs when simultaneously dispensing a plurality of kinds of liquid.SOLUTION: A dispensing device comprises: a dispensing nozzle; a pressure source; a sensor for detecting the internal pressure of the dispensing nozzle; a processor configured to draw in a first liquid and holding it, while drawing in a second liquid that is different from the first liquid by controlling the dispensing nozzle and the pressure source, and assess abnormality while the second liquid is being drawn in; and a storage device for storing reference pressure data and a prescribed threshold. At least one of the reference pressure data and the prescribed threshold is preliminarily acquired in plurality so as to correspond to each of different physical property values of the first liquid, and stored in the storage device. The processor acquires the pressure data to be assessed for abnormality, selects one of reference pressure data if stored in plurality in accordance with the physical property values of the first liquid, and selects one of prescribed thresholds if stored in plurality.SELECTED DRAWING: Figure 4

Description

[Technical field]

[0001] The present disclosure relates to a dispensing device, an automatic analyzer, and a dispensing method. [Background technology]

[0002] Automated analyzers that perform quantitative or qualitative analysis of specific components contained in biological samples such as blood and urine are indispensable for current diagnoses due to the reproducibility of analysis results and high processing speed. In recent years, along with the demand for reducing equipment costs and analysis costs, there is a demand to reduce the amount of reagents used in analysis. Therefore, the dispensing device installed in the automated analyzer is required to dispense samples and reagents with high precision.

[0003] Serum or plasma is often used as a sample to be dispensed by a dispenser of an automatic analyzer. When dispensing such a sample, an abnormality may occur due to reasons such as a high viscosity liquid or a solid matter such as fibrin clogging the nozzle of the dispenser. When an abnormality occurs, it is not possible to dispense a specified amount of sample, and therefore it is not possible to obtain accurate analysis results.

[0004] In order to deal with abnormal dispensing, a method has been proposed in which a pressure sensor is connected to the flow path of the dispensing device, and pressure fluctuations are measured to detect nozzle clogging. Patent Document 1 describes the following technology: "A pressure sensor 14 is connected to a dispensing flow path system including a sample probe 1 and a dispensing syringe 3, and multiple output values ​​from the pressure sensor during the sample dispensing operation are captured. A multi-item analysis (Mahalanobis distance) is performed using these multiple obtained pressure sensor output values ​​as items, and a comparison is made with a threshold value to determine whether dispensing was performed normally" (see Abstract of Patent Document 1).

[0005] Patent Document 2 describes the following technology: "An automatic analyzer includes a probe that dispenses liquid, a syringe that generates pressure fluctuations for the probe to dispense liquid, a flow path connecting the probe and the syringe, a pressure sensor that measures the pressure in the flow path when the probe dispenses liquid, a memory unit that stores time-series data of the pressure measured by the pressure sensor, a simulator that calculates a reference pressure waveform of the liquid flow in the flow path based on a physical model, and a determination unit that determines the dispensing state of the liquid to be determined based on information on the time-series data of the pressure when the probe dispenses the liquid to be determined and the reference pressure waveform calculated by the simulator" (see Abstract of Patent Document 2). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2008-224691 A [Patent Document 2] JP 2019-124529 A Summary of the Invention [Problem to be solved by the invention]

[0007] By the way, the means for reducing the cost of the device include reducing the cost and number of parts. For the dispensing device, dispensing the sample and the reagent with one dispensing device is effective for reducing the cost. In this case, after aspirating the reagent, aspirate the sample while holding it in the nozzle without discharging it, and discharge the reagent and the sample at the same time, thereby suppressing the decrease in the processing speed.

[0008] When dispensing a sample and a reagent at the same time in this way, differences in the viscosity of the reagent and the amount of liquid affect the pressure when determining whether a dispensing error occurs based on pressure fluctuations during sample aspiration, which may hinder accurate determination. Patent Documents 1 and 2 do not consider how to determine whether a dispensing error occurs when dispensing a sample and a reagent at the same time.

[0009] Therefore, the present disclosure provides a technique for determining with high accuracy any abnormality that occurs when multiple types of liquids are dispensed simultaneously. [Means for solving the problem]

[0010] In order to solve the above problems, a dispensing device of the present disclosure includes a dispensing nozzle, a pressure source that generates pressure fluctuations for aspirating and discharging a fluid by the dispensing nozzle, a sensor that detects pressure inside the dispensing nozzle, a processor configured to control driving of the dispensing nozzle and driving of the pressure source to aspirate a second liquid different from the first liquid while aspirating and holding a first liquid, and to determine an abnormality during aspirating of the second liquid, and a storage device that stores reference pressure data and a predetermined threshold value used for the determination, wherein at least one of the reference pressure data and the predetermined threshold value corresponds to each different physical property value of the first liquid. and the processor is configured to acquire a plurality of pressure data to be judged as being abnormal from a detection signal of the sensor during suction of the second liquid, select one of the reference pressure data if a plurality of the reference pressure data are stored according to a physical property value of the first liquid, select one of the predetermined threshold values ​​if a plurality of the predetermined threshold values ​​are stored, calculate a statistical distance between the pressure data to be judged and the reference pressure data, judge that there is an abnormality if the statistical distance is greater than the predetermined threshold, and judge that there is a normality if the statistical distance is equal to or less than the predetermined threshold.

