Patent Description:
In a field of automatic analyzers that perform qualitative and quantitative analysis of biological samples such as blood and urine, in clinical tests that analyze components contained in a biological sample such as blood and urine of a patient, the sample and a reagent react to perform qualitative and quantitative analysis of a target component in the sample. In this case, a liquid supply mechanism called a dispensing mechanism is used to supply a predetermined amount of the sample and the reagent to a reaction container in which the sample and the reagent react. In order to supply the liquid, a pressure in a nozzle that aspirates a liquid using a syringe is set as a negative pressure, the liquid to be aspirated is aspirated into the nozzle, and then a predetermined amount of the liquid is dispensed into the reaction container by setting the pressure in the nozzle to a positive pressure using a syringe.

PTL <NUM> discloses that a pressure sensor is provided in a pipe connecting a dispensing nozzle and a dispensing syringe, output in the pipe is measured by the pressure sensor, and an abnormality in any of an electromagnetic valve, a gear pump, and a water tank is detected based on the output. Further, PTL <NUM> discloses that malfunction of an electromagnetic valve is detected by equipping the electromagnetic valve with an operation sensor.

Automatic analyzers are further known from <CIT>, <CIT>, <CIT> and <CIT>. In particular, <CIT> discloses an automatic analyzer having a suction nozzle which sucks a predetermined amount of electrolyte sample from a container and supplies it to an electrode for electrolytic concentration analysis. An abnormality in the replenishment amount of the electrolyte sample can be detected.

Addition of a pressure sensor to a device or disposing of a sensor on an electromagnetic valve as in the related art leads to an increase in the cost of the device. Further, the addition of the sensor to a flow path or an electromagnetic valve changes a control circuit or a flow path with respect to the existing device configuration, which limits applicable products and applicable ranges.

Therefore, the invention provides an automatic analyzer that can detect an abnormality related to a flow path system by using a sensor that is originally provided in the automatic analyzer and detects an amount of liquid such as reagents, cleaning reagents, and measurement targets.

An automatic analyzer is provided according to claim <NUM>.

According to the invention, it is possible to detect an abnormality in a flow path including malfunction of an electromagnetic valve or a pressure change portion by using an existing sensor that measures a liquid amount in a container without mounting an operation sensor of an electromagnetic valve or a pressure sensor of a flow path system.

Other technical problems and novel characteristics will become apparent from a description of the description and the accompanying drawings.

Hereinafter, embodiments of the invention are described with reference to the drawings.

Embodiment <NUM> is an automatic analyzer <NUM> that detects an abnormality occurring in a flow path system by a sensor that measures a liquid amount.

<FIG> is a diagram schematically illustrating a flow path system for sending various types of liquid in the automatic analyzer <NUM>. The flow path system of the automatic analyzer <NUM> includes: a container <NUM> that contains liquid; a liquid amount sensor <NUM> that measures a liquid amount in the container <NUM>; a syringe <NUM> that aspirates or dispenses the liquid by changing a pressure in a flow path; a first electromagnetic valve <NUM> and a second electromagnetic valve <NUM> that are normally open (close the flow path when energized) ; a nozzle <NUM> that aspirates or dispenses the liquid from the container <NUM>; a flow path <NUM> that connects the nozzle <NUM> and the first electromagnetic valve <NUM>; a branch portion <NUM>; a flow path <NUM> that connects the branch portion <NUM> and the first electromagnetic valve <NUM>; a flow path <NUM> that connects the second electromagnetic valve <NUM> and the branch portion <NUM>; a flow path <NUM> that connects the branch portion <NUM> and the syringe <NUM>; and a flow path <NUM> that connects the second electromagnetic valve <NUM> and a liquid discharging unit <NUM>. The flow path system of the automatic analyzer <NUM> can send the liquid in the container <NUM> to the liquid discharging unit <NUM>.

Here, since the container <NUM> and the liquid discharging unit <NUM> have almost the same height, a pressure at a tip end of the nozzle <NUM> and a pressure at a tip end of the flow path <NUM> which is connected to the liquid discharging unit <NUM> become equal, and even if the electromagnetic valves <NUM>, <NUM> are opened, the liquid does not flow in the flow path system unless an action is applied by the syringe <NUM>. Therefore, in this example, electromagnetic valves that are normally open are used as the first electromagnetic valve <NUM> and the second electromagnetic valve <NUM>. However, the electromagnetic valve is only required to control whether to stop or allow a flow of a flow path, and depending on a structure of the flow path, the electromagnetic valve may be normally closed (open the flow path when energized), and a structure of the valve is not limited. A pinch valve, a diaphragm valve, a non-diaphragm valve, or the like may be used.

A first flow path <NUM> refers to a flow path including the nozzle <NUM>, the flow path <NUM>, the first electromagnetic valve <NUM>, and the flow path <NUM> from the container <NUM> to the branch portion <NUM>. Further, a second flow path <NUM> refers to a flow path including the flow path <NUM>, the second electromagnetic valve <NUM>, and the flow path <NUM> from the liquid discharging unit <NUM> to the branch portion <NUM>.

A controller <NUM> controls the first electromagnetic valve <NUM>, the second electromagnetic valve <NUM>, and the syringe <NUM>. The controller <NUM> also includes an output unit <NUM> and an input unit <NUM> that form an interface with a user. For example, the input unit <NUM> includes a keyboard and a mouse, and the output unit <NUM> includes a display and a printer. The controller <NUM> further includes a storage unit <NUM>, and stores, for example, an output result of the liquid amount sensor <NUM>.

