Automatic analysis system and dispensing probe state determination method

The automated analysis system integrates analyzers with diverse detection methods to evaluate probe cleanliness by dye recovery and spectrophotometric measurement, addressing the challenge of non-spectrophotometric detection units and ensuring reliable cleanliness assessment.

WO2026033909A1PCT designated stage Publication Date: 2026-02-12HITACHI HIGH TECH CORP
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Patent Information

Application Number
PCT/JP2025/011954
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-08-07
Filing Date
2025-03-26
Publication Date
2026-02-12

AI Technical Summary

Technical Problem

Existing methods for evaluating the cleanliness of dispensing probes in automated analyzers are inadequate for systems using detection units other than spectrophotometers, necessitating a solution to estimate surface conditions effectively.

Method used

An automated analysis system is proposed that integrates analyzers with different detection methods, involving a first dispensing process with a dye solution, a second process to recover dye from the probe surface, and a third process for absorbance measurement using a spectrophotometer to determine cleanliness.

Benefits of technology

Enables accurate estimation of dispensing probe cleanliness even in analyzers with non-spectrophotometric detection units, ensuring high sensitivity and reliability in sample analysis.

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Abstract

The purpose of the invention is to enable the estimation of a surface state of a dispensing probe even in an automatic analyzer having a detection unit based on a measurement method other than that of a spectrophotometer. A high-concentration colorant solution is dispensed by a dispensing probe of an automatic analyzer in which a detection unit is based on a measurement method other than that of a spectrophotometer, and then a low-concentration colorant solution is dispensed. A low-concentration colorant solution from which the colorant has been recovered is transferred to an automatic analyzer having a spectrophotometer as a detection unit. The low-concentration colorant solution from which the colorant has been recovered is dispensed into a reaction vessel by a dispensing probe of the automatic analyzer having the spectrophotometer as the detection unit, and absorbance is measured. The surface state of the dispensing probe of the automatic analyzer based on a measurement method other than that of a spectrophotometer is estimated on the basis of measured absorbance.
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Description

Automatic analysis system and method for determining the state of a dispensing probe

[0001] The present disclosure relates to an automated analysis system and a method for determining the state of a dispensing probe.

[0002] Automated analyzers are widely used in clinical chemistry analysis to analyze components such as inorganic ions, proteins, urea, sugars, lipids, enzymes, hormones, drugs, and tumor markers in biological samples such as blood and urine. Except for devices that use disposable tips for sample dispensing, automated analyzers use a system in which the sample probe is cleaned using a cleaning mechanism and reused.

[0003] In recent years, minimizing sample volumes and increasing analytical sensitivity have become important development trends in automated analyzers. Therefore, in order to further reduce variations in aspirated and discharged volumes and to achieve reduced contamination, it is more important than ever to maintain a high level of cleanliness on the surface of the sample probe. As techniques for maintaining the cleanliness of the sample probe surface, for example, Patent Documents 1 and 2 disclose methods for using ultrasonic cleaning or a cleaning acceleration mechanism such as a heater in combination with a conventional cleaning tank.

[0004] Furthermore, to evaluate the cleaning effect on the sample probe surface, a test method for confirming the cleanliness of the sample probe is required. For example, Patent Document 3 discloses a test method for confirming the cleanliness of the sample probe surface. In this test method, a rack containing test tubes containing a dye solution and a dye-free solution (e.g., physiological saline) is prepared and set in an apparatus. The dye solution is aspirated from the set test tube with the sample probe and dispensed into an empty reaction vessel. After repeating this aspirating and dispensing operation multiple times, the sample probe is washed with pure water. Then, the dye-free solution is aspirated and dispensed into the reaction vessel, and the sample probe is washed. The amount of dye carried into the dye-free solution at this time is calculated from the absorbance measured with a spectrophotometer, and the surface condition of the sample probe is estimated from this amount of dye carried. After the test is completed, the rack containing the test tubes is recovered.

[0005] Japanese Patent No. 4892384 Japanese Patent Publication No. 2008-202945 Japanese Patent No. 4909599

[0006] However, the method described in Patent Document 3 assumes the use of an automatic analyzer having a spectrophotometer as a detection unit. In other words, this method requires highly sensitive quantification of the dye, since the surface condition of the dispensing probe is estimated from the amount of dye carried over. Highly sensitive quantification of the dye is generally achieved by measuring absorbance. This requires a spectrophotometer. If the detection unit is based on a measurement method other than a spectrophotometer, such as an electrochemical method, a chemiluminescence method, or a fluorescence method, it is difficult to estimate the surface condition of the dispensing probe using the method described in Patent Document 3.