[0011] Further features related to the present disclosure will become apparent from the description of the present specification and the accompanying drawings. Also, the aspects of the present disclosure are achieved and realized by the elements and combinations of various elements and the following detailed description and the appended claims. The description of the present specification is merely exemplary and is not intended to limit the scope or application of the present disclosure in any way. Effect of the Invention

[0012] According to the technique of the present disclosure, it is possible to determine with high accuracy any abnormality that occurs when multiple types of liquid are dispensed simultaneously. Problems, configurations, and effects other than those described above will become apparent from the description of the embodiment below. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a schematic diagram showing a configuration of an automatic analyzer. [Diagram 2] FIG. 2 is a schematic diagram showing the configuration of a dispensing device. [Diagram 3] FIG. 2 is a schematic diagram showing a dispensing sequence for two types of liquid. [Figure 4] 13 is a flowchart showing a method for determining a dispensing abnormality. [Diagram 5] FIG. 13 is a schematic diagram showing an example of reference data for determination. [Figure 6] FIG. 13 is a diagram showing an example of a pressure waveform during aspiration of a sample in a state where a low-viscosity reagent is held. [Figure 7] FIG. 13 is a diagram showing an example of a pressure waveform during aspiration of a sample in a state where a highly viscous reagent is held. [Figure 8] FIG. 4 is a conceptual diagram illustrating a selection process of reference data for determination and a statistical distance threshold value based on the first embodiment. [Figure 9] FIG. 11 is a conceptual diagram illustrating a selection process of reference data for determination and a statistical distance threshold value based on the second embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] [First embodiment] <Example of automatic analyzer configuration> 1 is a schematic diagram showing the configuration of an automatic analyzer 10 according to a first embodiment. The automatic analyzer 10 includes a sample container 100, a sample rack 101, a reagent bottle 102, a reagent disk 103, a reaction cell 104, a cell disk 105, a dispensing device 106, a stirring unit 107, a measuring unit 108, a washing unit 109, and a washing unit 110. The automatic analyzer 10 is connected to a control device 20.

[0015] The sample container 100 contains a sample to be analyzed. A plurality of sample containers 100 can be arranged in the sample rack 101. The reagent bottle 102 contains a reagent. A plurality of reagent bottles 102 can be arranged in the reagent disk 103. The sample and the reagent are dispensed into the reaction cell 104, and a reaction liquid is obtained. A plurality of reaction cells 104 can be arranged in the cell disk 105. The dispensing device 106 moves a certain amount of the sample from the sample container 100 into the reaction cell 104, and moves a certain amount of the reagent from the reagent bottle 102 into the reaction cell 104. The stirring unit 107 stirs and mixes the sample and the reagent dispensed into the reaction cell 104. The measurement unit 108 irradiates light onto the reaction liquid in the reaction cell 104, receives light (reflected light, transmitted light, fluorescent light, etc.) obtained from the reaction cell 104, and outputs a detection signal to the control device 20. The cleaning unit 109 cleans the reaction cell 104. The cleaning unit 110 cleans the nozzle 113 of the dispensing device 106 .

[0016] The control device 20 can be configured as a computer device equipped with a processor, a memory for storing a program, and an input / output device. The control device 20 has a control unit 201, a storage unit 202, and a judgment unit 203 as functional modules realized by the processor executing the program. The control unit 201 controls each component of the automatic analyzer 10. The control unit 201 also analyzes components in the sample based on a detection signal received from the measurement unit 108. The storage unit 202 stores control parameters, measured data, and reference data for judging dispensing abnormalities in a memory or storage device. The judgment unit 203 judges dispensing abnormalities in the dispensing device 106.

[0017] Quantitative analysis of a certain component in a sample can be performed, for example, by the following procedure. First, a certain amount of the sample in the sample container 100 is dispensed into the reaction cell 104 by the dispensing device 106. Next, a certain amount of the reagent in the reagent bottle 102 is dispensed into the reaction cell 104 by the dispensing device 106. Then, the sample and the reagent in the reaction cell 104 are stirred by the stirring unit 107 to form a reaction liquid. If necessary, a plurality of reagents are added and dispensed into the reaction cell 104 by the dispensing device 106. During these dispensing operations, the sample container 100, the reagent bottle 102, and the reaction cell 104 are moved to a predetermined position by the transportation of the sample rack 101, the rotation of the reagent disk 103, and the rotation of the cell disk 105. After the reaction is completed, the inside of the reaction cell 104 is washed by the washing unit 109, and the next analysis is performed. The measuring unit 108 measures the absorbance of the reaction liquid and outputs it to the control unit 201, and the control unit 201 stores the absorbance data in the memory unit 202. The control unit 201 can analyze the amounts of components based on the Beer-Lambert law using the accumulated absorbance data and the calibration curve data.

