Patent Description:
An automatic analysis device such as a clinical chemistry analyzer or an immunoassay analyzer includes a pipetting mechanism that aspirates a predetermined amount of a specimen such as a biological sample and a reagent and that discharges the aspirated specimen and reagent into a reaction vessel, and an analysis mechanism that analyzes a reaction liquid of the specimen and the reagent.

The pipetting mechanism includes a probe inserted into a liquid such as the specimen or the reagent, a syringe serving as a pressure source for aspiration and discharge of the liquid, and a flow path connecting the probe and the syringe. The pipetting mechanism pipettes a predetermined amount of liquid by inserting the probe into the liquid in a specimen tube or a reagent bottle, operating the syringe and aspirating the predetermined amount of liquid, moving the probe to the reaction vessel, and discharging the liquid. At the time of pipetting, a disposable tip may be mounted on a tip end of the probe to prevent a component from being carried over to the next inspection.

Depending on an analysis item, a plurality of reagents or both reagents and specimens may be simultaneously held in the probe or the tip (pipetting nozzle) and pipetted into the reaction vessel. Thus, when a plurality of types of liquids are held in the pipetting nozzle at the same time, the plurality of types of liquids are continuously aspirated, and after all the liquids are aspirated, the liquids are pipetted by being discharged into the reaction vessel. By pipetting the plurality of types of liquids at the same time, the amount of used cleaning water, the number of used tips, and the time required for pipetting can be reduced.

At the time of pipetting, an abnormality such as aspiration of bubbles generated by handling the specimen tube and clogging of the flow path caused by a high-viscosity specimen or fibers such as fibrin in the specimen may occur. Therefore, an accuracy of an analysis result can be improved by accurately estimating a pipetting state and detecting the occurrence of the abnormality with high accuracy.

As a method for executing abnormality detection of pipetting, for example, PTL <NUM> discloses a technique of detecting a pipetting abnormality using an integral value of pressure data in a specific time interval and a difference between an average pressure calculated at the end of discharge and an average pressure calculated at the time of normal discharge as indices for a pressure fluctuation at the time of discharge of a specimen, and comparing the indices with preset thresholds.

PTL <NUM> discloses a technique of detecting an abnormality at the time of pipetting a predetermined liquid using a ratio between a pressure at the time of pipetting a reference liquid serving as a reference for abnormality detection and a pressure at the time of pipetting the predetermined liquid.

<CIT>
discloses an automatic analysis device with the features in the preamble of present claim <NUM>.

However, as described in PTL <NUM>, when the plurality of types of liquids are simultaneously pipetted, the accuracy of abnormality detection may decrease due to a difference in a pipetted amount or a physical property value of the other liquid aspirated into the nozzle before the liquid to be subjected to pipetting abnormality detection.

Similar to PTL <NUM>, in PTL <NUM>, the accuracy of abnormality detection may decrease due to a difference in the pipetted amount or the physical property value of the reference liquid aspirated into the pipetting nozzle before the predetermined liquid to be subjected to abnormality detection. Since a part is required for holding the reference liquid, it is difficult to reduce the size of the device.

Therefore, the present disclosure provides a technique capable of detecting, when a plurality of types of liquids are simultaneously pipetted, an abnormality at the time of pipetting a liquid to be subjected to abnormality detection with high accuracy regardless of a pipetted amount or a physical property value of the liquid aspirated before the liquid to be subjected to abnormality detection.

In order to solve the above problems, an automatic analysis device according to claim <NUM> and a pipetting method of a fluid using an automatic analysis device according to claim <NUM> is provided.

More features relevant to the present disclosure are clarified based on descriptions of the present description and accompanying drawings. Aspects of the present disclosure may be achieved and implemented using elements, combinations of various elements, the following detailed description, and accompanying claims.

The descriptions of the present description are merely exemplary, and are not intended to limit the scope of the claims or application in any sense.

According to the automatic analysis device in the present disclosure, an abnormality can be detected with high accuracy at the time of pipetting a liquid to be subjected to abnormality detection.

Problems, configurations, and effects other than those described above will be clarified according to the following descriptions of embodiments.

In a pipetting mechanism of an automatic analysis device according to a first embodiment, a tip is detachably attached to a tip end of a probe. The pipetting mechanism according to the present embodiment detects aspiration of bubbles (hereinafter referred to as "bubble aspiration") or clogging when a reagent and a specimen are sequentially aspirated into a tip and simultaneously pipetted into a reaction vessel and when the specimen is aspirated in a state in which the reagent is aspirated and held in the tip in advance in this manner.

<FIG> is a schematic configuration diagram showing a pipetting mechanism <NUM> of the automatic analysis device according to the first embodiment. As shown in <FIG>, the pipetting mechanism <NUM> includes a tip <NUM>, a probe <NUM>, a flow path <NUM>, a syringe <NUM>, a syringe drive unit <NUM>, a probe drive unit <NUM>, a control unit <NUM>, a water supply pump <NUM>, a water supply tank <NUM> that stores cleaning water <NUM>, a solenoid valve <NUM>, a reagent bottle <NUM> that stores a reagent <NUM> (first liquid) depending on an analysis item, a specimen tube <NUM> that stores a specimen <NUM> (second liquid), a reaction vessel <NUM>, a pressure sensor <NUM>, a branch block <NUM>, a signal amplifier <NUM>, an A/D converter <NUM>, a determination unit <NUM>, a display unit <NUM>, and a tip disposal unit <NUM>.

The tip <NUM> (pipetting nozzle) can be attached to and detached from a tip end of the probe <NUM>. The probe drive unit <NUM> such as a motor or an actuator (not shown) is connected to the probe <NUM>, whereby the probe <NUM> can be moved in horizontal and vertical directions and moved to a predetermined position. The tip <NUM> is held in, for example, a tip rack (not shown), and the probe drive unit <NUM> moves the probe <NUM> above the tip rack and lowers the probe <NUM>, whereby the tip <NUM> can be mounted on the probe <NUM>. The tip <NUM> may be attached to the probe <NUM> in a tip buffer that temporarily holds the tip <NUM>.

The probe <NUM> is connected to the syringe <NUM> via the flow path <NUM>, and the inside thereof is filled with the cleaning water <NUM>. The syringe <NUM> includes a cylinder 104a and a plunger 104b, and the plunger 104b is connected to the syringe drive unit <NUM>. The syringe drive unit <NUM> drives the plunger 104b with respect to the cylinder 104a in an upper-lower direction, whereby the tip <NUM> connected to the probe <NUM> aspirates and discharges a fluid (liquid and gas).

