Automatic analysis device, dispensing nozzle cleaning state determination method, and program

Abstract

The present invention makes it possible to determine a state related to cleaning of a dispensing nozzle in an automatic analysis device in a shorter time. An automatic analysis device according to one embodiment of the present invention comprises: a dispensing nozzle that suctions and discharges a liquid; a cleaning unit that supplies a cleaning liquid to the outer wall and the interior of the dispensing nozzle; a capacitance measurement unit that measures the capacitance between the dispensing nozzle and a reference potential portion; a control unit that controls the dispensing nozzle and the cleaning unit; and a determination unit that executes a determination based on the measured capacitance. The capacitance measurement unit measures the capacitance in a state in which the cleaning unit is supplying the cleaning liquid to the outer wall and the interior of the dispensing nozzle and over a temporal interval including a period during which the liquid that has been suctioned by the dispensing nozzle is being discharged. The determination unit determines the state related to cleaning of the dispensing nozzle on the basis of capacitance data representing the capacitance measured over the temporal interval.

Description

Automatic analyzer, method for determining dispensing nozzle cleaning state, and program

[0001] The present invention relates to an automatic analyzer, a method for determining a cleaning state of a dispensing nozzle, and a program.

[0002] Automated analyzers that analyze liquid samples such as blood are known. To prevent sample contamination, the dispenser nozzles of these analyzers are cleaned with detergent or water after each use. Insufficient cleaning of the dispenser nozzles can adversely affect the analysis.

[0003] Patent Document 1 describes that, in order to determine whether the cleaning operation has been performed sufficiently, after the nozzle has been internally cleaned, the nozzle is filled with system water (pure water), and the electrical physical quantity detected by the detection mechanism is compared with a reference value, and the degree of cleaning of the internal cleaning is determined from the comparison result.

[0004] International Publication No. 2015 / 115200

[0005] However, the method described in Patent Document 1 focuses on the electrical physical quantity after the inside of the nozzle is washed with system water, so in order to determine whether the nozzle has been sufficiently cleaned, the dispensing operation must be repeated multiple times until the system water becomes contaminated, which takes a relatively long time.

[0006] An object of the present invention is to make it possible to determine the cleaning status of a dispensing nozzle in an automatic analyzer in a shorter time.

[0007] An automated analyzer according to one embodiment of the present invention includes a dispensing nozzle that aspirates and dispenses liquid, a washing unit that supplies cleaning liquid to the outer wall and interior of the dispensing nozzle, a capacitance measurement unit that measures the capacitance between the dispensing nozzle and a reference potential portion, a control unit that controls the dispensing nozzle and the washing unit, and a determination unit that performs determination based on the measured capacitance. The capacitance measurement unit measures the capacitance over a time period that includes a period during which the washing unit is supplying the cleaning liquid to the outer wall and interior of the dispensing nozzle and dispensing the aspirated liquid. The determination unit determines the cleaning status of the dispensing nozzle based on capacitance data representing the capacitance measured over the time period.

[0008] According to the embodiment of the present invention, the cleaning status of the dispensing nozzle in the automatic analyzer can be determined in a shorter time.

[0009] 1 is a diagram showing an example of the configuration of an automatic analyzer according to a first embodiment. FIG. 2 is a diagram for explaining a method for acquiring the amount of change in capacitance value using a liquid level detection sensor. FIG. 3 is a diagram for explaining a typical cleaning operation of a dispensing nozzle. FIG. 4 is a diagram showing an example of the change in capacitance over time when a dispensing nozzle is cleaned with water. FIG. 5 is a diagram showing an example of the change in capacitance over time when a dispensing nozzle is cleaned with detergent and water. FIG. 6 is a flowchart showing an example of a process flow for detecting a flow path abnormality. FIG. 7 is a flowchart showing an example of a process flow for determining whether cleaning of a dispensing nozzle with detergent has been performed normally. FIG. 8 is a flowchart showing an example of a process flow for determining whether cleaning of a dispensing nozzle with water has been performed normally. FIG. 9 is a diagram showing an example of a plurality of thresholds that are set. FIG. 10 is a diagram showing an example of the flow path configuration of a dispensing mechanism. FIG. 11 is a diagram showing an example of a capacitance signal when internal cleaning by syringe discharge is performed during a dispensing nozzle cleaning operation after detergent has been aspirated.

[0010] <Background of the Study by the Inventors> To facilitate understanding of the embodiments of the present invention, the background of the study by the inventors will be described in detail before describing the embodiments.

[0011] In automated analyzers that use liquid samples such as blood, reaction vessels and dispensing nozzles (also called probes or nozzles) are cleaned using a cleaning solution. Detergents or water of appropriate concentrations are used as cleaning solutions for the above-mentioned cleaning. In this case, cleaning the reaction vessels and dispensing nozzles with an appropriate cleaning solution and ensuring that the cleaning solution is removed leads to improved reliability of the analysis results.

[0012] As mentioned above, when cleaning the dispensing nozzle with detergent, it is necessary to thoroughly rinse off any detergent components adhering to the nozzle to minimize their impact on the analysis results of the sample. If the detergent is not removed from the nozzle (if the nozzle is contaminated), it is necessary to perform cleaning again using system water to minimize their impact on the analysis results of the sample.

[0013] Meanwhile, as automated analyzers have become increasingly modular and offer higher throughput in recent years, they are increasingly required to have higher cleaning capabilities to prevent the accumulation of contamination (sometimes called carryover) on specimens and reagents. Accordingly, the locations where detergents are used and cleaning methods are becoming more diverse, including the addition of ultrasonic cleaning mechanisms that irradiate ultrasonic waves to clean dispensing nozzles during cleaning. Additionally, in areas where detergents are used, they may be temporarily replaced with water to prevent the deposition of detergent components due to evaporation, making it necessary to determine whether a sufficient concentration of detergent is being dispensed during cleaning.

[0014] In other words, it is considered necessary for an automatic analyzer to have a means of determining whether the appropriate detergent is being delivered to each cleaning mechanism properly, whether cleaning is being performed using the appropriate type and concentration of detergent, and whether the detergent used in cleaning has been sufficiently removed from the dispensing nozzle.

[0015] Against this background, Patent Document 1 (paragraph 0035, etc.) describes that in order to determine whether the cleaning operation has been performed sufficiently, "after performing internal cleaning of the nozzle, the electrical physical quantity detected by the detection mechanism is compared with a reference value while the nozzle is filled with system water (pure water), and the degree of cleaning of the internal cleaning is determined from the comparison result."

[0016] According to Example 2 described in Patent Document 1, contamination inside the probe (dispensing nozzle), i.e., insufficient cleaning, is determined by measuring the electrical physical quantity of the system water filled inside the probe (dispensing nozzle).

[0017] However, this method focuses on the electrical physical quantity after the inside of the dispensing nozzle is washed with system water, so the dispensing operation must be repeated multiple times until the system water becomes contaminated, which increases the number of cycles required for judgment and results in a slower processing speed.In addition, it cannot determine whether the cleaning liquid used in washing was a detergent.

[0018] Under these circumstances, an object of the present invention, that is, a problem to be solved, is to make it possible to determine the cleaning status of a dispensing nozzle in an automatic analyzer in a shorter time.

[0019] Here, as one aspect for solving the above problem, an automatic analyzer is provided which is equipped with a dispensing nozzle capable of aspirating liquid, a cleaning mechanism for cleaning the dispensing nozzle, and a liquid level detection sensor that measures the capacitance between the tip of the dispensing nozzle and a reference potential portion and outputs a capacitance signal, and which determines the state of the cleaning liquid used for cleaning by determining the electrical properties of the liquid inside the dispensing nozzle based on changes in the capacitance signal while the cleaning mechanism is cleaning the dispensing nozzle.