[0018] <Example of dispensing device configuration> 2 is a schematic diagram showing the configuration of the dispensing device 106. The dispensing device 106 includes a nozzle 113, an arm 114, a shaft 115, a pressure sensor 116, a syringe pump 117, piping 118, an electromagnetic valve 119, and a plunger 120.

[0019] Nozzle 113 is held at one end of arm 114. The other end of arm 114 is attached to the upper end of shaft 115. Arm 114 can be driven to rotate together with the rotation of shaft 115. Shaft 115 is configured to be movable up and down and rotatable by an actuator (not shown). Nozzle 113, pressure sensor 116, and syringe pump 117 are connected via piping 118. The tip side of this dispensing flow path is opened by nozzle 113, and the base side is configured to be opened or closed by solenoid valve 119. A plunger 120 is attached to syringe pump 117, and liquid can be sucked or discharged by driving plunger 120.

[0020] The liquid dispensing operation by the dispensing device 106 can be controlled by the control unit 201 of the control device 20. The shaft 115 and the plunger 120 are each driven by a motor, and a drive signal for the motor is transmitted from the control unit 201 of the control device 20. The control unit 201 reads out the generation conditions of the drive signal from the storage unit 202.

[0021] In the dispensing operation, first, the control unit 201 closes the solenoid valve 119 and drives the plunger 120 to aspirate and discharge the liquid to be dispensed at the tip of the nozzle 113. After the dispensing operation is completed, the control unit 201 opens the solenoid valve 119 and supplies cleaning water from the base side. During the dispensing operation, the control unit 201 receives a detection signal from the pressure sensor 116. The control unit 201 transmits time-series data of the pressure to the determination unit 203. The determination unit 203 determines whether or not there has been an abnormality in the dispensing using the data that serves as the basis for determining whether or not there has been an abnormality in the dispensing. The method of determining an abnormality according to this embodiment will be described in detail later.

[0022] <How to dispense multiple types of liquid> 3 is a schematic diagram showing a dispensing sequence for two types of liquid. In the following, a process will be described in which a reagent contained in a reagent bottle 102 and a sample contained in a sample container 100 are dispensed into a reaction cell 104 at one time by a dispensing device 106. Note that, although the main actor in the dispensing operation is actually the control device 20 that drives the dispensing device 106, for the sake of simplicity, the dispensing operation will be described below with the dispensing device 106 as the main actor.

[0023] Step (i) shows an initial state at the start of dispensing, in which the nozzle 113 is filled with the system water 121. Next, as shown in step (ii), the dispensing device 106 aspirates the segmented air 124 into the nozzle 113. Next, as shown in step (iii), the dispensing device 106 lowers the nozzle 113 to the liquid level of the reagent 122. Next, as shown in step (iv), the dispensing device 106 aspirates the reagent 122 into the nozzle 113 and holds it in the nozzle 113. Next, as shown in step (v), the dispensing device 106 raises and pulls out the nozzle 113 from the reagent bottle 102, and again aspirates the segmented air 124 into the nozzle 113. Next, as shown in step (vi), the dispensing device 106 cleans the nozzle 113 with the cleaning unit 110 to remove excess reagent adhering to the outer periphery of the nozzle 113. Next, as shown in step (vii), the dispenser 106 moves the nozzle 113 to the position of the sample container 100. Next, as shown in step (viii), the dispenser 106 lowers the nozzle 113 to the liquid level of the sample 123. Next, as shown in step (ix), the dispenser 106 aspirates the sample 123 into the nozzle 113 and holds it in the nozzle 113. Next, as shown in step (x), the dispenser 106 raises the nozzle 113 and pulls it out from the sample container 100. Next, as shown in step (xi), the dispenser 106 moves the nozzle 113 to the position of the reaction cell 104. Next, as shown in step (xii), the dispenser 106 ejects the sample 123 and the reagent 122 held in the nozzle 113 into the reaction cell 104. Finally, as shown in step (xiii), the dispensing device 106 cleans the inside and outside of the nozzle 113 using the cleaning unit 110, and proceeds to the next sample dispensing step.

[0024] As described above, it is possible to reduce the number of parts and thereby reduce costs by dispensing the sample 123 and the reagent 122 with one dispensing device 106. Furthermore, when dispensing the reagent and the sample with one dispensing device 106, it is possible to suppress a decrease in processing speed by continuously aspirating the reagent and the sample as described above.

