Patent ID: 12188952

DESCRIPTION OF EMBODIMENTS

Hereinafter, examples of the present invention will be described with reference to the figures.

EXAMPLE 1

First, in the present example, a case where aspiration of bubbles (hereinafter, air aspiration), which is one of the pipetting conditions, is detected will be described.

FIG.1is a configuration diagram schematically illustrating an automatic analysis device101of Example 1 according to examples of the present invention.

As shown inFIG.1, the automatic analysis device101includes a rack transportation line103for transporting a sample rack102, a reagent cooling unit104, an incubator disk (reaction disk)105, a sample pipetting mechanism (sample pipetting mechanism)106, and a reagent pipetting mechanism107, a consumable transportation unit108, and a detection unit109.

The sample rack102accommodates several sample tubes (sample containers)110for storing biological samples (specimens) such as blood and urine, and the sample rack102is conveyed on the rack transportation line103in a condition where the sample tubes110are accommodated.

Several reagent containers111for storing various reagents used for analyzing samples are accommodated and cooled in the reagent cooling unit104. At least a part of the upper surface of the reagent cooling unit104is covered with a reagent disk cover112.

The incubator disk105includes: a reaction vessel disposal unit114in which several reaction vessels113for making the sample and the reagent react with each other are arranged; and a temperature adjustment mechanism (not shown) for adjusting the temperature of the reaction vessel113to a desired temperature.

The sample pipetting mechanism106has a rotation drive mechanism or a vertical drive mechanism (not shown), and the sample can be pipetted from the sample tube110to the reaction vessel113stored in the incubator disk105by these drive mechanisms. The reagent pipetting mechanism107also has a rotation drive mechanism or a vertical drive mechanism (not shown), and the reagent is pipetted from the reagent container111to the reaction vessel113stored in the incubator disk105by these drive mechanisms. The detection unit109includes a photomultiplier tube, a light source lamp, a spectroscope, and a photodiode (not shown), has a function of adjusting the temperature of the photomultiplier tube, a light source lamp, and a photodiode (not shown), and analyzes the reaction solution.

FIG.2is a configuration diagram schematically illustrating the sample pipetting mechanism of the automatic analysis device shown inFIG.1. As shown inFIG.2, a probe202to which a freely removable tip201is attached is connected to a syringe204via a flow path203, and the inside thereof is filled with a liquid. The syringe204is configured with a cylinder204aand a plunger204b,and a syringe driving unit205is connected to the plunger204b.By driving the plunger204bvertically with respect to the cylinder204aby the syringe driving unit205, the sample is aspirated and discharged. A motor (not shown) is connected to the probe202as a probe driving unit206, and according to this, the probe202can be moved in the horizontal direction and the vertical direction and moved to a predetermined position. The syringe driving unit205and the probe driving unit206are controlled by a control unit207.

Before a sample (specimen)209within the container208is aspirated, air (separation air) is aspirated into the probe202to prevent the liquid that fills the probe202and the sample209from mixing with each other and the tip201is attached to the end of the probe202.

After this, the probe driving unit206makes the probe202descend until the bottom of the tip201reaches the liquid of the sample209, and further performs the aspiration operation. When the sample aspiration operation is completed, the probe202moves to the sample discharge position, and the syringe204performs the discharge operation.

After discharging, the probe202can be cleaned by discharging cleaning water212within a water supply tank211at a high pressure by a water supply pump210. The flow path to the water supply tank211is opened and closed by a solenoid valve213. The solenoid valve213is controlled by the control unit207.

A pressure sensor214for measuring the pressure in the flow path203is connected to a flow path system including the probe202, the flow path203, and the syringe204via a branch block215. Here, since the pressure sensor214measures the pressure variations of the opening of the probe202and the tip201with high sensitivity, it is desirable to install the pressure sensor214on the probe202side as much as possible. The output value of the pressure sensor214is amplified by a signal amplifier216and converted into a digital signal by an A/D converter217. The digitally converted signal is sent to a determination unit218.

