Automatic analyzer and control method thereof

By aspirating an amount of outside air equivalent to the air expansion, the dispensing probe's liquid leakage is prevented, ensuring accurate dispensing and analysis in automated analyzers.

JP7809193B2Active Publication Date: 2026-01-30HITACHI HIGH TECH CORP
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Patent Information

Application Number
JP2024500992
Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Priority Date
2022-02-16
Filing Date
2022-12-21
Publication Date
2026-01-30
Estimated Expiration
2042-12-21

AI Technical Summary

Technical Problem

Existing automated analyzers face issues with liquid leakage from dispensing probes that aspirate both air and liquid sequentially, leading to reduced dispensing and analytical accuracy due to the rapid up-and-down movements.

Method used

The solution involves controlling the dispensing unit to aspirate an amount of outside air equivalent to the expansion of air when the dispensing probe rises after aspirating both air and liquid, thereby preventing liquid leakage by balancing the inertial force with the expanding air.

Benefits of technology

This approach effectively suppresses liquid leakage during the upward movement of the dispensing probe, maintaining dispensing and analytical accuracy by synchronizing air aspiration with the probe's motion.

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Abstract

Provided are an automated analyzing device, and a control method for the same, capable of suppressing leakage of liquid when a dispensing probe that has sequentially sucked air and liquid is raised. This automated analyzing device for analyzing a sample comprises a dispensing unit for dispensing the sample and / or a reagent, and a control unit for controlling the dispensing unit, characterized in that, when a dispensing probe of the dispensing unit is raised after having sequentially sucked air and liquid, the control unit causes an amount of outside air corresponding to a length to which the air is stretched to be sucked from a tip end of the dispensing probe.
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Description

[Technical Field]

[0001] The present invention relates to an automatic analyzer and a control method thereof. [Background technology]

[0002] An automated analyzer that analyzes specific components contained in samples such as blood or urine provided by a patient is equipped with a dispensing unit that aspirates the sample or reagent from a sample container or reagent container and dispenses it into a reaction container. Regarding this dispensing unit, Patent Document 1 discloses that when the sample or air is aspirated, an abnormality is detected based on a detection signal output by a sensor that detects the presence or absence of liquid at a predetermined position in the dispensing unit. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Laid-Open No. 2015-10894 Summary of the Invention [Problem to be solved by the invention]

[0004] However, Patent Document 1 does not take into consideration the risk of liquid leakage when the dispensing probe, which has aspirated air and liquid in sequence, ascends. In an automated analyzer, efforts are made to speed up the operation of each component, such as the up-and-down movement of the dispensing probe, in order to shorten the time required for analysis. However, speeding up the up-and-down movement can cause liquid leakage from the dispensing probe, which has aspirated air and liquid in sequence, and liquid leakage from the dispensing probe reduces dispensing accuracy and analytical accuracy.

[0005] SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide an automatic analyzer that can prevent liquid leakage when a dispensing probe that has sucked air and liquid in sequence moves upward, and a control method thereof. [Means for solving the problem]

[0006] In order to achieve the above object, the present invention provides an automatic analyzer for analyzing samples, comprising a dispensing unit that dispenses the sample and / or reagent, and a control unit that controls the dispensing unit, wherein the control unit causes a quantity of outside air equivalent to the length of expansion of the air when a dispensing probe of the dispensing unit sequentially aspirates air and liquid and then rises from the tip of the dispensing probe.

[0007] The present invention also provides a method for controlling an automatic analyzer that analyzes samples, characterized in that when a dispensing probe provided in a dispensing section that dispenses the sample or reagent ascends after sequentially aspirating air and liquid, an amount of outside air equivalent to the length of expansion of the air is aspirated from the tip of the dispensing probe. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide an automatic analyzer that can suppress liquid leakage when a dispensing probe that has sucked air and liquid in sequence moves up, and a control method thereof. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is a schematic diagram showing an example of the overall configuration of an automatic analyzer. [Figure 2] FIG. 3 is a schematic diagram showing an example of the configuration of a dispensing unit. [Figure 3] FIG. 10 is a diagram showing an example of the operation of the dispensing unit. [Figure 4] FIG. 10 is a diagram illustrating the amount of air expansion when the dispensing probe is raised. [Figure 5] FIG. 10 is a diagram showing an example of the rising speed and acceleration of a dispensing probe. [Figure 6] FIG. 10 is a diagram showing an example of the operation of the dispensing unit when aspirating two types of liquid. [Figure 7] FIG. 10 is a diagram illustrating the amount of air expansion when a dispensing probe that has aspirated two types of liquid rises. DETAILED DESCRIPTION OF THE INVENTION