[0007] On the other hand, in recent years, there has been an important trend toward integrating automated analyzers based on multiple different measurement methods to improve the efficiency of clinical testing and expand the scope of testing. For this reason, there is a demand for a method to estimate the surface condition of dispensing probes for automated analyzers that have detection units based on measurement methods other than spectrophotometers.

[0008] In view of such circumstances, the present disclosure proposes a technique for estimating the surface condition of a dispensing probe even in an automatic analyzer having a detection unit based on a measurement method other than a spectrophotometer.

[0009] In order to solve the above-mentioned problems, the present disclosure provides, as an example, an automated analysis system having a plurality of automated analyzers each having a dispensing probe for dispensing a sample, the system comprising: a first automated analyzer having a first dispensing probe and a detection unit based on a measurement method other than a spectrophotometer; and a second automated analyzer having a second dispensing probe and a spectrophotometer as the detection unit, wherein the first automated analyzer performs a first dispensing process in which a dye solution of a predetermined concentration stored in a first container is dispensed by the first dispensing probe; and a second dispensing process in which, after the first dispensing process, the first dispensing probe dispenses a solution containing no dye, thereby recovering dye remaining on the inner surface of the first dispensing probe into the solution containing no dye, and storing the solution in a second container as a low-concentration dye solution having a lower concentration than the dye solution of the predetermined concentration, and after the second container is transferred from the first automated analyzer to the second automated analyzer, the second automated analyzer performs We propose an automatic analysis system that performs the following steps: a third dispensing process in which the low-concentration dye solution stored in the second container is dispensed using the second dispensing probe; an absorbance measurement process in which the absorbance of the low-concentration dye solution is measured using the spectrophotometer after the third dispensing process; and a determination process in which the cleanliness of the first dispensing probe is determined based on the absorbance measured in the absorbance measurement process.

[0010] Further features related to the present disclosure will become apparent from the description of this specification and the accompanying drawings. Also, aspects of the present disclosure are achieved and realized by the elements and combinations of various elements and the aspects of the following detailed description and the appended claims. The description of this specification is merely exemplary and does not limit the scope or application of the claims of the present disclosure in any way.

[0011] According to the technology of the present disclosure, it is possible to determine (estimate) the surface condition by measuring the amount of dye carried over, even for a dispensing probe of an automatic analyzer whose detection unit is based on a measurement method other than a spectrophotometer.

[0012] FIG. 1 is a diagram showing a schematic configuration example of an automatic analyzer having a spectrophotometer as a detection unit. FIG. 2 is a diagram showing a schematic configuration example of an automatic analyzer having a detection unit based on a measurement method other than a spectrophotometer. FIG. 3 is a diagram showing a configuration example of a rack 124 used in the automatic analyzer 100. FIG. 4 is a diagram showing a configuration example of an automatic analysis system according to Example 1. FIG. 5 is a flowchart for explaining a process for evaluating the surface state of the sample probe 122 according to Example 1. FIG. 6 is a flowchart for explaining a process for evaluating the surface state of the sample probe 122 according to Example 2. FIG. 7 is a diagram showing a physicochemical model when a dye is adsorbed to the inner wall surface of the sample probe 22.

[0013] Hereinafter, embodiments and examples of the present disclosure will be described with reference to the accompanying drawings. In the accompanying drawings, functionally identical elements may be designated by the same numerals. Note that the accompanying drawings show specific embodiments and implementation examples in accordance with the principles of the present disclosure, but these are intended to aid in understanding the present disclosure and are by no means to be used to interpret the present disclosure in a limiting manner.

[0014] Although the present embodiment has been described in sufficient detail to enable those skilled in the art to practice the present disclosure, it should be understood that other implementations and forms are possible, and that changes in configuration and structure and substitutions of various elements are possible without departing from the scope and spirit of the technical ideas of the present disclosure. Therefore, the following description should not be interpreted as being limited thereto.

[0015] <Idea of ​​the Inventors> In order to respond to the increasing sensitivity of analysis, automatic analyzers may strengthen the cleaning function so that no substances remain on the probe surface. For example, an ultrasonic cleaning function may be added to the automatic analyzer.

[0016] However, even if the cleaning function is strengthened, it is impossible to know whether the remaining substances have actually been removed without checking. For this reason, the inventors believed that there would be a future (potential) need to check the condition of the inner surface of the probe after cleaning (the amount of remaining substances), and devised a technology to check the condition of the probe surface.

[0017] <Configuration Example of an Automated Analyzer Having a Spectrophotometer> Fig. 1 is a diagram showing a schematic configuration example of an automated analyzer having a spectrophotometer as a detection unit. Since the functions of each unit are well known, detailed description will be omitted.