[0020] (First Embodiment) <Configuration of Automated Analyzer> Fig. 1 is a diagram showing an example of the configuration of an automated analyzer according to the first embodiment. As shown in Fig. 1, the automated analyzer 100 according to the first embodiment includes, as main components, a sample inlet 101, a transport line 102, sample dispensing mechanisms 103 and 104, a reaction disk 105, reaction vessels 106 arranged concentrically therewith, reagent dispensing mechanisms 107, 108, 109, and 110, a circular reagent disk 112 on which reagent bottles 111 containing reagents are arranged, a stirring mechanism 113, a photometric mechanism 114, sample dispensing nozzle cleaning mechanisms 115 and 116, reagent dispensing nozzle cleaning mechanisms 117, 118, 119, and 120, a reaction vessel cleaning mechanism 121, and an ultrasonic cleaning mechanism 122. Note that the above-mentioned various cleaning mechanisms are examples of the "cleaning unit" in this application.

[0021] The photometric mechanism 114 includes a light source 123 and a photodetector 124. The specimen dispensing nozzle cleaning mechanisms 115 and 116 and the reagent dispensing nozzle cleaning mechanisms 117 to 120 are installed within the operating ranges of the specimen dispensing mechanisms 103 and 104 and the reagent dispensing mechanisms 107, 108, 109, and 110.

[0022] The automated analyzer 100 includes a detection unit 125 that detects the operating status of each mechanism. The detection unit 125 includes various sensors. The detection unit 125 is an example of a "capacitance measurement unit" in this application. The automated analyzer 100 also includes an input unit 126 and an output unit 128. The input unit 126 includes a keyboard, mouse, touch panel, voice input unit, etc., which the user uses to input measurement items and measurement conditions. The output unit 128 includes a display monitor, etc., and displays operation details and analysis results to the user using a graphical user interface (GUI), etc.

[0023] The automated analyzer 100 includes a signal processing unit 127 that processes signals such as input data and output data. The signal processing unit 127 is electrically connected to the detection unit 125, the input unit 126, and the output unit 128. The signal processing unit 127 includes a control unit 129, a calculation unit 130, a memory unit 131, and a determination unit 132. The control unit 129 controls the operation of each mechanism in response to inputs. The calculation unit 130 performs calculations based on photometric data obtained by the photometric mechanism 114 and various signals. The memory unit 131 stores data necessary for the calculations, data obtained by the calculations, programs, etc. The determination unit 132 performs various determinations using threshold discrimination, etc. The control unit 129 is an example of a "control unit" in this application. The determination unit 132 is an example of a "determination unit" in this application.

[0024] The signal processing unit 127 is configured by, for example, a computer, etc. In this case, the computer has one or more processors such as an arithmetic processing unit (CPU, MPU), a microcontroller (MCU), a graphics processing unit (GPU), etc., and these processors execute programs stored in the storage unit 131 to function as each unit such as the control unit 129, the calculation unit 130, and the determination unit 132.

[0025] <Outline of Analysis Flow by Automated Analyzer> Analysis by the automated analyzer 100 is mainly performed as follows: An operator places a dedicated rack 134 capable of vertically storing sample containers 133 such as blood collection tubes in the sample entrance 101. The sample containers 133 contain samples such as blood to be used for analysis. The operator uses the input unit 126 to input measurement details into the automated analyzer 100, and starts operation.

[0026] When the operation starts, the control unit 129 sends operation instructions to each mechanism. When each mechanism receives the operation instructions, it performs preparations for the analysis operation, such as cleaning the reaction cells and checking for abnormalities in the mechanism. After the analysis preparation operation is performed, the analysis operation starts, and the rack 134 stored in the sample inlet 101 is automatically transferred to the transport line 102. The rack 134 transferred to the transport line is transported to the sample aspiration position via a belt on the transport line.

[0027] When the rack 134 is transported to the sample aspiration position, the control unit 129 instructs the motors of the drive units of the sample dispensing mechanisms 103, 104 to rotate, and the sample dispensing nozzles of the sample dispensing mechanisms 103, 104 move from the position of the sample dispensing nozzle cleaning mechanism 115 to the sample aspiration position. The sample dispensing mechanisms 103, 104 begin lowering the sample dispensing nozzles that have moved to the sample aspiration position. When the liquid level detection sensor detects that the sample dispensing nozzles have come into contact with the sample in the previously transported sample container 133, the sample dispensing mechanisms 103, 104 stop lowering the sample dispensing nozzles. The sample dispensing mechanisms 103, 104 cause the sample dispensing nozzles to aspirate the amount of sample required for analysis, and then raise the sample vertically while the sample is held in the sample dispensing nozzle.

[0028] The specimen dispensing mechanisms 103 and 104 move the specimen dispensing nozzle to the position of the specimen dispensing nozzle cleaning mechanisms 115 and 116, then move it to the top of the reaction vessel 106 where a chemical reaction will occur, and then lower it to the bottom of the reaction vessel 106, after which it discharges the specimen. After dispensing the specimen from the specimen dispensing nozzle into the reaction vessel 106, the specimen dispensing mechanism 103 raises the specimen dispensing nozzle vertically and moves it to the position of the specimen dispensing nozzle cleaning mechanism 115 by rotation of the motor, thereby completing the specimen dispensing operation.

[0029] The reaction vessel 106 containing the specimen moves to a reagent dispensing position as the reaction disk 105 rotates. The reagent dispensing mechanisms 107-110 aspirate the reagent appropriate for the items used in the analysis from the reagent bottle 111 into the reagent dispensing nozzle, and dispense the reagent into the reaction vessel 106 containing the specimen. After dispensing the reagent into the reaction vessel 106, the reagent dispensing mechanisms 107-110 use the rotation of the motor to move the reagent dispensing nozzle to the position of the reagent dispensing nozzle cleaning mechanisms 117-120, thereby completing the reagent dispensing operation.

[0030] When the reagent dispensing mechanisms 107-110 perform a reagent dispensing operation, they use a liquid level detection sensor to detect when the reagent dispensing nozzle comes into contact with the liquid level inside the reagent bottle 111, thereby checking whether there is an abnormality in the amount of reagent inside the reagent bottle 111. Furthermore, the dispensing mechanisms (referring to the specimen dispensing mechanisms 103, 104 and the reagent dispensing mechanisms 107-110; the same applies below) have pressure sensors that monitor the pressure in the flow paths and determine whether the dispensing operation has been performed normally. The specimen dispensing operations and reagent dispensing operations described above are performed at different cycles by the specimen dispensing mechanisms 103, 104 and the reagent dispensing mechanisms 107-110, improving processing capacity.

[0031] The reaction solution consisting of the specimen and reagent dispensed into the reaction vessel 106 by the above operation is stirred by the stirring mechanism 113, causing a chemical reaction and changing optical properties such as absorbance. The optical properties of the reaction solution are measured by the photodetector 124 detecting light from the light source 123 when the reaction vessel 106 passes through the photometric mechanism 114 as the reaction disk 105 rotates. The data obtained by the photometric mechanism 114 is sent to the calculation unit 130, which calculates the concentration of the component of the analysis item contained in the specimen and outputs the calculation result to the output unit 128.

[0032] The used reaction vessel 106 and the dispensing nozzle of the dispensing mechanism are washed with a cleaning solution by the reaction vessel washing mechanism 121 and the dispensing nozzle washing mechanisms 115-120, allowing them to be reused for the next analysis while maintaining analytical performance. The dispensing nozzle washing mechanisms 115-120 mainly perform internal washing, which cleans the inside of the dispensing nozzle by high-pressure ejection of system water, and external washing, which cleans the outer wall of the dispensing nozzle by supplying system water. When performing measurements that are susceptible to carryover, the dispensing nozzle is cleaned with the dispensing nozzle washing mechanisms 115-120 after aspirating detergent into the dispensing nozzle, thereby removing contamination from the dispensing nozzle. The detergent used for washing varies depending on the type of contamination and is used at various dilution ratios.

