WO2016132798A1 - Automated analysis device - Google Patents

Automated analysis device Download PDF

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Publication number
WO2016132798A1
WO2016132798A1 PCT/JP2016/051484 JP2016051484W WO2016132798A1 WO 2016132798 A1 WO2016132798 A1 WO 2016132798A1 JP 2016051484 W JP2016051484 W JP 2016051484W WO 2016132798 A1 WO2016132798 A1 WO 2016132798A1
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Prior art keywords
automatic analyzer
reagent
container
reaction liquid
reaction
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PCT/JP2016/051484
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French (fr)
Japanese (ja)
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昌彦 飯島
創 山崎
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株式会社 日立ハイテクノロジーズ
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Priority to JP2017500554A priority Critical patent/JP6470390B2/en
Priority to CN201680008708.9A priority patent/CN107533073A/en
Publication of WO2016132798A1 publication Critical patent/WO2016132798A1/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations

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  • the present invention relates to an automatic analyzer that analyzes a component of a biological sample such as blood and urine, and more particularly to an automatic analyzer that performs analysis under conditions where the temperature is higher when the reagent is used than when the reagent is stored.
  • the present invention relates to an analyzer.
  • An automatic analyzer that qualitatively and quantitatively analyzes a target component by mixing a sample and a reagent in a reaction vessel and measuring the optical characteristics of the reaction solution requires stable photometric performance.
  • automatic analyzers that perform analysis with a small amount of a reaction solution by reducing the consumption of samples and reagents from the viewpoint of reducing running costs and reducing the burden on patients have become widespread.
  • the reaction vessel is miniaturized to reduce the amount of reagents and samples used for measurement, and the area of the reaction solution that can be measured is reduced, so that the bundle of light from the light source used for photometry is reduced. It is necessary to make it thinner. Therefore, especially in these apparatuses, even bubbles having a smaller size than in the past may greatly affect photometry, which may hinder normal measurement.
  • Patent Document 1 in the automatic analyzer, in order to remove bubbles adhering to the inner wall of the reaction vessel from the path of the measurement light, the action of the buoyancy of the bubbles themselves and the acoustic radiation pressure of the sound waves emitted from the sound wave irradiation mechanism are disclosed. A technique that uses the action is described.
  • the reagent storage of the automatic analyzer is kept at a low temperature (eg, 5 to 15 ° C.) in order to maintain the quality of the reagent.
  • a thermostatic chamber equipped with a reaction vessel for mixing and measuring a sample and a reagent is kept at a higher temperature (eg, 37 ° C.) in order to increase the efficiency of the reaction and keep the reaction rate constant. ing.
  • the reagent In the reagent storage, the reagent is refrigerated and stored in contact with the atmosphere, so that oxygen, carbon dioxide, etc. in the atmosphere are dissolved in the reagent.
  • the temperature of the reagent dispensed by the reagent dispensing mechanism into the reaction vessel in the thermostatic chamber rises by 20 ° C. or more. Therefore, the dissolved gas dissolved in the reagent in the state of refrigeration and storage in the reagent storage gradually foams as the temperature rises in the reaction vessel, and the generated bubbles adhere to the inner wall and are used for photometry. May have an effect.
  • the present invention reduces the influence of bubbles on the cell inner wall caused by foaming of the dissolved gas in the reagent accompanying the temperature rise of the reaction solution, and the effect on photometry, thereby enabling highly accurate measurement.
  • An object of the present invention is to provide an automatic analyzer for performing.
  • a container that contains a reagent or a reaction liquid, a light source that irradiates light to the container, and a detector that detects a signal generated based on light emitted from the light source, A control unit that analyzes the reaction solution based on the output of the detector, and a sound wave irradiation unit that irradiates the container with sound waves, and the control unit includes a reagent contained in the container or a reaction
  • an automatic analyzer characterized by controlling the operation of the sound wave irradiation unit so as to deaerate by irradiating a liquid with a sound wave, and an analysis method using the apparatus.
  • photometry is performed using a reagent or a reaction solution that has been degassed in advance by a sound wave irradiation mechanism, so that the influence on data due to bubbles / foaming bubbles in the reaction vessel is prevented and stable.
  • a measurement result can be obtained and an automatic analyzer with high reliability can be provided.
  • FIG. 1 is a block diagram showing an example of the basic configuration of the automatic analyzer according to the present embodiment.
  • the automatic analyzer 100 mainly includes a sample container 103 that accommodates a sample disk 101 and its concentrically arranged sample 102, a reaction disk 104 and a reaction container 105 that is concentrically arranged, a sample dispensing mechanism 106, a reagent Reagent container 109 for accommodating various reagents 108 arranged concentrically with the disk 107, a reagent dispensing mechanism 110, a sound wave irradiation mechanism 111, a stirring mechanism 112, a constant temperature bath circulating liquid 113, a photometric mechanism 114, a reaction container cleaning mechanism 115, an overall control unit 121, an input unit 119, and an output unit 120.
  • the overall control unit 121 includes a control circuit 116, a photometry circuit 117, and a computer 118, an input unit 119 (for example, a pointing device, a keyboard, a tablet, and the like), a graphical user interface (GUI) relating to measurement results and various operations. Etc. are provided.
  • the overall control unit 121 is connected to each component unit and controls the entire apparatus, but may be configured to include an independent control unit for each component unit.
  • Analysis by the automatic analyzer 100 is mainly performed as follows. First, the sample 102 set on the sample disk 101 is dispensed from the sample container 103 to the reaction container 105 by the sample dispensing mechanism 106. The reaction container 105 containing the sample 102 is moved to the reagent dispensing position by the rotation operation of the reaction disk 104, and the reagent dispensing mechanism 110 puts the reagent 108 used for analysis into the sample 102 from the reagent container 109. Dispense into the reaction vessel 105.
  • the mixed solution of the sample 102 and the reagent 108 accommodated in the reaction vessel 105 is referred to as a reaction solution 122.
  • reaction solution 122 in the reaction vessel 105 is degassed by the sound wave irradiation mechanism 111, the reaction solution 122 in the reaction vessel 105 is stirred by the stirring mechanism 112.
  • the reaction vessel 105 is maintained at a constant temperature, for example, 37 ° C., by a constant temperature bath circulating liquid 113 filled in the lower part of the reaction disk 104 to promote the reaction and stabilize the progress of the reaction.
  • FIG. 2 is a flowchart showing the flow of deaeration and stirring operations in the automatic analyzer according to the present embodiment.
  • step 201 first, a sample to be analyzed is dispensed into a reaction container (step S201).
  • step 202 whether the degassing target is the reaction liquid in the reaction container or the reagent in the reagent container, that is, whether the place to be degassed is the reaction container or not.
  • the subsequent steps are divided into two patterns.
  • the object of the deaeration process can be set in advance as an analysis condition by the operator via the input unit 119 or the like and stored in the data storage unit 124 (step S202).
  • step S203 when the degassing target is the reaction liquid stored in the reaction container, the process proceeds to step 203, where the reagent is dispensed into the reaction container (step S203), and then into the reaction liquid in step 204.
  • the reaction solution is degassed by the sound wave irradiation (step S204), and then bubbles generated by stirring the reaction solution are removed (step S205).
  • step S206 If the target of the degassing process is a reagent contained in the reagent container, the reagent in the reagent container is degassed by irradiating with sound waves in step 206 (step S206), and then degassed in step 207.
  • step S207 The reagent thus dispensed is dispensed into the reaction container (step S207), and then the reaction solution is stirred in step 208 (step S208). Finally, in step 209, the optical property change is measured for the reaction solution that has undergone either step 205 or step 208 (step S209).
  • step 210 the result of the analysis process is acquired and processed. The process ends (step 210). Even when the second reagent is added, Step 201 to Step 210 are repeated in the same manner as the first reagent.
  • the example in which the reagent is dispensed after dispensing the sample into the reaction container has been described.
  • the sample is dispensed after the reagent has been dispensed into the reaction container first.
  • a reagent or reaction solution degassing step may be applied.
  • FIG. 3 is a block diagram showing an example of degassing and stirring of the reaction liquid in the reaction vessel using ultrasonic waves in the automatic analyzer according to the present embodiment.