[0018] The automated analyzer 10 is composed of a reagent disk 12 that mounts multiple reagent containers 11, a reaction disk 13 that mixes reagents and samples to measure reactions, a reagent dispensing mechanism 14 that aspirates and dispenses reagents, and a sample dispensing mechanism 15 that aspirates and dispenses samples. The reagent dispensing mechanism 14 is equipped with a reagent probe 21 for dispensing reagents, and the sample dispensing mechanism 15 is equipped with a sample probe 22 for dispensing samples.

[0019] The samples introduced into the device are placed in sample containers (test tubes) 23 and transported on racks 24. A plurality of sample containers 23 are mounted on the racks 24. The samples may be blood-derived samples such as serum or whole blood, urine, dye solutions, physiological saline, or the like.

[0020] The sample dispensing mechanism 15 moves the sample probe 22 by rotating it to an aspirating position where the sample is aspirated from the sample container 23, a dispensing position where the sample is dispensed into the reaction container 25, a washing position where the tip of the sample probe 22 is washed in a washing tank 26, and a special washing position where the tip of the sample probe 22 is washed in a special washing tank 27. Furthermore, the sample dispensing mechanism 15 lowers the sample probe 22 at the aspirating position, dispensing position, and washing position to match the heights of the sample container 23, reaction container 25, washing tank 26, and special washing tank 27, respectively.

[0021] The sample probe 22 is washed in the washing tank 26 and the special washing tank 27. The following methods are conceivable for using these washing tanks appropriately. When a normal analysis is being repeated, washing is performed using the washing tank 26. Since the washing time is limited during the analysis, washing with running pure water, for example, is performed. Furthermore, to maintain the cleanliness of the sample probe 22, the sample probe 22 may be washed in the special washing tank 27 before, after, or between analysis repetitions. In addition to washing with running pure water, the special washing tank 27 is equipped with a washing acceleration mechanism for more powerful washing. Examples of the washing acceleration mechanism include ultrasonic waves and heaters that exert a physicochemical effect on the surface of the sample probe 22 to accelerate the washing. The washing liquid used in the special washing tank 27 may be pure water, or a washing liquid with improved cleaning effectiveness achieved by adjusting the pH or adding a surfactant may also be used.

[0022] The sample probe 22 and the reagent probe 21 are equipped with sensors that detect the liquid level (sensors that use changes in capacitance or pressure) and the sensor signal can confirm that they have come into contact with the target liquid (sample or reagent).

[0023] The automatic analyzer 10 measures the photometry of the mixture of the sample and the reagent contained in the reaction vessel 25 using the spectrophotometer 28 to analyze the concentration of a predetermined component in the sample.

[0024] <Configuration example of an automatic analyzer having a detection unit other than a spectrophotometer> Fig. 2 is a diagram showing a schematic configuration example of an automatic analyzer having a detection unit based on a measurement method other than a spectrophotometer. The basic configuration other than the detection unit is the same as that of the automatic analyzer shown in Fig. 1.

[0025] The automated analyzer 100 is composed of a reagent disk 112 that mounts multiple reagent containers 111, a reagent dispensing mechanism 114 that aspirates and dispenses reagents, and a sample dispensing mechanism 115 that aspirates and dispenses samples. The reagent dispensing mechanism 114 is equipped with a reagent probe 121 for dispensing reagents. The sample dispensing mechanism 115 is equipped with a sample probe 122 for dispensing samples.

[0026] Samples loaded into the device are placed in sample containers (test tubes) 123 and transported on a rack 124. The rack 124 is equipped with multiple sample containers 123. The samples may be blood-derived samples such as serum or whole blood, urine, dye solutions, or saline solutions. The dye solution is a solution used to evaluate the performance of an automated analyzer, and may be, for example, a dye that easily adsorbs to proteins (blood). For example, a used probe is soaked in the dye solution and then washed. After washing, the dye adsorbed to the protein is dissolved in saline, and the absorbance is measured to check the surface condition of the probe. In this way, the dye solution is a solution for indirectly evaluating blood remaining on the probe surface.

[0027] The sample dispensing mechanism 115 moves the sample probe 122 by rotating it to an aspirating position where the sample is aspirated from the sample container 123, a dispensing position where the sample is dispensed into the analysis tank 201 through the discharge port 202, a washing position where the tip of the sample probe 122 is washed in the washing tank 126, and a special washing position where the tip of the sample probe 122 is washed in the special washing tank 127. Furthermore, the sample dispensing mechanism 115 lowers the sample probe 122 at the aspirating position, discharge position, and washing position to match the heights of the sample container 123, the discharge port 202 of the analysis tank 201, the washing tank 126, and the special washing tank 127, respectively.

