Automatic analysis system and dispensing probe state determination method

The automated analysis system integrates analyzers with different detection methods to estimate dispensing probe cleanliness by quantifying dye absorption, addressing the challenge of non-spectrophotometric detection units.

JP2026028352APending Publication Date: 2026-02-20HITACHI HIGH TECH CORP
View PDF 3 Cites 0 Cited by

Patent Information

Application Number
JP2024130689
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2024-08-07
Publication Date
2026-02-20

AI Technical Summary

Technical Problem

Existing automated analyzers face challenges in estimating the surface condition of dispensing probes when using detection units based on measurement methods other than spectrophotometers, as methods like electrochemical or fluorescence cannot accurately quantify dye absorption.

Method used

An automated analysis system that integrates an analyzer with a spectrophotometer and another with a different detection method, involving a series of dispensing and cleaning processes to measure dye absorption using a spectrophotometer, even when the primary analyzer lacks one.

Benefits of technology

Enables accurate estimation of dispensing probe cleanliness for analyzers with non-spectrophotometric detection units by quantifying dye absorption, ensuring effective cleaning and maintenance.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure 2026028352000001_ABST
    Figure 2026028352000001_ABST
Patent Text Reader

Abstract

To estimate the surface state of a dispensing probe even in an automatic analyzer having a detection part based on a measuring method other than a spectrophotometer.SOLUTION: After a high concentration pigment solution is dispensed by a dispensing probe of an automatic analyzer in which a detection part is based on a measuring method other than a spectrophotometer, a low concentration pigment solution is dispensed. The low-concentration dye solution from which the dye has been recovered is transferred to an automatic analyzer having a spectrophotometer as a detection unit. The low-concentration dye solution from which the dye has been recovered is dispensed into a reaction vessel by a dispensing probe of an automatic analyzer having a spectrophotometer as a detection unit, and the absorbance is measured. Based on the measured absorbance, the surface state of the dispensing probe of the automatic analyzer based on a measurement method other than the spectrophotometer is estimated.SELECTED DRAWING: Figure 5
Need to check novelty before this filing date? Find Prior Art

Description

[Technical Field]

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

[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 a technique for maintaining the cleanliness of the sample probe surface, for example, Patent Documents 1 and 2 disclose a method of using a cleaning acceleration mechanism, such as ultrasonic cleaning or 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 instrument. The dye solution is aspirated from the set test tube using 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 in. After the test is completed, the rack containing the test tubes is recovered. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 4892384 [Patent Document 2] Japanese Patent Application Laid-Open No. 2008-202945 [Patent Document 3] Patent No. 4909599 Summary of the Invention [Problem to be solved by the invention]

[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. For this reason, a spectrophotometer is required. 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. [Means for solving the problem]

[0009] In order to solve the above problems, the present disclosure provides, as an example, an automatic analysis system having a plurality of automatic analysis devices each having a dispensing probe for dispensing a sample, a first automated analyzer having a first dispensing probe and a detection unit based on a measurement method other than a spectrophotometer; a second automated analyzer having a second dispensing probe and a spectrophotometer as a detection unit; The first automated analyzer is 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; a second dispensing process in which a solution containing no dye is dispensed by the first dispensing probe after the first dispensing process, thereby recovering the dye remaining on the inner surface of the first dispensing probe into the solution containing no dye, and storing the recovered solution in a second container as a low-concentration dye solution having a lower concentration than the dye solution of the predetermined concentration; After the second container is transferred from the first automated analyzer to the second automated analyzer, The second automated analyzer is a third dispensing process of dispensing the low-concentration dye solution stored in the second container by the second dispensing probe; an absorbance measurement process of measuring the absorbance of the low-concentration dye solution with the spectrophotometer after the third dispensing process; and executing a determination process for determining the cleanliness of the first dispensing probe based on the absorbance measured in the absorbance measurement process. We propose an automated analysis system.