[0010] A preferred embodiment of the automatic analyzer according to the present invention will be described below with reference to the accompanying drawings. In the following description and accompanying drawings, components having the same functional configuration are designated by the same reference numerals, and redundant description will be omitted. [Example]

[0011] An example of the overall configuration of an automatic analyzer will be described using Figure 1. The automatic analyzer is a device that analyzes specific components contained in samples such as blood or urine provided by patients, and includes a disk 102, a dispensing unit 105, an incubator (reaction disk) 104, a measuring unit 106, a control unit 107, an input / output unit 108, and a memory unit 109. Each unit will be described below.

[0012] The disk 102 stores the specimen container 100 containing the specimen and the reagent bottle 101 containing the reagent, and also transports the specimen container 100 and the reagent bottle 101 to a position where the dispensing unit 105 can access them.

[0013] The dispensing unit 105 dispenses specimens and reagents from specimen containers 100 or reagent bottles 101 into reaction cells 103 stored in an incubator 104. The specimens and reagents may be dispensed by a single dispensing unit 105, or the specimens and reagents may be dispensed individually by each of a plurality of dispensing units 105. A more detailed configuration of the dispensing unit 105 will be described later using FIG. 2.

[0014] The incubator 104 stores the reaction cell 103, which contains a mixture of a specimen and a reagent, within a temperature range that allows the mixture to react, and transports the reaction cell 103 to a position that is accessible to the dispensing unit 105 and the measurement unit 106. The mixture in the reaction cell 103 becomes a reaction liquid to be used in measurement by storing the reaction cell 103 within a predetermined temperature range.

[0015] The measurement unit 106 irradiates the reaction cell 103 with light, measures the light from the reaction cell 103 , and transmits a measurement signal to the control unit 107 .

[0016] The control unit 107 is a computer that analyzes a specific component contained in the sample based on the measurement signal transmitted from the measurement unit 106 and controls the operation of each unit.

[0017] The input / output unit 108 is a device that receives input of data necessary for analysis and displays the results of the analysis, and is, for example, a keyboard, a mouse, a touch panel, a liquid crystal display, or the like.

[0018] The storage unit 109 is a device that stores data necessary for analysis and analysis results, and is, for example, a hard disk drive (HDD) or a solid state drive (SSD).

[0019] An example of the configuration of the dispensing unit 105 will be described with reference to Fig. 2. The dispensing unit 105 includes a shaft 201, an arm 202, a dispensing probe 203, a syringe pump 204, a tube 205, and an electromagnetic valve 206.

[0020] The shaft 201 is a hollow member extending vertically and can be moved up and down. The arm 202 is a hollow member extending horizontally, with one end connected to the upper end of the shaft 201 and the other end to which a dispensing probe 203 is attached, and is rotated around the shaft 201 as the rotation axis. By rotating the arm 202, the dispensing probe 203 is moved to directly above the sample container 100 or the reagent bottle 101.

[0021] The dispensing probe 203 is a thin tube that is inserted into the sample container 100 or the reagent bottle 101 by the up and down movement of the shaft 201, and its upper end is connected to a tube 205. The tube 205 passes through the arm 202 and the shaft 201 and connects the dispensing probe 203 to a syringe pump 204.

[0022] Syringe pump 204 applies pressure to the system water in dispensing probe 203 by driving plunger 207 to suck in and discharge specimens, reagents, and air from the lower end of dispensing probe 203. That is, specimens and the like are dispensed by sucking in the system water by creating negative pressure and discharging the system water by creating positive pressure.