The liquid amount sensor <NUM> only needs to be able to measure a liquid amount in the container <NUM>, a measuring method uses any one of a capacitance type, an electrode type, an optical type, an ultrasonic type, and a float type, and the liquid amount sensor <NUM> may be a weight sensor. The liquid amount sensor <NUM> is originally provided for preventing an aspiration amount from being insufficient in case that the liquid contained in the container <NUM> is insufficient. When the liquid amount sensor <NUM> detects that the liquid amount in the container <NUM> is less than a predetermined amount, the controller <NUM> ends an analysis operation and urges the user to replenish the liquid by giving the output unit <NUM> an alarm notifying the replenishment of the liquid or the replacement of the container <NUM>.

Further, the liquid discharging unit <NUM> may be in a form of a container or the like, and instead of providing the liquid amount sensor <NUM> in the container <NUM>, the liquid amount sensor <NUM> may be provided in the liquid discharging unit <NUM>.

An operation of sending the liquid in the container to the flow path is called aspiration, an operation of removing unnecessary liquid in the flow path (sending to the liquid discharging unit <NUM>) is called discharge, and an operation of sending the liquid in the flow path to the container is called dispensation.

<FIG> is an example of a flowchart of detecting an abnormality in the flow path system in the automatic analyzer <NUM>.

First, the controller <NUM> measures a liquid amount A0 in the container <NUM> by the liquid amount sensor <NUM> (step S200). Here, information obtained by the liquid amount sensor <NUM> differs depending on the type of the sensor provided in the container <NUM>. For example, if the sensor is a liquid level detecting sensor, the information is a height of a liquid level, and if the sensor is a weight sensor, the information is a weight of liquid. The controller <NUM> converts output information of the liquid amount sensor <NUM> into the liquid amount in the container <NUM> and stores the output information in the storage unit <NUM>. Further, if the liquid amount in the container <NUM> is determined in advance, step S200 can be omitted. In this case, the controller <NUM> may substitute an initial value corresponding to the liquid amount in the container <NUM> as the liquid amount A0.

Next, the controller <NUM> aspirates the liquid in the container <NUM> from the nozzle <NUM> and fills the first flow path <NUM> with the liquid by opening the first electromagnetic valve <NUM>, closing the second electromagnetic valve <NUM>, and generating a negative pressure in the flow path using the syringe <NUM> (step S201).

Next, the liquid is sent into the flow path <NUM> by further generating a negative pressure in the flow path using the syringe <NUM>. Further, in a state where the second electromagnetic valve <NUM> is opened and the first electromagnetic valve <NUM> is closed, a positive pressure is generated in the flow path by the syringe <NUM>. Accordingly, the liquid in the flow path <NUM> is discharged to the liquid discharging unit <NUM> via the second flow path <NUM> (step S202).

Next, the controller <NUM> determines whether the operations of steps S201 and S202 are performed a predetermined number of times (step S203). If the number of times is less than the predetermined number, the controller <NUM> repeats the operations of steps S201 and S202. A target value of an aspiration amount of the liquid aspirated from the container <NUM> assumed by performing the operations of steps S201 and S202 the predetermined number of times is B1.

Next, the controller <NUM> measures a liquid amount A1 in the container <NUM> by the liquid amount sensor <NUM> (step S204). The liquid amount A1 is stored in the storage unit <NUM>. The controller <NUM> calculates a liquid amount A3 obtained by subtracting the liquid amount A1 from the liquid amount A0 (step S205). The liquid amount A3 is an actual amount of the liquid aspirated from the container <NUM> in step S201. A target liquid amount B1 is subtracted from the actually aspirated liquid amount A3, and the difference is compared with a threshold C1 determined in consideration of a variation of a device and a measurement variation of the liquid amount sensor <NUM>, or the like (step S206). When |A3 - B1| < C1, the controller <NUM> determines that the aspiration amount is normal and the flow path system is normal (step S207). On the other hand, when |A3 - B1| ≥ C1, that is, when the actually aspirated liquid amount A3 deviates from the target value B1, the controller <NUM> determines that an abnormality occurs in the flow path system (step S208), displays an alarm on the output unit <NUM> (step S209), and ends the abnormality detection of the flow path system.

A method for determining an abnormality in the flow path system in step S206 is not limited to the above. For example, by using predetermined thresholds C2 and C3, when C2 < A1 < C3, the controller <NUM> may determine that the flow path system is normal. In this case, when A1 ≤ C2 or C3 ≤ A1, the controller <NUM> determines that an abnormality occurs in the flow path system.

Here, the thresholds C1, C2, and C3, which are used by the controller <NUM> to determine an abnormality in the flow path system in step S206, may be, for example, predetermined fixed values or statistics. For example, when the liquid amount sensor <NUM> is a liquid level sensor and a liquid level height is used as the liquid amount, it is also possible to set the threshold as <NUM> times a standard deviation calculated based on a measured value of the liquid level height so far. Further, determination of an abnormality is not limited to a determination method based on a threshold, and may use statistical processing by a Mahalanobis Taguchi (MT) method, a linear determination method, or the like.

As a reason of causing an abnormality in the flow path system of the automatic analyzer <NUM>, opening and closing malfunction of the first electromagnetic valve <NUM> and the second electromagnetic valve <NUM>, malfunction of the syringe <NUM>, clogging of the nozzle <NUM> and the liquid discharging unit <NUM>, a liquid leakage in the first flow path <NUM> and the second flow path <NUM>, or the like may be considered. Regardless of which malfunction occurs, a normal liquid amount of the liquid cannot be sent from the container <NUM> to the liquid discharging unit <NUM>, and therefore basic functions of the automatic analyzer cannot be guaranteed. Influences of each of the above-described malfunction will be described.