The syringe <NUM> includes a flow path communicating with the water supply tank <NUM>, and the flow path is provided with the solenoid valve <NUM> and the water supply pump <NUM>. The cleaning water <NUM> is stored in the water supply tank <NUM>, and the inside of the probe <NUM> can be cleaned by discharging the cleaning water <NUM> from the probe <NUM> by driving the water supply pump <NUM>. The probe <NUM> is cleaned, for example, before pipetting the reagent <NUM> and the specimen <NUM>.

Although not shown, the automatic analysis device includes a reagent storage that holds the reagent bottle <NUM>, a specimen tube rack that holds the specimen tube <NUM>, and a reaction disk that holds the reaction vessel <NUM>. Holding devices of the reagent bottle <NUM>, the specimen tube <NUM>, and the reaction vessel <NUM> are not limited to the above. The reagent <NUM> and the specimen <NUM> that are aspirated into the tip <NUM> are pipetted into the reaction vessel <NUM>.

The tip <NUM>, in which the reagent <NUM> and the specimen <NUM> have been pipetted into the reaction vessel <NUM>, is discarded in the tip disposal unit <NUM>.

The control unit <NUM> controls operations of the syringe drive unit <NUM>, the probe drive unit <NUM>, the water supply pump <NUM>, and the solenoid valve <NUM>. The control unit <NUM> may control not only the operation of each component of the pipetting mechanism <NUM> but also the operation of the entire automatic analysis device.

The pressure sensor <NUM> is connected to the branch block <NUM> provided in the middle of the flow path <NUM>, and measures a pressure in the flow path <NUM>. The pressure sensor <NUM> outputs a pressure detection signal to the signal amplifier <NUM>. A position of the pressure sensor <NUM> may be on a syringe <NUM> side as shown in <FIG>. However, by connecting the pressure sensor <NUM> to a position as close as possible to the probe <NUM>, a pressure fluctuation of an open portion of the tip <NUM> can be measured with high sensitivity.

The signal amplifier <NUM> amplifies a detection signal of the pressure sensor <NUM> and outputs the amplified signal to the A/D converter <NUM>. The A/D converter <NUM> converts the amplified signal into a digital signal and outputs the digital signal to the determination unit <NUM> as a pressure value.

The determination unit <NUM> is a circuit that determines the presence or absence of an abnormality during a pipetting operation of the pipetting mechanism <NUM>. The determination unit <NUM> includes a sampling unit <NUM> that receives an input of the pressure value from the A/D converter <NUM>, a storage unit <NUM> that stores data such as the pressure value input to the sampling unit <NUM>, and a calculation unit <NUM> that executes processing on the data stored in the storage unit <NUM>.

The determination unit <NUM> can communicate with the control unit <NUM>, and transmits the content of the operation to the control unit <NUM> when it is determined based on a result of data processing in the calculation unit <NUM> that a stop operation of the operation is necessary.

The determination unit <NUM> may be implemented as hardware in the automatic analysis device as a dedicated circuit board, or a processor may function as the determination unit <NUM> by reading and executing a program recorded in the storage unit <NUM>. Further, the processor in a server communicably connected to the automatic analysis device in a wireless or wired manner may read and execute the program and function as the determination unit <NUM>.

The display unit <NUM> is connected to the control unit <NUM> and the determination unit <NUM>, and displays the result of the data processing in the determination unit <NUM>, information related to the result, and the like.

<FIG> is a flowchart illustrating a pipetting method according to the first embodiment. The pipetting method according to the present embodiment is actually executed by the control unit <NUM> shown in <FIG> controlling the operation of each component (the syringe drive unit <NUM>, the probe drive unit <NUM>, the water supply pump <NUM>, the solenoid valve <NUM>, and the like) of the pipetting mechanism <NUM>. In the following, each component of the pipetting mechanism <NUM> may be described as a subject of the operation.

In step S201, the control unit <NUM> opens the solenoid valve <NUM>, drives the water supply pump <NUM>, and discharges the cleaning water <NUM> in the water supply tank <NUM> from the probe <NUM>. Accordingly, the inside of the probe <NUM> is cleaned.

In step S202, the syringe drive unit <NUM> drives the syringe <NUM> to aspirate a first air gap into the probe <NUM>. This is to prevent the cleaning water <NUM> filling the inside of the probe <NUM> from being mixed with the reagent <NUM> to be aspirated in the next step.

In step S203, the probe drive unit <NUM> mounts the tip <NUM> on the tip end of the probe <NUM> by moving the probe <NUM> above the tip rack or the tip buffer and then lowering the probe <NUM>.

In step S204, the probe drive unit <NUM> moves the probe <NUM> above the reagent bottle <NUM> and lowers the probe <NUM> until the tip end of the tip <NUM> is immersed in the reagent <NUM>.

In step S205, the syringe drive unit <NUM> drives the syringe <NUM> to aspirate the reagent <NUM> into the tip <NUM>.

In step S206, the probe drive unit <NUM> raises the probe <NUM> until the tip end of the tip <NUM> comes out from the reagent <NUM>. After that, the syringe drive unit <NUM> drives the syringe <NUM> to aspirate a second air gap into the tip <NUM>. This is to prevent the reagent <NUM> aspirated into the tip <NUM> from being mixed with the liquid aspirated in the next step.

In the present embodiment, only one type of reagent <NUM> is aspirated. Alternatively, a plurality of reagents may be pipetted depending on the analysis item. When the plurality of reagents are pipetted, steps S204-S206 are repeated as many times as necessary, and all the reagents to be pipetted and the second air gap separating the reagents are aspirated into the tip <NUM>.

In step S207, the probe drive unit <NUM> moves the probe <NUM> above the specimen tube <NUM>, and lowers the probe <NUM> until the tip end of the tip <NUM> is immersed in the specimen <NUM>.

In step S208, the syringe drive unit <NUM> drives the syringe <NUM> to aspirate the specimen <NUM> into the tip <NUM>. Here, the sampling unit <NUM> of the determination unit <NUM> receives an input of a pressure value during an aspiration operation of the specimen <NUM>, and stores, in the storage unit <NUM>, the pressure value during the aspiration operation of the specimen <NUM> as time-series data (hereinafter, may be referred to as a "pressure history").

In step S209, the probe drive unit <NUM> raises the probe <NUM> until the tip end of the tip <NUM> comes out from the specimen <NUM>, and moves the probe <NUM> such that the tip end of the tip <NUM> is located inside the reaction vessel <NUM>.

In step S210, the syringe drive unit <NUM> drives the syringe <NUM> to discharge the reagent <NUM> and the specimen <NUM> that are held in the tip <NUM> into the reaction vessel <NUM>. At this time, when the plurality of reagents are aspirated, all the reagents aspirated into the tip <NUM> are simultaneously discharged into the reaction vessel <NUM>.

In step S211, the probe drive unit <NUM> moves the probe <NUM> to the tip disposal unit <NUM>, and removes the tip <NUM> from the probe <NUM> by discarding the tip <NUM> in the tip disposal unit <NUM>.