[0023] The solenoid valve 206 is provided between the syringe pump 204 and a system water container 208 that stores system water, and is closed while the specimen or the like is being dispensed. When dispensing is complete, the solenoid valve 206 is opened, and the inner wall of the dispensing probe 203 is washed with the system water supplied from the system water container 208, and the inside of the tube 205 is filled with the system water. In other words, the tube 205 is filled with system water before dispensing.

[0024] 3, the case of aspirating a sample will be described as an example of the operation of dispensing unit 105 controlled by control unit 107. Note that the liquid to be aspirated is not limited to a sample, and may be a reagent.

[0025] (a) By rotating the arm 202, the dispensing probe 203 moves directly above the specimen container 100 containing the specimen 303. At the tip of the dispensing probe 203, there is air 302 for separating the system water 301 and the specimen 303.

[0026] (b) As the shaft 201 descends, the dispensing probe 203 is inserted into the sample container 100. When the lower end of the dispensing probe 203 falls below the liquid level of the sample 303, the descent of the shaft 201 and the dispensing probe 203 is stopped. Whether or not the lower end of the dispensing probe 203 is below the liquid level of the sample 303 is determined based on the output signal of a liquid level sensor (not shown).

[0027] (c) The syringe pump 204 creates a negative pressure in the system water 301, and the specimen 303 is sucked from the lower end of the dispensing probe 203. Note that the liquid level drops as the specimen 303 is sucked, so the height of the dispensing probe 203 during the suction is adjusted so that the lower end is not exposed to the air.

[0028] (d) After aspirating a predetermined amount of sample 303, the dispensing probe 203 begins to rise. As the dispensing probe 203 accelerates and rises, a downward inertial force acts on the aspirated sample 303, causing the air 302 to expand, which may push a portion of the aspirated sample 303 out of the dispensing probe 203, resulting in liquid leakage. Therefore, in Example 1, as the dispensing probe 203 begins to rise, suction is initiated to prevent liquid leakage. The amount of suction is controlled according to the amount of expansion of the air 302. The amount of expansion of the air 302 will be described later using Figure 4.

[0029] (e) The dispensing probe 203 continues to rise while accelerating, and the lower end of the dispensing probe 203 separates from the liquid surface. Even after the lower end of the dispensing probe 203 separates from the liquid surface, inertial force continues to act on the aspirated sample 303 while the dispensing probe 203 continues to rise while accelerating, so suction to prevent liquid leakage continues. After the lower end of the dispensing probe 203 separates from the liquid surface, air is aspirated.

[0030] (f) After the dispensing probe 203 reaches its maximum upward speed, it slows down and stops at the upper limit, which is the height when the dispensing probe 203 is in a standby state. Note that during the period when the upward speed is constant, the air 302 does not expand, and during the period when the upward speed is slowing, the air 302 contracts, so no liquid leakage occurs during either period. The period when the upward speed is constant includes the period when the speed is at its maximum and the period when the dispensing probe 203 is stopped at the upper limit. In other words, when the dispensing probe 203 is stopped at its upper limit, the air 302 does not expand or contract.

[0031] The amount of extension Δh of the air 302 will be explained using Figure 4. When the dispensing probe 203 containing the system water 301, air 302, and specimen 303 rises at an acceleration α, a downward inertial force acts on the specimen 303, causing the air 302 to extend. If the air 302 is considered to be an air spring with a spring constant k, the force kΔh generated by the amount of extension Δh balances with the inertial force mα acting on the specimen 303 with mass m, and the following equation holds:

[0032] kΔh-mα=0 … (Equation 1) The spring constant k of an air spring can be expressed by the following equation using Boyle-Charles' law and Hooke's law:

[0033] k=γ(A 2 P) / V a … (Formula 2) where γ is the polytropic exponent of the air 302, A is the cross-sectional area of ​​the dispensing probe 203, P is the pressure of the air 302, and V a is the volume of the air 302. If the series of operations in the dispensing probe 203 is considered an adiabatic cycle, then γ=1.4. Furthermore, since the bottom end of the dispensing probe 203 is open to the atmosphere before being inserted into the sample container 100, the pressure P is atmospheric pressure.