  • Show. 3A is a step of degassing the reaction liquid 122 by the sound wave irradiation mechanism 111 to positively foam the microbubbles 302
  • FIG. 3B is a step of removing the microbubbles 302 in the reaction liquid 122 by the stirring mechanism 112. It is a step to do.
  • the sound wave irradiation mechanism 111 and the stirring mechanism 112 can be used together by the same mechanism, that is, the sound wave irradiation mechanism 111 operates in FIG. 3A and the stirring mechanism 112 operates in FIG.
  • a deaeration-only sound irradiation mechanism 111 suitable for deaeration and a stirring-only stirring mechanism 112 suitable for stirring are provided in different places as shown in FIG. 1.
  • the deaeration step shown in FIG. 3A and the bubble removal step shown in FIG. 3B may be performed continuously in the same apparatus operation cycle, or may be performed in different operation cycles. .
  • the bubbles shown in FIG. 3A By performing agitation in the removal step and using the subsequent photometric data for concentration calculation, the bubble removal operation can be performed more reliably.
  • the sound wave irradiation mechanism 111 shown in FIG. 3A is mainly composed of a piezoelectric element 303 which is a sound source and a piezoelectric element driving circuit 304.
  • the piezoelectric element driving circuit 304 is connected to the control circuit 116 and controlled based on an instruction from the control circuit 116.
  • the control circuit 116 performs control in accordance with an instruction from the overall control unit 121 responsible for higher-level control.
  • One or a plurality of electrodes are arranged on the surface of the piezoelectric element 303, and the region to be irradiated with the sound wave is selected by selecting the position of the electrode to which the voltage is applied.
  • Parameters such as the intensity of the sound wave irradiated from the piezoelectric element 303 and the irradiation time include the total amount of the reaction liquid 122 and the height of the liquid surface stored in the reaction vessel 105, the viscosity of the reaction liquid 122, and the reaction liquid 122. It is configured to be adjustable depending on the wettability between the reaction vessel 105 and the like.
  • the ultrasonic wave 305 generated in the piezoelectric element 303 by the piezoelectric element driving circuit 304 reaches the reaction liquid 122 in the reaction vessel 105 through the constant temperature bath circulating liquid 113 filled in the constant temperature tank 301.
  • the drive region of the piezoelectric element 303 is selected according to the liquid level of the reaction liquid 122, It is desirable to control so that the ultrasonic wave 305 is irradiated to the whole area below the liquid level of the reaction liquid 122 so that the degassing can be performed efficiently.
  • the frequency and irradiation time of the ultrasonic wave 305 may be selected so that more efficient deaeration is possible depending on the properties of the reaction liquid 122.
  • microbubbles 302 are shown larger than the actual ratio, but in reality, the bubbles of the dissolved gas that are foamed are very small.
  • FIG. 3 shows an example of the sound wave irradiation mechanism 111.
  • the piezoelectric element 303 is disposed on any of the front surface, side surface, and upper and lower surfaces of the reaction vessel 105. May be.
  • the piezoelectric element 303 may be immersed in the reaction liquid 122 and the reaction liquid 122 may be directly irradiated with ultrasonic waves.
  • the microbubbles 302 are attached to the inner wall of the reaction vessel 105, and the measurement is performed using the region excluding the attached portion of the microbubbles 302 to the inner wall.
  • the measurement can be performed without performing the bubble removal step described later.
  • the microbubbles 302 are actually very small, and depending on the situation, it may be difficult to completely remove the bubbles only by irradiating sound waves.
  • the bubble removal step shown in FIG. 3B the ultrasonic wave 305 is irradiated only to the vicinity of the liquid surface of the reaction liquid 122 (the area near the liquid surface), and the liquid surface of the reaction liquid 122 is vibrated, and the reflection plate By the action of the ultrasonic wave 305 reflected by 306, large bubbles are actively taken in from the liquid surface and pushed into the reaction liquid 122. A swirling flow is generated in the entire reaction liquid 122 due to the movement of large bubbles taken into the reaction liquid 122, and stirring is performed.
  • the micro bubbles 302 adhering to the inner wall of the reaction vessel 105 can be removed as a result by the action of the large bubbles taken into the solution and the swirling flow of the entire reaction solution 122.
  • FIG. 4 is a block diagram showing an example of reaction liquid deaeration using ultrasonic waves and stirring using a stirring bar in the automatic analyzer according to the present embodiment.
  • FIG. 4A shows a step of degassing the reaction liquid 122 with the ultrasonic wave 305
  • FIG. 4B shows a step of removing microbubbles with the stirring rod 401.
  • FIG. 4 shows a configuration in which the sound wave irradiation step and the stirring step are performed at the same location, but as described above in the first embodiment, each step is performed at different locations. It doesn't matter.
  • the reaction liquid 122 is degassed more efficiently. It is good also as a structure.
  • the step of removing the microbubbles by the stirring mechanism 112 may be configured to stir the reaction liquid 122 by rotating the stirring bar 401. Even with this configuration, the microbubbles 302 attached to the inner wall of the reaction vessel 105 can be removed using the swirling flow of the entire reaction liquid 122.
  • FIG. 5 is a block diagram illustrating an example of reagent deaeration inside the reagent container using ultrasound in the automatic analyzer according to the present embodiment.
  • the present embodiment is characterized in that the sound wave irradiation mechanism 111 is installed at the installation position of the reagent container 109 in the reagent disk 107.
  • FIG. 5A shows a step of degassing the reagent 108 by the ultrasonic wave 305
  • FIG. 5B shows a step of sucking the degassed reagent 108 by the reagent nozzle 501 of the reagent dispensing mechanism 110.
  • the ultrasonic wave 305 is irradiated to the reagent 108 before being dispensed into the reaction container 105, and the reagent 108 is degassed in advance in the reagent container 109.
  • the microbubbles 302 generated at this time adhere to the inner wall of the reagent container 109.
  • only the reagent 108 is sucked by the reagent nozzle 501 of the reagent dispensing mechanism 110 so that the microbubbles 302 adhering to the inner wall are left behind.
  • the adhesion of the microbubbles 302 to the inner wall of the reaction vessel 105 can be suppressed.
  • the ultrasonic wave 305 is periodically irradiated to remove the reagent 108. It can also be set as the structure hold
  • FIG. 6 is a block diagram showing an example of reagent deaeration in the reaction container using ultrasound in the automatic analyzer according to the present embodiment.
  • FIG. 6A shows a step of degassing the reagent 108 by the ultrasonic wave 305
  • FIG. 6B shows a step of sucking the degassed reagent 108 by the reagent nozzle 501 of the reagent dispensing mechanism 110.
  • FIG. 6 shows a configuration in which the sound wave irradiation step and the reagent suction step are performed at the same location, but each step may be performed at different locations.
  • the reagent 108 is first dispensed into the first reaction container by the reagent dispensing mechanism 110, and is shown in FIG. 6A in the first container (a container for degassing).
  • the microbubbles 302 adhere to the inner wall of the first container 601. Subsequently, the reagent nozzle 501 sucks only the reagent 108 with respect to the degassed reagent 108 and performs a dispensing operation so as to leave the microbubbles 302 attached to the inner wall. The sucked and degassed reagent 108 is dispensed into a second container (reaction container) (not shown), mixed with the sample 102, and photometrically measured. By comprising in this way, the foaming in the 2nd container used for photometry and adhesion to the inner wall of the microbubble 302 can be suppressed.
  • reaction container not shown
  • the coagulation reaction starts when the sample and the reagent are mixed. Therefore, deaeration cannot be performed on the reaction solution in which the sample and the reagent are mixed. .
  • the reagent before mixing with the sample can be degassed, the generation of bubbles thereafter is suppressed, and the influence on the analysis result Can be reduced.
  • Reagent dispensing mechanism 111 ... Sound wave irradiation mechanism 112 ... Stirring mechanism 113 ... Constant temperature bath circulating liquid 114 ... Photometric mechanism 115 ... Reaction container cleaning mechanism 116 ... Control circuit 117 ... photometry circuit 118 ... computer 119 ... input unit 120 ... output unit 121 ... overall control unit 122 ... reaction liquid 123 ... calculation unit 124 ... memory Part 301 ... thermostat 302 ... microbubble 303 ... piezoelectric element 304 ... piezoelectric element drive circuit 305 ... ultrasonic wave 306 ... reflector 401 ... stirring bar 501 ... reagent Noz 601 ... container

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Abstract

The purpose of the present invention is to provide an automated analysis device that reduces foaming of dissolved gas associated with an increase in the temperature of a reaction solution, reduces impacts on measurement results, and makes stable photometry possible. The present invention is provided with an ultrasonic irradiation mechanism for irradiating a reagent or reaction solution with ultrasonic waves; degassing is performed in advance by irradiation with ultrasonic waves and is followed by mixing and photometry. Due to this configuration, stable photometry becomes possible, in which during the photometry the foaming of dissolved gas and adhesion to an inner wall of a reaction container are prevented.