In step S212, the calculation unit <NUM> of the determination unit <NUM> determines whether there is an abnormality such as clogging, bubble aspiration, or the like at the time of aspiration of the specimen <NUM> based on the pressure history at the time of specimen aspiration stored in the storage unit <NUM> (detects an abnormality). The pressure history when the abnormality such as bubble aspiration or clogging occurs at the time of aspiration of the specimen <NUM> is different from the pressure history when normal pipetting is performed. Therefore, the presence or absence of the abnormality can be determined by referring to the pressure history. A method for determining the presence or absence of an abnormality using the pressure history will be described later.

In step <NUM>, the determination unit <NUM> transmits a determination result of the presence or absence of the abnormality to the display unit <NUM> and the control unit <NUM>. The display unit <NUM> displays the determination result.

If it is determined in step S212 that there is no abnormality (No), the process proceeds to step S213. In step S213, the control unit <NUM> determines that the pipetting is terminated normally based on the determination result received from the determination unit <NUM>, and terminates the pipetting operation. The control unit <NUM> may repeat steps S201 to S213 depending on the analysis item.

If it is determined in step S212 that there is an abnormality (Yes), the process proceeds to step S214. In step S214, the control unit <NUM> determines that there is an abnormality at the time of aspiration of the specimen <NUM> based on the determination result received from the determination unit <NUM>. At this time, an alert is displayed on the display unit <NUM>, and the relevant pipetting operation of the specimen <NUM> is terminated. The specimen <NUM> is returned to a user. In this way, by stopping the pipetting of the specimen <NUM> having an abnormality, the consumption of the reagent used for the subsequent analysis can be reduced.

The order of steps S212 to S214 and steps S209 to S211 may be changed. In this case, step S212 is performed after step S208. When it is determined in step S212 that there is an abnormality and the process proceeds to step S214, the control unit <NUM> terminates the pipetting operation without shifting to step S209. Accordingly, since it is not necessary to discharge the abnormal specimen <NUM> having the abnormality into the reaction vessel <NUM>, the time and effort for consuming or cleaning the reaction vessel <NUM> can be reduced.

<FIG> is a flowchart illustrating a method for determining the presence or absence of an abnormality by the determination unit <NUM> in step S212 in <FIG>.

In step S301, the calculation unit <NUM> reads the pressure history at the time of aspiration of the specimen stored in the storage unit <NUM>. In the present description, the "pressure history at the time of aspiration of the specimen" refers to a pressure value in a predetermined time range including the operation time (aspiration operation time) of the syringe <NUM> when the specimen <NUM> is aspirated in step S208.

In step S302, the calculation unit <NUM> calculates a determination index used for determining the presence or absence of an abnormality based on the pressure history at the time of specimen aspiration. Examples of the "determination index" include an average value of the pressure values during the aspiration operation of the specimen <NUM>, an average value of the pressure values before or after the aspiration operation of the specimen <NUM>, a maximum value or a minimum value of the pressure values, a pressure pulsation cycle or an amplitude of the pressure history, and a statistical distance such as a Euclidean distance between a preset reference pressure history and the pressure history acquired in step S302. The "reference pressure history" is set based on, for example, a number of pressure values acquired in the past, and may be a pressure value when it is determined that the specimen is normally aspirated, or may be a pressure value when it is determined that there is an abnormality at the time of aspiration of the specimen. The degree of similarity or dissimilarity between the reference pressure history and the pressure history may be used as the determination index. A plurality of indexes described above may be combined and used as the determination index.

In the present embodiment, a difference between the average value of the pressure values during the aspiration operation of the specimen <NUM> and the average value of the pressure values before the aspiration operation is calculated as the determination index, and the difference is used to determine whether the pipetting is normal or bubble aspiration. As a cause of the bubble aspiration, erroneous detection of a liquid surface due to air bubbles unintentionally generated by handling of the specimen tube <NUM>, or the like is considered. The bubbles are generated when the blood specimen <NUM> is shaken while being transported.

In step S303, the calculation unit <NUM> determines the presence or absence of an abnormality at the time of aspiration of the specimen <NUM> based on the determination index. Examples of the method for determining the presence or absence of an abnormality include a method of comparing the determination index with a preset determination threshold, and a method of determining an abnormality when a combination of a plurality of determination indexes satisfies a certain condition. In the present embodiment, an algorithm of comparing a constant determination threshold with the determination index and determining the presence or absence of an abnormality is used. The determination threshold used for determining the presence or absence of an abnormality is stored in advance in the storage unit <NUM>.

In order to detect an abnormality at the time of aspiration of the specimen <NUM> with high accuracy, as a result of intensive studies, the present inventors have found that it is effective to reduce the influence of the pipetted amount (volume) of the reagent <NUM> (first liquid) aspirated before the aspiration of the specimen <NUM> (second liquid) on the pressure history described above.

The pipetted amount of reagent <NUM> depends on the analysis item. As an example of a physical formula expressing a pressure loss due to the friction of the flow in a pipe, the following Hagen-Poiseuille equation (<NUM>) can be mentioned.

Here, Ploss represents the pressure loss, µ represents a fluid viscosity, L represents a length in which the fluid occupies the pipe, π represents a circumferential ratio, d represents a pipe diameter, and Q represents a flow rate in the pipe.

When there are a plurality of types of fluids in the pipe, the pressure loss Ploss is calculated for each fluid component. When the pipetted amounts of the reagents <NUM> are different, the length L in which the fluid occupies the pipe of the tip <NUM> or the probe <NUM> changes. Accordingly, the pressure loss Ploss changes, which influences the pressure history used for determining the presence or absence of an abnormality. The pressure history is also influenced by a difference in fluid arrangement in the pipe caused by a difference in a pipetted amount of the reagent <NUM> because a pressure wave is reflected by a boundary of the fluid component in the pipe. Therefore, by reducing the influence of the pipetted amount of the reagent <NUM> on the pressure history, an abnormality can be detected with high accuracy. Therefore, the pipetting operation for reducing the influence of the difference in the pipetted amount of the reagent <NUM> on the pressure history will be described below.

<FIG> is a schematic diagram showing a state of a fluid in the probe <NUM> and the tip <NUM> in the pipetting operation in <FIG>. <FIG> of <FIG> shows a state immediately after the inside of the probe <NUM> is cleaned with the cleaning water <NUM> in step S201. As shown in (a) of <FIG>, the inside of the probe <NUM> is filled with the cleaning water <NUM>.