[0028] The sample probe 122 is washed in the washing tank 126 and the special washing tank 127. The following methods are conceivable for using these washing tanks appropriately. When a normal analysis is being repeated, washing is performed in the washing tank 126. Because the washing time is limited during the analysis, washing with running pure water is performed. Furthermore, to maintain the cleanliness of the sample probe 122, the sample probe 122 may be washed in the special washing tank 127 before, after, or between analysis repetitions. In addition to washing with running pure water, the special washing tank 127 is equipped with a washing acceleration mechanism for more powerful washing. Examples of the washing acceleration mechanism include ultrasonic waves and heaters that exert a physicochemical effect on the surface of the sample probe 122 to accelerate the washing. The washing liquid used in the special washing tank may be pure water, or a washing liquid with improved cleaning effect achieved by adjusting the pH or adding a surfactant may also be used.

[0029] The sample probe 122 and the reagent probe 121 are equipped with sensors that detect the liquid level (sensors that use changes in capacitance or pressure) and the sensor signal can confirm that they have come into contact with the target liquid (sample or reagent).

[0030] The automated analyzer 100 analyzes the concentration of a predetermined component in the sample by measuring a mixture of a sample and a reagent contained in an analysis tank 201 using a detection unit 203 based on a measurement method other than a spectrophotometer. Here, the measurement method used by the detection unit 203 may be an electrochemical method, a fluorescence method, a luminescence method, a mass spectrometry method, or the like.

[0031] 3 is a diagram showing an example of the configuration of the rack 124 used in the automatic analyzer 100. The rack 24 used in the automatic analyzer 10 can also have a similar configuration.

[0032] Sample containers (test tubes) 301, 302, 303, 304, and 305 are loaded onto a rack 124 and transported. In this example, five sample containers 301, 302, 303, 304, and 305 are loaded onto the rack 124. However, the number of sample containers is not limited to five. The samples may be blood-derived samples such as serum or whole blood, urine, dye solutions, physiological saline, or the like.

[0033] <Example 1> (1) Configuration Example of an Automated Analysis System Example 1 proposes an automated analysis system 200 that integrates an automated analyzer 10 having a spectrophotometer as a detection unit and an automated analyzer 100 having a detection unit based on a measurement method other than spectrophotometer. The automated analyzers 10 and 100 are integrated so that racks are exchanged on a conveyance line. Figure 4 is a diagram showing a configuration example of the automated analysis system 200 according to Example 1. As shown in Figure 4, racks 24 and racks 124 can be exchanged on the conveyance line.

[0034] The automated analysis system 200 includes an automated analyzer 10, an automated analyzer 100, and a control device 300 that controls the operation of both analyzers. The control device 300 can be configured, for example, by a computer that includes an output device (e.g., a display, a printer, etc.), an input device (a keyboard, a mouse, a touch panel, etc.), a storage device, and a communication device.

[0035] The sample containers stored in each rack can be accessed by sample probe 122 in the automatic analyzer 100 and by sample probe 22 in the automatic analyzer 10, allowing the liquid in the sample container to be dispensed.

[0036] (2) Evaluation of the Surface Condition of the Probe FIG. 5 is a flowchart for explaining the process of evaluating the surface condition (condition of the inner surface) of the sample probe 122 according to the first embodiment.

[0037] (i) Step S501: The user (operator) places a dye solution in sample container 301 of rack 124, and a dye-free solution in sample container 302. In the following, physiological saline is used as an example of a dye-free solution. Other dye-free solutions, such as a pH-adjusted phosphate buffer solution, can also be used.

[0038] (ii) Step S502 When the user presses the start button (for example, the start button of the GUI on the display screen of the control device 300), the control device 300 starts the surface condition evaluation process.

[0039] (iii) Step S503 The control device 300 transports the rack 124 via the transport line, and moves the sample container 301 to the dispensing position of the sample probe 122.

[0040] (iv) Step S504: The control device 300 lowers the sample dispensing mechanism 115 to the dispensing position and dispenses the dye solution. At this time, the dispensed dye solution may be discharged into the analysis tank 201 through the analysis tank outlet 202, or into the washing tank 126 or sample container 301. Dispensing may be performed once or multiple times.

[0041] (v) Step S505 The control device 300 washes the sampling probe 122 in the washing tank 126. At this time, washing may be performed using the special washing tank 127. Furthermore, after washing in the washing tank 126, washing may be performed in the special washing tank 127.

[0042] (vi) Step S506: The control device 300 moves the sample container 302 together with the rack via the transport line to the dispensing position of the sample probe 122. The sample dispensing mechanism 115 then descends to the dispensing position and dispenses saline. At this time, the control device 300 controls the sample dispensing mechanism 115 to eject the dispensed saline into the sample container 302, thereby recovering the dye remaining on the surface of the sample probe 122. Specifically, the salt concentration of the saline causes a change in the interaction of the dye with the probe surface, causing the dye attached to the probe surface to detach from the probe surface and dissolve in the saline. This allows the dye attached to the probe surface to be recovered. At this time, dispensing may be performed once or multiple times.