The determination unit218is configured with: a sampling unit219which samples the signal from the A/D converter217; a storage unit220which stores the data of the sampling unit; and a calculation unit221which calculates an average value or the like from the information stored in the storage unit220.

A liquid level sensor222determines whether or not the tip201at the end of the probe202is immersed in the sample209at the time of pipetting. The information on the relative immersion depth of the probe202calculated from the immersion time with respect to the sample209is sent to the storage unit220.

A flow path position determination unit223determines the position of the probe202or the flow path203at the time of pipetting. Specific configurations of the flow path position determination unit223include a mechanism for determining the height of the probe202based on the drive history of the motor of the probe driving unit206, a mechanism for detecting the position of the probe202or the flow path203with a sensor, and so on. The position information of the probe202or the flow path203at the time of pipetting, which is determined by the flow path position determination unit223, is sent to the storage unit220.

The result of determination performed by the determination unit218and the countermeasures for the result of determination are displayed to the user using a display unit224. The operation change information based on the determination result is transmitted to the control unit207.

The determination unit218may be configured as hardware in the device as a dedicated circuit board, or may perform input and output using the information communication network using hardware in the vicinity of the device or in a remote location.

FIG.3illustrates the fluid movement in the tip during air aspiration, which is one of the pipetting conditions. The upper part ofFIG.3illustrates the fluid movement during aspiration, and the lower part ofFIG.3illustrates the fluid movement during discharge. When the sample209is aspirated, bubbles301are erroneously aspirated into the tip201, and accordingly, the air aspiration occurs. As the reason of the air aspiration, false detection of the liquid surface due to bubbles unintentionally generated by handling the sample tube is considered.

When comparing a case where the bubbles move in the tip and a case where the sample moves, the pressure loss in the pipe line due to the viscosity of the fluid is different. As an example of a physical equation that expresses the pressure loss due to friction in the pipe line, the Hagen-Poiseuille equation (1) hereinafter can be employed.
Ploss=128 μLQ/(πd4)  (1)

Here, Plossis the pressure loss, μ is the viscosity of the fluid, L is the length of the pipe line, π is the ratio of the circumference, d is the diameter of the pipe line, and Q is the flow rate in the pipe line. In the present example, the air aspiration condition is detected by using the pressure data of the aspiration step or the discharge step in which the flow in the pipe line is generated.

FIG.4is a diagram illustrating pressure variations in an aspiration or discharge step. As shown inFIG.4, the probe starts descending from a horizontal rotational movement stop time401of the probe to the sample tube110, and the damped oscillation by the inertial force of the descent stop occurs between a probe descent stop time402and a pipetting syringe operation start time403, and the pressure oscillation occurs due to the flow in the pipe line between the pipetting syringe operation start time403and a pipetting syringe operation end time404. Among these, the influence of bubbles in the tip201appears in the pressure oscillation due to the flow within the pipe line between the pipetting syringe operation start time403and the pipetting syringe operation end time404. Therefore, it is effective to use this section in detecting the air aspiration.

In the example, the air aspiration is determined from the relative pressure value between the pipetting syringe operation start time403and the pipetting syringe operation end time404, in which the pressure between the probe descent stop time402and the pipetting syringe operation start time403is used as a reference pressure value. By using the pressure between the probe descent stop time402and the pipetting syringe operation start time403as a reference, it is possible to detect air aspiration that is not affected by the difference in height during pipetting. Depending on the length of the pipetting operation time, the influence of bubbles may appear after the pipetting syringe operation end time404. In this case, the determination may be made using the pressure data after the pipetting syringe operation end time404.

Here, when the probe descent stop time402and the pipetting syringe operation start time403are close to each other in 1 second or less, there is a possibility that the reference pressure value is affected by the damped oscillation due to the inertial force. In order to use a stable reference pressure value without being affected by the damped oscillation, the immersion depth information by the liquid level sensor222and the probe height information by the flow path position determination unit223are used.

FIG.5illustrates the probe, the pressure sensor, and the flow path that connects the probe and the pressure sensor, in the sample pipetting mechanism ofFIG.2.