As described above, the presence or absence of an abnormality is determined using the pressure history at the time of aspiration of the specimen <NUM>. In the state ((d) of <FIG>) before aspirating the specimen <NUM>, a position of a boundary <NUM> between the cleaning water <NUM> and the first air gap <NUM> varies depending on the pipetted amount (volume) of the reagent <NUM>. By fixing the position of the boundary <NUM>, the influence of the pipetted amount of the reagent <NUM> on the pressure history at the time of aspiration of the specimen <NUM> can be reduced.

The position of the boundary <NUM> between the cleaning water <NUM> and the first air gap <NUM> varies depending on a sum (total volume of the fluids) of an amount of the first air gap <NUM> aspirated in step S202, an amount of the reagent <NUM> aspirated in step S205, and an amount of the second air gap <NUM> aspirated in step S206. Therefore, the position of the boundary <NUM> can be fixed by controlling an operation of the syringe <NUM> to set the total volume of the fluids aspirated before the aspiration of the specimen <NUM> to be constant. The fact that the position of the boundary <NUM> is "fixed" does not necessarily mean that the boundary <NUM> is located at exactly the same position in the pipetting operation of all analyses. Depending on the used device, probe, and tip, the total volume may vary by, for example, <NUM>µL. Even if the total volume of the fluids is constant, it is needless to say that the position of the boundary <NUM> between the cleaning water <NUM> and the first air gap <NUM> changes according to an inner diameter of the probe or the tip.

<FIG> is a flowchart showing a method for calculating aspiration amounts of the reagent <NUM>, the first air gap <NUM>, and the second air gap <NUM> in the pipetting operation in <FIG>. This method is executed by the control unit <NUM>, for example, before the pipetting operation shown in <FIG> is started, and the aspiration operation of the reagent or the air gap is performed based on the calculated aspiration amounts. Before executing this method, the total volume of the reagent <NUM>, the first air gap <NUM>, and the second air gap <NUM> is stored in advance in a storage unit of the control unit <NUM>. The total volume of these fluids can be the same regardless of the analysis item.

In step S501, the control unit <NUM> calculates the amount of the reagent <NUM> aspirated in step S205 and the amount of the second air gap <NUM> aspirated in step S206. The aspiration amount of the reagent <NUM> can be set according to the analysis item and the type of the reagent. When the plurality of types of reagents are aspirated into the same tip by repeating steps S204 to S206, the control unit <NUM> calculates a sum of the amounts of the reagents aspirated in step S205 and a sum of the amounts of the second air gap aspirated in step S206.

In step S502, the control unit <NUM> calculates an amount of the first air gap <NUM> to be aspirated in step S202 based on the amount of the reagent <NUM> and the amount of the air gap that are calculated in step S501. At this time, the amount of the first air gap <NUM> is calculated such that a sum of the amount of the first air gap <NUM>, the amount of the reagent <NUM>, and the amount of the second air gap <NUM> is constant. The control unit <NUM> determines an operation amount of the syringe <NUM> based on each calculated aspiration amount, and issues an instruction to the syringe drive unit <NUM>.

When the tip <NUM> has a sufficient volume to prevent the reagent <NUM> from flowing from the tip <NUM> into the probe <NUM>, the arrangement (the position of the boundary <NUM> between the cleaning water <NUM> and the first air gap <NUM>) of the fluid inside the probe <NUM> before the aspiration of the specimen <NUM> can be fixed by adjusting the amount of the first air gap <NUM> as described above. By fixing the arrangement of the fluid inside the probe <NUM>, the influence of the difference in the pipetted amount of the reagent <NUM> on the pressure history at the time of aspiration of the specimen can be reduced.

As described above, in the present embodiment, the amount of the reagent <NUM> aspirated in step S205 and the amount of the second air gap <NUM> aspirated in step S206 are first calculated, and then the amount of the first air gap <NUM> to be aspirated in step S201 is adjusted. Instead, the amount of the first air gap <NUM> and the amount of the reagent <NUM> may be first calculated, and then the amount of the second air gap <NUM> may be adjusted.

A plurality of reference values (such as a sum of <NUM>µL, <NUM>µL, and <NUM>µL) may be stored in advance in the storage unit <NUM> for the sum of the amount of the first air gap <NUM>, the amount of the reagent <NUM>, and the amount of the second air gap <NUM>, and when the amount of the reagent <NUM> used depending on the analysis item differs greatly, which reference value is to be used may be determined. For example, if the amount of the used reagent <NUM> is <NUM>µL, the sum can be set to <NUM>µL, and if the amount of the used reagent <NUM> is <NUM>µL, the sum can be set to <NUM>µL. Accordingly, the aspiration amounts of the air gaps <NUM> and <NUM> do not increase even though the amount of the reagent <NUM> is small. Therefore, an increase in a driving amount of the syringe <NUM> can be prevented, and a life of the syringe <NUM> can be prolonged.

Effects of improving the accuracy of abnormality detection according to the present embodiment will be described. (a) of <FIG> shows a relationship between the determination index (for example, the average value of the pressure values) and the pipetted amount of the reagent <NUM> when the amount of the first air gap <NUM> is set to be constant without being adjusted (when processing in <FIG> is not performed). A plot of o shows the determination index when the specimen <NUM> is normally pipetted (normal pipetting group <NUM>). A plot of × shows the determination index when bubble aspiration occurs at the time of aspiration of the specimen <NUM> (bubble aspiration group <NUM>). As shown in (a) of <FIG>, the determination index of the normal pipetting group <NUM> and the determination index of the bubble aspiration group <NUM> greatly vary depending on the pipetted amount of the reagent <NUM>. Therefore, it is difficult to determine whether bubble aspiration has occurred by comparing the calculated determination index with the constant determination threshold.

On the other hand, (b) of <FIG> shows a relationship between the determination index (for example, the average value of the pressure values) and the pipetted amount of the reagent <NUM> when the amount (total volume of the fluids) of the first air gap <NUM> is adjusted according to the method shown in <FIG>. The plot of o shows the determination index when the specimen <NUM> is normally pipetted (normal pipetting group <NUM>). The plot of × shows the determination index when bubble aspiration occurs at the time of aspiration of the specimen <NUM> (bubble aspiration group <NUM>). As shown in (b) of <FIG>, by adjusting the amount of the first air gap <NUM>, the determination index of the normal pipetting group <NUM> and the determination index of the bubble aspiration group <NUM> become almost constant values regardless of the pipetted amount of the reagent <NUM>. Therefore, by setting a constant determination threshold <NUM> in advance and comparing the calculated determination index with the determination threshold <NUM>, it is possible to determine whether bubble aspiration occurs.

An example has been described above in which whether bubble aspiration occurs is detected at the time of aspiration of the specimen <NUM>, and the method according to the present embodiment can be similarly applied to the determination of whether clogging occurs. That is, regardless of the pipetted amount of the reagent <NUM>, it is possible to determine whether clogging occurs at the time of aspiration by comparing the calculated determination index with a constant determination threshold.