Description

自動分析装置Automatic analyzer
 本発明は、血液や尿等の生体試料の成分分析を行う自動分析装置に係り、特に、試薬保管時の温度に比べ、試薬使用時の方が高い温度となる条件の下で分析を行う自動分析装置に関するものである。 The present invention relates to an automatic analyzer that analyzes a component of a biological sample such as blood and urine, and more particularly to an automatic analyzer that performs analysis under conditions where the temperature is higher when the reagent is used than when the reagent is stored. The present invention relates to an analyzer.
 試料と試薬とを反応容器内で混合し、反応液の光学的な特性を測定することにより目的成分の定性・定量分析を行う自動分析装置では、安定した測光性能が要求される。また、近年では、ランニングコスト低減や、患者の負担低減等の観点から、試料・試薬の消費量を減らし、少ない反応液量での分析を行う自動分析装置が普及している。このような装置においては、測定に使用する試薬、試料の微量化のために反応容器を小型化し、測光可能な反応液の面積を小さくしていることから、測光に用いる光源からの光の束を細くする必要がある。そのため、特にこれらの装置にあっては、従来に比べ微小なサイズの気泡までもが測光に大きく影響し、正常な測定の妨げとなることがある。 An automatic analyzer that qualitatively and quantitatively analyzes a target component by mixing a sample and a reagent in a reaction vessel and measuring the optical characteristics of the reaction solution requires stable photometric performance. In recent years, automatic analyzers that perform analysis with a small amount of a reaction solution by reducing the consumption of samples and reagents from the viewpoint of reducing running costs and reducing the burden on patients have become widespread. In such an apparatus, the reaction vessel is miniaturized to reduce the amount of reagents and samples used for measurement, and the area of the reaction solution that can be measured is reduced, so that the bundle of light from the light source used for photometry is reduced. It is necessary to make it thinner. Therefore, especially in these apparatuses, even bubbles having a smaller size than in the past may greatly affect photometry, which may hinder normal measurement.
 特許文献1には、自動分析装置において、反応容器の内壁に付着した気泡を測定光の経路から除去するために、気泡自体の浮力の作用と音波照射機構から照射された音波の音響放射圧の作用とを利用する技術について説明されている。 In Patent Document 1, in the automatic analyzer, in order to remove bubbles adhering to the inner wall of the reaction vessel from the path of the measurement light, the action of the buoyancy of the bubbles themselves and the acoustic radiation pressure of the sound waves emitted from the sound wave irradiation mechanism are disclosed. A technique that uses the action is described.
特開2002-200725号公報Japanese Patent Laid-Open No. 2002-200725
 ところで、一般的に、自動分析装置の試薬保管庫は、試薬の品質を維持するために低温(例:5~15℃)に保たれている。これに対して、試料と試薬を混合して測光するための反応容器が設置される恒温槽は、反応の効率を上げ反応速度を一定に保つため、より高温(例:37℃)に保たれている。 By the way, in general, the reagent storage of the automatic analyzer is kept at a low temperature (eg, 5 to 15 ° C.) in order to maintain the quality of the reagent. On the other hand, a thermostatic chamber equipped with a reaction vessel for mixing and measuring a sample and a reagent is kept at a higher temperature (eg, 37 ° C.) in order to increase the efficiency of the reaction and keep the reaction rate constant. ing.
 試薬保管庫において、試薬は大気に接した状態で冷蔵・保管されるため、試薬中には大気中の酸素や二酸化炭素などが溶け込んだ状態で保管されている。一方、反応に用いる際、試薬分注機構により恒温槽内の反応容器へと分注された試薬の温度は、20℃以上上昇する。そのため、試薬保管庫内で冷蔵・保管されている状態では試薬中に溶け込んでいた溶存気体が、反応容器内での温度上昇に伴い徐々に発泡し、発生した気泡が内壁に付着し、測光に影響を与えることがある。 In the reagent storage, the reagent is refrigerated and stored in contact with the atmosphere, so that oxygen, carbon dioxide, etc. in the atmosphere are dissolved in the reagent. On the other hand, when used for the reaction, the temperature of the reagent dispensed by the reagent dispensing mechanism into the reaction vessel in the thermostatic chamber rises by 20 ° C. or more. Therefore, the dissolved gas dissolved in the reagent in the state of refrigeration and storage in the reagent storage gradually foams as the temperature rises in the reaction vessel, and the generated bubbles adhere to the inner wall and are used for photometry. May have an effect.
 しかしながら、特許文献1に開示された手法においては、攪拌によって既に反応容器の内壁に付着した気泡を除去することはできるものの、このように、試薬中に溶け込んでいた溶存気体から発生した気泡については、何ら考慮がなされていない。そのため、攪拌動作の終了後、温度上昇に伴って徐々に新たに発生する気泡の影響を防ぐことはできない。また、攪拌動作の直後に溶存気体が発泡した場合にも、直径0.1mm以下程度の小さいサイズの気泡(マイクロバブル)が発生してセル内壁に付着することが多く、気泡自体の浮力は非常に小さい。よって、特許文献1に示されるように、音響放射圧を用いた手法によっては、このような小さな気泡を除去することは困難である。 However, in the technique disclosed in Patent Document 1, although the bubbles already attached to the inner wall of the reaction vessel can be removed by stirring, the bubbles generated from the dissolved gas dissolved in the reagent in this way are as follows. No consideration has been made. For this reason, after the stirring operation is finished, it is impossible to prevent the influence of bubbles that are newly generated as the temperature rises. In addition, even when dissolved gas is foamed immediately after the stirring operation, small bubbles (microbubbles) with a diameter of about 0.1 mm or less are often generated and adhere to the inner wall of the cell, and the buoyancy of the bubbles themselves is extremely high. Small. Therefore, as shown in Patent Document 1, it is difficult to remove such small bubbles by a method using acoustic radiation pressure.
 上記課題に鑑み、本発明は、反応液の温度上昇に伴う試薬中の溶存気体の発泡により生じた気泡のセル内壁への付着、およびこれによる測光への影響を低減し、高精度な測定を行う自動分析装置を提供することを目的とする。 In view of the above problems, the present invention reduces the influence of bubbles on the cell inner wall caused by foaming of the dissolved gas in the reagent accompanying the temperature rise of the reaction solution, and the effect on photometry, thereby enabling highly accurate measurement. An object of the present invention is to provide an automatic analyzer for performing.
 上記課題を解決するための一態様として、試薬、または反応液を収容する容器と、前記容器に光を照射する光源と、当該光源から照射される光に基づいて生じる信号を検出する検出器と、当該検出器の出力に基づいて、前記反応液を分析する制御部と、前記容器に音波を照射する音波照射部と、を備え、前記制御部は、当該容器に収容された試薬、または反応液に音波を照射することで脱気するように前記音波照射部の動作を制御することを特徴とする自動分析装置、及び、当該装置を用いた分析方法を提供する。 As one aspect for solving the above-described problems, a container that contains a reagent or a reaction liquid, a light source that irradiates light to the container, and a detector that detects a signal generated based on light emitted from the light source, A control unit that analyzes the reaction solution based on the output of the detector, and a sound wave irradiation unit that irradiates the container with sound waves, and the control unit includes a reagent contained in the container or a reaction Provided is an automatic analyzer characterized by controlling the operation of the sound wave irradiation unit so as to deaerate by irradiating a liquid with a sound wave, and an analysis method using the apparatus.
 上記一態様によれば、音波照射機構により予め脱気の処理を施した試薬または反応液を用いて測光を行うため、反応容器内で発泡・付着した気泡によるデータへの影響を防ぎ、安定した測定結果が得られ、信頼性の高い自動分析装置を提供することができる。 According to the above aspect, photometry is performed using a reagent or a reaction solution that has been degassed in advance by a sound wave irradiation mechanism, so that the influence on data due to bubbles / foaming bubbles in the reaction vessel is prevented and stable. A measurement result can be obtained and an automatic analyzer with high reliability can be provided.