InFIG.5, fluid pressure Pheadbased on gravitational acceleration in the pressure sensor position is represented by the following equation (2).
Pheadρg(H+h)  (2)

Here, ρ is the density of the fluid within the probe, the flow path, and the sample tube, g is the gravitational acceleration, H is the probe height, and h is the immersion depth. When the tip, the probe, the flow path, and the sample tube contain fluids having different densities, fluid pressure based on the gravitational acceleration may be calculated for each fluid.

In the present example, as the reference pressure value between the probe descent stop time402and the pipetting syringe operation start time403, the above-described hydraulic head Pheadcalculated from the immersion depth information h by the liquid level sensor222and the probe height H by the flow path position determination unit223is used as a reference pressure value. By setting the Pheadas a reference pressure value, the reference pressure value is not affected by the damped oscillation due to the inertial force.

FIG.6is an operation flow of the sample pipetting mechanism, and illustrates a flowchart of the air aspiration determination in the present example.

The following air aspiration determination is executed when pipetting the sample input by the user and the reagent used for analysis. First, in step S601, the probe driving unit206and the flow path position determination unit223execute the probe descent stop before pipetting and probe height information acquisition. After this, in step S602, the syringe driving unit205executes the pipetting syringe operation and time series pressure data collection. In step S603, the calculation unit221calculates the reference pressure value according to the above-described equation (2), and executes the creation of the relative pressure history between the pipetting syringe operation start time403and the pipetting syringe operation end time404with respect to the reference pressure value Phead(step S604).

Here, in creating the relative pressure history in step S604, it is necessary to align the position of the relative pressure history in the time direction. In the present example, the reference pressure value calculated from the reference pressure value calculation (step S603) is used to perform the alignment in the time direction.

FIG.7illustrates a procedure of creating a relative pressure history.

As shown in the upper part ofFIG.7, first, in step S701, the calculation unit221executes the calculation of a threshold pressure. The threshold pressure is used as a trigger for determining the time reference point when aligning the relative pressure history in the time direction. Here, a value offset by a constant value from a reference pressure value701acalculated in step S603(reference pressure value calculation) described above is set as a threshold pressure701b(lower part ofFIG.7). The offset may be constant for all pipetting volumes or may be varied for each pipetting volume. By setting the threshold pressure701bbased on the reference pressure value701a,it is possible to create a relative pressure history that is not affected by the probe height and the immersion depth at the time of pipetting.

Using the calculated threshold pressure701b,the calculation unit221calculates the reference time in step S702. A reference time702a(lower part ofFIG.7) is a time corresponding to the threshold pressure701b,and is used to align the pressure pulsation due to the syringe operation in the time direction. In determining the reference time702a,it is preferable to limit the search range of the time corresponding to the threshold pressure701bby using the pipetting syringe operation start time403. Since the pressure pulsation due to the syringe operation occurs after the pipetting syringe operation start time403, it is desirable to search for a certain time section after the pipetting syringe operation start time403. In addition, it is desirable to set the threshold pressure701bto a point where the slope of the pressure pulsation is large. By setting the threshold pressure701bto a point where the slope of the pressure pulsation is large, it is possible to improve the accuracy of determining the reference time702ain the time direction. In the search for the reference time702a,it is desirable to determine the reference time702aby using a known interpolation method such as linear interpolation or spline interpolation for the discrete time series data.

In step S703, the calculation unit221offsets the pressure history using the calculated threshold pressure701band the reference time702a.In offsetting the pressure history (step S703), the acquired time series pressure data is translated in the pressure history such that the point corresponding to the threshold pressure701band the reference time702ais a starting point703a.By offsetting the pressure history (step S703), it is possible to cancel out the difference in the hydraulic head due to the probe height and the immersion depth and the difference in the pressure history due to the difference in the aspiration time, and to cut out only the pressure variation due to the pipetting syringe operation with high accuracy.