[0010] Further features related to the present disclosure will become apparent from the description and accompanying drawings of this specification, and aspects of the present disclosure may be realized and realized by the elements and combinations of various elements and aspects set forth in the following detailed description and the appended claims. The descriptions herein are exemplary and illustrative only and are not intended to limit the scope or application of the present disclosure in any way. [Effects of the Invention]

[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. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 is a diagram showing an example of the schematic configuration of an automatic analyzer having a spectrophotometer as a detection unit. [Figure 2] FIG. 1 is a diagram showing an example of the schematic configuration of an automatic analyzer having a detection unit based on a measurement method other than that of a spectrophotometer. [Figure 3] 1 is a diagram showing an example of the configuration of a rack 124 used in the automatic analyzer 100. FIG. [Figure 4] 1 is a diagram illustrating an example of the configuration of an automatic analysis system according to a first embodiment. [Figure 5] 10 is a flowchart for explaining a process for evaluating the surface state of the sample probe 122 according to the first embodiment. [Figure 6] 10 is a flowchart illustrating a process for evaluating the surface state of the sample probe 122 according to the second embodiment. [Figure 7] FIG. 10 is a diagram showing a physicochemical model when a dye is adsorbed onto the inner wall surface of the sample probe 22. DETAILED DESCRIPTION OF THE INVENTION

[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 implement 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 by inventors> In order to respond to the increasing sensitivity of analysis, automatic analyzers may strengthen the cleaning function to prevent substances from remaining on the probe surface, for example, by adding an ultrasonic cleaning function 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 need (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 automatic analyzer with a spectrophotometer> 1 is a diagram showing an example of the schematic configuration of an automatic 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 the reaction, 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, or urine, or dye solutions or physiological saline solutions.

[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 cleaned in the cleaning tank 26 and the special cleaning tank 27. The following methods are conceivable for using these cleaning tanks appropriately. When a normal analysis is repeated, cleaning is performed using the cleaning tank 26. Because the cleaning time is limited during the analysis, cleaning with running pure water, for example, is performed. Furthermore, to maintain the cleanliness of the sample probe 22, cleaning of the sample probe 22 may be performed in the special cleaning tank 27 before, after, or between analysis repetitions. In addition to cleaning with running pure water, the special cleaning tank 27 is equipped with a cleaning acceleration mechanism for more powerful cleaning. Examples of cleaning acceleration mechanisms include ultrasonic waves and heaters that exert a physicochemical effect on the surface of the sample probe 22 to accelerate cleaning. The cleaning solution used in the special cleaning tank 27 may be pure water, or a cleaning solution 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 a spectrophotometer 28, thereby analyzing the concentration of a predetermined component in the sample.

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

[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 a plurality of 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 cleaned in the cleaning tank 126 and the special cleaning tank 127. The following methods are conceivable for using these cleaning tanks appropriately. When a normal analysis is being repeated, cleaning is performed in the cleaning tank 126. Because the cleaning time is limited during the analysis, cleaning with running pure water, for example, is performed. Furthermore, to maintain the cleanliness of the sample probe 122, cleaning of the sample probe 122 may be performed in the special cleaning tank 127 before, after, or between analysis repetitions. In addition to cleaning with running pure water, the special cleaning tank 127 is equipped with a cleaning acceleration mechanism for more powerful cleaning. Examples of cleaning acceleration mechanisms include ultrasonic waves and heaters that exert a physicochemical effect on the surface of the sample probe 122 to accelerate cleaning. The cleaning solution used in the special cleaning tank may be pure water, or a cleaning solution with improved cleaning effectiveness 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] <Rack 124 configuration example> 3 is a diagram showing an example of the configuration of a 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. Here, an example is shown in which 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) Example of an automated analysis system configuration Example 1 proposes an automatic analysis system 200 that integrates an automatic analyzer 10 having a spectrophotometer as a detection unit and an automatic analyzer 100 having a detection unit based on a measurement method other than spectrophotometer. The automatic analyzers 10 and 100 are integrated so that racks are exchanged on a conveyance line. Figure 4 is a diagram showing an example configuration of the automatic 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 equipped with 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 probe surface condition FIG. 5 is a flowchart for explaining a process for evaluating the surface state (state of the inner surface) of the sample probe 122 according to the first embodiment.