[0034] The mass m of the specimen 303 is determined by the density ρ and volume V of the specimen 303. m By using the above formula, it can be expressed as follows:

[0035] m=ρV m … (Formula 3) Furthermore, the height of specimen 303 is h m and the height of air 302 h a is the volume V of the specimen 303 m and the volume V of air 302 a and the cross-sectional area A of the dispensing probe 203, it can be expressed by the following equation.

[0036] h a =V m / A … (Formula 4) h a =V a / A … (Formula 5) Then, by using (Equation 2) to (Equation 5), we can solve (Equation 1) for Δh, resulting in the following equation.

[0037] Δh=h a h m ρα / (γP) … (Equation 6) Furthermore, the leakage amount ΔV of the sample 303 pushed out from the dispensing probe 203 due to the expansion of the air 302 is proportional to the acceleration α, as shown in the following equation.

[0038] ΔV=AΔh+C =V a V m ρα / (γPA)+C … (Equation 7) Here, C is a noise component including viscous friction between the inner wall of the dispensing probe 203 and the specimen 303, vibration of the dispensing probe 203, etc., and is set in advance according to the type and amount of the specimen 303. a V m This is a value that is much smaller than ρα / (γPA).

[0039] An example of the ascending speed u and acceleration α of the dispensing probe 203 will be described using Figure 5. In Figure 5, the ascending speed u is shown by a solid line, which continuously changes from a maximum speed u_max during the time from when the dispensing probe 203, which has aspirated a predetermined amount of sample 303, begins ascending at time t1 until it stops at its upper limit at time t6. The acceleration α, which continuously changes throughout the acceleration period from time t1 to time t3, the constant-speed period from time t3 to time t4, and the deceleration period from time t4 to time t6, is shown by a dotted line. The acceleration α reaches a maximum value α_max at time t2 and a minimum value α_min at time t5. The maximum value α_max and minimum value α_min of the acceleration α are determined by the maximum speed u_max of the dispensing probe 203 and the time (t6-t1) required for the ascent.

[0040] As shown in (Equation 7), the leakage amount ΔV of the specimen 303 is proportional to the acceleration α, so when the ascending speed u and acceleration α of the dispensing probe 203 change as shown in Fig. 5, the leakage amount ΔV becomes maximum at time t2. In other words, liquid leakage can be suppressed by sucking in an amount of outside air from the dispensing probe 203 that corresponds to the leakage amount ΔV calculated by substituting α = α_max into (Equation 7).

[0041] Furthermore, since liquid leakage occurs during the acceleration period from time t1 to time t3, the suction of outside air from the dispensing probe 203 may be limited to the acceleration period from time t1 to time t3. By limiting the suction of outside air to the acceleration period, the area where the inner wall of the dispensing probe 203 comes into contact with the aspirated sample 303 can be made narrower. [Example]

[0042] In Example 1, a case where one type of liquid is aspirated by the dispensing probe 203, that is, a case where only the specimen 303 is aspirated, is described. The liquid aspirated by the dispensing probe 203 is not limited to one type, and multiple types may be aspirated. In Example 2, a case where two types of liquid are aspirated by the dispensing probe 203 is described. Note that the difference from Example 1 is that the dispensing probe 203 aspirates two types of liquid instead of one type, and therefore other explanations will be omitted.

[0043] Referring to FIG. 6, an example of the operation of dispensing unit 105 controlled by control unit 107 will be described, in which first liquid 602 is aspirated and then second liquid 604 is aspirated.

[0044] (a) By rotating the arm 202, the dispensing probe 203 moves to a position directly above a container 605 containing a second liquid 604. Note that the dispensing probe 203 has aspirated a first air 601 and a first liquid 602. In addition, at the tip of the dispensing probe 203, there is a second air 603 for separating the first liquid 602 and the second liquid 604.

[0045] (b) As the shaft 201 descends, the dispensing probe 203 is inserted into the container 605. When the lower end of the dispensing probe 203 falls below the liquid level of the second liquid 604, the descent of the shaft 201 and the dispensing probe 203 is stopped. Whether or not the lower end of the dispensing probe 203 is below the liquid level of the second liquid 604 is determined based on the output signal of the liquid level sensor, as in the first embodiment.