As described above, according to the automatic analysis device in the present embodiment, the pipetting operation is performed such that the total volume of the fluids (air gap and reagent) aspirated before the aspiration of the specimen becomes constant, and the position of the boundary between the cleaning liquid and the air gap that are present in the probe is fixed. Accordingly, the influence of the difference in the pipetted amount of the reagent on the pressure history at the time of aspiration of the specimen can be reduced. More specifically, the determination index calculated based on the pressure history in normal pipetting and the determination index calculated based on the pressure history in abnormal pipetting can be set to be substantially constant regardless of the pipetted amount of the reagent. Therefore, the constant determination threshold can be set regardless of the pipetted amount of the reagent, that is, regardless of the analysis item, and thus the presence or absence of an abnormality can be detected with high accuracy.

Since the abnormality can be detected with high accuracy, the reliability of the analysis result of the automatic analysis device can also be improved. Furthermore, since the pipetting operation is terminated when an abnormality is detected, loss of the reagent can also be reduced.

The method for detecting an abnormality such as bubble aspiration and clogging at the time of aspiration of the specimen <NUM> has been described above, and the method according to the present embodiment can also be directly applied to an estimation of the pipetted amount of the specimen <NUM> and an estimation of the viscosity of the specimen <NUM>.

In the present embodiment, the specimen <NUM> is used as the liquid to be detected for the pipetting abnormality. Alternatively, the method according to the present embodiment may be applied to the abnormality detection, the estimation of the pipetted amount, and the estimation of the viscosity at the time of aspiration of the reagent <NUM>. In this case, the "specimen <NUM>" in the above may be read as the "reagent <NUM>".

In the present embodiment, as described with reference to <FIG>, the amount of the first air gap <NUM> aspirated in step S202 is adjusted such that the sum of the amount of the first air gap <NUM> aspirated in step S202, the amount of the reagent <NUM> aspirated in step S205, and the amount of the second air gap <NUM> aspirated in step S206 is constant. This is for the purpose of reducing the influence of the pipetted amount of the reagent <NUM> on the pressure history at the time of aspiration of the specimen <NUM> by fixing the position of the boundary <NUM> between the cleaning water <NUM> and the first air gap <NUM> with respect to the probe.

Instead of setting the total volume of the fluids aspirated before the aspiration of the specimen <NUM> to be constant, according to the configuration and structure of the pipetting mechanism of the automatic analysis device, the amount of the first air gap <NUM> aspirated in step S202 may be calculated by a function depending on the amount of the reagent <NUM> aspirated in step S205 and the amount of the second air gap <NUM> aspirated in step S206. This function may be determined for each analysis item.

In the present embodiment, the amount of the air gap may be adjusted according to the pipetted amount of the reagent <NUM>, and an operation such as a flow rate of the syringe <NUM> or a depth at which the tip <NUM> is immersed into the specimen <NUM> at the time of aspiration of the specimen <NUM> may be adjusted.

In the first embodiment, the pipetting mechanism (<FIG>) has been described in which a disposable tip is mounted on the tip end of the probe and the reagent and the specimen are aspirated into the tip. However, the configuration of the pipetting mechanism is not limited to that shown in <FIG>. Therefore, in a second embodiment, as another configuration of the pipetting mechanism, an example is provided in which the reagent and the specimen are directly aspirated into the probe without using the tip. Thus, even if the configuration of the pipetting mechanism is different, clogging or bubble aspiration at the time of aspiration of the specimen can be detected in the same manner as in the first embodiment.

<FIG> is a schematic configuration diagram showing a pipetting mechanism <NUM> of an automatic analysis device according to the second embodiment. As shown in <FIG>, the pipetting mechanism <NUM> includes a probe <NUM> (pipetting nozzle) instead of the tip <NUM> and the probe <NUM> shown in <FIG>. A length of a pipe of the probe <NUM> can be the same as the total length of the pipes when the tip <NUM> in <FIG> is mounted on the probe <NUM>. Since the configurations other than the probe <NUM> are similar to those of the pipetting mechanism <NUM> according to the first embodiment, a description thereof will be omitted.

The pipetting mechanism <NUM> according to the present embodiment directly aspirates the reagent <NUM> and the specimen <NUM> into the probe <NUM>. The operation of the probe <NUM> is controlled by the probe drive unit <NUM>.

<FIG> is a flowchart illustrating a pipetting method according to the second embodiment. The pipetting method according to the present embodiment is actually performed by the control unit <NUM> shown in <FIG> controlling the operation of each component of the pipetting mechanism <NUM>, and in the following, each component of the pipetting mechanism <NUM> may be described as the subject of the operation. The same reference numerals are given to the steps similar to those of the pipetting method (<FIG>) according to the first embodiment. In the following, only the differences from the first embodiment will be described.

In the present embodiment, since the tip <NUM> is not used, steps S203 and S211 in <FIG> are not performed.

First, instead of step S201, in step S801, the control unit <NUM> opens the solenoid valve <NUM>, drives the water supply pump <NUM>, and discharges the cleaning water <NUM> in the water supply tank <NUM> from the probe <NUM>. Accordingly, the inside of the probe <NUM> is cleaned.

After step S202 is performed, step S802 is performed instead of step S204. In step S802, the probe drive unit <NUM> moves the probe <NUM> above the reagent bottle <NUM> and lowers the probe <NUM> until the tip end of the probe <NUM> is immersed in the reagent <NUM>.

After steps S205 and S206 are performed, step S803 is performed instead of step S207. In step S803, the probe drive unit <NUM> moves the probe <NUM> above the specimen tube <NUM> and lowers the probe <NUM> until the tip end of the probe <NUM> is immersed in the specimen <NUM>.

The subsequent operations are the same as those in the first embodiment. The method for determining the presence or absence of an abnormality in step S212 is the same as the method shown in <FIG>.

<FIG> is a schematic diagram showing a state of the fluid in the probe <NUM> in the pipetting operation in <FIG>. <FIG> of <FIG> shows a state immediately after the inside of the probe <NUM> is cleaned with the cleaning water <NUM> in step S801. As shown in (a) of <FIG>, the inside of the probe <NUM> is filled with the cleaning water <NUM>.

As described above, the presence or absence of an abnormality is determined using the pressure history at the time of aspiration of the specimen <NUM>. In the state ((d) of <FIG>) before the specimen <NUM> is aspirated, a position of a boundary <NUM> between the cleaning water <NUM> and the first air gap <NUM> varies depending on the pipetted amount (volume) of the reagent <NUM>. By fixing the position of the boundary <NUM>, the influence of the pipetted amount of the reagent <NUM> on the pressure history at the time of aspiration of the specimen <NUM> can be reduced.