[0033] In addition to the cleaning performed by the dispensing nozzle cleaning mechanisms 115-120, the dispensing nozzles of the dispensing mechanisms are cleaned by an ultrasonic cleaning mechanism 122, which is provided separately from the dispensing nozzle cleaning mechanisms 115-120, in response to a user maintenance instruction or at any timing during operation to prevent carryover and accumulation of dirt. The ultrasonic cleaning mechanism 122 not only aspirates the detergent but also irradiates the dispensing nozzle with ultrasonic waves. The dispensing nozzle cleaning mechanisms 115-120 then perform internal and external cleaning to remove contamination. To prevent deterioration of the flow path and crystallization of detergent components, the ultrasonic cleaning mechanism 122 replaces the water in the ultrasonic cleaning tank with pure water during device standby, and then replaces it with detergent when cleaning is performed.

[0034] If the detergent concentration in each cleaning mechanism, including the ultrasonic cleaning tank, is not as expected, cleaning will be insufficient and analytical performance will deteriorate. There is also the possibility that an abnormality has occurred in the mechanism or flow path that delivers detergent to each cleaning mechanism.

[0035] Therefore, the automated analyzer 100 according to this embodiment detects the electrical properties (conductivity) of the liquid aspirated by the dispensing nozzle by detecting an electrical physical quantity that changes in accordance with the properties of the liquid dispensed from the tip of the dispensing nozzle during cleaning by the dispensing nozzle cleaning mechanism. This allows the automated analyzer 100 to determine whether the detergent used in cleaning was appropriate, whether the detergent was removed, and whether there are any abnormalities in the liquid delivery mechanism or flow path. Here, the electrical physical quantity refers to a voltage value or a capacitance value. In this embodiment, the capacitance value acquired by the liquid level detection sensor is used to detect the electrical properties of the liquid aspirated by the dispensing nozzle.

[0036] Here, a method for obtaining the amount of change in capacitance value using a liquid level detection sensor will be described with reference to the drawings.

[0037] FIG. 2 is a diagram illustrating a method for acquiring the amount of change in capacitance value using a liquid level detection sensor. The dispensing mechanism 200 shown in FIG. 2 corresponds to the sample dispensing mechanisms 103 and 104 and the reagent dispensing mechanisms 107 to 110 shown in FIG. 1. As shown in FIG. 2, the dispensing mechanism 200 is connected to a detection unit 125 that detects the state of the dispensing nozzle 202 and the flow path 205. As described above, the detection unit 125 includes a liquid level detection sensor 1251. The liquid level detection sensor 1251 is, for example, a capacitance-type sensor, and may be stored inside the arm 201 to save space.

[0038] The liquid level detection sensor 1251 measures the capacitance Cs (hereinafter, the capacitance signal or capacitance signal value may be referred to as Cs) between the tip of the dispensing nozzle 202 and a reference potential portion. The reference potential portion is, for example, a portion at the GND level of the housing. After the tip of the dispensing nozzle 202 comes into contact with the specimen 204 in the container 203, such as the specimen container 133, the capacitance signal Cs becomes C1, and contact between the dispensing nozzle 202 and the specimen 204 is detected from this change in capacitance Cs.

[0039] Next, a typical washing operation of a dispensing nozzle will be described with reference to the drawings.

[0040] 3 is a diagram illustrating a typical cleaning operation of a dispensing nozzle. As shown in FIG. 3, dispensing mechanism 200 of dispensing nozzle 202 moved to the position of dispensing nozzle cleaning mechanism 115 performs an internal cleaning operation, which cleans the inside, i.e., the inner wall, of dispensing nozzle 202 by discharging system water (internal cleaning water) 302 from dispensing nozzle 202 at high pressure through flow path 205. In addition, dispensing mechanism 200 performs an external cleaning operation, which cleans the outside, i.e., the outer wall, of dispensing nozzle 202 with system water (external cleaning water) 301 discharged by dispensing nozzle cleaning mechanism 115 and supplied to the outer wall of dispensing nozzle 202. Internal cleaning is performed during the external cleaning operation in order to prevent water from splashing from dispensing nozzle cleaning mechanism 115 and to shorten the cleaning cycle.

[0041] As described above, the dispensing nozzle 202 may be cleaned with detergent when dispensing an analysis item that is susceptible to carryover or when an abnormality is detected in the dispensing nozzle 202. In this case, the dispensing mechanism 200 cleans the dispensing nozzle 202 with detergent by sucking the detergent sent to a cleaning tank such as an ultrasonic cleaning tank with the dispensing nozzle 202, and the dispensing mechanism 200 performs internal cleaning in the cleaning tank, and at the same time, the dispensing nozzle cleaning mechanism 115 performs external cleaning in the cleaning tank, thereby removing the detergent from the dispensing nozzle 202.

[0042] 4 is a diagram showing an example of the change in capacitance over time when the dispensing nozzle is washed with water. Fig. 4 shows capacitance signal data (hereinafter also referred to as capacitance data) obtained by converting the change in capacitance over time of the dispensing nozzle 202 acquired by the liquid level detection sensor 1251 into an analog voltage signal when the dispensing nozzle 202 is washed with water by the dispensing nozzle washing mechanism 115. As described above, the measured capacitance is the capacitance between the dispensing nozzle 202 and the GND level, and the detection unit 125 or the dispensing mechanism 200 incorporates a circuit whose output voltage increases as the capacitance on the dispensing nozzle 202 side increases.

[0043] In Figure 4, time period a corresponds to the period during which cleaning is being performed. During time period a, internal and external cleaning of the dispensing nozzle 202 is performed as described above. When the outer wall of the dispensing nozzle 202 comes into contact with the external cleaning water 301, the capacitance of the dispensing nozzle 202 increases, and the capacitance signal also increases. When the liquid dispensed during internal cleaning is system water (pure water), the conductivity of the external cleaning water does not change even though the outer wall near the tip of the dispensing nozzle 202 comes into contact with the water. Therefore, as shown in Figure 4, the capacitance signal of the dispensing nozzle 202 during cleaning remains roughly constant.

[0044] Fig. 5 is a diagram showing an example of the change in capacitance over time when the dispensing nozzle is washed with detergent and water. Fig. 5 shows capacitance signal data obtained by converting the change in capacitance over time of the dispensing nozzle 202 acquired by the liquid level detection sensor 1251 into a voltage signal when the dispensing nozzle 202 is washed with water by the dispensing nozzle washing mechanism 115 after the detergent is aspirated by the dispensing nozzle 202.

[0045] When the dispensing nozzle 202 is washed with a liquid such as water after aspirating detergent, the liquid discharged by the internal wash contains detergent. Detergent is generally rich in ions. Therefore, the conductivity of the outer wall near the tip of the dispensing nozzle 202 temporarily increases due to the contact between the external wash water and the internal wash water containing detergent. This causes a temporary increase in the capacitance signal, and a peak, i.e., a spike signal, specific to the use of detergent appears in the time-dependent change in the capacitance signal.

[0046] For example, as shown in Figure 5, when focusing on the capacitance signal during section a during washing when outer wash water and inner wash water are supplied almost simultaneously, a peak specific to the use of detergent is seen in section b at the beginning of section a. Then, as the detergent components are discharged, the capacitance signal decreases, and as the discharge of the detergent components is completed, a state in which the capacitance signal overlaps with the capacitance signal when system water is discharged is seen in section c at the end of section a during washing. Note that sections a, b, and c are expected to be, for example, approximately 500 ms, 150 ms, and 150 ms, respectively.

[0047] Therefore, by measuring the capacitance data while the dispensing nozzle 202 of the sample dispensing mechanism 103, 104 is being cleaned by the dispensing nozzle cleaning mechanism 115, 116, it is possible to determine whether the liquid being sucked into the dispensing nozzle 202 is detergent.