[0046] (c) The syringe pump 204 creates a negative pressure in the system water 301, and the second liquid 604 is sucked from the lower end of the dispensing probe 203. The height of the dispensing probe 203 during suction is adjusted so that the lower end is not exposed to the air.

[0047] (d) After aspirating a predetermined amount of second liquid 604, the dispensing probe 203 begins to rise. As the dispensing probe 203 rises while accelerating, a downward inertial force acts on the first liquid 602 and the second liquid 604, causing the first air 601 and the second air 603 to expand, and some of the aspirated second liquid 604 is pushed out of the dispensing probe 203, which may result in liquid leakage. Therefore, in Example 2, as the dispensing probe 203 begins to rise, suction is also started to prevent liquid leakage. The amount of suction is controlled according to the amount of expansion of the first air 601 and the second air 603. The amount of expansion of the first air 601 and the second air 603 will be described later using FIG. 7.

[0048] (e) The dispensing probe 203 continues to rise while accelerating, and the lower end thereof separates from the liquid surface. Even after the lower end of the dispensing probe 203 separates from the liquid surface, inertial force continues to act on the first liquid 602 and the second liquid 604 while the dispensing probe 203 continues to rise while accelerating, so suction to prevent liquid leakage continues. After the lower end of the dispensing probe 203 separates from the liquid surface, air is sucked in.

[0049] (f) After the dispensing probe 203 reaches its maximum ascending speed, the ascending speed is decelerated and the dispensing probe 203 stops at the upper limit point, which is the height when the dispensing probe 203 is in a standby state. Note that, as in Example 1, no liquid leakage occurs during the constant-speed period and the decelerating period of the ascending speed.

[0050] Using FIG. 7, the expansion amount Δh of the first air 601 a1 and the expansion amount Δh of the second air 603 a2 When the dispensing probe 203 containing the first air 601, the first liquid 602, the second air 603, and the second liquid 604 rises at an acceleration α, a downward inertial force acts on the first liquid 602 and the second liquid 604, causing the first air 601 and the second air 603 to expand. If the first air 601 is considered as an air spring with a spring constant k1, the expansion amount Δh of the first air 601 is a1 The force k1Δh generated by a1 is balanced with the inertial force (m1+m2)α acting on the first liquid 602 of mass m1 and the second liquid 604 of mass m2, so the following equation holds:

[0051] k1Δh a1 -(m1+m2)α=0 … (Equation 8) Also, if the second air 603 is regarded as an air spring with a spring constant k2, the expansion amount Δh of the second air 603 is a2 The force k2Δh generated by a2 is balanced with the inertial force m2α acting on the second liquid 604, so the following equation holds:

[0052] k2Δh a2 -m2α=0 … (Formula 9) The spring constants k1 and k2 of the air spring are calculated using Equation 2.

[0053] The amount of extension Δh that pushes out the second liquid 604 is calculated from (Equation 8) and (Equation 9), respectively. a1 and Δh a2 is the sum of the following equation:

[0054] Δh=Δh a1 +Δh a2 … (Equation 10) Furthermore, the leakage amount ΔV of the second liquid 604 pushed out from the dispensing probe 203 due to the expansion of the first air 601 and the second air 603 is expressed by the following equation using (Equation 2) to (Equation 5) and (Equation 8) to (Equation 10).

[0055] ΔV=AΔh+C ={V a1 (V m1 +V m2 )+V a2 V m2}ρα / (γPA)+C ... (Equation 11) As shown in (Equation 11), even when two types of liquids are aspirated, the leakage amount ΔV is proportional to the acceleration α when the dispensing probe 203 rises. In other words, even when multiple types of liquids are aspirated, liquid leakage can be suppressed by aspirating from the dispensing probe 203 an amount of outside air equivalent to the leakage amount ΔV obtained by substituting the maximum value of the acceleration α into (Equation 11). Furthermore, by limiting the suction of outside air to the acceleration period, the area where the suctioned liquid comes into contact with the inner wall of the dispensing probe 203 can be made narrower.