[0037] (i) Step S501 The user (operator) places the dye solution in sample container 301 of rack 124, and the dye-free solution in sample container 302. In the following, physiological saline is used as an example of the 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 a start button (for example, a start button on 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 may be repeated multiple times.

[0041] (v) Step S505 The control device 300 cleans the sample probe 122 in the cleaning tank 126. At this time, cleaning may be performed using the special cleaning tank 127. Furthermore, after cleaning is performed in the cleaning tank 126, cleaning may be performed in the special cleaning 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. After this, the sample dispensing mechanism 115 descends to the dispensing position and dispenses the physiological saline. At this time, the control device 300 controls the sample dispensing mechanism 115 to eject the dispensed physiological saline into the sample container 302, thereby recovering the dye remaining on the surface of the sample probe 122. More specifically, the salt concentration of the physiological saline causes a change in the interaction of the dye on the probe surface, causing the dye attached to the probe surface to detach from the probe surface and dissolve in the physiological saline. This allows the dye attached to the probe surface to be recovered. At this time, dispensing may be performed once or may be repeated 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 a transport line to a position where the sample probe 22 of the automatic analyzer 10, which has 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 from which the remaining dye has been collected, from the sample container 302. The control device 300 then discharges the saline solution from which the aspirated dye has been collected into the reaction container 25. By repeating this dispensing operation of aspirating and dispensing multiple times, the amount of saline solution from which the aspirated dye has been collected 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 physiological saline solution containing the recovered dye has been dispensed at the stirring position, and analyzes the result with the spectrophotometer 28.

[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. In formula (1), 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] ((AB) / (CB)) × D × E (1)

[0049] If the absorbance of the dye solution exceeds the upper limit of the spectrophotometer's measurement, 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 above 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 when 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, processing by the automatic analyzer 100 is performed before processing by the automatic analyzer 10).

[0053] <Example 2> In the first embodiment, the case where the automatic analyzer 100 and the automatic analyzer 10 are integrated by a transfer line has been described. When the automatic analyzer 100 and the automatic analyzer 10 are not integrated by a transfer line, the evaluation can be performed using the following procedure. When the automatic analyzer 100 and the automatic analyzer 10 are not integrated by a transfer line, each automatic analyzer may be controlled by a separate control device, or one control device may control two automatic analyzers. Below, the process of 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. FIG. 6 is a flowchart illustrating the process of evaluating the surface condition of the sample probe 122 according to the second embodiment.

[0054] (i) Steps S501 to S507 The process of recovering the dye remaining on the surface of the sample probe 122 of the automatic analyzer 100 into physiological saline (steps S501 to S507) is the same as 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, which has 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 and transports the rack 124 to a position where the sample probe 22 of the automatic analyzer 10, which has 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 solution 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] <Correction of absorbance: amount of recovered dye taking into account adhesion to the inner wall surface of the sample probe 22> (i) In Examples 1 and 2, an automatic analyzer 10 having a spectrophotometer as a detection unit performs a dispensing operation of aspirating and dispensing saline from which residual dye has been recovered from a sample container 302 and dispensing it into a reaction container 25, under the assumption that the dye is not adsorbed onto the surface of the sample probe 22 and that 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 have investigated how much error can occur due to adhesion and how much correction should be made.

[0061] (ii) Figure 7 shows 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 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 in which the dye is adsorbed 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 is difficult to estimate the rate constants 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 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 = (Dm ×t m 2 ) 1 / 2 (2)

[0067] where 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 it is dispensed. 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 Using the radius R of the sample probe, the maximum proportion of dye that can be adsorbed, P, can be estimated as follows:

[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 various dispensing volume conditions, stirring the solution with stirring mechanism 29, and then 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 if a correction coefficient is derived under the worst-case conditions, it can 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 The reciprocal of 1 / P theory It 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 the present 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 the system or device reads the program code stored in the storage medium. In this case, the program code read from the storage medium itself 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 providing such program code include flexible disks, CD-ROMs, DVD-ROMs, hard disks, optical disks, magneto-optical disks, CD-Rs, magnetic tapes, non-volatile memory cards, and ROMs.