[0025] <How to determine dispensing abnormalities> When determining whether a dispensing error has occurred in the dispensing method described above, it is possible to determine whether a dispensing error has occurred based on the output of the pressure sensor 116 installed in the dispensing device 106 in the step (iv) of aspirating the reagent 122, the step (ix) of aspirating the sample 123, and the step (xii) of discharging the sample 123 and the reagent 122. In particular, in the step (ix) of aspirating the sample 123, since the reagent 122 is held in the nozzle 113, the pressure fluctuation is influenced not only by the aspirated state of the sample 123 but also by physical properties such as the viscosity and liquid volume of the reagent 122. Therefore, in this embodiment, a method of determining whether a dispensing error has occurred based on the pressure fluctuation when the sample 123 (second liquid) is aspirated while the reagent 122 (first liquid) is held in the nozzle 113 is proposed.

[0026] FIG. 4 is a flowchart showing an outline of a method for determining a dispensing abnormality executed by the control device 20. As shown in FIG.

[0027] (Step S10) The control unit 201 acquires analysis parameters from the storage unit 202. The analysis parameters include at least information such as the type, liquid volume, and viscosity of the reagent 122 (first liquid) used in the analysis, information such as the liquid volume of the sample 123 (second liquid) to be analyzed, and other information necessary for the analysis (for example, analysis items, wavelength of light to be detected in the measurement unit 108, etc.).

[0028] (Step S20) The control unit 201 drives the dispensing device 106 based on the analysis parameters, and causes the nozzle 113 to aspirate the reagent 122 (first liquid).

[0029] (Step S30) The control unit 201 drives the dispensing device 106 based on the analysis parameters, and aspirates the sample 123 (second liquid) into the nozzle 113.

[0030] (Step S31) The control unit 201 acquires a detection signal of the pressure during the suction of the sample 123 from the pressure sensor 116, and outputs it to the determination unit 203 as time-series data of the pressure (pressure data) to be determined as abnormal.

[0031] (Step S40) Simultaneously with step S30, the control unit 201 extracts the physical property values ​​of the reagent 122, including the liquid volume and viscosity of the reagent 122, from the analysis parameters, and outputs them to the determination unit 203.

[0032] (Step S41) At the same time as step S31, the control unit 201 calculates the reference data for judgment and the statistical distance D M and the threshold value, reads it out from the storage unit 202, and outputs it to the judgment unit 203. The judgment reference data is a collection of known data acquired in advance, and the pressure value at each time when the sample 123 is normally aspirated is stored as a feature variable (reference pressure data) for each variation (event) of the physical property values ​​of the reagent 122 and the sample 123. The method of selecting the judgment reference data and the statistical distance threshold value will be described later.

[0033] (Step S50) The determination unit 203 calculates a statistical distance D between the pressure data to be determined and the determination reference data. M The statistical distance indicates how far the pressure data to be judged deviates from the reference data for judgment. In other words, the statistical distance is an index that quantifies the similarity between two events represented by multiple feature variables. In this embodiment, the Mahalanobis distance is calculated as an example of the statistical distance.

[0034] (Step S60) The determination unit 203 determines the calculated statistical distance D M Determine whether the statistical distance D is less than or equal to the threshold. M If the statistical distance D is equal to or smaller than the threshold (yes), the process proceeds to step S70. M If is greater than the threshold (no), the process proceeds to step S90.

[0035] (Step S70) The determining unit 203 outputs a determination result indicating that there is no abnormality to the control unit 201, and the control unit 201 drives the dispensing device 106 to dispense the reagent 122 and the sample 123 into the predetermined reaction cell 104.

[0036] (Step S80) The control unit 201 determines whether there is a next dispensing. If there is a next dispensing (yes), the process returns to step S20. If there is no next dispensing (no), that is, if all dispensings have been completed, the process ends.

[0037] (Step S90) statistical distance D M is greater than the threshold value, the determination unit 203 determines that there is an aspiration abnormality, and outputs the determination result to the control unit 201. When the control unit 201 receives the determination result that there is an abnormality, it performs a recovery process and ends the process. The recovery process is a process in which the control unit 201 outputs an alarm to an output device such as a display device or a speaker, and a process in which the control unit 201 executes an operation to proceed to the processing of the next sample.

[0038] (Regarding the criteria data for judgment) FIG. 5 is a schematic diagram showing an example of the reference data for judgment according to the first embodiment. As shown in FIG. 5, the reference data for judgment is provided for each of n events, and each data of the n events has k feature variables (n and k are positive integers). The events indicate variations (conditions) of the characteristics (physical property values) of the reagent 122 and the sample 123. Specifically, the event No. 1 corresponds to, for example, an event that the viscosity of the reagent 122 is low and the liquid amount is small. The event No. 2 corresponds to, for example, an event that the viscosity of the reagent 122 is low and the liquid amount is medium. Each event of the reference data for judgment may also correspond to the liquid amount of the sample 123. The feature variables are output values ​​from the pressure sensor 116 at each time k when the sample 123 with normal physical property values ​​is aspirated while the reagent 122 is held.

[0039] As shown in FIG. 5, for example, in event No. 1, the output value from the pressure sensor 116 when the sample 123 is aspirated is set as a feature variable X (time series of reference pressure data) as X 1,1 , X 1,2 , , X 1,k-1 , X 1,k In step S31 described above, the control unit 201 stores the feature variable Y (the time series of the pressure data to be determined) for the event to be determined in the form of Y1, Y2, . . . , Y k-1 , Y k and outputs it to the determination unit 203.