The position of the boundary <NUM> between the cleaning water <NUM> and the first air gap <NUM> varies depending on a sum (total volume of the fluids) of an amount of the first air gap <NUM> aspirated in step S202, the amount of the reagent <NUM> aspirated in step S205, and an amount of the second air gap <NUM> aspirated in step S206. Therefore, the position of the boundary <NUM> can be fixed by controlling the operation of the syringe <NUM> to set the total volume of the fluids aspirated before the aspiration of the specimen <NUM> to be constant. Aspiration amounts of the first air gap <NUM>, the reagent <NUM>, and the second air gap <NUM> are also calculated in the same manner as in the method shown in <FIG>. The control unit <NUM> determines the operation amount of the syringe <NUM> based on each calculated aspiration amount, and issues the instruction to the syringe drive unit <NUM>.

Also in the second embodiment, as in the first embodiment, the pipetting operation is performed such that the total volume of the fluids (air gap and reagent) aspirated before the aspiration of the specimen becomes constant, and the position of the boundary between the cleaning liquid and the air gap that are present in the probe is set to be constant. Accordingly, the influence of the difference in the pipetted amount of the reagent on the pressure history at the time of aspiration of the specimen can be reduced, and an abnormality at the time of aspiration of the specimen <NUM> can be detected with high accuracy. Therefore, the reliability of the analysis result of the automatic analysis device can be improved. Further, in the present embodiment, since it is not necessary to mount or remove the tip <NUM>, the pipetting operation can be performed more quickly as compared with that according to the first embodiment.

In the first embodiment and the second embodiment, the method of reducing the influence of the pipetted amount of the reagent on the pressure history at the time of aspiration of the specimen and detecting an abnormality at the time of aspiration of the specimen with high accuracy by setting a sum of the aspiration amount of the air gap aspirated before the specimen and the aspiration amount of the reagent aspirated before the specimen to be constant has been described. Therefore, in a third embodiment, a method of further reducing an influence of a pipetted amount of a reagent and detecting an abnormality at the time of aspiration of a specimen with higher accuracy is provided.

As a configuration of a pipetting mechanism of an automatic analysis device according to the present embodiment, the same configuration as that according to the first embodiment (<FIG>) can be adopted. A pipetting operation is almost the same as the pipetting method (<FIG>) according to the first embodiment. However, in the present embodiment, a method for determining the presence or absence of an abnormality in step S212 is different from that in the first embodiment.

<FIG> is a flowchart illustrating a method for determining the presence or absence of an abnormality according to the third embodiment. A determination method shown in <FIG> is executed by the determination unit <NUM> instead of the determination method according to the first embodiment shown in <FIG>. The same reference numerals are given to the steps similar to those in <FIG>, and the description thereof will be omitted.

First, steps S301 and S302 are performed in the same manner as in the first embodiment, and a determination index is calculated based on the pressure history at the time of aspiration of the specimen.

Next, in step S1001, the determination unit <NUM> acquires information on the aspiration amount of the reagent <NUM> aspirated in step S205 from the control unit <NUM>. When the plurality of reagents are aspirated, in step S1001, the determination unit <NUM> acquires, from the control unit <NUM>, information on the sum of the amounts of reagents aspirated in step S205 and the sum of the amounts of the second air gap in step S206.

In step S1002, the calculation unit <NUM> determines the presence or absence of an abnormality at the time of aspiration of the specimen <NUM> based on the determination index calculated in step S302 and the information on the aspiration amount of the reagent <NUM> acquired in step S1001. At this time, as in the first embodiment, the difference between the average value of the pressure values during the aspiration operation of the specimen <NUM> and the average value of the pressure values before the aspiration operation is used as the determination index to determine whether the pipetting is normal or bubble aspiration.

In the present embodiment, the presence or absence of an abnormality is determined by setting the determination threshold to be a function that varies depending on the pipetted amount of the reagent <NUM> and comparing a magnitude relationship between the determination threshold and the determination index. The function of the determination threshold is stored in the storage unit <NUM> in advance.

The determination threshold according to the present embodiment will be described. <FIG> is a diagram showing a relationship between the determination index (for example, the average value of the pressure values) and the pipetted amount of the reagent <NUM>, and the determination threshold. The plot of o shows the determination index when the specimen <NUM> is normally pipetted (normal pipetting group <NUM>). The plot of × shows the determination index when bubble aspiration occurs at the time of aspiration of the specimen <NUM> (bubble aspiration group <NUM>). As shown in <FIG>, for each of a distance between the normal pipetting group <NUM> and the determination threshold <NUM> and a distance between the bubble aspiration group <NUM> and the determination threshold <NUM>, the determination threshold <NUM> is set as a polygonal line function such that a fluctuation due to the pipetted amount of the reagent <NUM> is minimized. The determination threshold <NUM> is not limited to the polygonal line function, and may be, for example, a linear function or any polynomial.

In this way, by setting the determination threshold used for abnormality determination as a function that varies depending on the pipetted amount of the reagent <NUM>, an influence of a change in the pipetted amount of the reagent <NUM> on the distance between the normal pipetting group <NUM> and the determination threshold <NUM> and the distance between the bubble aspiration group <NUM> and the determination threshold <NUM> can be reduced. Accordingly, the presence or absence of an abnormality can be determined with higher accuracy as compared with the case of using a constant determination threshold ((b) of <FIG>).

In the present embodiment, as in the first embodiment, the total volume of the fluids before the specimen <NUM> is aspirated is set to be constant, and the determination threshold used for the abnormality determination is set to be a function that varies depending on the pipetted amount of the reagent <NUM>. However, even when the total volume of the fluids before the specimen <NUM> is aspirated is not constant, the present embodiment is effective in which the determination threshold is the function that varies depending on the pipetted amount of the reagent <NUM>.

As described above, the third embodiment adopts a configuration in which the determination threshold is set as the function that varies depending on the pipetted amount of the reagent, and the determination index calculated based on the pressure history at the time of aspiration of the specimen is compared with the function to determine the presence or absence of an abnormality. Accordingly, an abnormality can be detected with higher accuracy than that in the case of comparing the determination index and a constant determination threshold as in the first embodiment. Therefore, the reliability of the analysis result of the automatic analysis device can be further improved.

In the first embodiment to the third embodiment, the method of detecting an abnormality at the time of aspiration of the specimen with high accuracy by reducing the influence of the pipetted amount of the reagent (first liquid) aspirated before the aspiration of the specimen (second liquid) on the pressure history has been described. However, it is also effective to reduce an influence of not only the pipetted amount of the reagent but also physical property values such as the viscosity of the reagent on the pressure history. Therefore, in a fourth embodiment, in order to detect an abnormality with higher accuracy, a method is provided in which an influence of a physical property value of a reagent on a pressure history is also considered.