本実施の形態に係る自動分析装置の基本構成の一例を示すブロック図である。It is a block diagram which shows an example of the basic composition of the automatic analyzer which concerns on this Embodiment. 本実施の形態に係る自動分析装置における、脱気および攪拌の動作の流れを示すフロー図である。It is a flowchart which shows the flow of operation | movement of deaeration and stirring in the automatic analyzer which concerns on this Embodiment. 本実施の形態(第1の実施の形態)に係る自動分析装置における、超音波による反応容器内での反応液の脱気および攪拌の一例を示すブロック図である。It is a block diagram which shows an example of deaeration and stirring of the reaction liquid in the reaction container by an ultrasonic wave in the automatic analyzer according to the present embodiment (first embodiment). 本実施の形態(第2の実施の形態)に係る自動分析装置における、超音波による反応液脱気と攪拌棒による攪拌の一例を示すブロック図である。It is a block diagram which shows an example of the reaction liquid deaeration by an ultrasonic wave, and the stirring by a stirring rod in the automatic analyzer which concerns on this Embodiment (2nd Embodiment). 本実施の形態(第3の実施の形態)に係る自動分析装置における、超音波による試薬容器内での試薬脱気の一例を示すブロック図である。It is a block diagram which shows an example of the reagent deaeration in the reagent container by an ultrasonic wave in the automatic analyzer which concerns on this Embodiment (3rd Embodiment). 本実施の形態(第4の実施の形態)に係る自動分析装置における、超音波による容器内での試薬脱気の一例を示すブロック図である。It is a block diagram which shows an example of the reagent deaeration in the container by an ultrasonic wave in the automatic analyzer which concerns on this Embodiment (4th Embodiment).
 以下、本発明を実施するための形態について、図面を用いて説明する。なお、全体を通して、各図における同一の各構成部分には同一の符号を付して説明を省略することがある。
〈装置構成〉
 図1は、本実施の形態に係る自動分析装置の基本構成の一例を示すブロック図である。自動分析装置100は、主として、試料ディスク101とその同心円状に配置された試料102を収容する試料容器103、反応ディスク104とその同心円状に配置された反応容器105、試料分注機構106、試薬ディスク107とその同心円状に配置された種々の試薬108を収容する試薬容器109、試薬分注機構110、音波照射機構111、撹拌機構112、恒温槽循環液体113、測光機構114、反応容器洗浄機構115、全体制御部121、入力部119、出力部120から構成される。全体制御部121の内部には、制御回路116、測光回路117、コンピュータ118を備え、入力部119(例えば、ポインティングデバイス、キーボード、タブレット等)、測定結果や各種操作に係るグラフィカルユーザーインターフェース(GUI)等が表示される出力部120を備える。なお、本図において全体制御部121は各々の構成部に接続され、装置全体を制御するものとしたが、構成部ごとに独立した制御部を備えるように構成することもできる。
Hereinafter, embodiments for carrying out the present invention will be described with reference to the drawings. Throughout the description, the same components in the drawings may be denoted by the same reference numerals and description thereof may be omitted.
<Device configuration>
FIG. 1 is a block diagram showing an example of the basic configuration of the automatic analyzer according to the present embodiment. The automatic analyzer 100 mainly includes a sample container 103 that accommodates a sample disk 101 and its concentrically arranged sample 102, a reaction disk 104 and a reaction container 105 that is concentrically arranged, a sample dispensing mechanism 106, a reagent Reagent container 109 for accommodating various reagents 108 arranged concentrically with the disk 107, a reagent dispensing mechanism 110, a sound wave irradiation mechanism 111, a stirring mechanism 112, a constant temperature bath circulating liquid 113, a photometric mechanism 114, a reaction container cleaning mechanism 115, an overall control unit 121, an input unit 119, and an output unit 120. The overall control unit 121 includes a control circuit 116, a photometry circuit 117, and a computer 118, an input unit 119 (for example, a pointing device, a keyboard, a tablet, and the like), a graphical user interface (GUI) relating to measurement results and various operations. Etc. are provided. In this figure, the overall control unit 121 is connected to each component unit and controls the entire apparatus, but may be configured to include an independent control unit for each component unit.
 自動分析装置100による分析は、主に以下のように実施される。まず、試料ディスク101に設置された試料102が試料容器103から反応容器105へと試料分注機構106により分注される。試料102が収容された反応容器105は、反応ディスク104の回転動作により、試薬分注位置まで移動し、試薬分注機構110が、分析に使用する試薬108を試薬容器109から試料102の入った反応容器105へと分注する。ここで、反応容器105内に収容された、試料102と試薬108との混合液を反応液122という。続いて、音波照射機構111により反応容器105内の反応液122が脱気された後、撹拌機構112により反応容器105内の反応液122の撹拌が行われる。反応容器105は反応ディスク104の下部に満たされた恒温槽循環液体113によって、一定の温度、例えば37℃に保たれており、反応の促進と反応の進行の安定化が図られている。 Analysis by the automatic analyzer 100 is mainly performed as follows. First, the sample 102 set on the sample disk 101 is dispensed from the sample container 103 to the reaction container 105 by the sample dispensing mechanism 106. The reaction container 105 containing the sample 102 is moved to the reagent dispensing position by the rotation operation of the reaction disk 104, and the reagent dispensing mechanism 110 puts the reagent 108 used for analysis into the sample 102 from the reagent container 109. Dispense into the reaction vessel 105. Here, the mixed solution of the sample 102 and the reagent 108 accommodated in the reaction vessel 105 is referred to as a reaction solution 122. Subsequently, after the reaction solution 122 in the reaction vessel 105 is degassed by the sound wave irradiation mechanism 111, the reaction solution 122 in the reaction vessel 105 is stirred by the stirring mechanism 112. The reaction vessel 105 is maintained at a constant temperature, for example, 37 ° C., by a constant temperature bath circulating liquid 113 filled in the lower part of the reaction disk 104 to promote the reaction and stabilize the progress of the reaction.
 反応容器105内の反応液122は、反応ディスク104の回転動作に伴い、測光機構114を通過するときにその光学特性変化が測光回路117を介して測定される。このようにして得られた測光データは、コンピュータ118に送られ、コンピュータ118内の演算部123によって、試料中の対象成分の濃度が求められるとともに、得られたデータはデータ記憶部124に記憶され、出力部120に結果が表示される。反応後の反応容器105は、反応容器洗浄機構115により洗浄され、次の反応に繰り返し使用される、あるいは、図示しない反応容器廃棄部に廃棄される。
<動作フロー>
 図2は、本実施の形態に係る自動分析装置における、脱気および攪拌の動作の流れを示すフロー図である。本フローに基づく各動作の指示は、図1にて示した全体制御部121によって発せられる。図2において、ステップ201では、まず、分析対象の試料の反応容器への分注を行う(ステップS201)。次に、ステップ202では、脱気処理の対象が、反応容器内の反応液であるのか、試薬容器内の試薬であるのか、すなわち、脱気処理を施す場所が、反応容器であるのか試薬容器であるのかに応じて、その後のステップは2パターンに分かれる。ここで、脱気処理の対象については、オペレータにより、分析条件として入力部119等を介して予め設定し、データ記憶部124に記憶することができる(ステップS202)。ここで、脱気処理の対象が反応容器に収容された反応液である場合には、ステップ203に進み、試薬を反応容器に分注し(ステップS203)、次にステップ204にて反応液への音波照射により反応液を脱気し(ステップS204)、続いて、反応液の攪拌により発生した気泡を除去する(ステップS205)。また、脱気処理の対象が試薬容器に収容された試薬である場合には、ステップ206にて音波照射により試薬容器内の試薬を脱気し(ステップS206)、次にステップ207にて脱気した試薬を反応容器に分注し(ステップS207)、続いて、ステップ208にて反応液の攪拌を行う(ステップS208)。最後に、ステップ209にて、ステップ205、あるいはステップ208のいずれかのステップを経た反応液に対する光学特性変化の測定を行い(ステップS209)、ステップ210にて分析処理の結果を取得して処理を終了する(ステップ210)。第2試薬を添加する場合にも、第1試薬と同様にステップ201からステップ210を繰り返す。
When the reaction liquid 122 in the reaction vessel 105 passes through the photometric mechanism 114 as the reaction disk 104 rotates, its optical characteristic change is measured via the photometric circuit 117. The photometric data obtained in this way is sent to the computer 118, the concentration of the target component in the sample is obtained by the calculation unit 123 in the computer 118, and the obtained data is stored in the data storage unit 124. The result is displayed on the output unit 120. The reaction vessel 105 after the reaction is washed by the reaction vessel washing mechanism 115 and repeatedly used for the next reaction, or discarded in a reaction vessel discarding section (not shown).