[0043] (vii) Step S507 The control device 300 controls the sample dispensing mechanism 115 to wash the sample probe 122 in the washing tank 126. At this time, washing may be performed using the special washing tank 127. Furthermore, after washing in the washing tank 126, washing may be performed in the special washing tank 127.

[0044] (viii) Step S508 The control device 300 transfers the rack 124 via the transport line to a position where the sample probe 22 of the automatic analyzer 10 having a spectrophotometer as a detection unit can dispense the sample container 302.

[0045] (ix) Step S509 The control device 300 lowers the sample dispensing mechanism 15 to the dispensing position and aspirates the saline solution in which the remaining dye has been recovered from the sample container 302. The control device 300 then discharges the saline solution in which the aspirated dye has been recovered into the reaction container 25. By repeating this dispensing operation of aspirating and dispensing multiple times, the amount of saline solution in which the aspirated dye has been recovered required for analysis by the spectrophotometer may be dispensed into the reaction container 25.

[0046] (x) Step S510 The control device 300 controls the stirring mechanism 20 to stir the reaction vessel 25 into which the saline solution containing the recovered dye has been dispensed at the stirring position, and analyzes the result using the spectrophotometer .

[0047] The amount of dye recovered in the saline solution can be estimated using the following formula (1) based on information such as the absorbance of the dye solution and the absorbance of the saline solution, where A is the absorbance of the saline solution from which the dye was recovered, B is the absorbance of the saline solution, C is the absorbance of the dye solution, D is the concentration of the dye solution, and E is the volume of the solution from which the dye was recovered.

[0048] ((A-B) / (C-B))×D×E... (1)

[0049] If the absorbance of the dye solution exceeds the upper measurement limit of the photometer, it is difficult to measure the absorbance of the dye solution directly. In this case, the absorbance of the dye solution stock can be obtained by measuring the absorbance of a solution obtained by diluting the dye solution stock (dilution ratio K) and multiplying the absorbance of the diluted solution by 1 / K.

[0050] Based on the test results, for example, a threshold value can be set for the amount of dye carried over, and a judgment can be made to evaluate the surface condition of the sample probe 122. Then, based on this result (the amount of dye calculated by formula (1) is compared with the threshold value, and if the calculated amount of dye is equal to or greater than the threshold value), maintenance or replacement of the sample probe 122 can be performed.

[0051] It is also possible to manage information about the state of the sample probe 122 obtained from such tests on a server, etc. Based on this information, it is possible to determine whether the sample probe 122 needs to be replaced or cleaned in the special cleaning tank 127.

[0052] In the above-described first embodiment, an example has been given of a configuration in which an automatic analyzer 100 having a detection unit based on a measurement method other than a spectrophotometer is arranged in front of an automatic analyzer 10 having a spectrophotometer as a detection unit. However, even if the automatic analyzer 100 is arranged in back of the automatic analyzer 10, evaluation can be performed using the same operations as long as the transport direction is not restricted (in terms of the processing timeline, the processing by the automatic analyzer 100 is performed before the processing by the automatic analyzer 10).

[0053] Example 2 Example 1 described a case where the automatic analyzer 100 and the automatic analyzer 10 are integrated via a transport line. When the automatic analyzer 100 and the automatic analyzer 10 are not integrated via a transport line, evaluation can be performed using the following procedure. Note that when the automatic analyzer 100 and the automatic analyzer 10 are not integrated via a transport line, each automatic analyzer may be controlled by a separate control device, or one control device may control both automatic analyzers. Below, a process for evaluating the surface condition of the sample probe 122 will be described assuming that a first control device controls the automatic analyzer 100 and a second control device controls the automatic analyzer 10. Figure 6 is a flowchart for explaining a process for evaluating the surface condition of the sample probe 122 according to Example 2.

[0054] (i) Steps S501 to S507 The process (steps S501 to S507) for recovering the dye remaining on the surface of the sample probe 122 of the automatic analyzer 100 into physiological saline is the same as that in the case of integration on the transport line in Example 1. In this case, the first control device that controls the automatic analyzer 100 executes the processes of steps S501 to S507.

[0055] (ii) Step S601: The user (operator) removes the rack 124 from the automatic analyzer 100 and sets it in the automatic analyzer 10 having a spectrophotometer as a detection unit. Here, the user moves the rack 124 using a hand carrier, but an arm-type robot may be provided to move the rack 124.