Returning toFIG.6, in step S605, the calculation unit221compares the relative pressure history with the pressure history standard. Here, the pressure history standard is a pressure history acquired in advance, and the air aspiration is determined by comparing the relative pressure history with the pressure history standard. As the pressure history standard, a pressure history at the time of normal pipetting or a pressure history at the time of air aspiration, which is obtained in advance, can be used. This is, for example, to suppress the machine difference for each syringe.

In the comparison of the relative pressure history and the pressure history standard at the time of pipetting (step S605), the known statistical distances, such as the average value of the pressure in a certain section, the integrated value of the pressure, the Euclidean distance between the two histories, and the Mahalanobis distance, can be used for the comparison. Since both the relative pressure history and the pressure history standard include the pressure pulsation during the pipetting syringe operation, by comparing the relative pressure history with the pressure history standard, it is possible to detect the pipetting condition without depending on the pressure pulsation due to the pipetting syringe operation.

In step S606, the calculation unit221determines the pipetting condition from the result of comparison of the relative pressure history and the pressure history standard. Examples of the determination of the pipetting condition include determination based on the average value of pressure in a certain section and the magnitude difference between the integrated value of pressure and a certain threshold value, which are obtained by comparing the relative pressure history during pipetting and the pressure history standard (step S605), determination based on the magnitude relationship of values such as the Euclidean distance, the Mahalanobis distance or the like with respect to a plurality of pressure history standards, and so on. When it is determined to be normal (step S607), the subsequent analysis operation may be performed for the sample, and when it is determined to be the air aspiration (step S608), the analysis of the sample may be canceled or an alert may be issued, and a message that prompts the user to perform reanalysis may be displayed. An operation of compensating for air aspiration may be performed, such as performing the pipetting step again. The reliability of analysis results can be ensured by canceling analysis or issuing alerts.

FIG.8is a procedure for creating a pressure history standard, and illustrates a detailed procedure for creating the pressure history standard in step S605ofFIG.6. The calculation unit221executes each of the following steps.

The creation of the pressure history standard is started by setting a calibration mode (step S801) by the service engineer or the user. The service engineer or the user provides the determined calibration sample (step S802) to the device. Here, it is desirable that the sample used as the calibration sample includes both a sample that serves as a reference for normal pipetting and a sample that serves as a reference for air aspiration. The reference for normal pipetting may be set to a sample with the lowest viscosity among the samples that can be an analysis target of the device. Among the samples that can be the analysis target of the device, in a case where the sample with the lowest viscosity is approximately the same as pure water, when setting the sample having 1.5 mPa·s or less in an environment of 25° C. as a reference for normal pipetting such that the reference of the normal pipetting is approximately the same as or less than the viscosity of pure water, the determination with high accuracy is possible for all samples. In addition, it is desirable to use a sample containing gas as the reference for air aspiration. It is preferable to set a completely empty sample tube to reduce variability. As a calibration sample, two or more references for normal pipetting or references for air aspiration may be set. At this time, it is desirable that the pipetting volume of the calibration sample into the sample tube is set near the median value of the upper limit and the lower limit of the liquid level height that can be analyzed by the device. When necessary, a pressure history standard may be created by setting several pipetting volumes according to the liquid level height.

The pipetting sequence for calibration is started (step S803) for the provided calibration sample, and the pipetting sequence is executed for a specified number of times (step S804). Here, it is desirable that the pipetting sequence is the same as the operation at the time of actual sample analysis. While executing the pipetting sequence for a specified number of times (step S804), probe height information is acquired at the time of probe descent stop before pipetting, and time series pressure data is collected at the time of the pipetting syringe operation, and the collected data is stored in the storage unit220. Pipetting may be performed for several pipetting volumes and the calibration pipetting volume may be set to cover all possible syringe operating speeds. Since the pressure pulsation during the syringe operation is highly dependent on the syringe operating speed, by creating several pressure history standards and covering all possible syringe operating speeds, determination of the air aspiration that is not affected by the pressure pulsation during the syringe operation can be achieved. It is desirable to pipette both the sample that is the reference for normal pipetting and the sample that is the reference for air aspiration with the same pipetting volume, and to pipette both samples multiple times. When the same sample is pipetted multiple times with the same pipetting volume, the reliability of the pressure history standard can be improved by comparing the time series pressure data of multiple-times pipetting and confirming that the difference is small. Here, in order to confirm that the difference is small, the average value of pressure in a certain section, the integrated value of pressure, the Euclidean distance between two histories, the Mahalanobis distance, and the like can be used.