[0048] For example, the signal processing unit 127 analyzes the change in the capacitance signal during a time period a while the dispensing nozzle 202 is being washed, and calculates the maximum value of the capacitance signal during an initial period b within period a. The signal processing unit 127 compares the calculated maximum value of the capacitance signal with a reference capacitance signal stored in advance in the memory unit 131, for example, the maximum value of the signal during period b after pure water has been aspirated, thereby determining whether the aspirated liquid is a detergent of the expected concentration.

[0049] In this method, the electrical characteristics of the sample aspirated by the dispensing nozzle 202 can be directly measured, and therefore, after the dispensing nozzle 202 has aspirated the sample or detergent, it is possible to determine the type and concentration of the aspirated liquid simply by performing a single cleaning operation of the dispensing nozzle 202. Furthermore, because cleaning by the dispensing nozzle cleaning mechanisms 115 and 116 is pre-integrated into the analysis cycle, the above determination can be made without reducing throughput.

[0050] The capacitance signal in section b varies depending on the type and concentration of detergent aspirated by the dispensing nozzle, the volume of detergent, etc. Therefore, by storing in advance in memory unit 131 the capacitance signals obtained when a detergent is used in a specific washing operation, it is possible to determine whether washing was performed properly using detergent of an appropriate concentration, as well as whether there are any abnormalities in the supply of detergent, at various locations where detergent is used, without reducing throughput.

[0051] For example, if the capacitance signal obtained when the dispensing nozzle 202 is washed after sucking liquid deviates from the capacitance signal obtained when washed with an appropriate detergent concentration, which is stored in the memory unit 131, an abnormality in the detergent flow path or the detergent supply device can be detected.

[0052] For example, if there is an abnormality in the dilution flow path and the detergent cannot be sufficiently diluted, the detergent concentration used in washing will be high, and therefore the maximum value of the capacitance signal from the dispensing nozzle 202 will be higher than the maximum value of the capacitance signal stored in the memory unit 131 when washing is performed with the appropriate detergent concentration.

[0053] On the other hand, if there is an abnormality in the detergent supply flow path and the detergent cannot be sufficiently delivered, the detergent concentration used in washing will be low, and therefore the maximum value of the capacitance signal from the dispensing nozzle 202 will be lower than the maximum value of the capacitance signal stored in the memory unit 131 when washing is performed with the appropriate detergent concentration.

[0054] As described above, by comparing the maximum value of the capacitance signal represented by the acquired capacitance data with a specific value of the capacitance signal obtained when the nozzle is washed under pre-stored appropriate or reference conditions, it becomes easy to determine whether there is a flow path abnormality. Note that if the nozzle has a circuit that reduces voltage as the capacitance value of the dispensing nozzle 202 increases, the amount of change in voltage will be negative.

[0055] By using the above-described criteria, it is possible to detect flow path abnormalities at various locations in the automatic analyzer 100.

[0056] For example, consider a case where the dispensing nozzle 202 is used to aspirate the liquid in the reaction vessel 106, and then the washing mechanism washes the dispensing nozzle 202 in a washing tank. In this case, by acquiring and analyzing capacitance data of the dispensing nozzle 202 during washing, it is possible to detect an abnormality in the flow path that supplies detergent and system water to the reaction vessel 106.

[0057] Also, for example, consider a case where the dispensing nozzle 202 sucks up the liquid supplied to the cleaning tank of the ultrasonic cleaning mechanism 122, and then the cleaning mechanism cleans the dispensing nozzle 202 in the cleaning tank. In this case, by acquiring and analyzing capacitance data of the dispensing nozzle 202 during cleaning, it is possible to determine whether detergent is being supplied to the cleaning tank of the ultrasonic cleaning mechanism 122 and whether any detergent remains after replacing it with water, thereby detecting an abnormality in the mechanism for sending liquid to the cleaning tank of the ultrasonic cleaning mechanism 122.

[0058] In this way, it is possible to detect a flow path abnormality at a location accessible to the dispensing nozzle 202 of the dispensing mechanism 200. Note that the automated analyzer 100 may be configured to output an alarm when a flow path abnormality is detected to prompt the user to check the flow path where the abnormality is presumed to have occurred. This can reduce the number of visits by a service technician, lighten the burden on the service technician, and shorten the downtime of the automated analyzer 100, for example.

[0059] <Processing Flow for Detecting Abnormality in Flow Path> Here, the processing flow for detecting abnormality in a flow path based on the capacitance signal of the dispensing nozzle will be described.

[0060] 6 is a flowchart showing an example of the process flow for detecting a flow path abnormality. Detection of a flow path abnormality is preferably performed during analysis preparation, which is performed immediately after the start of operation. When analysis preparation begins (S1), the control unit 129 sets liquid information (a reference capacitance signal threshold) used in the mechanism for which flow path abnormality detection is to be performed (S2) and begins recording the capacitance signal Cs detected by the liquid level detection sensor 1251 of the detection unit 125 (S3). Thereafter, the dispensing mechanism, upon receiving a command from the control unit 129, aspirates the liquid used for cleaning (S4), and the dispensing nozzle cleaning mechanism cleans the dispensing nozzle 202 (S5).

[0061] When the cleaning is completed, the control unit 129 stops recording the capacitance signal Cs. That is, the liquid level detection sensor 1251 of the detection unit 125 detects and measures the capacitance over a time period that includes the time when the dispensing and cleaning mechanism is supplying cleaning liquid to the outer wall and interior of the dispensing nozzle 202 and the time when the dispensing nozzle 202 is discharging the aspirated liquid.

[0062] The calculation unit 130 then calculates a statistical distance using the waveform of the capacitance signal obtained during cleaning of the dispensing nozzle 202 (S6). The determination unit 132 then performs a determination based on the measured capacitance. That is, the determination unit 132 determines the cleaning status of the dispensing nozzle 202 based on capacitance data representing the capacitance measured over the time period. In this example, the determination unit 132 compares the calculated statistical distance of the capacitance signal with the capacitance signal threshold value set in S2 to determine whether or not an abnormality exists (S7). If it is determined that no abnormality exists (S7: No abnormality), the control unit 129 continues the analysis operation (S8). On the other hand, if it is determined that an abnormality exists (S7: Abnormality detected), the control unit 129 stores the number of times an abnormality has been determined, i.e., the number of abnormality detections, in the memory unit 131.

[0063] The determination unit 132 determines whether the current abnormality detection is the first time (S9). If the abnormality detection is the first time (S9: Yes), the control unit 129 controls each mechanism to prime (retry) the relevant flow path (S10). This prevents a determination of an abnormality even when there is no abnormality in the flow path system, such as an air bubble accidentally entering the flow path. After the retry, steps S3 to S6 are performed again, that is, the dispensing nozzle 202 sucks liquid, the dispensing nozzle 202 is washed, and capacitance data is acquired while the dispensing nozzle 202 is being washed.

[0064] If an abnormality is detected again in the threshold judgment in step S7 (S7: Abnormality detected), and this is the second time that an abnormality has been detected (S9: No), the control unit 129 causes the output unit 128 to output an alarm regarding the abnormal flow path and stops the analysis operation (S11).

[0065] The above flowchart is merely an example, and the response after an abnormality determination varies depending on the configuration of the automated analyzer 100. For example, if the concentration of the detergent used in cleaning can be adjusted using a proportional solenoid valve or other device, even if an abnormality is detected, there is a possibility that there is no abnormality in the flow path and the opening ratio of the proportional solenoid valve is inappropriate. Therefore, if an abnormality is detected for the second time in the flowchart, an operation to adjust the detergent concentration by increasing or decreasing the opening ratio of the proportional solenoid valve can be performed and the determination can be performed again. For example, to increase the detergent concentration, the opening ratio of the proportional solenoid valve on the detergent side can be increased, or the opening ratio of the proportional solenoid valve on the dilution side can be decreased. Conversely, to decrease the detergent concentration, the opening ratio of the proportional solenoid valve on the detergent side can be decreased, or the opening ratio of the proportional solenoid valve on the dilution side can be increased. Furthermore, the timing for starting recording the capacitance signal is arbitrary, as long as the capacitance data during cleaning by the dispensing nozzle cleaning mechanism, which is used for determination, is obtained.