[0056] (iii) Step S602 The second control device controls the transport line to transport the rack 124 to a position where the sample probe 22 of the automatic analyzer 10 having a spectrophotometer as a detection unit can dispense the sample container 302.

[0057] (iv) Step S603 The second control device controls the sample dispensing mechanism 15 to lower the sample probe 22 to the dispensing position and aspirate the saline solution from which the remaining dye has been recovered from the sample container 302. The second control device then controls the sample dispensing mechanism 15 to discharge the aspirated saline solution (containing the remaining dye) into the reaction container 25. The second control device may repeat this aspirating and dispensing dispensing operation multiple times to dispense into the reaction container 25 an amount of saline solution from which the dye required for analysis by the spectrophotometer has been recovered.

[0058] (v) Step S604 The second control device stirs the reaction vessel 25 into which the physiological saline containing the recovered dye has been dispensed, using the stirring mechanism 29 at the stirring position, and then analyzes the result using the spectrophotometer .

[0059] <Amount of dye recovered taking into account adhesion to the inner wall surface of the sample probe 22: Correction of absorbance> (i) In Examples 1 and 2, the automatic analyzer 10, which has a spectrophotometer as a detection unit, performs an aspirating / dispensing dispensing operation in which saline solution from which residual dye has been recovered is aspirated from the sample container 302 and dispensed into the reaction container 25, but it is assumed that the dye is not adsorbed to the surface of the sample probe 22 and the absorbance of the solution from which the dye has been recovered does not change.

[0060] However, if the inner wall surface of the sample probe is extremely contaminated, the dye may be adsorbed to the inner wall surface of the sample probe, and the measured absorbance may be smaller than the true value due to the adsorption of the dye. Therefore, the inventors investigated the extent of the error that may occur due to adsorption and the extent of correction that should be performed.

[0061] (ii) Figure 7 is a diagram showing a physicochemical model of the adsorption of a dye onto the inner wall surface of the sample probe 22. The inside of the sample probe 22 is assumed to be filled with a solution containing a dye. Of this, the dye that is adsorbed onto the inner wall surface between suction and discharge cannot be discharged from the sample probe 22 into the reaction vessel 25 during discharge. This could result in an apparent decrease in absorbance.

[0062] The inventors have also estimated the maximum amount of dye that can be adsorbed onto the inner wall surface of the sampling probe 22 as follows: First, the steps of dye adsorption can be considered to be divided into the following two stages.

[0063] First step: The dye diffuses and reaches the inner wall surface of the sample probe 22. Second step: The dye that reaches the inner wall surface is adsorbed onto the inner wall surface.

[0064] In this case, in order to estimate the adsorption probability in the second step, the rate constants of adsorption and desorption are required. However, the inventors determined that it would be difficult to estimate the rate constant of adsorption and desorption, and assumed that all of the dye that reaches the inner wall surface of the sampling probe 22, where the amount of adsorption is at its maximum, is adsorbed onto the inner wall surface (i.e., adsorption probability = 1).

[0065] Next, the inventors estimated the probability of the first step occurring, and assumed that the dye diffuses and reaches the inner wall surface of the sample probe 22. In this case, it is considered that the dye must be located within a range closer to the inner wall surface than the distance L expressed by the following formula (2):

[0066] L = (D m ×t m 2 ) 1/2 ... (2)

[0067] Here, D m is the diffusion coefficient of the dye, t m indicates the time that the dye solution remains inside the sample probe 22. m is the time from when the dye solution is aspirated to when the discharge is completed, t p Therefore, L is the estimated maximum distance L as shown in the following formula (3). p It will be a smaller value than

[0068] L < L p = (D m ×t p 2 ) 1/2 ... (3)

[0069] The diffusion coefficient of the dye can be estimated from the Wilke-Chung equation as shown in the following equation (4).

[0070] D m ×η / T = 8.34 × 10 -15 M W -1/3 ... (4)

[0071] where η is the viscosity coefficient of the dye solution (approximately the same as that of water), T is the temperature of the dye solution, and M W is the molecular weight of the dye. p and the radius R of the sample probe, the maximum proportion P of the dye that can be adsorbed can be estimated by the following formula (5):

[0072] P = π × (2RL p -L p 2 ) / (π × R 2 ) ... (5)

[0073] The inventors experimentally calculated P by changing the suction volume. The inventors also used orange G solutions of approximately 0.5 Abs. and approximately 2.0 Abs. as the dye solution, dispensing the dye solution into reaction vessels 25 under multiple dispensing volume conditions, stirring the solution with stirring mechanism 29, and measuring the absorbance with spectrophotometer 28. Here, the sample probe 22 used was one to which an excessive amount of contamination was forcibly attached compared to that expected in actual operation. This is because it is believed that deriving a correction coefficient under the worst-case conditions will enable it to be adapted to all users.