[0040] (How statistical distance is calculated) In step S50, the judgment unit 203 calculates the average Z of each feature variable X for events No. 1 to n in the judgment reference data as Z1, Z2, . . . , Z k Let the standard deviation σ be σ1, σ2, . . . , σ k Alternatively, the average Z and standard deviation σ of the feature variable X may be calculated in advance by the control unit 201 and stored in the memory unit 202, and may be read out by the determination unit 203 in step S50, or may be read out by the control unit 201 in step S41 and output to the determination unit 203. The determination unit 203 then performs the calculation of formula (1) using the average Z and each standard deviation σ of the feature variables of the determination reference data, and normalizes the pressure data to be determined.

[0041]

number

[0042] Then, the judgment unit 203 calculates a correlation matrix for each feature variable of n events and k items of the judgment reference data as a k×k matrix A, and calculates the inverse matrix A -1 The Mahalanobis distance D M Request.

[0043]

number

[0044] In addition to the Mahalanobis distance, other statistical distances that can be applied to the abnormality determination in this embodiment include Euclidean distance, standard Euclidean distance, Manhattan distance, Chebyshev distance, Minkowski distance, and multivariate normal density.

[0045] (Selection of criteria data and thresholds) The significance of selecting the reference data and thresholds depending on the event to be analyzed (that is, changing the reference data and thresholds to be used depending on the event to be analyzed) will be described below.

[0046] The characteristics of the sample 123 to be analyzed vary for each analysis item, and there are differences in viscosity and liquid volume in particular. When the liquid volume of the sample 123 varies, the suction speed and the time required for suction vary, so it is necessary to set the pressure data acquisition time and the like individually. Therefore, by preparing individual reference data for judgment for each liquid volume of the sample 123, it is possible to calculate the statistical distance more accurately and to judge anomalies with high accuracy. On the other hand, a sample 123 whose viscosity property value is within a specific range can be treated as a liquid that can be normally dispensed.

[0047] Fig. 6 is a diagram showing an example of pressure waveforms during aspirating of sample 123 (low-viscosity sample and high-viscosity sample) with low-viscosity reagent 122 held in nozzle 113. As shown in Fig. 6, for example, there is a difference in pressure waveform between a low-viscosity sample and a high-viscosity sample. By using the pressure waveform (reference pressure data) during aspirating of sample 123, which has a viscosity within a range that can be normally dispensed, as the reference data for judgment, the statistical distance between the pressure waveform during aspirating a normal sample 123 and the reference data for judgment becomes a low numerical value, and if it falls below the threshold value, it is judged to be normal.

[0048] In addition, the viscosity and the liquid amount of the reagent 122 vary depending on the analysis item. FIG. 7 is a diagram showing an example of a pressure waveform during aspirating the sample 123 in a state where a high-viscosity reagent 122 is held in the nozzle 113. As shown in FIG. 7, even when the sample 123 with the same physical properties as those in FIG. 6 is aspirated, there is a difference in the pressure during aspirating. Therefore, when a pressure data group acquired when aspirating the sample 123 with a normal range of physical property values ​​in a state where a low-viscosity reagent is held is used as the reference data for judgment, even if the same sample 123 is dispensed in a state where a high-viscosity reagent is held, the statistical distance is calculated as a higher value compared to the state where a low-viscosity reagent is held. Therefore, when the same threshold value is applied, there is a possibility that the threshold value is exceeded and the sample 123 is judged to be abnormal. In particular, applying a pressure data group (reference data for judgment) during aspirating the sample 123 in a state where a reagent 122 with a specific physical property (first physical property) is held and a threshold value to a reagent 122 with a significantly different physical property (second physical property) leads to a deterioration in judgment accuracy.

[0049] Therefore, in the first embodiment, the control unit 201 selects and reads out the reference data for determination and the statistical distance threshold value in accordance with the physical property value of the reagent 122 in step S41.

[0050] Fig. 8 is a conceptual diagram showing a selection process between reference data for judgment and statistical distance thresholds. As shown on the right side of Fig. 8, for example, reference data for judgment 1 to 9 (corresponding to each row in Fig. 5) and statistical distance thresholds T1 to T9 corresponding to the reference data for judgment 1 to 9 are stored as a set in the storage unit 202. As described above, the reference data for judgment 1 to 9 are each reference pressure data acquired during normal aspirating of the sample 123 while holding a reagent 122 with specific physical properties.