[0056] If equation (11) is expanded to the leakage amount ΔV when n types of liquid are aspirated, the following equation is obtained:

[0057] ΔV={V a1 (V m1 +V m2 +…+V mn )+…+V an V mn}ρα / (γPA)+C … (Equation 12) From (Equation 11) and (Equation 12), it can be seen that when a single dispensing probe 203 aspirates multiple types of liquid, the volume of the first air 601 has a large effect.

[0058] The above describes several embodiments of the present invention. The present invention is not limited to the above embodiments, and the components may be modified within the scope of the gist of the invention. Furthermore, the components disclosed in the above embodiments may be appropriately combined. Furthermore, some components may be omitted from all the components shown in the above embodiments. [Explanation of symbols]

[0059] 100: sample container, 101: reagent bottle, 102: disk, 103: reaction cell, 104: incubator, 105: dispensing unit, 106: measurement unit, 107: control unit, 108: input / output unit, 109: memory unit, 201: shaft, 202: arm, 203: dispensing probe, 204: syringe pump, 205: tube, 206: solenoid valve, 207: plunger, 208: system water container, 301: system water, 302: air, 303: sample, 601: first air, 602: first liquid, 603: second air, 604: second liquid, 605: container

Claims

1. An automated analyzer for analyzing a sample, a dispensing unit that dispenses the sample and / or reagent; a control unit for controlling the dispensing unit, When the dispensing probe of the dispensing unit sequentially aspirates first air and first liquid, and then sequentially aspirates second air and second liquid, and then ascends, the control unit regards the first air and the second air as an air spring, and calculates an amount ΔV corresponding to the sum of the length of extension of the first air and the length of extension of the second air, based on the acceleration α when the dispensing probe ascends, the volume Va1 of the first air, the volume Vm1 of the first liquid, the volume Vm2 of the second air, and the acceleration α when the dispensing probe ascends. a volume Va2 of the first liquid, a volume Vm2 of the second liquid, a density ρ of the first liquid and the second liquid, a polytropic index γ of the first air and the second air, a pressure P of the first air and the second air, a cross-sectional area A of the dispensing probe, and a noise component C, and calculates ΔV as follows: ΔV = {Va1(Vm1+Vm2) + Va2Vm2}ρα / (γPA) + C, and then aspirates the calculated amount of outside air from the tip of the dispensing probe.

2. The automatic analyzer according to claim 1, The automatic analyzer is characterized in that the control unit causes the outside air to be sucked in during an acceleration period when the dispensing probe is raised.

3. A method for controlling an automatic analyzer for analyzing a sample, comprising: When a dispensing probe provided in a dispensing unit that dispenses the sample or reagent aspirates first air and a first liquid in that order, and then aspirates second air and a second liquid in that order, and then rises, the first air and the second air are regarded as air springs, and an amount ΔV corresponding to the sum of the length of extension of the first air and the length of extension of the second air is calculated by the acceleration α when the dispensing probe rises, the volume Va1 of the first air, the volume Vm1 of the first liquid, and the amount ΔV of the second air. A control method characterized by calculating ΔV = {Va1(Vm1+Vm2)+Va2Vm2}ρα / (γPA) + C using the volume of air Va2, the volume of the second liquid Vm2, the density ρ of the first liquid and the second liquid, the polytropic index γ of the first air and the second air, the pressure P of the first air and the second air, the cross-sectional area A of the dispensing probe, and a noise component C, and then aspirating the calculated amount of outside air from the tip of the dispensing probe.

4. An automatic analyzer for analyzing a sample, comprising: a dispensing unit that dispenses the sample and / or reagent; a control unit for controlling the dispensing unit, The control unit regards each of the n air particles as an air spring when the dispensing probe of the dispensing unit sequentially aspirates air and liquid n times and then rises, and calculates an amount ΔV equivalent to the sum of the extension lengths of each of the n air particles using the acceleration α when the dispensing probe rises, the volume Van of the nth air particle, the volume Vmn of the nth liquid particle, the density ρ of the liquid, the polytropic exponent γ of the air, the pressure P of the air, the cross-sectional area A of the dispensing probe, and the noise component C, as ΔV = {Va1(Vm1+Vm2+...+Vmn)+...+VanVmn}ρα / (γPA)+C, and causes the calculated amount of outside air to be aspirated from the tip of the dispensing probe.

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