First, the malfunction of the first electromagnetic valve <NUM> means that a closing operation cannot be performed. Therefore, in step S202, the liquid flows back into the container <NUM> while the first electromagnetic valve <NUM> is in an open state. The malfunction of the second electromagnetic valve <NUM> also means that a closing operation cannot be performed, and thus the liquid is aspirated from the second flow path <NUM> in step S201 while the second electromagnetic valve <NUM> is in an open state, and a predetermined amount of the liquid cannot be aspirated from the container <NUM>.

Further, when the syringe <NUM> malfunctions, the predetermined amount of the liquid cannot be aspirated in step S201. Clogging of the liquid discharging unit <NUM> generates an excessive pressure in the second flow path <NUM> in step S202, and when the first electromagnetic valve <NUM> is opened again in step S201, the liquid flows back into the container <NUM>. Thus, the abnormality in the flow path system is finally reflected in the amount of the liquid aspirated from the container <NUM>. Therefore, it is possible to determine an abnormality in the flow path system regardless of the reason of the abnormality.

When the electromagnetic valves are normally closed, contrary to the electromagnetic valves that are normally open, the flow path cannot be opened if the electromagnetic valves malfunction. Therefore, due to the malfunction of the first electromagnetic valve <NUM>, the aspiration amount becomes insufficient during the aspiration from the container <NUM>. Similarly, since the liquid cannot be discharged due to the malfunction of the second electromagnetic valve <NUM>, a pressure higher than normal is applied to the second flow path <NUM>, and similar to the case of clogging of the liquid discharging unit <NUM> described above, when the first electromagnetic valve <NUM> is opened again, the liquid flows back into the container <NUM>. Thus, when the electromagnetic valve is normally closed, the abnormality in the flow path system can also be determined from the flowchart of <FIG>.

<FIG> illustrates an example of a flowchart of specifying an abnormal position of the flow path system. The processing is performed when it is determined that there is an abnormality in the flow path system in the flowchart of <FIG> or when the user checks an operation of a unit related to the flow path system.

First, as a preparation operation, the controller <NUM> performs steps S201 and S202 of the flowchart of <FIG> to fill the first flow path <NUM> and the second flow path <NUM> with the liquid (step S300).

Next, in the same manner as in step S200, a liquid amount A30 in the container <NUM> is measured, and the output information of the liquid amount sensor <NUM> is stored in the storage unit <NUM> (step S301).

Next, the controller <NUM> causes the liquid to flow back into the container <NUM> and discharges the liquid to the liquid discharging unit <NUM> by applying a positive pressure to the syringe <NUM> in a state where the first electromagnetic valve <NUM> and the second electromagnetic valve <NUM> are opened (step S302). As described above, the liquid discharging unit <NUM> and the aspiration nozzle <NUM> are set to the same height so that the flow of the liquid due to a pressure difference in the atmospheric pressure does not occur.

Next, the controller <NUM> measures a liquid amount A31 in the container <NUM> after dispensing in the same manner as in step S200, obtains a backflow liquid amount (dispense amount) A32 by subtracting the liquid amount A30 before backflow, and stores the liquid amount A32 in the storage unit <NUM> (step S303).

Next, the controller <NUM> obtains a difference between the liquid amount A32 that actually flows back and a target liquid amount B31 when backflow occurs in a normal state, and compares the difference with a threshold C31 determined in consideration of the variation of the device, the measurement variation of the liquid amount sensor <NUM>, or the like (step S304). when |A32 - B31| ≥ C31 (when there is a deviation between the target value and a measured value), the controller <NUM> determines that a dispense amount is insufficient due to an insufficient pressure caused by malfunction other than the electromagnetic valve, that is, malfunction of the syringe <NUM>, and the first flow path <NUM> or the second flow path <NUM> is clogged or leaks (step S312), displays an alarm on the output unit <NUM>, and then ends the measurement (step S315). Further, when |A32 - B31| < C31, the controller <NUM> determines that the dispensation is normal, and subsequently performs abnormality determination of the electromagnetic valve.

The controller <NUM> closes the second electromagnetic valve <NUM> and aspirates the liquid from the container <NUM> by the syringe <NUM> in the same manner as in step S201 of the flowchart of <FIG> (step S305). Next, the controller <NUM> measures a liquid amount A33 in the container <NUM> after aspiration in the same manner as in step S200, obtains an aspirated liquid amount A34 by subtracting the liquid amount A33 from the liquid amount A31 before aspiration, and stores the liquid amount A34 in the storage unit <NUM> (step S306).

Next, in the same manner as in step S206 of the flowchart of <FIG>, the controller <NUM> obtains a difference between a target liquid amount B32 when aspirated in a normal state and the actually aspirated liquid amount A34, and compares the difference with a threshold C32 (step S307). When |A34 - B32| ≥ C32 (when there is a deviation between the target value and the measured value), the controller <NUM> determines that the second electromagnetic valve <NUM> malfunctions (step S313), displays an alarm on the output unit <NUM>, and then ends the measurement (step S315). This is because when the normally open second electromagnetic valve <NUM> malfunctions, the second electromagnetic valve <NUM> is always in an open state, and the syringe <NUM> unintentionally aspirates the liquid in the second flow path <NUM>. On the other hand, when |A34 - B32| < C32, the controller <NUM> determines that the second electromagnetic valve <NUM> is normal, and subsequently performs abnormality determination of the first electromagnetic valve <NUM>.