[0077] In addition, 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 a memory on a 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 in use, 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 embodiments are described in this disclosure, they are intended in all respects to be illustrative and not restrictive. Those skilled in the art will recognize that there are numerous combinations of hardware, software, and firmware suitable for implementing the disclosed technology. For example, the described software can be implemented in a wide variety of programming or scripting languages, such as assembler, C / C++, Perl, Shell, PHP, Java, 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 present disclosure being indicated by the following claims. [Explanation of symbols]

[0083] 10 Automatic analyzer 11 Reagent container 12 Reagent Disks 13 Reaction Disc 14 Reagent dispensing mechanism 15 Sample dispensing mechanism 21 Reagent probe 22 sample probes 23 Sample container 24 racks 25 Reaction vessel 26 Cleaning tank 27 Special cleaning 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 racks 125 Reaction vessel 126 Cleaning tank 127 Special cleaning 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, a first automated analyzer having a first dispensing probe and a detection unit based on a measurement method other than a spectrophotometer; a second automated analyzer having a second dispensing probe and a spectrophotometer as a detection unit; The first automated analyzer is a first dispensing process in which a dye solution having a predetermined concentration stored in a first container is dispensed by the first dispensing probe; a second dispensing process is carried out in which a solution not containing a dye is dispensed by the first dispensing probe after the first dispensing process, thereby recovering the dye remaining on the inner surface of the first dispensing probe into the solution not containing a 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; After the second container is transferred from the first automated analyzer to the second automated analyzer, The second automated analyzer is a third dispensing process of dispensing the low-concentration dye solution stored in the second container by the second dispensing probe; an absorbance measurement process of measuring the absorbance of the low-concentration dye solution with the spectrophotometer after the third dispensing process; and executing a determination process for determining the cleanliness of the first dispensing probe based on the absorbance measured in the absorbance measurement process. Automated analysis system.

2. In claim 1, The first automated analyzer further comprises: performing a process of washing the first dispensing probe after the first dispensing process between the first dispensing process and the second dispensing process; 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. In claim 1, The dye-free solution is saline or a pH-adjusted phosphate buffer solution.

4. In claim 1, further comprising a conveyance line connecting the first automated analyzer and the second automated analyzer; an automatic analysis system, wherein the second container containing the low-concentration dye solution is transported from the first automatic analysis device to the second automatic analysis device via the transport line;

5. In claim 1, An automated analysis system, 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. In claim 1, Furthermore, it is equipped with an arm-type robot, an automatic analysis system, wherein the arm-type robot transfers the second container containing the low-concentration dye solution from the first automatic analysis device to the second automatic analysis device;

7. In claim 1, The first automatic analyzer is an automatic analysis system that uses electrochemistry, fluorescence, luminescence, or mass spectrometry as a measurement method other than the spectrophotometer.

8. In claim 1, The second automated analyzer is Furthermore, a correction process for correcting the absorbance is performed, An automatic analysis system, wherein the determination process determines the cleanliness of the first dispensing probe based on the corrected absorbance.

9. In claim 8, 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 dispensing is completed.

10. In claim 8, The second automatic analysis device performs the correction process using a correction coefficient that has been prepared in advance and calculated by examining the results of an experiment using the first dispensing probe having contamination attached to its inner surface, an automatic analysis system.

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

12. In claim 11, further comprising: correcting the absorbance in the second automated analyzer; Determining the state of the first dispensing probe includes determining the cleanliness of the first dispensing probe based on the corrected absorbance. Probe status determination method.

13. In claim 12, The probe state determination method 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 the discharge is completed.

14. In claim 12, A probe status determination method in which 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

Patent Citations

  • JP1973092384A

  • JP1974009599A

  • Autoanalyzer and its washing method

    JP2008202945A