[0051] The left side of FIG. 8 illustrates an example in which pressure data is acquired when the sample is aspirated in a state in which each of the reagents A to I is held as an abnormality determination target. As shown in FIG. 8, when performing dispensing abnormality determination, the control unit 201 selects reference data for determination and a statistical distance threshold value that are close to the physical property values ​​of the reagent in the event to be determined (step S41). Note that, in FIG. 8, the event to be determined and a set of reference data for determination and threshold values ​​are shown to correspond one-to-one, but reference data for determination can be selected so that they correspond many-to-many. Also, in FIG. 8, the reference data for determination is classified into three stages of viscosity of the reagent, namely, low, medium, and high, and the liquid volume is classified into three stages of small, medium, and large. The number of stages of the physical property values ​​of the reagent is not limited to three, and may be two, or may be four or more. In FIG. 8, the physical property values ​​of the reagents to be determined of each reference data for determination are classified into stages such as small, medium, and large, but the physical property values ​​of the reagent may be specified by specific numerical values.

[0052] (Modification) The above describes an example of a method for selecting both the reference data for judgment and the statistical distance threshold. Alternatively, the reference data for judgment may be common regardless of the physical property value of the reagent 122, and the statistical distance threshold may be selected according to the physical property value of the reagent 122. Or, the statistical distance threshold may be common, and the reference data for judgment may be selected according to the physical property value of the reagent 122. In this way, at least one of the reference data for judgment and the statistical distance threshold is stored for each physical property value of the reagent 122, and by selecting according to the physical property value of the reagent 122 in the event to be judged, the accuracy of abnormality judgment can be improved.

[0053] As for the physical property values ​​of the reagent 122, a method has been exemplified in which the viscosity range and the liquid volume range are individually set, and the judgment reference data and the threshold value are selected under the combined conditions. Alternatively, the judgment reference data and the threshold value may be selected based on the pressure loss of the reagent 122 in the nozzle 113 when the sample 123 is aspirated. An example of a physical formula expressing the pressure loss due to friction in a pipe line is the Hagen-Poiseuille equation of Equation (3).

[0054]

number

[0055] Here, P loss represents the pressure loss, μ represents the viscosity of the fluid, L represents the length of the pipe, π represents the circular constant, d represents the diameter of the pipe, and Q represents the flow rate in the pipe. The diameter d of the pipe is determined by the shape of the nozzle 113. The flow rate Q in the pipe is determined by the speed at which the sample 123 is aspirated. The viscosity μ of the fluid is the viscosity of the reagent 122. The length L of the pipe is calculated from the liquid volume of the reagent 122 and the diameter of the pipe. In this way, the pressure loss P of the reagent 122 is loss By using this, it becomes easy to compare the influence of the physical property values ​​of the reagent 122. In other words, by selecting, from among a plurality of reference data for judgment, the reference data for judgment that is closest in pressure loss due to the reagent 122 at the time of acquiring the pressure data to be subjected to abnormality judgment, it is possible to prevent deterioration in the accuracy of suction abnormality judgment.

[0056] <Summary of the First Embodiment> As described above, the dispensing device 106 of the first embodiment includes the nozzle 113, the plunger 120 (pressure source) that generates pressure fluctuations for aspirating and discharging a fluid through the nozzle 113, the pressure sensor 116 that detects the pressure inside the nozzle 113, the control device 20 (processor) configured to aspirate a sample 123 (second liquid) while aspirating and holding a reagent 112 (first liquid) and determine an abnormality during aspirating the sample 123, and a storage unit 202 (storage device) that stores reference data for determination (reference pressure data) and a statistical distance threshold value used for the determination. At least one of the reference data for determination and the threshold value is acquired and stored in advance in a plurality of pieces so as to correspond to different physical property values ​​of the reagent 112. The control device 20 acquires pressure data to be judged for abnormality from the detection signal of the pressure sensor 116 during aspirating of the sample 123, selects one of the multiple reference data for judgment if multiple threshold values ​​are stored depending on the physical property value of the reagent 112, calculates the statistical distance between the pressure data to be judged and the reference data for judgment, judges that there is an abnormality if the statistical distance is greater than the threshold, and judges that there is no abnormality if the statistical distance is equal to or less than the threshold.

[0057] In this way, when determining whether or not there is an abnormality in the aspirating of the second liquid, by selecting appropriate parameters in accordance with the physical property values ​​of the first liquid, it is possible to accurately determine whether or not there is an abnormality in the dispensing.

[0058] [Second embodiment] In the first embodiment, it has been described that one piece of reference data for judgment is configured for each physical property value of one reagent. Alternatively, one piece of reference data for judgment may be configured for each range of physical property values ​​specified by the physical property values ​​of a plurality of (e.g., two) reagents. In the second embodiment, an example in which reference data for judgment is configured for each range of physical property values ​​in this manner will be described.