The controller <NUM> closes the first electromagnetic valve <NUM> and discharges the liquid to the liquid discharging unit <NUM> by the syringe <NUM> in the same manner as in step S202 of the flowchart of <FIG> (step S308). Next, the controller <NUM> measures a liquid amount A35 in the container <NUM> after discharge in the same manner as in step S200, obtains a changed liquid amount A36 by subtracting the liquid amount A33 before discharge, and stores the liquid amount A36 in the storage unit <NUM> (step S309). If the first electromagnetic valve <NUM> is closed as normal, the liquid amount in the container <NUM> does not change before and after discharge, so that the changed liquid amount A36 becomes almost <NUM>.

Therefore, the controller <NUM> compares a threshold C33 determined in consideration of various variations with the changed liquid amount A36 (step S310). When |A36| ≥ C33, it is considered that the container <NUM> is unintentionally dispensed, therefore, the controller <NUM> determines that the first electromagnetic valve <NUM> malfunctions (step S314), displays an alarm on the output unit <NUM>, and then ends the measurement (step S315). Further, when |A36| < C33, the controller <NUM> determines that the flow path system is normal and ends the operation (step S311).

Further, the controller <NUM> may count the number of times i of operations of steps S300 to S311 and repeat the operations of steps S300 to S311 the number of times n which is specified in advance. Repeated inspection can improve the detection accuracy of the malfunction of the electromagnetic valve.

Further, in each abnormality determination, thresholds may be classified in more detail, and processing may be added to determine a liquid leakage if a changed amount is small or malfunction of the electromagnetic valve if a changed amount is relatively large. Further, a step may be added to measure a liquid amount change in the container <NUM> and determine a liquid leakage in a state where the first electromagnetic valve <NUM> and the second electromagnetic valve <NUM> are opened and the syringe <NUM> is stationary.

By specifying a reason of an abnormality including the malfunction of the electromagnetic valve, quick repair is possible, a period in which the device is unusable by a customer can be shortened, and an influence of malfunction on clinical laboratory work can be minimized.

Embodiment <NUM> is an automatic analyzer <NUM> using an immunoassay method, which detects an abnormality occurring in a flow path system by a sensor for measuring a liquid amount. In the figure, the same members as those described in Embodiment <NUM> are designated by the same reference numerals and the description thereof will be omitted.

<FIG> extracts and illustrates a detecting unit on which the immunoassay method is performed and a configuration related thereto from the automatic immunoassay analyzer <NUM>. The automatic immunoassay analyzer <NUM> measures a biological sample (hereinafter referred to as a sample) such as blood or urine derived from a patient.

A flow cell detecting unit <NUM> includes: a flow path <NUM> through which a reaction solution aspirated by the nozzle <NUM> and a light-emitting auxiliary reagent or a cleaning reagent that assists detection flow; and a detector <NUM> that detects light emission of a measurement target substance. In a reaction container <NUM>, the measurement target substance forms a composite modified with magnetic particles and a light-emitting substance by using a reaction between an antigen and an antibody. The detector <NUM> includes a magnetic particle holding unit (not illustrated), and the magnetic particle holding unit holds and adsorbs the composite that has reached the detector <NUM> on the flow cell detecting unit <NUM>. Then, the reaction solution which is a solvent of the composite is removed, the light-emitting substance bound to the composite is induced by the light-emitting auxiliary reagent, and a light-emitting amount thereof is detected by the detector <NUM>. The controller <NUM> calculates a concentration of the measurement target substance based on a result detected by the detector <NUM>, and the calculated concentration of the measurement target substance is output from the output unit <NUM>. This series of steps performed by the flow cell detecting unit <NUM> is called the immunoassay method.

The automatic analyzer <NUM> includes a container exchange mechanism <NUM> capable of moving the reaction container <NUM>, a light-emitting auxiliary reagent container <NUM>, and a cleaning reagent container <NUM> in an up and down direction and a left and right direction by a pulse motor. A rotation amount of the pulse motor is determined by a commanded number of pulses, and a rotation amount of the motor is proportional to a moving distance of a container, so that accurate positioning is possible. The nozzle <NUM> can aspirate liquid in the container disposed by the container exchange mechanism <NUM> without moving.

The first flow path <NUM> refers to a flow path including the nozzle <NUM>, a flow path <NUM> connecting the nozzle <NUM> and the flow path <NUM>, the flow path <NUM>, the flow path <NUM> connecting the flow path <NUM> and the first electromagnetic valve <NUM>, the first electromagnetic valve <NUM>, and the flow path <NUM> from the container <NUM> or the like to the branch portion <NUM>. Further, the second flow path <NUM> refers to a flow path including the flow path <NUM>, the second electromagnetic valve <NUM>, an atmospheric pressure opening unit <NUM>, and the flow path <NUM> from the liquid discharging unit <NUM> to the branch portion <NUM>. Since the second flow path <NUM> includes the atmospheric pressure opening unit <NUM>, and a hydrostatic pressure acting on the nozzle <NUM> and the atmospheric pressure opening <NUM> becomes constant, the liquid can be held in the flow path even when the first electromagnetic valve <NUM> and the second electromagnetic valve <NUM> are opened.