[0066] Furthermore, the capacitance data obtained during cleaning by the dispensing nozzle cleaning mechanism can also be used to determine whether the detergent inside the dispensing nozzle has been removed by cleaning. For example, the maximum capacitance signal value during section c, just before the end of cleaning, is compared with a pre-stored reference capacitance signal. If the detergent inside the dispensing nozzle is not completely removed by the internal cleaning, the capacitance signal will deviate from the reference capacitance signal, making it possible to determine whether the internal cleaning of the dispensing nozzle was sufficient. If the cleaning was insufficient, a data alarm can be issued and cleaning can be performed again, minimizing the impact on the analysis results.

[0067] By using the above criteria, it is possible to determine whether various locations accessible to the dispensing nozzle have been properly cleaned and whether the detergent has been sufficiently removed. As an example, the case of a reaction vessel will be described.

[0068] After the reaction has completed, the reaction vessel is cleaned by having the reaction liquid removed and an alkaline or acidic detergent dispensed from the rinse mechanism. The liquid is aspirated from the reaction vessel into which the detergent has been dispensed using a dispensing nozzle, and the dispensing nozzle is then moved to a cleaning tank for a dispensing nozzle cleaning operation. By focusing on section b of the capacitance signal, it is possible to determine whether the detergent dispensed into the reaction vessel was of an appropriate concentration. The detergent in the reaction vessel is removed by the rinse mechanism and washed multiple times with system water. Liquid is aspirated from a reaction vessel filled with system water using a dispensing nozzle, and the capacitance signal is measured using the procedure described above. By focusing on section c, it is possible to determine whether the detergent has been removed.

[0069] Furthermore, since residual detergent components affect analytical performance, if it is determined that the detergent has not been sufficiently removed, the reaction vessel can be discontinued for analysis, thereby reducing waste of specimens and reagents.

[0070] Furthermore, the comparison of capacitance signals when making the above judgment is not limited to a comparison using the maximum value in a specific section during cleaning, and a discrimination model may be created using various statistical methods, machine learning, etc. For example, in order to reduce the influence of electrical noise, comparison may be made using an integral value in a specific section, or a statistical distance such as Mahalanobis distance or k-means by extracting any feature variable from a specific section of the capacitance signal, or a comparison may be made using a differential amount focusing on the amount of change in the capacitance signal.

[0071] For example, a first threshold and a second threshold are set for the change in capacitance in section c, and subsequent behavior can be changed depending on the determination threshold, such as performing additional cleaning using the probe cleaning mechanism when the capacitance exceeds the first threshold, or performing ultrasonic cleaning when the capacitance exceeds the second threshold.

[0072] <Process flow for determining whether cleaning of the dispensing nozzle with detergent has been performed successfully> Here, we will explain the process flow for determining whether cleaning of the dispensing nozzle 202 with detergent has been performed successfully based on the capacitance signal of the dispensing nozzle 202.

[0073] 7 is a flowchart showing an example of the flow of a process for determining whether the dispensing nozzle 202 has been properly cleaned with detergent. Fig. 7 shows a flowchart for determining whether the dispensing nozzle 202 has been properly cleaned with detergent and whether the detergent has been removed from the inside of the dispensing nozzle 202, based on the capacitance signal.

[0074] As described above, cleaning using a detergent, such as ultrasonic cleaning, is initiated at any timing during analysis (S12). The control unit 129 begins recording the capacitance signal Cs (S13). During analysis, as described above, cleaning using ultrasonic cleaning is performed depending on the state of the dispensing nozzle 202. The dispensing mechanism causes the dispensing nozzle 202 to suck the liquid used in the ultrasonic cleaning (S14) and moves the dispensing nozzle 202 to the position of the dispensing nozzle cleaning mechanism. The dispensing nozzle cleaning mechanism performs external and internal cleaning of the dispensing nozzle 202 (S15). After cleaning is completed, the control unit 129 stops recording the capacitance signal Cs, and the calculation unit 130 calculates the statistical distance using the capacitance signal waveform during cleaning (S16).

[0075] The determination unit 132 first performs a threshold determination on the statistical distance of capacitance during interval b, which is the time interval during which detergent components are ejected from the dispensing nozzle 202 (S17). The threshold here is the lower limit of the statistical distance corresponding to the peak capacitance when washing is performed with an appropriate detergent concentration. If the acquired statistical distance of capacitance falls below this threshold, an abnormality determination is made (S17: abnormality detected). In this case, there is a possibility that washing was not performed properly due to insufficient detergent concentration. Therefore, if the abnormality determination is the first time (S18: Yes), the process returns to S13, and the dispensing nozzle cleaning mechanism again performs a cleaning operation in which detergent is sucked into the dispensing nozzle 202 to perform external and internal cleaning. The control unit 129 records the capacitance signal Cs during the cleaning operation.

[0076] On the other hand, if the abnormality determination is not the first time but the second time or more (S18: No), the control unit 129 records the capacitance signal Cs again (S19) and changes the determination of section b to no abnormality (S20). If the determination of section b is changed to no abnormality, the next threshold determination in S17 will determine no abnormality. After that, by additionally performing external and internal washing using the dispensing nozzle washing mechanism in S15, it is considered that washing with a normal concentration detergent has been performed.

[0077] If the threshold judgment in section b determines that there is no abnormality (S17: No abnormality), the judgment unit 132 performs threshold judgment on the statistical distance of the capacitance in section c, which is a section in which the inside of the dispensing nozzle 202 is replaced with system water and the system water is being discharged from the dispensing nozzle 202 (S21). The threshold here is the upper limit value of the statistical distance corresponding to the capacitance signal Cs when the dispensing nozzle 202 is properly cleaned and is not contaminated. If the acquired statistical distance of the capacitance in section c is equal to or less than this threshold, it is determined that there is no abnormality, and if the statistical distance exceeds this threshold, it is determined that an abnormality has been detected.

[0078] If the threshold judgment in section c of S21 determines that there is no abnormality (S21: No abnormality), there is no liquid such as detergent remaining inside the dispensing nozzle 202 and replacement with system water has been completed, so the dispensing operation of the next sample is started (S22).

[0079] On the other hand, if an abnormality is detected in the threshold judgment in section c of S21 (S21: Abnormality Detected), there is a possibility that detergent components remain inside the dispensing nozzle 202. Therefore, if the abnormality judgment is the first time (S23: Yes), the control unit 129 records the capacitance signal Cs again (S24), and the dispensing nozzle cleaning mechanism additionally performs an internal and external wash of the dispensing nozzle 202 (S15). This washes away any remaining components inside the dispensing nozzle 202. If the abnormality judgment is the second time in section c (S23: No), it is estimated that detergent components or sample components have not been removed from inside the dispensing nozzle 202 due to clogging or the like inside the dispensing nozzle 202. Therefore, the control unit 129 controls the output unit 128 to display an alarm for the target dispensing nozzle (S25) and stop the dispensing operation (S26).

[0080] <Process flow for determining whether cleaning of the dispensing nozzle with water was performed normally> Here, we will explain the process flow for determining whether cleaning of the dispensing nozzle with water was performed normally based on the capacitance signal of the dispensing nozzle.

[0081] Fig. 8 is a flowchart showing an example of the flow of a process for determining whether washing of the dispensing nozzle with water has been performed normally. Fig. 8 shows a flowchart for determining, based on a capacitance signal, whether washing of the dispensing nozzle 202 with system water has been performed normally and whether a specimen, reagent, etc. has been removed from the inside of the dispensing nozzle 202. In the flowchart of Fig. 8, the same processes as or corresponding processes in the flowchart of Fig. 7 are denoted by the same reference numerals.