[0074] The inventors then calculated P based on Equation 5 using the molecular weight of the dye Orange G used in the experiment, the radius of the sample probe, and the time from suction to completion of discharge. theory As a result, under any conditions of the amount dispensed and the absorbance of the dye, P < P theory Therefore, even if adhesion to the inner wall surface of the sampling probe 22 is taken into consideration, the inventors have confirmed that P theory 1 / P, which is the reciprocal of theoryIt was confirmed that the amount of dye recovered would not be underestimated by multiplying by a safety factor. In summary, the absorbance correction can be performed using a correction factor that is prepared in advance and calculated by conducting an experiment using a sample probe 122 with contamination attached to its inner surface (the inner surface of the sample probe 122) and examining the results of the experiment.

[0075] Although the method for testing the surface condition of a sample probe has been described here to derive the correction coefficient, the present invention is not limited to this and may also be used for a reagent probe.

[0076] <Other> The functions of this embodiment and each example can also be realized by software program code. In this case, a storage medium on which the program code is recorded is provided to a system or device, and the computer (or CPU or MPU) of that system or device reads the program code stored in the storage medium. In this case, the program code itself read from the storage medium realizes the functions of the above-mentioned embodiments, and the program code itself and the storage medium on which it is stored constitute the present disclosure. Examples of storage media for supplying such program code include flexible disks, CD-ROMs, DVD-ROMs, hard disks, optical disks, magneto-optical disks, CD-Rs, magnetic tape, non-volatile memory cards, and ROMs.

[0077] Furthermore, an operating system (OS) running on a computer may perform some or all of the actual processing based on instructions in the program code, and the functions of the above-described embodiments may be realized by this processing.Furthermore, after the program code is read from a storage medium and written to memory on the computer, a CPU of the computer may perform some or all of the actual processing based on instructions in the program code, and the functions of the above-described embodiments may be realized by this processing.

[0078] Furthermore, the program code of the software that realizes the functions of the embodiments and each example may be distributed via a network and stored in a storage means such as a hard disk or memory of the system or device, or in a storage medium such as a CD-RW or CD-R, so that when used, the computer (or CPU or MPU) of the system or device reads and executes the program code stored in the storage means or storage medium.

[0079] The processes and techniques described herein are not inherently related to any specific device and can be implemented by a combination of components. Various types of general-purpose devices can also be added. A dedicated device may be constructed to perform the functions of this embodiment and each example. Various functions can also be formed by appropriately combining multiple components disclosed in this embodiment and each example. For example, some components may be omitted from all the components shown in the embodiment and each example, or components from different examples may be appropriately combined.

[0080] Although specific examples are described in this disclosure, they are in all respects for the purpose of explanation (understanding the technology of the present disclosure) and not for the purpose of limitation. Those skilled in the art will recognize that there are many combinations of hardware, software, and firmware suitable for implementing the technology of the present disclosure. For example, the software described can be implemented in a wide variety of programming or scripting languages, such as assembler, C / C++, Perl, Shell, PHP, Java (registered trademark), etc.

[0081] Furthermore, in the above-described embodiment, the control lines and information lines are those that are considered necessary for the explanation, and not all control lines and information lines in the product are necessarily shown. All components may be interconnected.

[0082] In addition, other implementations of the present disclosure will be apparent to those skilled in the art from consideration of the present embodiments and examples. The specification and examples are exemplary only, with the scope and spirit of the technology of the present disclosure being indicated by the following claims.

[0083] 10 Automatic analyzer 11 Reagent container 12 Reagent disk 13 Reaction disk 14 Reagent dispensing mechanism 15 Sample dispensing mechanism 21 Reagent probe 22 Sample probe 23 Sample container 24 Rack 25 Reaction container 26 Washing tank 27 Special washing tank 28 Spectrophotometer 29 Stirring mechanism 100 Automatic analyzer 111 Reagent container 112 Reagent disk 114 Reagent dispensing mechanism 115 Sample dispensing mechanism 121 Reagent probe 122 Sample probe 123 Sample container 124 Rack 125 Reaction container 126 Washing tank 127 Special washing tank 201 Analysis tank 202 Analysis tank outlet 301 Sample container 302 Sample container 303 Sample container 304 Sample container 305 Sample container