In the cleaning reagent container <NUM>, a cleaning reagent is appropriately supplied from a reagent supply bottle <NUM> to the cleaning reagent container <NUM> by a dispensing machine <NUM> including a flow path <NUM>, an electromagnetic valve <NUM>, a syringe <NUM>, and an electromagnetic valve <NUM>. Although not illustrated, the reagent is supplied to the light-emitting auxiliary reagent container <NUM> with the same configuration. In Embodiment <NUM>, the first electromagnetic valve <NUM> and the second electromagnetic valve <NUM> are pinch valves that are normally open (close the flow path when energized), and the electromagnetic valves <NUM>, <NUM> are solenoid valves that are normally closed.

As a preparation operation before the start of measurement, the controller <NUM> dispenses the light-emitting auxiliary reagent into the light-emitting auxiliary reagent container <NUM> by the dispensing machine <NUM>, and dispenses the cleaning reagent into the cleaning reagent container <NUM> with a liquid amount required for the next measurement (step S500).

First, the container exchange mechanism <NUM> inserts the nozzle <NUM> into the reaction container <NUM> by rotating and moving the reaction container <NUM> up and down. Next, the reaction solution in the reaction container <NUM> is aspirated from the nozzle <NUM> by opening the first electromagnetic valve <NUM>, closing the second electromagnetic valve <NUM>, and generating a negative pressure in the first flow path <NUM> by the syringe <NUM> (step S501). The measurement target object is held in the flow path <NUM> of the detecting unit <NUM> by adsorbing and holding the magnetic particles of the composite using the magnetic particle holding unit (not illustrated).

Next, the light-emitting auxiliary reagent container <NUM> is disposed at a position where the nozzle <NUM> can aspirate the light-emitting auxiliary reagent, by the container exchange mechanism <NUM>, and the light-emitting auxiliary reagent in the light-emitting auxiliary reagent container <NUM> is aspirated (step S502). Accordingly, the light-emitting auxiliary reagent is aspirated into the flow path <NUM>.

Next, in the detecting unit <NUM>, an unreacted component of the reaction solution is removed and replaced with the light-emitting auxiliary reagent to induce a light-emitting reaction of a light-emitting label in the composite of the measurement target object, and the measurement target object is detected and qualitative and quantitative analysis is performed by detecting the light emission (step S503). The flow cell detecting unit <NUM> disperses the composite, in which the magnetic particles are adsorbed and held, in the light-emitting auxiliary reagent by opening the magnetic particle holding unit. The first electromagnetic valve <NUM> is closed, the second electromagnetic valve <NUM> is opened, and the syringe <NUM> is operated for dispensing. The above operations are to return a plunger of the syringe to a home position and enable the aspirating operation again. Accordingly, a part of the reaction solution and the light-emitting auxiliary reagent used for the measurement is discharged into the liquid discharging unit <NUM> (step S504).

Next, the container exchange mechanism <NUM> moves the cleaning reagent container <NUM> under the nozzle <NUM> and then raises the cleaning reagent container <NUM> towards the nozzle <NUM>. When a liquid level of the cleaning reagent container <NUM> is detected by a liquid level detecting sensor 102b, which is disposed parallel to the nozzle <NUM> and whose tip end is disposed at the same height as the tip end of the nozzle <NUM>, the rise is stopped. The controller <NUM> calculates a liquid amount in the container <NUM> based on the number of remaining pulses (hereinafter, remaining pulses) up to a position of an upper limit of movement of a pulse motor that has detected the liquid level, and stores the liquid amount in the storage unit <NUM>. A physical amount to be stored may be remaining pulses or moving pulses, and may be a value that can grasp the liquid amount (step S505).

The controller <NUM> determines a state of the flow path system based on the liquid amount in the cleaning reagent container <NUM> (step S506), determines that malfunction occurs in the flow path system when a difference is out of a threshold range determined in consideration of a variation of a device and a measurement variation (step S514), displays an alarm on the output unit <NUM>, and then ends the measurement (step S515). Details of a method for determining malfunction of the flow path system will be described later.

Next, the controller <NUM> causes the syringe <NUM> to perform an aspirating operation in a state where the first electromagnetic valve <NUM> is opened and the second electromagnetic valve <NUM> is closed (step S507). At this time, by raising the cleaning reagent container <NUM> by the container exchange mechanism <NUM>, a state where the tip end of the nozzle <NUM> is always immersed under a liquid level is maintained, and aspiration of air bubbles is prevented. Next, the first electromagnetic valve <NUM> is closed, the second electromagnetic valve <NUM> is opened, and the syringe <NUM> is operated for dispensing (a positive pressure is generated in the flow path). Accordingly, the reaction solution, the light-emitting auxiliary reagent, and the cleaning reagent used for the measurement are discharged into the liquid discharging unit <NUM> (step S508).

Next, the liquid level detecting sensor 102b measures a liquid level of the light-emitting auxiliary reagent container <NUM> and stores a result in the storage unit <NUM> in the same manner as in step S505. The controller <NUM> determines a state of the flow path system based on a liquid amount in the light-emitting auxiliary reagent container <NUM> (step S510), determines that malfunction occurs in the flow path system when the difference is out of the threshold range determined in consideration of the variation of the device and the measurement variation (step S514), displays an alarm on the output unit <NUM>, and then ends the measurement (step S515). Details of a method for determining malfunction of the flow path system will be described later.

Next, the light-emitting auxiliary reagent is aspirated in the same manner as in step S502, and the light-emitting auxiliary reagent fills the flow path <NUM> of the detecting unit <NUM> (step S511). This is because an electrochemical condition of the flow path <NUM> of the detecting unit <NUM> is stabilized by pre-filling the detecting unit <NUM> with the light-emitting auxiliary reagent in preparation for the next measurement.