When the viscosity among the physical property values of the reagent changes, the fluid viscosity µ in the pipe in the Hagen-Poiseuille equation (<NUM>) described above changes. Accordingly, the pressure loss Ploss changes, which influences the pressure history used for determining the presence or absence of an abnormality. When the reagent passes through a pipe having a small diameter, the pressure in the pipe changes due to a difference in the surface tension of the reagent in addition to a difference in the viscosity of the reagent. When a vertical length of a portion occupied by the reagent in the pipe is large, the pressure in the pipe also changes due to a difference in gravity caused by a difference in density of the reagent.

<FIG> is a schematic configuration diagram showing a pipetting mechanism <NUM> of an automatic analysis device according to the fourth embodiment. As shown in <FIG>, the pipetting mechanism <NUM> is substantially the same as the pipetting mechanism (<FIG>) according to the first embodiment, and further includes a reagent physical property value storage unit <NUM>.

The reagent physical property value storage unit <NUM> is a database in which physical property values such as viscosity, surface tension, and density of various reagents used for analysis are stored. The reagent physical property value storage unit <NUM> is connected to the determination unit <NUM> or is communicable with the determination unit <NUM>. The information stored in the reagent physical property value storage unit <NUM> can be read out by the determination unit <NUM>.

A pipetting operation according to the present embodiment is almost the same as the pipetting method (<FIG>) according to the first embodiment. However, in the present embodiment, a method for determining the presence or absence of an abnormality in step S212 is different from that in the first embodiment.

<FIG> is a flowchart illustrating a method for determining the presence or absence of an abnormality according to the fourth embodiment. The determination method shown in <FIG> is executed instead of the determination method according to the first embodiment shown in <FIG>. The same reference numerals are given to the steps similar to those in <FIG>, and the description thereof will be omitted.

Next, in step S1301, the determination unit <NUM> acquires information on the physical property values such as viscosity, surface tension, and density of the reagent <NUM> from the reagent physical property value storage unit <NUM>.

In step S1302, the determination unit <NUM> determines the presence or absence of an abnormality at the time of aspiration of the specimen <NUM> based on the information on the determination index calculated in step S302 and the physical property values of the reagent <NUM> acquired in step S1301. At this time, as in the first embodiment, the difference between the average value of the pressure values during the aspiration operation of the specimen <NUM> and the average value of the pressure values before the aspiration operation is used as the determination index to determine whether the pipetting is normal or bubble aspiration.

Here, the presence or absence of an abnormality is determined based on the viscosity as an example of the physical property values of the reagent <NUM>. More specifically, the presence or absence of an abnormality is determined by setting the determination threshold to be a function that varies depending on the viscosity of the reagent <NUM> and comparing the magnitude relationship between the determination threshold and the determination index. The function of the determination threshold is stored in the storage unit <NUM> in advance.

The determination threshold according to the present embodiment will be described. <FIG> is a diagram showing a relationship between the determination index (for example, the average value of the pressure values) and the viscosity of the reagent <NUM>, and the determination threshold. The plot of o shows the determination index when the specimen <NUM> is normally pipetted (normal pipetting group <NUM>). The plot of × shows the determination index when bubble aspiration occurs at the time of aspiration of the specimen <NUM> (bubble aspiration group <NUM>). As shown in <FIG>, for each of the distance between the normal pipetting group <NUM> and the determination threshold <NUM> and the distance between the bubble aspiration group <NUM> and the determination threshold <NUM>, the determination threshold <NUM> is set as a linear line function such that a fluctuation due to the viscosity of the reagent <NUM> is minimized. The determination threshold <NUM> is not limited to the linear line function, and may be, for example, a linear function or any polynomial.

In this way, by setting the determination threshold used for abnormality determination as a function that varies depending on the viscosity of the reagent <NUM>, an influence of a difference in the viscosity of the reagent <NUM> on a distance between the normal pipetting group <NUM> and the determination threshold <NUM> and a distance between the bubble aspiration group <NUM> and the determination threshold <NUM> can be reduced. Accordingly, the presence or absence of an abnormality can be determined with higher accuracy as compared with the case of using a constant determination threshold.

In the present embodiment, the function of the viscosity of the reagent <NUM> is used, and when the surface tension or density of the reagent <NUM> has a large influence on the pressure history due to characteristics of the pipetting mechanism, an abnormality can be detected with high accuracy by setting the determination threshold as a function of the surface tension or density of the reagent <NUM>. Accordingly, an abnormality can be detected in consideration of which physical property value has a large influence on the pressure history depending on, for example, a diameter of a tip or a probe to be used.

In the present embodiment, as in the first embodiment, the total volume of the fluids before the specimen <NUM> is aspirated is set to be constant, and the determination threshold used for the abnormality determination is set to be a function that varies depending on the physical property values of the reagent <NUM>. However, even when the total volume of the fluids before the specimen <NUM> is aspirated is not constant, the present embodiment is effective in which the determination threshold is the function that varies depending on the physical property values of the reagent <NUM>.

As described above, the fourth embodiment adopts a configuration in which the determination threshold is set as the function that varies depending on the physical property values of the reagent, and the function is compared with the determination index of the pressure history at the time of aspiration of the specimen to determine the presence or absence of an abnormality. Accordingly, an abnormality can be determined with higher accuracy than that in the case of comparing the certain constant determination threshold with the determination index as in the first embodiment. Since the influence of the physical property values of the reagent on the pressure history at the time of aspiration of the specimen can be reduced, an abnormality can be detected with higher accuracy based on the pressure history regardless of the physical property values of the reagent. Therefore, the reliability of the analysis result of the automatic analysis device can be further improved.

In the fourth embodiment, an example has been described in which the presence or absence of an abnormality is determined in consideration of the influence of physical property values such as the viscosity, surface tension, and density of the reagent on the pressure history. However, when there are the plurality of types of reagents, it is difficult to measure the physical property values of all types of reagents and hold the physical property values in the database (reagent physical property value storage unit). Therefore, in a fifth embodiment, a method for estimating a physical property value of the reagent <NUM> before the aspiration of a specimen is provided.

As a configuration of a pipetting mechanism of an automatic analysis device according to the present embodiment, the same configuration as that according to the fourth embodiment (<FIG>) can be adopted, and thus a description thereof will be omitted.

A pipetting method according to the present embodiment is almost the same as the pipetting method shown in <FIG>, and in step S205, the sampling unit <NUM> receives an input of a pressure value during the aspiration operation of the reagent <NUM> from the pressure sensor <NUM>, and stores, in the storage unit <NUM>, the pressure value during the aspiration operation of the reagent <NUM> as time-series data (pressure history at the time of aspiration of the reagent). The "pressure history at the time of aspiration of the reagent" refers to a pressure value in a predetermined time range including the operation time (aspiration operation time) of the syringe <NUM> when the reagent <NUM> is aspirated in step S205.