Claims

1. An automated analysis system having a plurality of automated analyzers each having a dispensing probe for dispensing a sample, comprising: a first automated analyzer having a first dispensing probe and a detection unit based on a measurement method other than a spectrophotometer; and a second automated analyzer having a second dispensing probe and a spectrophotometer as a detection unit, wherein the first automated analyzer performs a first dispensing process in which a dye solution of a predetermined concentration stored in a first container is dispensed using the first dispensing probe; and a second dispensing process in which, after the first dispensing process, the first dispensing probe dispenses a solution containing no dye, thereby recovering dye remaining on the inner surface of the first dispensing probe into the solution containing no dye, and storing the solution in a second container as a low-concentration dye solution having a lower concentration than the dye solution of the predetermined concentration; and after the second container is transferred from the first automated analyzer to the second automated analyzer, the second automated analyzer performs a third dispensing process in which the second dispensing probe dispenses the low-concentration dye solution stored in the second container. an absorbance measurement process for measuring the absorbance of the low-concentration dye solution with the spectrophotometer after the third dispensing process; and a determination process for determining the cleanliness of the first dispensing probe based on the absorbance measured in the absorbance measurement process.

2. An automatic analysis system according to claim 1, wherein the first automatic analyzer further performs a process of washing the first dispensing probe after the first dispensing process between the first dispensing process and the second dispensing process, and in the second dispensing process, the washed first dispensing probe dispenses a solution that does not contain the dye and recovers the remaining dye.

3. The automated analysis system according to claim 1, wherein the dye-free solution is physiological saline or a pH-adjusted phosphate buffer solution.

4. An automatic analysis system according to claim 1, further comprising a transfer line connecting the first automatic analysis device and the second automatic analysis device, wherein the second container containing the low-concentration dye solution is transferred from the first automatic analysis device to the second automatic analysis device via the transfer line.

5. An automated analysis system according to claim 1, wherein the second container containing the low-concentration dye solution is transported from the first automated analyzer to the second automated analyzer by a user's handcarry.

6. An automated analysis system according to claim 1, further comprising an arm-type robot, wherein the arm-type robot transfers the second container containing the low-concentration dye solution from the first automated analysis device to the second automated analysis device.

7. An automatic analysis system according to claim 1, wherein the first automatic analysis device uses any one of electrochemistry, fluorescence, luminescence, or mass spectrometry as a measurement method other than the spectrophotometer.

8. An automatic analysis system according to claim 1, wherein the second automatic analysis device further executes a correction process to correct the absorbance, and in the determination process, determines the cleanliness of the first dispensing probe based on the corrected absorbance.

9. An automatic analysis system according to claim 8, wherein the second automatic analysis device performs the correction process using a correction coefficient calculated based on the diffusion coefficient of the dye in the dye solution and the time from when the low-concentration dye solution stored in the second container is aspirated by the second dispensing probe to when the discharge is completed.

10. An automatic analysis system according to claim 8, wherein the second automatic analysis device performs the correction process using a correction coefficient that is prepared in advance and calculated by examining the results of an experiment using the first dispensing probe with contamination attached to its inner surface.

11. A probe status determination method for determining the status of a first dispensing probe in a first automatic analyzer having a first dispensing probe and a detection unit based on a measurement method other than a spectrophotometer, in a second automatic analyzer having a second dispensing probe and a spectrophotometer as a detection unit, the method comprising: (i) in the first automatic analyzer, (i-1) dispensing a dye solution of a predetermined concentration stored in a first container using the first dispensing probe; (i-2) after dispensing the dye solution of the predetermined concentration, dispensing a solution containing no dye with the first dispensing probe, thereby recovering dye remaining on the inner surface of the first dispensing probe in the solution containing no dye, and storing the solution in a second container as a low-concentration dye solution having a lower concentration than the dye solution of the predetermined concentration; (ii) transferring the second container from the first automatic analyzer to the second automatic analyzer; and (iii) in the second automatic analyzer, (iii-1) dispensing the low-concentration dye solution stored in the second container using the second dispensing probe. (iii-2) after dispensing the low-concentration dye solution, measuring the absorbance of the low-concentration dye solution with the spectrophotometer; and (iii-3) determining the state of the first dispensing probe based on the measured absorbance.

12. A probe condition determination method according to claim 11, further comprising correcting the absorbance in the second automatic analyzer, and determining the condition of the first dispensing probe includes determining the cleanliness of the first dispensing probe based on the corrected absorbance.

13. A probe state determination method according to claim 12, wherein correcting the absorbance includes correcting the absorbance using a correction coefficient calculated based on the diffusion coefficient of the dye in the dye solution and the time from when the low-concentration dye solution stored in the second container is aspirated by the second dispensing probe to when discharge is completed.

14. A method for determining a probe state according to claim 12, wherein correcting the absorbance includes correcting the absorbance using a correction coefficient that is prepared in advance and calculated by examining the results of an experiment using the first dispensing probe having contamination attached to its inner surface.

Citation Information

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