Next, the controller <NUM> dispenses the light-emitting auxiliary reagent or the cleaning reagent to each container up to a target value by the dispensing machine <NUM> based on the liquid amounts in the light-emitting auxiliary reagent container <NUM> and the cleaning reagent container <NUM> stored in the storage unit <NUM> (step S512).

Then, steps S501 to S512 are repeated until a predetermined number of analyzes are ended (step S513).

In this flowchart, liquid level detection is performed for the liquid aspirating operation in steps <NUM> and <NUM>, and the liquid amount in the container is detected by using the liquid level detection (steps S505 and S509). Therefore, in one measurement cycle (steps S501 to S512), liquid amounts are measured once for each of the cleaning reagent and the light-emitting auxiliary reagent, so that malfunction of the flow path system is determined by comparing with a measurement result in the previous measurement cycle. By not adding a new step only for detecting the liquid amount in the container, it is not necessary to redefine a sequence of the automatic analyzer, and it is possible to prevent a time required for one cycle from being extended. On the other hand, since malfunction of the flow path system can be detected in the next measurement cycle when the malfunction of the flow path system occurs in the current measurement cycle, the controller <NUM> gives an alarm retroactively to the measurement result one cycle before. Further, it is recommended to a user to perform a maintenance operation (flowchart in <FIG>) for specifying a malfunction position, which will be described later. The system may be configured such that the maintenance operation illustrated in <FIG> is automatically performed after the alarm is output.

The method for determining an abnormality in the flow path system in steps S506 and S510 will be described. When malfunction occurs in the flow path system, the liquid amount in the container changes as follows. When the first electromagnetic valve <NUM> malfunctions and is in an always-open state, the liquid flows back into the first flow path <NUM> in the operations (steps S504 and S508) of the syringe <NUM> discharging the liquid into the liquid discharging unit <NUM>. Accordingly, the liquid amounts in the light-emitting auxiliary reagent container <NUM> and the cleaning reagent container <NUM> increase from a normal state. Further, when the second electromagnetic valve <NUM> malfunctions, the liquid contained in the second flow path <NUM> is unintentionally aspirated in the operations (steps S505 and S509) of aspirating the light-emitting auxiliary reagent and the cleaning reagent. Accordingly, since a specified amount of the liquid cannot be aspirated from the first flow path <NUM>, aspiration is insufficient in the liquid amounts in the light-emitting auxiliary reagent container <NUM> and the cleaning reagent container <NUM> as compared with the normal state. Further, when a pressure in the flow path is lowered due to malfunction such as a liquid leakage of the syringe <NUM> or when the flow path <NUM> is clogged or leaks, the aspiration of the nozzle <NUM> is insufficient, so that the aspiration in the liquid amounts in the light-emitting auxiliary reagent container <NUM> and the cleaning reagent container <NUM> is insufficient as compared with the normal state. Therefore, it is possible to determine malfunction of the flow path system by detecting such insufficient aspiration.

A statistic used for determining an abnormality in the flow path system may be a value related to the liquid amount, and may be the remaining pulses or the liquid amount calculated based on the remaining pulses, or a height of the liquid level or a weight of the liquid depending on a type of the sensor. Further, as a method for determining an abnormality in the flow path system, not only a determination method of using a predetermined fixed range (threshold), but also a method of determining a difference between a measured value and a previous measured value or a difference between a target value and an actually measured value using a threshold, and a method of performing statistical processing by comparing with the past numerical values stored in a storage unit can be adopted. For example, the threshold may be a variable threshold obtained by adding <NUM> times an average value and a standard deviation calculated based on the measured values of the liquid level height so far.

In this flowchart, an abnormality in the flow path system is detected by using both the cleaning reagent and the light-emitting auxiliary reagent. This is because the detection accuracy can be improved by increasing the number of detections. The detection may be performed by using only one of the cleaning reagent and the light-emitting auxiliary reagent.

<FIG> illustrates an example of a flowchart of specifying an abnormal position of the flow path system. The above processing may be performed when it is determined that there is an abnormality in the flow path system in the flowchart of <FIG> or before and after the start of the analysis operation.

First, the controller <NUM> dispenses a predetermined amount of the cleaning reagent into the empty cleaning reagent container <NUM> by the dispensing machine <NUM> (step S600). Here, the cleaning reagent container <NUM> will be described as an example, but the light-emitting auxiliary reagent container <NUM> and other containers that can contains liquid may be used. Therefore, in <FIG>, these containers are referred to as "container *". Next, the liquid level detecting sensor 102b measures a liquid level of the cleaning reagent container <NUM>. The controller <NUM> determines whether the liquid level of the cleaning reagent container <NUM>, that is, the dispensing amount is normal (step S601). If the dispensing amount is equal to or less than the threshold, it is determined that the dispensing machine <NUM> malfunctions, the cleaning reagent container <NUM> is damaged, or the liquid level detecting sensor 102b is abnormal (step S609), and an alarm is displayed on the output unit <NUM> to end the measurement (step S613). Since the electromagnetic valves <NUM>, <NUM> of the dispensing machine <NUM> are solenoid valves that are normally closed, the electromagnetic valves <NUM>, <NUM> do not open during malfunction. Therefore, when the electromagnetic valve <NUM> and the electromagnetic valve <NUM> malfunction, a normal amount cannot be aspirated from the reagent supply bottle <NUM>, so that the liquid amount in the cleaning reagent container <NUM> becomes insufficient. Further, the liquid amount becomes insufficient due to damage to the cleaning reagent container <NUM>, clogging and liquid leakage of the flow path <NUM> of the dispensing machine <NUM>, or malfunction of the syringe <NUM>.