<Operation flow>
FIG. 2 is a flowchart showing the flow of deaeration and stirring operations in the automatic analyzer according to the present embodiment. The instruction of each operation based on this flow is issued by the overall control unit 121 shown in FIG. In FIG. 2, in step 201, first, a sample to be analyzed is dispensed into a reaction container (step S201). Next, in step 202, whether the degassing target is the reaction liquid in the reaction container or the reagent in the reagent container, that is, whether the place to be degassed is the reaction container or not. Depending on whether or not, the subsequent steps are divided into two patterns. Here, the object of the deaeration process can be set in advance as an analysis condition by the operator via the input unit 119 or the like and stored in the data storage unit 124 (step S202). Here, when the degassing target is the reaction liquid stored in the reaction container, the process proceeds to step 203, where the reagent is dispensed into the reaction container (step S203), and then into the reaction liquid in step 204. The reaction solution is degassed by the sound wave irradiation (step S204), and then bubbles generated by stirring the reaction solution are removed (step S205). If the target of the degassing process is a reagent contained in the reagent container, the reagent in the reagent container is degassed by irradiating with sound waves in step 206 (step S206), and then degassed in step 207. The reagent thus dispensed is dispensed into the reaction container (step S207), and then the reaction solution is stirred in step 208 (step S208). Finally, in step 209, the optical property change is measured for the reaction solution that has undergone either step 205 or step 208 (step S209). In step 210, the result of the analysis process is acquired and processed. The process ends (step 210). Even when the second reagent is added, Step 201 to Step 210 are repeated in the same manner as the first reagent.
 図2を用いて上述した本実施の形態においては、試料を反応容器に分注してから試薬を分注する例について説明したが、先に試薬を反応容器に分注してから試料を分注する構成の装置において、試薬または反応液の脱気ステップを適用することもできる。 In the present embodiment described above with reference to FIG. 2, the example in which the reagent is dispensed after dispensing the sample into the reaction container has been described. However, the sample is dispensed after the reagent has been dispensed into the reaction container first. In the apparatus configured to be poured, a reagent or reaction solution degassing step may be applied.
 また、本実施の形態において、音波の照射により溶存気体を脱気する液体としては、試薬に限らず、緩衝液や希釈液、前処理液を対象としても良い。
(第1の実施の形態)
 図3を用いて、第1の実施の形態について説明する。図3は、本実施の形態に係る自動分析装置における、超音波による反応容器内での反応液の脱気および攪拌の一例を示すブロック図である。具体的には、本実施の形態に係る自動分析装置の反応ディスク104における、音波照射機構111および攪拌機構112が設置された領域に相当する、恒温槽301と、反応容器105の縦断面図を示している。図3(a)が音波照射機構111により反応液122を脱気し、微小気泡302を積極的に発泡させるステップ、図3(b)が攪拌機構112により反応液122中の微小気泡302を除去するステップである。なお、図3においては、音波照射機構111と攪拌機構112とが同一の機構で併用できる構成、すなわち、図3(a)では音波照射機構111として、図3(b)では攪拌機構112として動作する構成について示しているが、図1に示したように、脱気に適した脱気専用の音波照射機構111と、攪拌に適した攪拌専用の攪拌機構112とを、それぞれ別の場所に設ける構成とすることもできる。図3(a)に示す脱気ステップと、図3(b)に示す気泡除去ステップとは、同一の装置動作サイクル内で連続して行っても良いし、別の動作サイクルで行っても良い。例えば、図3(a)に示す脱気ステップにおいて反応容器105の内壁に付着した微小気泡302を、反応液122の温度上昇により一定時間大きく成長させた後で、図3(b)に示す気泡除去ステップの攪拌を行い、その後の測光データを濃度演算に使用するように構成することで、より確実に気泡除去動作を行うようにすることもできる。
Moreover, in this Embodiment, as a liquid which deaerates dissolved gas by irradiation of a sound wave, it is good not only for a reagent but for a buffer solution, a diluent, and a pretreatment liquid.
(First embodiment)
The first embodiment will be described with reference to FIG. FIG. 3 is a block diagram showing an example of degassing and stirring of the reaction liquid in the reaction vessel using ultrasonic waves in the automatic analyzer according to the present embodiment. Specifically, in the reaction disk 104 of the automatic analyzer according to the present embodiment, a vertical cross-sectional view of the thermostatic chamber 301 and the reaction vessel 105 corresponding to the area where the sound wave irradiation mechanism 111 and the stirring mechanism 112 are installed. Show. 3A is a step of degassing the reaction liquid 122 by the sound wave irradiation mechanism 111 to positively foam the microbubbles 302, and FIG. 3B is a step of removing the microbubbles 302 in the reaction liquid 122 by the stirring mechanism 112. It is a step to do. In FIG. 3, the sound wave irradiation mechanism 111 and the stirring mechanism 112 can be used together by the same mechanism, that is, the sound wave irradiation mechanism 111 operates in FIG. 3A and the stirring mechanism 112 operates in FIG. As shown in FIG. 1, a deaeration-only sound irradiation mechanism 111 suitable for deaeration and a stirring-only stirring mechanism 112 suitable for stirring are provided in different places as shown in FIG. 1. It can also be configured. The deaeration step shown in FIG. 3A and the bubble removal step shown in FIG. 3B may be performed continuously in the same apparatus operation cycle, or may be performed in different operation cycles. . For example, after the microbubbles 302 attached to the inner wall of the reaction vessel 105 in the degassing step shown in FIG. 3A are greatly grown for a certain time due to the temperature rise of the reaction liquid 122, the bubbles shown in FIG. By performing agitation in the removal step and using the subsequent photometric data for concentration calculation, the bubble removal operation can be performed more reliably.
 図3(a)に示す音波照射機構111は、主として、音源である圧電素子303と圧電素子駆動回路304から構成される。圧電素子駆動回路304は制御回路116と接続され、制御回路116の指示に基づいて制御される。制御回路116は、より上位の制御を担う全体制御部121の指示に応じた制御を行う。圧電素子303の表面には、図示しない単数または複数の電極が配置されており、音波を照射する領域は、電圧を印加する電極の位置を選択することで選択される。圧電素子303から照射される音波の強度や照射時間等のパラメータは、反応容器105内に収容される反応液122の総液量や液面の高さ、反応液122の粘性や反応液122と反応容器105との間の濡れ性などによって調整可能に構成される。圧電素子駆動回路304により圧電素子303で発生した超音波305は、恒温槽301に満たされた恒温槽循環液体113を介して反応容器105内の反応液122へと到達する。 The sound wave irradiation mechanism 111 shown in FIG. 3A is mainly composed of a piezoelectric element 303 which is a sound source and a piezoelectric element driving circuit 304. The piezoelectric element driving circuit 304 is connected to the control circuit 116 and controlled based on an instruction from the control circuit 116. The control circuit 116 performs control in accordance with an instruction from the overall control unit 121 responsible for higher-level control. One or a plurality of electrodes (not shown) are arranged on the surface of the piezoelectric element 303, and the region to be irradiated with the sound wave is selected by selecting the position of the electrode to which the voltage is applied. Parameters such as the intensity of the sound wave irradiated from the piezoelectric element 303 and the irradiation time include the total amount of the reaction liquid 122 and the height of the liquid surface stored in the reaction vessel 105, the viscosity of the reaction liquid 122, and the reaction liquid 122. It is configured to be adjustable depending on the wettability between the reaction vessel 105 and the like. The ultrasonic wave 305 generated in the piezoelectric element 303 by the piezoelectric element driving circuit 304 reaches the reaction liquid 122 in the reaction vessel 105 through the constant temperature bath circulating liquid 113 filled in the constant temperature tank 301.