Since the pressure history at the time of aspiration of the reagent <NUM> reflects the viscosity of the reagent <NUM> as shown in equation (<NUM>), the viscosity of the reagent <NUM> can be estimated based on the pressure history. The calculation unit <NUM> calculates the viscosity of the reagent <NUM> based on the pressure history at the time of aspiration of the reagent <NUM> stored in the storage unit <NUM>, and stores the viscosity in the reagent physical property value storage unit <NUM> (<FIG>).

In the determination of the presence or absence of an abnormality at the time of aspiration of the specimen <NUM> in step S212, the same steps as the determination method according to the fourth embodiment shown in <FIG> are executed.

An example has been described above in which the viscosity is estimated as one of the physical property values of the reagent <NUM>. Alternatively, the density of the reagent <NUM> may be estimated and used for determining the presence or absence of an abnormality. In this case, the density may be calculated based on a gravitational head of the pressure value after the aspiration of the reagent <NUM> in step S205.

In the fifth embodiment, the physical property value of the reagent is estimated based on the pressure history at the time of aspiration of the reagent, and the determination threshold used for determining the presence or absence of an abnormality is set as a function that varies depending on the estimated physical property value of the reagent. Accordingly, in addition to attaining the same effect as that according to the fourth embodiment, an abnormality can be detected with high accuracy even if the information on the physical property value of the reagent used for the analysis is not stored in the reagent physical property value storage unit.

In the fifth embodiment, a method of estimating a physical property value of the reagent using the pressure history at the time of aspiration of the reagent has been described. However, when there are a plurality of reagents to be simultaneously pipetted, the physical property values are estimated for each of the reagents to be aspirated by repeating steps S204 to S206 in <FIG>, which complicates the processing. If the physical property values are estimated for each of the plurality of reagents, errors may accumulate and the accuracy of abnormality detection may decrease.

Therefore, in a sixth embodiment, a method is provided in which, when a plurality of reagents are pipetted, an influence of the plurality of reagents aspirated before the aspiration of a specimen on a pressure history at the time of aspiration of the specimen is considered.

A pipetting method according to the present embodiment is almost the same as the pipetting method shown in <FIG>, but differs in the following points. That is, an aspiration flow rate of the syringe <NUM> at the time of aspiration of the second air gap in step S206 is equal to an aspiration flow rate of the syringe <NUM> at the time of aspiration of the specimen <NUM> in step S208. Step S206 is performed last among steps S204 to S206 repeated as many times as the necessary number of reagents. Accordingly, the influence of the plurality of reagents held in the tip <NUM> on the pressure history at the time of aspiration of the specimen can be estimated.

More specifically, in step S206, the sampling unit <NUM> receives an input of a pressure value during the aspiration operation of the second air gap from the pressure sensor <NUM>, and stores, in the storage unit <NUM>, the pressure value during the aspiration operation of the second air gap as time-series data (pressure history). The calculation unit <NUM> acquires the pressure history at the time of aspiration of the air gap in step S206, and estimates an average value (representative value) of the viscosities of the plurality of reagents <NUM> based on the pressure history and the above equation (<NUM>). The other steps can be performed in the same manner as those in the fifth embodiment.

In the sixth embodiment, when the plurality of reagents are simultaneously pipetted, the representative value of the physical property values of the plurality of reagents is estimated, and a determination threshold used for determining the presence or absence of an abnormality is set as a function that varies depending on the estimated physical property values of the reagents. Accordingly, since it is not necessary to estimate the physical property values for all of the plurality of reagents, the processing is simple and errors are not accumulated. Therefore, an abnormality can be detected with high accuracy regardless of the physical property values of the plurality of reagents aspirated before the aspiration of the specimen.

According to a configuration in which the aspiration flow rate of the syringe <NUM> at the time of aspiration of the second air gap in step S206 performed last among steps S204 to S206 is equal to the aspiration flow rate of the syringe <NUM> at the time of aspiration of the specimen <NUM> in step S208, an influence of the viscosities of the reagents <NUM> on the pressure history at the time of aspiration of the specimen <NUM> can be more accurately estimated.

As described above, instead of estimating the representative value of the physical property values of the plurality of reagents, a determination index in which the influence of the physical property values or the pipetted amounts of the reagents is canceled can also be used as the determination index. Specifically, in the method for determining the presence or absence of an abnormality shown in <FIG>, a difference between the pressure history in the aspiration of the second air gap in step S206 and the pressure history in the aspiration of the specimen <NUM> in step S208 is calculated as the determination index. Since the determination index calculated here is a difference between a pressure history immediately before the aspiration of the specimen and a pressure history after the aspiration of the specimen, an influence of the physical property values or the pipetted amounts of the plurality of reagents aspirated before the aspiration of the specimen is canceled out. By using such a determination index, the presence or absence of an abnormality can be determined with high accuracy regardless of the pipetted amounts or the physical property values of the reagents.

The present disclosure is not limited to the above embodiments, and includes various modifications. For example, the above embodiments have been described in detail for easy understanding of the present disclosure, and are not necessarily limited to those including all the configurations described above. It should be noted and understood that there can be improvements and modifications made of the present invention described in detail above without departing from the scope of the invention as set forth in the accompanying claims.

Claim 1:
An automatic analysis device comprising:
a pipetting nozzle (<NUM>; <NUM>) configured to pipette a fluid,
a pressure source (<NUM>) configured to generate a pressure fluctuation for pipetting the fluid by the pipetting nozzle (<NUM>; <NUM>),
a flow path (<NUM>) connecting the pipetting nozzle (<NUM>; <NUM>) and the pressure source (<NUM>),
a pressure sensor (<NUM>) configured to measure the pressure in the flow path (<NUM>) when the pipetting nozzle (<NUM>; <NUM>) pipettes the fluid,
a storage unit (<NUM>) configured to store time-series data of the pressure measured by the pressure sensor (<NUM>), and
a control unit (<NUM>) configured to control the driving of the pipetting nozzle (<NUM>; <NUM>) and the pressure source (<NUM>), wherein the control unit (<NUM>) controls the pipetting nozzle (<NUM>; <NUM>) and the pressure source (<NUM>) to aspirate first air gap (<NUM>; <NUM>), a first liquid (<NUM>), second air gap (<NUM>; <NUM>), and a second liquid (<NUM>) in this order into the pipetting nozzle (<NUM>; <NUM>),
characterized in that the control unit (<NUM>) determines at least one of the aspiration amount of the first air gap (<NUM>; <NUM>) and the aspiration amount of the second air gap (<NUM>; <NUM>) based on the aspiration amount of the first liquid (<NUM>).