After executing the pipetting sequence for a specified number of times (step S804), by acquiring the probe height information at the time of probe descent stop before pipetting and using the time series pressure data during the pipetting syringe operation, which are recorded in the storage unit220, the reference pressure value calculation (step S805) and the creation of the relative pressure history (step S806) are performed. It is desirable that the reference pressure value calculation (step S805) is the same process as the reference pressure value calculation (step S603), and the creation of the relative pressure history (step S806) is the same process as the creation of the relative pressure history (step S604). By performing the same process, when the pressure history standard and the relative pressure history at the time of determination are compared with each other, it is possible to detect the pipetting condition without depending on the probe height, the immersion depth, and the pressure pulsation due to the pipetting syringe operation.

Using the created relative pressure history, the pressure history standard is created (step S807). The created pressure history standard may be the acquired relative pressure history itself, or may be a feature amount of the relative pressure history such as the average value of the pressure in a certain section or the coordinates of the peak of the history. When the same pipetting volume and the same sample are pipetted multiple times, a representative pressure history standard may be created by using the average value or the median value. Both the sample that serves as the reference for normal pipetting and the sample that serves as the reference for air aspiration may be used as the pressure history standard, or only the average thereof may be used as the pressure history standard.

The created pressure history standard is stored (step S808). When only the feature amount is stored for the pressure history standard as the feature amount of the relative pressure history, the capacity of the stored data can be reduced.

After storing the pressure history standard (step S808), the end of the calibration mode (step S809) is performed. Before the end of the calibration mode (step S809), the time series pressure data at the time of multiple-times pipetting is compared to confirm that the difference is small. In a case where the difference is large, when an alert that encourages the service engineer or the user to perform the calibration again is displayed, it is possible to improve the reliability of the pressure history standard. It is also effective to improve the reliability of the pressure history standard by comparing the time series pressure data at the time of multiple-times pipetting and comparing with the pressure history standard created in the previous calibration and confirming that the difference is small. By creating the pressure history standard according toFIG.8for each certain period, it is possible to determine a highly reliable air aspiration that cancels out the long-term change of the device.

It is desirable that the pressure history standard is created on an average weather day at the location where the device will be installed. By creating a pressure history standard at the place where the device is installed, it is possible to determine air aspiration without depending on changes in pressure pulsation due to external air pressure. In order to correspond to an environment in which the temperature changes greatly, it is also preferable to correct the pressure history standard with respect to the air temperature and use the corrected pressure history standard in determining air aspiration, in order to improve the accuracy of the determination.

In the present example, by adopting a pressure reference value that is not affected by damped oscillation due to inertial force, it becomes possible to detect the pipetting condition with high accuracy without depending on pressure pulsation due to the probe operation before and after pipetting. By comparing the relative pressure history with respect to the pressure reference value with the pressure history standard acquired in advance, it is possible to detect the pipetting condition without depending on the pressure pulsation by the pipetting syringe operation. The pipetting condition detection here can be widely applied not only to air aspiration but also a case of detecting an unintended pipetting condition such as clot in the flow path. Further, when the matching degree between the pressure history at the time of pipetting and the pressure history standard is high, this pipetting condition detection can also be applied to the evaluation of the result, for example, indicating that the pipetting result is excellent.

MODIFICATION OF EXAMPLE 1

FIG.9is a modification example of the configuration diagram schematically illustrating the sample pipetting mechanism of the automatic analysis device of the above-described Example 1 shown inFIG.2. In the following, the same components as those in Example 1 will be given the same reference numerals, and the description overlapping with that of the Example 1 will be omitted.

As shown inFIG.9, the difference fromFIG.2is that the information of the liquid level sensor222is transmitted to the control unit207instead of the storage unit220.