 図3(a)において、超音波305を持続的に照射することで、反応液122の中でキャビテーション(液体の流れの中で圧力差により短時間に泡の発生と消滅が起きる現象のことをいう)が発生し、溶存気体が微小気泡302となって反応容器105の内壁に付着することで反応液122は脱気される。図3(a)に示すように、超音波305の照射により反応液122を脱気するステップにおいては、反応液122の液面の高さに応じて、圧電素子303の駆動領域を選択し、効率的に脱気できるよう反応液122の液面より下の領域全体に超音波305が照射されるよう制御することが望ましい。反応液122の中でキャビテーションが発生しやすくするためには、1MHz以下の周波数の超音波を照射することが望ましい。さらに、反応液122の性状に応じて、より効率的な脱気が可能となるよう、超音波305の周波数や照射時間を選択できるよう構成しても良い。 In FIG. 3A, by continuously irradiating the ultrasonic wave 305, cavitation in the reaction liquid 122 (a phenomenon in which bubbles are generated and disappeared in a short time due to a pressure difference in the liquid flow). And the dissolved gas becomes microbubbles 302 and adheres to the inner wall of the reaction vessel 105, whereby the reaction liquid 122 is degassed. As shown in FIG. 3A, in the step of degassing the reaction liquid 122 by the irradiation of the ultrasonic wave 305, the drive region of the piezoelectric element 303 is selected according to the liquid level of the reaction liquid 122, It is desirable to control so that the ultrasonic wave 305 is irradiated to the whole area below the liquid level of the reaction liquid 122 so that the degassing can be performed efficiently. In order to easily cause cavitation in the reaction liquid 122, it is desirable to irradiate ultrasonic waves having a frequency of 1 MHz or less. Furthermore, the frequency and irradiation time of the ultrasonic wave 305 may be selected so that more efficient deaeration is possible depending on the properties of the reaction liquid 122.
 なお、図3では、説明の便宜上、微小気泡302を実際の比率よりも大きく図示しているが、実際には発泡した溶存気体の気泡は非常に小さい。 In FIG. 3, for convenience of explanation, the microbubbles 302 are shown larger than the actual ratio, but in reality, the bubbles of the dissolved gas that are foamed are very small.
 また、図3に示したのは、音波照射機構111の一例であり、反応液122中の溶存気体を脱気できれば、圧電素子303は反応容器105の正面、側面、上下面のいずれに配置しても良い。あるいは反応液122の中に圧電素子303を浸漬し、反応液122に直接超音波を照射するように構成しても構わない。 FIG. 3 shows an example of the sound wave irradiation mechanism 111. If the dissolved gas in the reaction liquid 122 can be degassed, the piezoelectric element 303 is disposed on any of the front surface, side surface, and upper and lower surfaces of the reaction vessel 105. May be. Alternatively, the piezoelectric element 303 may be immersed in the reaction liquid 122 and the reaction liquid 122 may be directly irradiated with ultrasonic waves.
 ここで、図3(a)にて示した脱気のステップにて、微小気泡302を反応容器105の内壁に付着させ、この微小気泡302の内壁への付着部分を除く領域を用いて測定を行うようにする等の場合には、後述する気泡除去のステップを行わずに、測定を実行することもできる。但し、上述の通り、微小気泡302は実際には非常に小さいため、状況によっては、音波の照射等のみによる気泡の完全な除去は困難である場合がある。 Here, in the degassing step shown in FIG. 3A, the microbubbles 302 are attached to the inner wall of the reaction vessel 105, and the measurement is performed using the region excluding the attached portion of the microbubbles 302 to the inner wall. In the case of performing the measurement, the measurement can be performed without performing the bubble removal step described later. However, as described above, the microbubbles 302 are actually very small, and depending on the situation, it may be difficult to completely remove the bubbles only by irradiating sound waves.
 そこで、次に図3(b)に示した気泡除去のステップについて説明する。図3(b)に示す気泡除去ステップにおいては、反応液122の液面付近(液面の近傍の領域)のみに超音波305を照射し、反応液122の液面を振動させるとともに、反射板306で反射した超音波305の作用により、液面から大きな気泡を積極的に取り込み、反応液122内に押し入れるようにする。反応液122の液中に取り込んだ大きな気泡の動きにより反応液122全体に旋回流が発生し、攪拌が行われる。この攪拌の動作において、液中に取り込んだ大きな気泡と反応液122全体の旋回流の作用により、結果的に反応容器105の内壁に付着した微小気泡302を除去することが可能となる。超音波305の照射により反応液122を攪拌するステップにおいては、液面の振動と旋回流の持続に適したパラメータ・周波数の超音波305を選択することが望ましい。 Therefore, the bubble removal step shown in FIG. In the bubble removing step shown in FIG. 3B, the ultrasonic wave 305 is irradiated only to the vicinity of the liquid surface of the reaction liquid 122 (the area near the liquid surface), and the liquid surface of the reaction liquid 122 is vibrated, and the reflection plate By the action of the ultrasonic wave 305 reflected by 306, large bubbles are actively taken in from the liquid surface and pushed into the reaction liquid 122. A swirling flow is generated in the entire reaction liquid 122 due to the movement of large bubbles taken into the reaction liquid 122, and stirring is performed. In this agitation operation, the micro bubbles 302 adhering to the inner wall of the reaction vessel 105 can be removed as a result by the action of the large bubbles taken into the solution and the swirling flow of the entire reaction solution 122. In the step of stirring the reaction liquid 122 by irradiation with the ultrasonic wave 305, it is desirable to select the ultrasonic wave 305 having parameters and frequencies suitable for the vibration of the liquid surface and the sustaining of the swirling flow.
 本実施の形態に示すように、反応液122を脱気するステップに続いて、反応液122を攪拌するステップを実行することで、攪拌ステップにおける超音波305の照射に伴う新たな微小気泡302の発泡も抑制することができる。
(第2の実施の形態)
 第1の実施の形態では、脱気のステップと、気泡除去のステップとを音波照射機構111を利用して実行する態様について説明した。ここでは、脱気のステップを音波照射機構111により、気泡除去のステップを攪拌機構112により実行する例について述べる。
As shown in this embodiment, by performing a step of stirring the reaction liquid 122 subsequent to the step of degassing the reaction liquid 122, new microbubbles 302 associated with the irradiation of the ultrasonic wave 305 in the stirring step are generated. Foaming can also be suppressed.
(Second Embodiment)
In the first embodiment, the aspect in which the deaeration step and the bubble removal step are performed using the sound wave irradiation mechanism 111 has been described. Here, an example in which the deaeration step is executed by the sound wave irradiation mechanism 111 and the bubble removal step is executed by the stirring mechanism 112 will be described.
 図4を用いて、第2の実施の形態について説明する。図4は、本実施の形態に係る自動分析装置における、超音波による反応液脱気と攪拌棒による攪拌の一例を示すブロック図である。図4(a)が超音波305により反応液122を脱気するステップ、図4(b)が攪拌棒401により微小気泡を除去するステップを示す。なお、図4においては、音波照射ステップと攪拌ステップとを同一の場所で行う構成を示しているが、第1の実施の形態にて上述したようにそれぞれのステップを別々の場所で行う構成としても構わない。 The second embodiment will be described with reference to FIG. FIG. 4 is a block diagram showing an example of reaction liquid deaeration using ultrasonic waves and stirring using a stirring bar in the automatic analyzer according to the present embodiment. FIG. 4A shows a step of degassing the reaction liquid 122 with the ultrasonic wave 305, and FIG. 4B shows a step of removing microbubbles with the stirring rod 401. FIG. 4 shows a configuration in which the sound wave irradiation step and the stirring step are performed at the same location, but as described above in the first embodiment, each step is performed at different locations. It doesn't matter.