[0082] First, cleaning using system water is initiated (S12). The control unit 129 begins recording the capacitance signal Cs (S13). During analysis, as described above, cleaning of the dispensing nozzle 202 with system water is performed. The dispensing mechanism moves the dispensing nozzle 202 to the position of the dispensing nozzle cleaning mechanism. The dispensing nozzle cleaning mechanism performs external and internal cleaning of the dispensing nozzle 202 with system water (S15). After cleaning is completed, the control unit 129 stops recording the capacitance signal Cs, and the calculation unit 130 calculates the statistical distance using the capacitance signal waveform during cleaning (S16).

[0083] The determination unit 132 performs threshold determination on the statistical distance of the capacitance in section c, which corresponds to the end of section a during which external and internal washing of the dispensing nozzle 202 is performed (S21). The threshold here is the upper limit of the statistical distance corresponding to the peak of the capacitance when external and internal washing is performed, the dispensing nozzle 202 is properly cleaned with system water, and there is no contamination. If the acquired statistical distance of the capacitance in section c exceeds this threshold, an abnormality is determined (S21: abnormality detected). If the statistical distance is equal to or less than this threshold, no abnormality is determined (S21: no abnormality).

[0084] If it is determined in S21 that there is no abnormality, the control unit 129 starts the dispensing operation of the next sample (S22).

[0085] If an abnormality is detected in S21, it is possible that liquid components such as specimen or chemical solution remain inside the dispensing nozzle 202 and that cleaning has not been performed properly. Therefore, if this is the first abnormality detection (S23: Yes), the process proceeds to S24, where the control unit 129 resumes recording of the capacitance signal Cs during the cleaning operation (S24). The dispensing nozzle cleaning mechanism again performs a cleaning operation to clean the inside and outside of the dispensing nozzle 202 (S15).

[0086] On the other hand, if the abnormality determination is not the first but the second or subsequent time (S23: No), the control unit 129 presumes that specimen components or chemical solution components have not been removed from inside the dispensing nozzle 202 due to clogging or the like inside the dispensing nozzle 202. Therefore, the control unit 129 controls the output unit 128 to display an alarm for the target dispensing nozzle (S25) and stop the dispensing operation (S26).

[0087] FIG. 9 is a diagram showing an example of a plurality of thresholds that are set. As described above, a plurality of thresholds may be set for use in the determination. In FIG. 9, a schematic diagram of the capacitance signal waveform during cleaning is overlaid with lines representing the plurality of thresholds that are set. For example, as shown in FIG. 9, a first threshold TH1, a second threshold TH2, and a third threshold TH3 are set as the plurality of thresholds.

[0088] The first threshold value TH1 is an example of a threshold value used to determine a representative value, such as a statistical distance or maximum value, of the capacitance signal waveform measured during section c, which corresponds to the end of time section a, from the start to the end of external and internal cleaning of the dispensing nozzle 202. The first threshold value TH1 can be a signal value slightly greater than the value of the capacitance signal waveform measured while the dispensing nozzle 202 is discharging water. If the representative value of the capacitance signal waveform of the dispensing nozzle 202 during section c exceeds this first threshold value TH1, it can be determined that contamination such as detergent, specimen, or chemical solution remains on the dispensing nozzle 202, which may increase the conductivity of the dispensing nozzle 202 and cause a high capacitance.

[0089] The second threshold value TH2 is an example of a threshold value used to determine a representative value, such as a statistical distance or minimum value, of the capacitance signal waveform measured while the dispensing nozzle 202 is being cleaned with detergent. The second threshold value TH2 can be a signal value that is higher than the first threshold value TH1 and slightly smaller than the value of the capacitance signal waveform measured while the dispensing nozzle 202 is dispensing detergent. If the representative value of the capacitance signal waveform of the dispensing nozzle 202 in section a or in section b, an initial section of section a, exceeds this second threshold value TH2, it can be determined that the liquid aspirated into and dispensed by the dispensing nozzle 202 is detergent, and that the conductivity of the dispensing nozzle 202 has increased, resulting in a high capacitance.

[0090] The third threshold value TH3 is an example of a threshold value used to determine a representative value, such as a statistical distance or minimum value, of a capacitance signal waveform measured while dispensing nozzle 202 is being washed with detergent or with water only. The third threshold value TH3 can be a signal value smaller than the value of the capacitance signal waveform measured while dispensing water from dispensing nozzle 202. If the representative value of the capacitance signal waveform of dispensing nozzle 202 in section a or in section c at the end of section a is lower than this third threshold value TH3, it can be determined that an insulating material such as silicon has adhered to the outer wall of dispensing nozzle 202, reducing the conductivity of dispensing nozzle 202 and possibly reducing the capacitance.

[0091] In an actual cleaning flow for the dispensing nozzle 202, for example, if a representative value of the capacitance signal waveform of the dispensing nozzle 202 exceeds a first threshold value TH1, additional cleaning is performed using the dispensing nozzle cleaning mechanism as shown in S15 of Figures 7 and 8. However, if the representative value exceeds a second threshold value TH2, it is also possible to perform more powerful ultrasonic cleaning during additional cleaning. Also, for example, if the measured capacitance signal value is compared with a normal capacitance waveform during cleaning with water and is lower than a third threshold value TH3, it is possible to determine that an insulating material has adhered to the outer wall of the dispensing nozzle 202, and to perform cleaning with a high cleaning power using the dispensing nozzle 202.

[0092] The capacitance waveform during cleaning may vary depending on the type of detergent used and the volume of detergent held inside the dispensing nozzle 202 when cleaning the dispensing nozzle 202. Therefore, sections b and c can be set arbitrarily. Additionally, the capacitance waveform also varies depending on syringe assembly, altitude, and supply water temperature. Therefore, false detections can be reduced by calibrating the reference waveform using a detergent of a certain concentration when installing the device or registering detergent items. In this case, it is desirable to have a reference waveform that corresponds to the amount of suctioned during cleaning. Furthermore, the sections from which features are extracted are not limited to sections b and c shown in the figure, as long as they are within the range of section a being cleaned. The width and number of sections used in the judgment can be set arbitrarily depending on the characteristics of the waveform.

[0093] As described above, the electrical properties of the dispensing nozzle 202 change depending on the cleaning state of the dispensing nozzle 202, for example, the liquid inside the dispensing nozzle 202 or foreign matter or insulating material adhering to the outer wall thereof, and this change appears as a change in capacitance between the dispensing nozzle 202 and the reference potential portion. Therefore, the determination unit 132 can determine the type, concentration, or volume of liquid aspirated into the dispensing nozzle 202 based on the magnitude of the value corresponding to the maximum value of the spike waveform in the time-varying capacitance represented by the capacitance data. The determination unit 132 can also determine whether the liquid aspirated into the dispensing nozzle 202 has been removed based on the magnitude of the value corresponding to the minimum value of the spike waveform in the time-varying capacitance represented by the capacitance data. Furthermore, the determination unit 132 can also determine the type, concentration, or volume of liquid aspirated into the dispensing nozzle 202 based on the magnitude of the value corresponding to the area of ​​the spike waveform in the time-varying capacitance represented by the capacitance data.

[0094] The above describes a method that focuses on the capacitance signal during cleaning using the dispensing nozzle cleaning mechanism. However, because internal cleaning uses a high-pressure gear pump, the force of the liquid being ejected is strong. Therefore, if the amount of detergent aspirated is small and the concentration is low, the width of the peak waveform, i.e., spike waveform, that appears in section b will be small, and it may be difficult to distinguish it from noise. Therefore, instead of using a gear pump for internal cleaning, it is possible to use a syringe to push and inject liquid, such as cleaning solution, into the inside of the dispensing nozzle. This increases the liquid ejection time and ensures the width of the peak waveform, i.e., spike waveform, of the capacitance signal, thereby reducing the effects of noise.