The liquid level sensor222determines whether or not the tip201at the end of the probe202is immersed in the sample209at the time of pipetting. In the present modification, a configuration is employed in which, by directly transmitting the immersion detection information of the liquid level sensor222to the control unit207, and by driving downward and then stopping a certain amount of the probe202after the immersion detection time, the relative immersion depth of the probe202immediately before the pipetting operation for the sample209is set to be constant.

In the present modification, the immersion depth h in the above-described equation (2) has a constant value, and the following is satisfied.
Phead=ρgH+α(3)

Here, α is a constant fixed number. In this case, it is not necessary to refer to the immersion depth h for each pipetting, and only the probe height H needs to be referred to.

FIG.10illustrates a method for determining the constant fixed number α in the present modification.

As shown inFIG.10, in step S1001, pressure is acquired at a probe height H0. The probe height H0 is acquired by the liquid level sensor222and the control unit207. The pressure is acquired by the pressure sensor214, the signal amplifier216, and the determination unit218. The pressure acquired here is P0. Here, it is desirable that the height, such as the upper limit point of the probe, is predetermined as H0. It is desirable to acquire the pressure at a time when the pressure pulsation is small, such as a time when the probe is stationary or the operating direction of the probe is orthogonal to the flow path direction. When the probe moves horizontally, the operating direction of the probe is orthogonal to the flow path direction, and thus, the pressure pulsation is small and is suitable as the pressure acquisition time. It is desirable that the pressure is acquired in a certain time section and the average value is used as the pressure value.

The calculation of the fixed number α (step S1002) can be performed by the following equation (4).
α=ρgH−P0  (4)

Using the fixed number α determined using the procedure ofFIG.10, the fluid pressure Pheadbased on the gravitational acceleration is calculated from the above-described equation (3), Pheadis adopted as the reference pressure value, and the air aspiration is determined.

Since the reference pressure value Pheadcalculated by the modification of the present example does not depend on the pressure pulsation due to the probe operation before and after pipetting, the determination with high accuracy without depending on the pressure pulsation is possible.

It is preferable that the procedure ofFIG.10of the modification of the present example is performed for each pipetting sequence. By performing this procedure for each pipetting sequence, even when the measured pressure value of the pressure sensor214is offset in the entire pipetting sequence, or even when the hydraulic head changes throughout the whole pipetting sequence due to the mixing of bubbles in the flow path, these effects can be canceled out by calculating the reference pressure value Phead, and thus, it is possible to stably determine air aspiration.

According to the present example described above, it is possible to provide an automatic analysis device capable of detecting a pipetting condition with high accuracy even when pressure pulsation occurs due to a pipetting syringe operation or a probe operation before and after pipetting.

By detecting the pipetting condition with high accuracy, bubbles generated by the handling of the sample tube by the user or fibrin that causes clot is detected with high accuracy, and accordingly, it is possible to provide the automatic analysis device that can reduce the loss of samples or reagents and reduce the labor of the user, such as re-test.

EXAMPLE 2

FIG.11is a diagram illustrating a procedure of determining the air aspiration of Example 2 according to other examples of the present invention. In the following, only the differences between the present example and Example 1 are shown.

As shown inFIG.11, the difference in the present example is that the processes of steps S601to S604ofFIG.6of the above-described Example 1 are changed to the processes of steps S1101to S1104ofFIG.11. Hereinafter, only steps S1101to S1104will be described.

The probe descent stop before pipetting and the stop time and flow path position information acquisition are performed (step S1101). Here, similar to Example 1, the flow path position information may be acquired only by the probe height, or the flow path shape may be measured by using the flow path position determination unit223as a sensor for determining the shape of the flow path. As for the stop time, the pressure data including the probe descent stop time402as shown inFIG.4may be acquired, then, the probe descent stop time402may be read from the pressure data.

For the data obtained in the pipetting syringe operation and the time series pressure data collection (step S1102), the calculation of the pressure pulsation by the descent stop before pipetting (step S1103) is performed.