A change in the liquid amount that can be detected by the liquid level detecting sensor 102b depends on a time resolution of the liquid level detection. In order to detect a small change in the liquid amount such as liquid leakage, it is necessary to increase the time resolution of the liquid level detection. Normally, a sampling interval of a liquid level detecting sensor is about <NUM> msec, and in order to narrow the sampling interval, it is necessary to change a control board of the sensor. However, it is possible to increase the time resolution of the liquid level detection without changing the sampling interval of the liquid level detecting sensor. That is, a fact is used that a resolution for detecting a change in a liquid amount in a container by the liquid level detecting sensor, that is, a determinable liquid amount is determined according to a sampling cycle of the liquid level detecting sensor 102b and a plunge speed of the liquid level detecting sensor 102b into the liquid level of the container. Specifically, if an aspiration nozzle is moved at a speed of about <NUM>/sec during a normal analysis operation (the flowchart in <FIG>), during the maintenance operation (the flowchart in <FIG>), a moving speed of the aspiration nozzle is reduced to about <NUM>/sec. Accordingly, a liquid level detecting resolution of the liquid level detecting sensor 102b is improved <NUM> times, a change in the liquid amount of <NUM>µl can be determined, and even a small amount of liquid leakage can be detected.

Since the processing after step S602 in <FIG> is the same as the processing after step S302 in the flowchart of <FIG>, detailed description thereof will be omitted.

Embodiment <NUM> is an automatic analyzer <NUM> (<FIG>) that measures an electrolytic concentration and detects an abnormality occurring in a flow path system by a sensor for measuring a liquid amount. In the figure, the same members as those described in Embodiment <NUM> or Embodiment <NUM> are designated by the same reference numerals and the description thereof will be omitted.

In the flow type electrolyte concentration measuring device <NUM>, <NUM>µl of a sample in a test tube (not illustrated) is separated by a dispensing nozzle <NUM> of a dispensing unit <NUM> and discharged to a diluent tank <NUM>. The dispensing unit <NUM> has a drive mechanism <NUM>, a nozzle <NUM>, and the liquid level detecting sensor 102b. The liquid level detecting sensor 102b is a capacitance type sensor using a fact that the dispensing nozzle <NUM> is charged with an electric charge and a capacitance changes when the nozzle <NUM> adheres to a liquid surface. For blood used for measurement by an automatic analyzer, in order to aspirate serum, that is, a supernatant layer of the sample by the dispensing nozzle <NUM>, the dispensing nozzle <NUM> needs a capacitance type sensor that detects the liquid level.

The automatic analyzer <NUM> includes a first detector <NUM> and a second detector <NUM>. The first detector <NUM> is an ion-selective electrode unit that includes three types of electrodes, that is, a chlorine ion electrode, a potassium ion electrode, and a sodium ion electrode, and is provided inside a flow path <NUM>. The second detector <NUM> is a reference electrode, and is provided inside a flow path <NUM>. By appropriately operating the syringe <NUM> and a second electromagnetic valve <NUM>, a third electromagnetic valve <NUM>, and a fourth electromagnetic valve <NUM> which are normally closed, reference electrode liquid in a reference electrode liquid bottle <NUM> is introduced into the flow path <NUM> of the second detector <NUM>. The dispensing machine <NUM> replenishes the diluent tank <NUM> with internal standard solution or diluent from the reagent supply bottle <NUM>. Since a potential difference (electromotive force) between each ion-selective electrode of the first detector <NUM> and the reference electrode of the second detector <NUM> changes depending on a concentration of an ion to be analyzed in liquid introduced into each flow path, the electromotive force is measured by a potential measuring unit <NUM>, an ion concentration is calculated by the controller <NUM>, and is output to the output unit <NUM>.

The first electromagnetic valve <NUM> is a normally open pinch valve, and the second electromagnetic valve <NUM>, the third electromagnetic valve <NUM>, and the fourth electromagnetic valve <NUM> are normally closed electromagnetic valves. All of the electromagnetic valves can switch and open and close a flow path, and operate appropriately according to a direction and a timing of introducing liquid.

In the present embodiment, the liquid level detecting sensor 102b of the dispensing nozzle <NUM> that measures a liquid level of the sample is used so as to measure a liquid level of the diluent tank <NUM>, thereby detecting a defect related to the flowpath system. Therefore, it is possible to implement a function of detecting an abnormality in the flow path system without requiring an additional device. As long as the liquid level of the diluent tank <NUM> can be measured, the type of the sensor is not limited, and the liquid level detecting sensor of the dispensing nozzle <NUM> may be an electrode type sensor. Instead of using the liquid level detecting sensor 102b of the dispensing nozzle <NUM>, the diluent tank <NUM> may be provided with an optical type, ultrasonic type, or float type liquid amount sensor for measuring the liquid level. Further, a weight sensor may be attached to the diluent tank in order to measure a liquid amount in the diluent tank <NUM>.

<FIG> illustrates an example of a flowchart of detecting an abnormality in the flow path system. The above operation is different from an electrolyte concentration measuring operation usually performed by the flow type electrolytic concentration measuring device <NUM>.