[0059] FIG. 9 is a conceptual diagram showing a selection process of the reference data for judgment and the statistical distance threshold value based on the second embodiment. As shown in FIG. 9, the storage unit 202 stores, for example, reference data for judgment 1 to 4 (corresponding to each row in FIG. 5) and statistical distance threshold values ​​T1 to T4 corresponding to the reference data for judgment 1 to 4 as a set. In this embodiment, each of the reference data for judgment 1 to 4 is data obtained by integrating pressure data groups in two events. More specifically, of the two events integrated in one reference data for judgment, reference data for judgment is set for each range of the physical property value of the reagent, with the physical property value of the reagent in one event as the lower limit and the physical property value of the reagent in the other event as the upper limit. For example, reference data for judgment 1 is an integration of a pressure data group during sample aspirating when the viscosity of the reagent is low and the amount of liquid is small, and a pressure data group during sample aspirating when the viscosity of the reagent is medium and the amount of liquid is medium.

[0060] For example, if the event to be judged is the aspiration of a sample while holding reagent A (low viscosity and small liquid volume), the event corresponds to the lower limit of the viscosity and the lower limit of the liquid volume of the reagent 122 that is the object of judgment in the reference data for judgment 1. Also, if the event to be judged is the aspiration of a sample while holding reagent B (low viscosity and medium liquid volume), the event corresponds to the upper limit of the liquid volume of the reagent in the reference data for judgment 1. If the event to be judged is the aspiration of a sample while holding reagent E (medium viscosity and medium liquid volume), the event corresponds to the upper limit of the viscosity and the upper limit of the liquid volume of the reagent 122 that is the object of judgment in the reference data for judgment 1.

[0061] 9, the combination of pressure data groups integrated into one judgment reference data may be, for example, a combination of ranges of adjacent physical property values. Specifically, in the judgment reference data 1, a pressure data group in the case of low viscosity and small liquid volume is integrated with a pressure data group in the case of medium viscosity and medium liquid volume.

[0062] As described above, the reference data for judgment 1 is a combination of a group of pressure data when a sample is aspirated while holding a reagent 122 with the same physical property values ​​as reagent A, and a group of pressure data when a sample is aspirated while holding a reagent 122 with the same physical property values ​​as reagent E. Since the reference data for judgment is configured for each range of the physical property values ​​of the reagent in this manner, when an abnormality is judged, it is possible to select the reference data for judgment that corresponds to the physical property values ​​of the reagent to be judged.

[0063] (Modification) In the second embodiment, a pressure data group acquired using a reagent with an upper limit of physical property value and a pressure data group acquired using a reagent with a lower limit of physical property value are integrated in one judgment reference data. Alternatively, each judgment reference data may include a pressure data group acquired using a reagent with an intermediate physical property value.

[0064] In the second embodiment, the physical property values ​​of the acquisition conditions of the pressure data group to be integrated have upper and lower limits for both viscosity and liquid volume. Alternatively, the reference data for judgment may be configured so that either the viscosity or the liquid volume is a fixed value, and the other has an upper and lower limit.

[0065] 9, the upper and lower limits of the physical property values ​​of the reagent 122 that are the acquisition conditions for the pressure data group are the same as the upper and lower limits of the physical property values ​​of the reagent 122 that are the acquisition conditions for the data to be judged. However, it is sufficient that the range of the physical property values ​​of the reference data for judgment and the physical property values ​​of the reagent in the event to be judged overlap, and the upper and lower limits do not necessarily have to be the same.

[0066] 9, reagents B and E are illustrated as belonging to the target range of judgment reference data 1. However, since reagents B and E are boundary conditions between the judgment target range of judgment reference data 1 and the judgment target range of judgment reference data 2, it is essentially possible to judge an abnormality by applying either judgment reference data 1 or 2.

[0067] 9 shows that the judgment target range of the judgment reference data is set in four ranges of physical property values. Alternatively, the judgment target range of the judgment reference data may be combined into one. In this case, the judgment reference data can be configured by integrating a group of pressure data when a sample is aspirated while holding a reagent 122 having the same physical property value as reagent A and a group of pressure data when a sample is aspirated while holding a reagent 122 having the same physical property value as reagent I.

[0068] In the second embodiment, an example was shown in which the viscosity and the liquid volume are individually combined to select the reference data for judgment and the statistical distance threshold in the comparison of the physical property values ​​of the reagent 122 between the judgment target data and the reference data for judgment. Alternatively, similar to the first embodiment, the magnitude of the physical property values ​​of the reagent 122 may be compared based on the pressure loss in the nozzle 113 caused by the reagent 122 when the sample 123 is aspirated.

[0069] <Summary of the second embodiment> As described above, in the second embodiment, pressure data for a plurality of first liquids with different physical property values ​​is integrated to be used as reference data for determination (reference pressure data). This results in reference data for determination with less variation in statistical distance relative to variation in the physical property values ​​of the first liquid, making it possible to avoid a decrease in determination accuracy due to differences in the physical property values ​​of the first liquid.