[0095] Figure 10 is a diagram showing an example of the flow path configuration of the dispensing mechanism. As shown in Figure 10, dispensing nozzle 202 is connected to a flow path within arm 201, and the flow path is connected to syringe 701. The syringe is connected to gear pump 704 via solenoid valve 703, and during internal cleaning, system water is discharged from the dispensing nozzle at high pressure by opening the solenoid valve. With the solenoid valve closed, the syringe plunger 702 operates, causing the dispensing mechanism to suck and discharge liquid.

[0096] 11 is a diagram showing an example of a capacitance signal waveform when detergent is dispensed by syringe operation without performing internal washing during cleaning by the dispensing nozzle cleaning mechanism. Note that external washing is still performed during cleaning (section a). The capacitance signal increases during syringe operation (section d). A characteristic of the capacitance signal in section d is that the peak width is broader than when internal washing is performed (section b in FIG. 5), which makes it possible to distinguish between low detergent concentrations without being affected by noise.

[0097] This example describes a method for determining whether detergent has been aspirated, but if the sample or reagent is conductive, the capacitance signal generated during cleaning will deviate from the capacitance signal generated during system water discharge. Therefore, the above determination can be made even when the liquid is something other than detergent.

[0098] For example, if a conductive sample or specimen remains inside the dispensing nozzle, it is necessary to determine whether the inside of the dispensing nozzle has been completely replaced with system water to prevent carryover. Therefore, carryover can be prevented by determining whether the system water has been replaced with system water from the capacitance signal during the cleaning operation immediately before the next sample and reagent measurement, using the signal in the range corresponding to section c in Figure 3 . If it is determined that the replacement with system water is insufficient, additional cleaning can be performed to prevent waste of sample or reagent. Even in this case, having multiple thresholds makes it possible to switch cleaning methods depending on the condition inside the dispensing nozzle, such as implementing a cleaning method with higher cleaning performance depending on the level of liquid remaining inside the dispensing nozzle. While the flowchart describes the determination when detergent is used, this also applies during normal analysis operations. Even without detergent, the internal contamination state can be determined by focusing on the waveform during internal cleaning (see step S15 and subsequent steps in the flowchart in Figure 5 ). By performing detergent cleaning only when an abnormality is detected, cleaning can be performed according to the contamination state, thereby reducing detergent consumption.

[0099] As mentioned above, capacitance signals can be used to detect conductive samples or liquids inside the dispensing nozzle, making it possible to determine the clogging state of the dispensing nozzle. For example, blood collection tubes are separated into a serum layer used for analysis and a blood clot layer not used for analysis by centrifugation. To prevent the serum and blood clot layers from mixing, a separating agent containing silicone oil or other substances is held between the serum and blood clot layers. If the dispensing nozzle descends below the serum layer and into the separating agent during dispensing, the separating agent may clog the dispensing nozzle. If a clog occurs, the pressure during suction changes, and the device detects the abnormality using a pressure sensor. The clog is then removed by ultrasonic cleaning or other methods. While the pressure sensor determines whether the clog has been removed, if a trace amount of separating agent remains inside the dispensing nozzle, the pressure change may be insufficient and the pressure sensor may not be able to determine the presence of the separating agent. Therefore, by simultaneously performing a determination based on capacitance, it is possible to more reliably determine whether the separating agent inside the dispensing nozzle has been removed.

[0100] After performing the dispensing nozzle clog removal operation, the dispenser nozzle is aspirated. The dispenser nozzle is then cleaned in a cleaning tank. Under conditions such as a partial clog, where a trace amount of separating agent is present inside the dispenser nozzle, the flow rate of the liquid ejected from the dispenser nozzle changes, presumably causing the capacitance signal to deviate from a clog-free state. For example, when an internal cleaning operation is performed, the capacitance peak width in section b of Figure 3 increases, and the slope of the decreasing peak becomes gentler. Additionally, if the detergent is ejected using a syringe rather than an internal cleaning operation, the difference in flow rate is more pronounced, making the capacitance signal deviation more pronounced and easier to distinguish. While the above describes clogs caused by separating agent, abnormalities inside the dispenser nozzle can also be detected when clogs are caused by dried and condensed reagents, etc.

[0101] While we have described a determination focused on the interior of the dispensing nozzle, if contamination accumulates outside the dispensing nozzle, the capacitance of the nozzle itself changes, resulting in a change in capacitance. For example, if the dispensing nozzle comes into contact with the separating agent during sample aspiration, silicone oil, which has high insulating properties, will adhere to the outer wall of the dispensing nozzle. As a result, the change in capacitance signal when the dispensing nozzle is cleaned will differ from the change in capacitance signal when no separating agent is adhered. Therefore, contamination on the outer wall of the dispensing nozzle can also be detected by focusing on the capacitance signal and comparing it with a preset threshold.

[0102] The cleaning operation by the dispensing nozzle cleaning mechanism may be performed between the time of liquid suction and the time of liquid discharge in order to clean the tip of the dispensing nozzle, or may be performed after liquid discharge as described in the examples. In other words, the timing is not limited to a specific one.

[0103] <Effects of the Embodiment> As described above, according to the first embodiment of the present invention, the cleaning status of the dispensing nozzle in the automatic analyzer can be determined in a shorter time.

[0104] For example, the automated analyzer according to the first embodiment of the present invention can determine the cleaning status of the dispensing nozzle based on capacitance data obtained by a single measurement of capacitance over the time period during which the dispensing nozzle is being cleaned. This allows the status to be determined in an extremely short time, enabling highly reliable analysis to be performed without slowing down the analysis processing speed.

[0105] Furthermore, according to the first embodiment of the present invention, by detecting the properties of the liquid aspirated by the dispensing nozzle while the cleaning operation of the dispensing nozzle is being performed, it is possible to determine whether the detergent concentration of the cleaning liquid used in the cleaning is appropriate and whether there are any abnormalities in the liquid delivery path of the cleaning liquid, etc.

[0106] Furthermore, according to the first embodiment of the present invention, it is possible to improve the reliability of the measurement results by determining whether the cleaning liquid aspirated by the dispensing nozzle has been removed at the end of cleaning.

[0107] Furthermore, according to the first embodiment of the present invention, by detecting the electrical properties of the liquid inside the dispensing nozzle, it is possible to ensure that there is no abnormality in the supply flow path of the cleaning liquid, as well as that the cleaning liquid used in the cleaning is normal and that the cleaning liquid used in the cleaning has been removed at the end of the cleaning, thereby improving the reliability of the measurement results of the automatic analyzer.

[0108] Furthermore, according to the first embodiment of the present invention, it is also possible to detect abnormalities in the liquid flow path based on capacitance data measured during cleaning. Therefore, with this automatic analyzer, there is no need to provide a new measurement unit that measures the conductivity, etc. in the flow path in order to detect flow path abnormalities, which also contributes to the miniaturization of the automatic analyzer.

[0109] (Embodiment 2) A description will be given of embodiment 2 of the present invention. The method described below is also one embodiment of the present invention.

[0110] A method for determining the cleaning state of a dispensing nozzle, comprising: aspirating a liquid into a dispensing nozzle of an automatic analyzer; and, after or while discharging the aspirated liquid into the dispensing nozzle, supplying a cleaning liquid to the outer wall of the dispensing nozzle and sending the cleaning liquid into the interior of the dispensing nozzle to clean the dispensing nozzle; measuring the capacitance between the dispensing nozzle and a reference potential portion over a time period including the time period during which the dispensing nozzle is being cleaned; and determining the cleaning state of the dispensing nozzle based on the measured capacitance.