FIG.12illustrates pressure data before pulsation process1201obtained by the pipetting syringe operation and time series pressure data collection (step S1102), and pressure data after pulsation process1203obtained by subtracting descent stop pressure pulsation1202calculated by the calculation of the pressure pulsation by the descent stop before pipetting (step S1103).

Descent stop pressure pulsation Poscbetween the probe descent stop time402and the pipetting syringe operation start time403can be described by, for example, the following damped oscillation equation (5).
Posc=×exp{−B(t−t0)}×sin{C(t−t0)+D}+E(5)

Here, t is a time, and t0 is a probe descent stop time. A, B, C, D, and E are all fixed numbers that depend on the shape of the flow path, and by determining the relationship between these fixed numbers and the flow path shape in advance by an experiment or a physical model, the descent stop pressure pulsation Posccan be calculated. The fixed numbers of A, B, C, D and E or the probe descent stop time t0 may be determined from the measurement data between the probe descent stop time402and the pipetting syringe operation start time403. As for the modeling of vibration, not only the equation (5) but also various modifications such as adding a higher-order oscillation component can be considered, and may be used.

By subtracting the descent stop pressure pulsation Poscfrom the acquired pressure data before pulsation process1201, the pressure data after pulsation process1203can be obtained. By performing the procedure for creating the relative pressure history shown inFIG.7for the pressure data after pulsation process1203, it is possible to cancel out the difference in the pressure history, which are caused by the difference in the hydraulic head due to the probe height and the immersion depth and the difference in the aspiration time, to derive a relative pressure history that is not affected by pressure pulsation due to the inertial force of the probe descent stop.

The present example is effective when the probe descent stop time402and the pipetting syringe operation start time403are close to each other and the pressure pulsation due to the inertial force of the probe descent stop overlaps the pressure pulsation due to the pipetting syringe operation. In the example, by deriving and subtracting the pressure pulsation Poscdue to the inertial force of the probe descent stop, it is possible to cancel out the pressure pulsation due to the inertial force of the probe descent stop remaining after the pipetting syringe operation start time403. Accordingly, it is possible to cut out only the pressure pulsation caused by the pipetting syringe operation, and detect the pipetting condition with high accuracy.

As described above, according to the present example, in addition to the effect of Example 1, a case where the probe descent stop time402and the pipetting syringe operation start time403are close to each other, and the pressure pulsation due to the inertial force of the probe descent stop overlaps the pressure pulsation due to the pipetting syringe operation, is effective.

The present invention is not limited to the examples described above, but includes various modifications.

For example, the above-described examples are examples which are described in detail in order to make it easy to understand the present invention, and are not limited to a case where all of the described configurations are necessarily provided. In addition, apart of the configuration of a certain example can be replaced with the configuration of other examples, and the configuration of the other example can also be added to the configuration of a certain example.

REFERENCE SIGNS LIST

101: Automatic analysis device102: Sample rack103: Rack transportation line104: Reagent cooling unit105: Incubator disk106: Sample pipetting mechanism107: Reagent pipetting mechanism108: Consumable transportation unit109: Detection unit110: Sample tube (Sample container)111: Reagent container112: Reagent disk cover113: Reaction vessel114: Reaction vessel disposal unit201: Tip202: Probe203: Flow path204: Syringe204a:Cylinder204b:Plunger205: Syringe driving unit206: Probe driving unit207: Control unit208: Container209: Sample (Sample)210: Water supply pump211: Water supply tank212: Cleaning water213: Solenoid valve214: Pressure sensor215: Branch block216: Signal amplifier217: A/D Converter218: Determination unit219: Sampling unit220: Storage unit221: Calculation unit222: Liquid level sensor223: Flow path position determination unit224: Display unit301: Bubbles401: Horizontal rotational movement stop time of the probe402: Probe descent stop time403: Pipetting syringe operation start time404: Pipetting syringe operation end time701a:Reference pressure value701b:Threshold pressure702a:Reference time703a:Starting point1201: Pressure data before pulsation process1202: Descent stop pressure pulsation1203: Pressure data after pulsation process