[0070] [Variations] The present disclosure is not limited to the above-described embodiments, and includes various modified examples. For example, the above-described embodiments have been described in detail to clearly explain the present disclosure, and it is not necessary to include all of the configurations described. In addition, a part of an embodiment can be replaced with a configuration of another embodiment. In addition, a configuration of another embodiment can be added to a configuration of an embodiment. In addition, a part of the configuration of each embodiment can be added to, deleted from, or replaced with a part of the configuration of another embodiment. [Explanation of symbols]

[0071] 10…Automatic analyzer 20...Control device (processor) 100...Sample container 102…Reagent bottle 103...Reagent disk 104…Reaction cell 106...Dispensing device 113...Nozzle (dispensing nozzle) 116...Pressure sensor 117... Syringe pump (pressure source) 120...Plunger (pressure source)

Claims

1. A dispensing nozzle; a pressure source that generates pressure fluctuations for aspirating and dispensing a fluid through the dispensing nozzle; A sensor for detecting a pressure inside the dispensing nozzle; a processor configured to control driving of the dispensing nozzle and driving of the pressure source to aspirate a second liquid different from the first liquid while aspirating and holding a first liquid, and to determine an abnormality during the aspirating of the second liquid; A storage device that stores reference pressure data and a predetermined threshold value used in the determination, at least one of the reference pressure data and the predetermined threshold value is previously acquired in a plurality of values ​​corresponding to different physical property values ​​of the first liquid and stored in the storage device; The processor, acquiring pressure data to be used for determining whether an abnormality exists from a detection signal of the sensor during the aspirating of the second liquid; Selecting one of the reference pressure data when a plurality of reference pressure data are stored according to a physical property value of the first liquid, and selecting one of the predetermined threshold values ​​when a plurality of predetermined threshold values ​​are stored according to a physical property value of the first liquid; A dispensing device characterized by being configured to calculate a statistical distance between the pressure data to be judged and the reference pressure data, and to judge that there is an abnormality if the statistical distance is greater than the predetermined threshold, and to judge that there is normality if the statistical distance is equal to or less than the predetermined threshold.

2. The reference pressure data is The dispensing device according to claim 1, characterized in that the data is composed of normal pressure data during normal aspira- tion of the second liquid while the first liquid is held in the dispensing nozzle, the data being acquired in advance for each different physical property value of the first liquid.

3. 2. The dispensing device according to claim 1, wherein the physical property values ​​are viscosity and liquid volume.

4. 2. The dispensing device according to claim 1, wherein the physical property value is a pressure loss caused by the first liquid in the dispensing nozzle when the second liquid is sucked.

5. The storage device stores a plurality of sets each including one of the reference pressure data and one of the predetermined threshold values; The dispensing device according to claim 1 , wherein the processor, in the determination, selects one of the plurality of sets depending on a physical property value of the first liquid.

6. The reference pressure data is 3. The dispensing apparatus according to claim 2, wherein the normal pressure data is configured by integrating a plurality of normal pressure data for a plurality of first liquids having different physical properties.

7. The plurality of normal pressure data first normal pressure data acquired when aspirating the second liquid in a state in which the first liquid having a physical property value that is an upper limit of the range of the physical property values ​​is held in the dispensing nozzle; and second normal pressure data acquired when aspirating the second liquid while the first liquid having a physical property value that is the lower limit of the range of the physical property values ​​is held in the dispensing nozzle.

8. The plurality of normal pressure data first normal pressure data acquired when aspirating the second liquid in a state in which the first liquid, which is an upper limit of a pressure loss in the dispensing nozzle due to the first liquid, is held in the dispensing nozzle; and and second normal pressure data acquired when aspirating the second liquid while the first liquid is held in the dispensing nozzle, the second normal pressure data being a lower limit of pressure loss in the dispensing nozzle due to the first liquid.

9. 2. The dispensing apparatus according to claim 1, wherein the statistical distance is any one of a Mahalanobis distance, a Euclidean distance, a standard Euclidean distance, a Manhattan distance, a Chebyshev distance, a Minkowski distance, and a multivariate normal density.

10. An automatic analyzer comprising the dispensing device according to claim 1.

11. 1. A method of dispensing executed by a processor of a dispensing device, comprising: driving a pressure source that generates pressure fluctuations for aspirating and discharging a fluid through a dispensing nozzle of the dispensing device, and aspirating a second liquid different from the first liquid while aspirating and holding a first liquid in the dispensing nozzle; receiving a detection signal of a pressure during aspirating of the second liquid from a sensor provided in the dispensing device, and acquiring pressure data to be used for determining whether an abnormality exists; Reading out from a storage device reference pressure data and a predetermined threshold value used for determining the abnormality; calculating a statistical distance between the pressure data to be judged and the reference pressure data, and judging that there is an abnormality when the statistical distance is greater than the predetermined threshold, and judging that there is a normality when the statistical distance is equal to or less than the predetermined threshold, at least one of the reference pressure data and the predetermined threshold value is previously acquired in a plurality of values ​​corresponding to different physical property values ​​of the first liquid and stored in the storage device; The reading includes: A dispensing method comprising: selecting one of the reference pressure data when a plurality of the reference pressure data are stored, and selecting one of the predetermined threshold values ​​when a plurality of the predetermined threshold values ​​are stored, depending on a physical property value of the first liquid.

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