[0111] By executing this method for determining the cleaning state of a dispensing nozzle, an automated analyzer can determine the cleaning state of the dispensing nozzle simply by acquiring capacitance data of the dispensing nozzle once, and can determine the cleaning state of the dispensing nozzle in a shorter time. Furthermore, this method achieves the same effects as those of the first embodiment described above.

[0112] (Embodiment 3) A third embodiment of the present invention will be described below. The program described below is also one embodiment of the present invention.

[0113] A program for causing one or more computers to function as the signal processing unit 127 constituting the above-described automated analyzer 100. Alternatively, a program for causing one or more computers to execute the following processes: a process for aspirating a liquid into a dispensing nozzle constituting the automated analyzer; a process for cleaning the dispensing nozzle by supplying a cleaning liquid to the outer wall of the dispensing nozzle and sending the cleaning liquid into the inside of the dispensing nozzle after or while discharging the liquid aspirated into the dispensing nozzle; a process for measuring the capacitance between the dispensing nozzle and a reference potential portion over a time period that includes the time while the dispensing nozzle is being cleaned; and a process for determining the cleaning status of the dispensing nozzle based on the measured capacitance.

[0114] Furthermore, a non-transitory tangible computer-readable storage medium storing such a program is also an embodiment of the present invention.

[0115] By reading and executing such a program from a predetermined storage unit or storage medium, the computer functions as the signal processing unit 127 that constitutes the automated analyzer 100, and is able to determine the cleaning status of the dispensing nozzle 202 simply by acquiring the capacitance data of the dispensing nozzle 202 once, thereby enabling a shorter determination of the cleaning status of the dispensing nozzle 202. Furthermore, the program and storage medium provide the same effects as those of the first embodiment described above.

[0116] Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, and various modifications are possible within the scope of the present invention. For example, in a certain embodiment, certain components may be added, omitted, or replaced with other components. Furthermore, the numerical values ​​and names of each part described in the above-described embodiments are merely examples, and the present invention is not limited to these.

[0117] 101...Sample inlet, 102...Transport line, 103, 104...Sample dispensing mechanism, 105...Reaction disk, 106...Reaction vessel, 107, 108, 109, 110...Reagent dispensing mechanism, 111...Reagent bottle, 112...Reagent disk, 113...Stirring mechanism, 114...Photometric mechanism, 115, 116...Sample dispensing nozzle cleaning mechanism, 117, 118, 119, 120...Reagent dispensing nozzle cleaning mechanism, 121...Reaction vessel cleaning mechanism, 122...Ultrasonic cleaning mechanism Cleaning mechanism, 123...light source, 124...photodetector, 125...detection unit, 126...input unit, 127...signal processing unit, 128...output unit, 129...control unit, 130...arithmetic unit, 131...storage unit, 132...determination unit, 133...specimen container, 134...rack, 200...dispensing mechanism, 201...arm, 202...dispensing nozzle, 203...container, 204...specimen, 205...flow path, 701...syringe, 702...plunger, 703...solenoid valve, 704...gear pump

Claims

1. An automated analyzer comprising: a dispensing nozzle that aspirates and discharges liquid; a cleaning unit that supplies cleaning liquid to the outer wall and interior of the dispensing nozzle; a capacitance measuring unit that measures the capacitance between the dispensing nozzle and a reference potential portion; a control unit that controls the dispensing nozzle and the cleaning unit; and a judgment unit that makes a judgment based on the measured capacitance, wherein the capacitance measuring unit measures the capacitance over a time period that includes a period during which the cleaning unit is supplying the cleaning liquid to the outer wall and interior of the dispensing nozzle and the dispensing nozzle is dispensing the aspirated liquid, and the judgment unit judges a cleaning state of the dispensing nozzle based on capacitance data representing the capacitance measured over the time period.

2. An automatic analyzer as described in claim 1, wherein the control unit aspirates the liquid into the dispensing nozzle and then ejects it, the capacitance measuring unit measures the capacitance over a time period that includes a period during which the cleaning unit is supplying the cleaning liquid to the outer wall and interior of the dispensing nozzle and the dispensing nozzle is ejecting the aspirated liquid, and the determination unit determines whether the liquid has been removed from inside the dispensing nozzle based on capacitance data representing the capacitance measured over the time period.

3. An automatic analyzer as described in claim 1, comprising: a container placed in a position accessible to the dispensing nozzle; and a flow path for supplying the liquid to the container, wherein the control unit causes the dispensing nozzle to aspirate the liquid supplied into the container through the flow path and then eject it, the capacitance measuring unit measures the capacitance over a time period that includes a period during which the cleaning unit is in a state in which the cleaning liquid is supplied to the outer wall and interior of the dispensing nozzle and the dispensing nozzle is ejecting the aspirated liquid, and the determination unit determines whether the liquid has been removed from inside the dispensing nozzle based on capacitance data representing the capacitance measured over the time period.

4. The automatic analyzer according to claim 3, wherein the control unit determines whether or not the state of the flow path is abnormal based on the capacitance data.

5. An automatic analyzer according to claim 2, wherein the control unit causes the cleaning unit to supply additional cleaning liquid to the dispensing nozzle when the determination unit determines that the liquid has not been removed from inside the dispensing nozzle.

6. An automatic analyzer as described in claim 2, wherein the cleaning unit has a function of performing cleaning that is stronger than supplying the cleaning liquid, and the control unit causes the cleaning unit to perform the stronger cleaning of the dispensing nozzle when the determination unit determines that the liquid has not been removed from inside the dispensing nozzle.

7. The automatic analyzer according to claim 6, wherein the powerful cleaning is ultrasonic cleaning.

8. An automatic analyzer as described in claim 1, wherein the cleaning unit supplies the cleaning liquid to the inside of the dispensing nozzle by injecting it with a syringe action, and the capacitance measuring unit measures the capacitance over a time period during which the cleaning unit is discharging the liquid aspirated by the dispensing nozzle by injecting the cleaning liquid with the syringe action.

9. The automatic analyzer according to claim 1, wherein the liquid is a specimen, and the cleaning liquid is water.

10. The automatic analyzer according to claim 1, wherein the liquid is a detergent, and the cleaning liquid is water.

11. An automatic analyzer according to claim 1, wherein the determination unit determines the type, concentration, or volume of the liquid based on the magnitude of a value corresponding to the maximum value of a spike waveform in the time change of the capacitance represented by the capacitance data.

12. An automatic analyzer according to claim 1, wherein the determination unit determines whether or not the liquid has been removed based on the magnitude of a value corresponding to the minimum value of a spike waveform in the time change of the capacitance represented by the capacitance data.

13. An automatic analyzer according to claim 1, wherein the determination unit determines the type, concentration, or volume of the liquid based on the magnitude of a value corresponding to an area of ​​a spike waveform in the change in capacitance over time represented by the capacitance data.

14. A method for determining a cleaning state of a dispensing nozzle in an automatic analyzer, comprising: aspirating a liquid into a dispensing nozzle of an automatic analyzer; supplying a cleaning liquid to an outer wall of the dispensing nozzle after or while discharging the liquid aspirated into the dispensing nozzle, and sending the cleaning liquid into the inside of the dispensing nozzle, thereby cleaning the dispensing nozzle; measuring the capacitance between the dispensing nozzle and a reference potential portion over a time period including the time during which the dispensing nozzle is being washed; and determining the cleaning state of the dispensing nozzle based on the measured capacitance.

15. A program for causing a computer to execute the following processes: a process for aspirating liquid into a dispensing nozzle that constitutes an automatic analyzer; a process for cleaning the dispensing nozzle by supplying a cleaning solution to the outer wall of the dispensing nozzle and sending the cleaning solution into the inside of the dispensing nozzle after or while discharging the liquid aspirated into the dispensing nozzle; a process for measuring the capacitance between the dispensing nozzle and a reference potential portion over a time period that includes the period during which the dispensing nozzle is being cleaned; and a process for determining the cleaning status of the dispensing nozzle based on the measured capacitance.

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