 図4に示したように、音波照射機構111に複数の圧電素子303を設け、反応容器105に対して複数の方向から超音波305を照射することで、より効率よく反応液122を脱気する構成としても良い。また、図4(b)に示したように、攪拌機構112により微小気泡を除去するステップとしては、攪拌棒401の回転動作により反応液122の攪拌を行う構成としても良い。このようなに構成しても、反応液122全体の旋回流を利用して、反応容器105の内壁に付着した微小気泡302を除去することができる。
(第3の実施の形態)
 上述した実施の形態では、試薬を反応容器に分注したのちに、脱気、気泡除去のステップを実行する態様について説明した。ここでは、試薬容器内に収容される、分注前の試薬に対して脱気の処理を施す例について述べる。
As shown in FIG. 4, by providing a plurality of piezoelectric elements 303 in the sound wave irradiation mechanism 111 and irradiating the reaction vessel 105 with ultrasonic waves 305 from a plurality of directions, the reaction liquid 122 is degassed more efficiently. It is good also as a structure. Further, as shown in FIG. 4B, the step of removing the microbubbles by the stirring mechanism 112 may be configured to stir the reaction liquid 122 by rotating the stirring bar 401. Even with this configuration, the microbubbles 302 attached to the inner wall of the reaction vessel 105 can be removed using the swirling flow of the entire reaction liquid 122.
(Third embodiment)
In the above-described embodiment, the aspect in which the steps of deaeration and bubble removal are performed after dispensing the reagent into the reaction container has been described. Here, an example in which a degassing process is performed on a reagent before dispensing, which is stored in a reagent container, will be described.
 図5を用いて、第3の実施の形態について説明する。図5は、本実施の形態に係る自動分析装置における、超音波による試薬容器内での試薬脱気の一例を示すブロック図である。本実施の形態では、試薬ディスク107内の試薬容器109の設置ポジションに音波照射機構111を設置する構成を特徴とする。図5(a)が超音波305により試薬108を脱気するステップ、図5(b)が試薬分注機構110の試薬ノズル501により脱気済みの試薬108を吸引するステップである。反応容器105に分注する前の試薬108に超音波305を照射し、予め試薬容器109内で試薬108を脱気する。このとき生じた微小気泡302は、試薬容器109の内壁に付着する。その後、試薬分注機構110の試薬ノズル501により試薬108のみを吸引し、内壁に付着した微小気泡302を取り残すようにすることで、後のステップにおける反応容器105内での温度上昇に伴う発泡や、反応容器105の内壁への微小気泡302の付着を抑制することができる。図5に示した音波照射機構111は、試薬ディスク107内の全ての設置ポジションに配置しても良いし、特定の設置ポジションにのみ配置し、微小気泡302の付着が問題となる試薬108を選択的にここに設置するためのポジションとしても良い。さらに、第3の実施の形態に示した構成においては、試薬108の脱気は反応容器105への分注前に完了していればよいため、定期的に超音波305を照射し試薬108を常に脱気された状態で保持しておく構成とすることもできる。あるいは、試薬ディスク107での保管中に接している気体の試薬108への再溶存を考慮して、当該試薬108を分注する直前のタイミングにおいて超音波305を照射し脱気する構成としても良い。
(第4の実施の形態)
 次に、試料が入っていない反応容器に分注された試薬を脱気、気泡除去する態様について述べる。図6を用いて第4の実施の形態を説明する。図6は、本実施の形態に係る自動分析装置における、超音波による反応容器内での試薬脱気の一例を示すブロック図である。図6(a)が超音波305により試薬108を脱気するステップ、図6(b)が試薬分注機構110の試薬ノズル501により脱気済みの試薬108を吸引するステップである。なお、図6においては、音波照射ステップと試薬吸引ステップとを同一の場所で行う構成を示しているが、それぞれのステップを別々の場所で行う構成としても構わない。本実施の形態においては、まず試薬分注機構110によって試薬108を第一の反応容器へと分注し、第一の容器(脱気のための容器)内で、図6(a)に示す脱気ステップと、図6(b)に示す試薬吸引ステップとを行う。脱気ステップにおける超音波305の照射により、微小気泡302は第一の容器601の内壁に付着する。続いて、脱気済みの試薬108に対し、試薬ノズル501は試薬108のみを吸引し、内壁に付着した微小気泡302は取り残すように分注の動作を行う。吸引された脱気済みの試薬108は、図示しない第二の容器(反応容器)へと分注され、試料102と混合後、測光される。このように構成することで、測光に用いられる第二の容器内における発泡と微小気泡302の内壁への付着を抑制することができる。
A third embodiment will be described with reference to FIG. FIG. 5 is a block diagram illustrating an example of reagent deaeration inside the reagent container using ultrasound in the automatic analyzer according to the present embodiment. The present embodiment is characterized in that the sound wave irradiation mechanism 111 is installed at the installation position of the reagent container 109 in the reagent disk 107. FIG. 5A shows a step of degassing the reagent 108 by the ultrasonic wave 305, and FIG. 5B shows a step of sucking the degassed reagent 108 by the reagent nozzle 501 of the reagent dispensing mechanism 110. The ultrasonic wave 305 is irradiated to the reagent 108 before being dispensed into the reaction container 105, and the reagent 108 is degassed in advance in the reagent container 109. The microbubbles 302 generated at this time adhere to the inner wall of the reagent container 109. Thereafter, only the reagent 108 is sucked by the reagent nozzle 501 of the reagent dispensing mechanism 110 so that the microbubbles 302 adhering to the inner wall are left behind. The adhesion of the microbubbles 302 to the inner wall of the reaction vessel 105 can be suppressed. The sound wave irradiation mechanism 111 shown in FIG. 5 may be arranged at all the installation positions in the reagent disk 107, or only at a specific installation position, and selects the reagent 108 in which the attachment of the microbubbles 302 becomes a problem. It is good also as a position to install here. Furthermore, in the configuration shown in the third embodiment, since the degassing of the reagent 108 may be completed before dispensing into the reaction vessel 105, the ultrasonic wave 305 is periodically irradiated to remove the reagent 108. It can also be set as the structure hold | maintained in the deaerated state always. Alternatively, in consideration of re-dissolution of the gas in contact with the reagent 108 during storage in the reagent disk 107, a configuration may be adopted in which the ultrasonic wave 305 is irradiated and degassed immediately before the reagent 108 is dispensed. .
(Fourth embodiment)
Next, a mode in which the reagent dispensed in the reaction container containing no sample is degassed and bubbles are removed will be described. A fourth embodiment will be described with reference to FIG. FIG. 6 is a block diagram showing an example of reagent deaeration in the reaction container using ultrasound in the automatic analyzer according to the present embodiment. FIG. 6A shows a step of degassing the reagent 108 by the ultrasonic wave 305, and FIG. 6B shows a step of sucking the degassed reagent 108 by the reagent nozzle 501 of the reagent dispensing mechanism 110. FIG. 6 shows a configuration in which the sound wave irradiation step and the reagent suction step are performed at the same location, but each step may be performed at different locations. In the present embodiment, the reagent 108 is first dispensed into the first reaction container by the reagent dispensing mechanism 110, and is shown in FIG. 6A in the first container (a container for degassing). A deaeration step and a reagent suction step shown in FIG. Due to the irradiation of the ultrasonic wave 305 in the deaeration step, the microbubbles 302 adhere to the inner wall of the first container 601. Subsequently, the reagent nozzle 501 sucks only the reagent 108 with respect to the degassed reagent 108 and performs a dispensing operation so as to leave the microbubbles 302 attached to the inner wall. The sucked and degassed reagent 108 is dispensed into a second container (reaction container) (not shown), mixed with the sample 102, and photometrically measured. By comprising in this way, the foaming in the 2nd container used for photometry and adhesion to the inner wall of the microbubble 302 can be suppressed.
 例えば血液凝固反応等を分析する場合、試料と試薬とが混合されると凝固反応が開始されてしまうため、試料と試薬とが混合された反応液に対しては脱気を実行することはできない。しかしながら、上述した第3、第4の実施の形態によれば、試料との混合前の試薬に対して脱気を施すことができるので、それ以降の気泡の発生を抑え、分析結果への影響を低減することが可能となる。 For example, when analyzing a blood coagulation reaction or the like, the coagulation reaction starts when the sample and the reagent are mixed. Therefore, deaeration cannot be performed on the reaction solution in which the sample and the reagent are mixed. . However, according to the third and fourth embodiments described above, since the reagent before mixing with the sample can be degassed, the generation of bubbles thereafter is suppressed, and the influence on the analysis result Can be reduced.