First, as a preparation operation, predetermined amounts of the sample and the diluent are dispensed into the diluent tank <NUM> by the dispensing machine <NUM> (step S800). Next, the liquid amount in the diluent tank <NUM> is measured by the liquid level detecting sensor 102b of the dispensing nozzle <NUM> (step S801). The controller <NUM> determines whether the liquid level of the diluent tank <NUM>, that is, the dispensing amount is normal (step S801). The method of determining whether the dispensing amount is normal is the same as in step S601 in the flowchart of <FIG>. When the liquid amount in the diluent tank <NUM> is small, damage to the diluent tank <NUM>, malfunction of the syringe <NUM>, the electromagnetic valve <NUM>, and the electromagnetic valve <NUM> of the dispensing machine <NUM>, malfunction of the liquid level detecting sensor 102b, or the like is considered (step S811). In a case of malfunction, an alarm is output and the measurement is ended (step S815).

Next, the first electromagnetic valve <NUM> and the third electromagnetic valve <NUM> are opened, and the second electromagnetic valve <NUM> and the fourth electromagnetic valve <NUM> are closed. Next, the syringe <NUM> applies a negative pressure to the flow path to aspirate the diluted sample from the diluent tank <NUM> into the flow path <NUM> of the first detector <NUM>. After that, the third electromagnetic valve <NUM> is closed and the fourth electromagnetic valve <NUM> is opened, and the syringe <NUM> is operated for dispensing. The above operations are to return a plunger of the syringe to a home position and enable the aspirating operation again (step S803).

Here, the controller <NUM> measures a liquid amount after aspiration by the liquid level detecting sensor 102b of the dispensing nozzle <NUM>. A determination method of an aspiration amount in step S804 uses the same method as in step S307 in the flowchart of <FIG>. When the liquid amount aspirated here is small, it is determined that the syringe <NUM> malfunctions, the third electromagnetic valve <NUM> and the fourth electromagnetic valve <NUM> malfunction, the flow path <NUM> leaks or is clogged, or the like (step S812). In the case of malfunction, an alarm is output and the measurement is ended (step S815).

Next, the second electromagnetic valve <NUM> and the third electromagnetic valve <NUM> are opened, and the first electromagnetic valve <NUM> and the fourth electromagnetic valve <NUM> are closed. Next, the syringe <NUM> applies a negative pressure to the flow path to introduce the reference electrode liquid from the inside of the reference electrode liquid bottle <NUM> into the flow path <NUM> of the second detector <NUM> (step S805).

Here, the controller <NUM> measures a change amount of the diluent by the liquid level detecting sensor 102b of the dispensing nozzle <NUM> (step S806). A determination method of the change amount in step S807 uses the same method as in step S310 in the flowchart of <FIG>. Here, when the liquid amount changes, it is considered that the first electromagnetic valve <NUM> malfunctions (step S813).

Next, backflow is generated in the reference electrode liquid bottle <NUM> and the diluent tank <NUM> by opening the first electromagnetic valve <NUM>, the second electromagnetic valve <NUM>, and the third electromagnetic valve <NUM>, closing the fourth electromagnetic valve <NUM>, and applying a positive pressure to the flow path by the syringe <NUM> (step S808).

Next, the liquid amount in the diluent tank <NUM> after dispensation is measured by the liquid level detecting sensor 102b of the dispensing nozzle <NUM>. A determination method of the dispensation in step S809 uses the same method as in step S304 in the flowchart of <FIG> (step S809). Here, when the liquid amount increases, it is considered that the second electromagnetic valve <NUM> malfunctions. When the above steps are completed normally, it is determined that the flow path system is normal, and the measurement is ended (step S810).

Also in the present embodiment, as in the flowchart of <FIG> according to Embodiment <NUM>, an operation for determining malfunction is added to the flowchart during analysis processing.

Claim 1:
An automatic analyzer (<NUM>, <NUM>) comprising:
a sensor (<NUM>) configured to measure a liquid amount of a container (<NUM>) containing liquid;
a flow path system;
a liquid discharging unit (<NUM>) configured to discharge liquid from the flow path system;
a syringe (<NUM>, <NUM>) that is connected to a branch portion (<NUM>) of the flow path system and configured to change an internal pressure of the flow path; and
a controller (<NUM>), wherein
the flow path system includes a first flow path (<NUM>), a second flow path (<NUM>), a first electromagnetic valve (<NUM>), and a second electromagnetic valve (<NUM>), the first flow path (<NUM>) ranging from a nozzle (<NUM>) to the branch portion (<NUM>), the nozzle (<NUM>) aspirating or dispensing liquid from or to the container (<NUM>), the second flow path (<NUM>) ranging from the branch portion (<NUM>) to the liquid discharging unit (<NUM>), the first electromagnetic valve (<NUM>) being provided on the first flow path (<NUM>) and opening and closing the first flow path (<NUM>), and the second electromagnetic valve (<NUM>) being provided on the second flow path (<NUM>) and opening and closing the second flow path (<NUM>), and
the controller (<NUM>) is configured to operate the syringe (<NUM>, <NUM>), the first electromagnetic valve, and the second electromagnetic valve such that a predetermined aspirating, dispensing and discharging liquid operation is performed in the container (<NUM>), the liquid discharging unit (<NUM>), and the flow path system and wherein the controller is further configured to determine whether or not an abnormality occurs in the flow path system based on a difference between
a. a predetermined threshold or a liquid amount measured by the sensor (<NUM>) before the predetermined aspirating, dispensing and discharging liquid operation, and
b. a liquid amount measured by the sensor (<NUM>) after the predetermined liquid aspirating and discharging operation.