101・・・試料ディスク
102・・・試料
103・・・試料容器
104・・・反応ディスク
105・・・反応容器
106・・・試料分注機構
107・・・試薬ディスク
108・・・試薬
109・・・試薬容器
110・・・試薬分注機構
111・・・音波照射機構
112・・・撹拌機構
113・・・恒温槽循環液体
114・・・測光機構
115・・・反応容器洗浄機構
116・・・制御回路
117・・・測光回路
118・・・コンピュータ
119・・・入力部
120・・・出力部
121・・・全体制御部
122・・・反応液
123・・・演算部
124・・・記憶部
301・・・恒温槽
302・・・微小気泡
303・・・圧電素子
304・・・圧電素子駆動回路
305・・・超音波
306・・・反射板
401・・・攪拌棒
501・・・試薬ノズル
601・・・容器
101 ... Sample disc 102 ... Sample 103 ... Sample container 104 ... Reaction disc 105 ... Reaction vessel 106 ... Sample dispensing mechanism 107 ... Reagent disc 108 ... Reagent 109 ... Reagent container 110: Reagent dispensing mechanism 111 ... Sound wave irradiation mechanism 112 ... Stirring mechanism 113 ... Constant temperature bath circulating liquid 114 ... Photometric mechanism 115 ... Reaction container cleaning mechanism 116 ... Control circuit 117 ... photometry circuit 118 ... computer 119 ... input unit 120 ... output unit 121 ... overall control unit 122 ... reaction liquid 123 ... calculation unit 124 ... memory Part 301 ... thermostat 302 ... microbubble 303 ... piezoelectric element 304 ... piezoelectric element drive circuit 305 ... ultrasonic wave 306 ... reflector 401 ... stirring bar 501 ... reagent Noz 601 ... container

Claims (12)

  1.  試薬、または反応液を収容する容器と、
     前記容器に光を照射する光源と、
     当該光源から照射される光に基づいて生じる信号を検出する検出器と、
     当該検出器の出力に基づいて、前記反応液を分析する制御部と、
     前記容器に音波を照射する音波照射部と、を備え、
     前記制御部は、
     当該容器に収容された試薬、または反応液に音波を照射することで脱気するように前記音波照射部の動作を制御することを特徴とする自動分析装置。
    A container for storing a reagent or reaction solution;
    A light source for irradiating the container with light;
    A detector for detecting a signal generated based on light emitted from the light source;
    Based on the output of the detector, a control unit for analyzing the reaction solution;
    A sound wave irradiation unit for irradiating the container with sound waves,
    The controller is
    An automatic analyzer characterized in that the operation of the sound wave irradiation unit is controlled so as to deaerate by irradiating the reagent or reaction liquid stored in the container with sound waves.
  2. 請求項1に記載された自動分析装置であって、
     前記制御部は、
     当該脱気された反応液に対し、さらに音波を照射することで攪拌するように前記音波照射部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 1, wherein
    The controller is
    An automatic analyzer characterized by controlling the operation of the sound wave irradiation unit so that the degassed reaction liquid is further stirred by irradiation with sound waves.
  3.  請求項1に記載された自動分析装置であって、
     前記制御部は、
     当該容器に収容された試薬、または反応液に対し、液面よりも下方の領域に全体的に音波を照射することで脱気するように前記音波照射部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 1, wherein
    The controller is
    The operation of the sound wave irradiation unit is controlled so that the reagent or reaction liquid stored in the container is degassed by irradiating the entire region below the liquid level with sound waves. Automatic analyzer.
  4.  請求項1に記載された自動分析装置であって、
     前記制御部は、
     当該容器に収容された反応液に対し、液面よりも下方の領域に全体的に音波を照射することで脱気し、
     当該脱気された反応液に対し、液面の近傍の領域に選択的に音波を照射することで攪拌するように、
     前記音波照射部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 1, wherein
    The controller is
    The reaction liquid stored in the container is degassed by irradiating the entire region with sound waves below the liquid level,
    The degassed reaction liquid is stirred by selectively irradiating a sound wave in a region near the liquid surface,
    An automatic analyzer for controlling an operation of the sound wave irradiation unit.
  5.  請求項1に記載された自動分析装置であって、
     前記容器に収容された反応液を攪拌する攪拌部を備え、
     前記制御部は、
     当該脱気された反応液に対し、前記攪拌部により攪拌するように前記攪拌部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 1, wherein
    A stirring unit for stirring the reaction solution contained in the container;
    The controller is
    An automatic analyzer characterized by controlling the operation of the agitation unit to agitate the degassed reaction liquid by the agitation unit.
  6.  請求項5に記載された自動分析装置であって、
     前記攪拌部は回転可能な攪拌棒を備え、
     前記制御部は、
     前記攪拌棒の回転により当該脱気された反応液を攪拌するように前記攪拌部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 5, wherein
    The stirring unit includes a rotatable stirring bar,
    The controller is
    An automatic analyzer characterized by controlling the operation of the stirring section so as to stir the degassed reaction liquid by the rotation of the stirring bar.
  7.  請求項1に記載された自動分析装置であって、
     前記試薬を吸引、吐出する分注部を備え、
     前記制御部は、
     当該脱気された試薬を前記容器から吸引し、試料が収容されている他の容器に吐出するように、前記分注部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 1, wherein
    A dispensing part for aspirating and discharging the reagent;
    The controller is
    An automatic analyzer that controls the operation of the dispensing unit so that the degassed reagent is aspirated from the container and discharged to another container containing a sample.
  8.  請求項7に記載された自動分析装置であって、
     前記制御部は、
     当該吐出の動作ののちに、当該他の容器に収容される試料と試薬との混合液に光を照射し、当該照射に基づいて生じる信号を検出するように、前記光源、及び前記検出部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 7,
    The controller is
    After the discharge operation, the light source and the detection unit are configured to irradiate light to the mixed solution of the sample and the reagent stored in the other container and detect a signal generated based on the irradiation. An automatic analyzer characterized by controlling its operation.
  9.  請求項4に記載された自動分析装置であって、
     前記音波照射部から照射された音波を反射する反射板を備え、
     前記制御部は、
     当該脱気された反応液に対し、液面の近傍の領域であって、かつ前記反射板に到達するように選択的に音波を照射することで攪拌するように前記音波照射部の動作を制御することを特徴とする自動分析装置。
    An automatic analyzer according to claim 4, wherein
    A reflector for reflecting the sound wave emitted from the sound wave irradiation unit;
    The controller is
    The operation of the sound wave irradiation unit is controlled so that the degassed reaction liquid is agitated by selectively irradiating a sound wave in a region near the liquid surface and reaching the reflection plate. The automatic analyzer characterized by doing.
  10.  試料と試薬とを含む反応液を収容する容器と、
     前記容器に光を照射する光源と、
     当該光源から照射される光に基づいて生じる信号を検出する検出器と、
     当該検出器の出力に基づいて、前記反応液を分析する制御部と、を備えた自動分析装置における分析方法であって、
     前記制御部は、
     当該容器に収容された反応液に対し、液面よりも下方の領域に全面的に音波を照射することで脱気する第1のステップと、
     当該第1のステップののちに、当該脱気された反応液を攪拌する第2のステップと、を実行することを特徴とする分析方法。
    A container containing a reaction solution containing a sample and a reagent;
    A light source for irradiating the container with light;
    A detector for detecting a signal generated based on light emitted from the light source;
    A control unit for analyzing the reaction liquid based on the output of the detector, and an analysis method in an automatic analyzer comprising:
    The controller is
    A first step of degassing the reaction liquid stored in the container by irradiating the entire area below the liquid surface with sound waves;
    After the first step, a second step of stirring the degassed reaction liquid is performed.
  11.  請求項10に記載された分析方法であって、
     前記制御部は、前記第2のステップにおいて、当該脱気された反応液に対し、液面の近傍の領域に選択的に音波を照射することで攪拌することを特徴とする分析方法。
    The analysis method according to claim 10, comprising:
    In the second step, the control unit stirs the degassed reaction liquid by selectively irradiating a sound wave in a region near the liquid surface.
  12.  請求項10に記載された分析方法であって、
     前記自動分析装置は、回転可能な攪拌棒を有する攪拌部を備え、
     前記制御部は、前記第2のステップにおいて、前記攪拌棒の回転の回転により、当該脱気された反応液を攪拌することを特徴とする分析方法。
    The analysis method according to claim 10, comprising:
    The automatic analyzer includes a stirring unit having a rotatable stirring bar,
    In the second step, the control unit agitates the degassed reaction liquid by rotating the stirring rod.
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