JPWO2021089841A5 - - Google Patents

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Publication number
JPWO2021089841A5
JPWO2021089841A5 JP2022525257A JP2022525257A JPWO2021089841A5 JP WO2021089841 A5 JPWO2021089841 A5 JP WO2021089841A5 JP 2022525257 A JP2022525257 A JP 2022525257A JP 2022525257 A JP2022525257 A JP 2022525257A JP WO2021089841 A5 JPWO2021089841 A5 JP WO2021089841A5
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Japan
Prior art keywords
container
sample
monochromatic light
light source
photodetector
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JP2022525257A
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Japanese (ja)
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JP2023501942A (en
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Priority claimed from PCT/EP2020/081378 external-priority patent/WO2021089841A1/en
Publication of JP2023501942A publication Critical patent/JP2023501942A/en
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Claims (18)

溶液中の粒子の特徴を測定する方法であって、
- 溶液中の前記粒子のサンプルを含む容器を提供するステップ
- 少なくとも1つの単色光源および少なくとも1つの光検出器を提供するステップと、
- 前記単色光源からの光を前記サンプルを含む前記容器へ伝送するステップと、
- 前記容器から放出された光を前記光検出器によって検出するステップと、
前記サンプルに含まれる溶液中の前記粒子および/または前記容器の材料の蛍光を測定するステップ
- 前記測定された蛍光に基づいて、前記容器の位置を判定するステップと、
- 動的光散乱(DLS)測定に基づいて、前記サンプルに含まれる溶液中の前記粒子の特徴を判定するステップとを含む方法。
A method for measuring characteristics of particles in a solution, the method comprising:
- providing a container containing a sample of said particles in solution ;
- providing at least one monochromatic light source and at least one photodetector;
- transmitting light from the monochromatic light source to the container containing the sample;
- detecting light emitted from the container by the photodetector;
- measuring the fluorescence of the particles in the solution contained in the sample and/or the material of the container;
- determining the position of the container based on the measured fluorescence;
- determining characteristics of the particles in a solution contained in the sample based on dynamic light scattering (DLS) measurements.
溶液中の粒子の特徴を測定する方法であって、
- 溶液中の前記粒子のサンプルを含む容器を提供するステップと、
- 少なくとも1つの単色光源および少なくとも1つの光検出器を提供するステップと、
- 前記単色光源からの光を前記サンプルを含む前記容器へ伝送するステップと、
- 前記容器から放出された光を前記光検出器によって検出するステップと、
- 前記サンプルに含まれる溶液中の前記粒子および/または前記容器の材料の蛍光を測定するステップと、
前記サンプルを含む前記容器の後方反射を測定し、前記測定された後方反射に基づいて、前記容器の位置を判定するステップと、
- 動的光散乱(DLS)測定に基づいて、前記サンプルに含まれる溶液中の前記粒子の特徴を判定するステップと
を含む方法。
A method for measuring characteristics of particles in a solution, the method comprising:
- providing a container containing a sample of said particles in solution;
- providing at least one monochromatic light source and at least one photodetector;
- transmitting light from the monochromatic light source to the container containing the sample;
- detecting light emitted from the container by the photodetector;
- measuring the fluorescence of the particles in the solution contained in the sample and/or the material of the container;
- measuring the back reflection of the container containing the sample and determining the position of the container based on the measured back reflection ;
- determining characteristics of the particles in a solution contained in the sample based on dynamic light scattering (DLS) measurements;
method including.
前記測定された蛍光および/または後方反射ならびに前記判定された容器位置に基づいて、前記容器を位置決めするステップと
を含む、請求項1または2に記載の方法。
- positioning the container based on the measured fluorescence and/or back reflection and the determined container position.
- ナノ示差走査蛍光定量法(ナノDSF)測定を実行するステップ
さらに含む、請求項1から3のいずれか一項に記載の方法。
- performing nano differential scanning fluorimetry (nano DSF) measurements;
4. The method according to any one of claims 1 to 3, further comprising:
各容器に対する蛍光測定に続いて、各容器に対するDLS測定が行われ、または
各容器に対するDLS測定に続いて、各容器に対する蛍光測定が行われ、または
複数の容器のうちの1つの容器に対して蛍光測定およびDLS測定が実行されるのに続いて、前記複数の容器のうちの別の容器に対して蛍光測定およびDLS測定が実行される、
請求項1から4のいずれか一項に記載の方法。
A fluorescence measurement for each container is followed by a DLS measurement for each container, or a DLS measurement for each container is followed by a fluorescence measurement for each container, or for one of the containers. After the fluorescence measurement and DLS measurement are performed, the fluorescence measurement and DLS measurement are performed on another container of the plurality of containers.
A method according to any one of claims 1 to 4.
前記単色光源ダイオードレーザである、請求項1からのいずれか一項に記載の方法。 6. A method according to any preceding claim , wherein the monochromatic light source is a diode laser. 前記単色光が、レーザ波長単一モードファイバを介して前記単色光源から送達される、請求項からのいずれか一項に記載の方法。 7. A method according to any preceding claim , wherein the monochromatic light is delivered from the monochromatic light source via a laser wavelength single mode fiber. 前記伝送単色光が、対物レンズを使用して、前記サンプルを含む前記容器内で集束させられる、請求項1からのいずれか一項に記載の方法。 8. A method according to any one of claims 1 to 7 , wherein the transmitted monochromatic light is focused within the container containing the sample using an objective lens. 前記光検出器が、光電子増倍管(PMT)、シリコン光電子増倍管(SiPM)、またはアバランシェフォトダイオード(APD)光子計数検出器ある、請求項1からのいずれか一項に記載の方法。 9. The photodetector according to any one of claims 1 to 8 , wherein the photodetector is a photomultiplier tube (PMT), a silicon photomultiplier tube (SiPM), or an avalanche photodiode (APD) photon counting detector. Method. 前記DLS測定が、
- 前記光検出器から取得されたアナログ出力信号を取得するステップと、
- 前記取得されたアナログ出力信号を処理するステップとを含み、前記取得されたアナログ出力信号を処理する前記ステップが、前記取得されたアナログ出力信号を、デジタル化された出力信号にデジタル化するステップを含み、前記デジタル化された出力信号が、
i)前記デジタル化された出力信号を、デジタル化された単一光子パルス信号として処理するステップ、
および/または
i)前記デジタル化された出力信号を、アナログ信号の離散値として処理するステップ
によってさらに処理される、
請求項1からのいずれか一項に記載の方法。
The DLS measurement is
- obtaining an analog output signal obtained from the photodetector;
- processing the obtained analog output signal, the step of processing the obtained analog output signal digitizing the obtained analog output signal into a digitized output signal. , the digitized output signal comprising:
i) processing the digitized output signal as a digitized single photon pulse signal;
and/or i i) further processed by processing said digitized output signal as discrete values of an analog signal;
A method according to any one of claims 1 to 9 .
- 少なくとも第1の時点の第1の温度および第2の時点の第2の温度で、前記容器を時間とともに調温するステップ
をさらに含む、請求項1から10のいずれか一項に記載の方法。
- a method according to any one of claims 1 to 10 , further comprising: - temperature conditioning the container over time, at least at a first temperature at a first point in time and at a second temperature at a second point in time. .
少なくとも第1の時点の第1の温度および第2の時点の第2の温度で、前記容器を時間とともに調温する前記ステップが、1分当たり0.01℃~1分当たり30℃焼戻し速度で、前記容器を調温するステップを含み、ならびに/または前記第1の温度および前記第2の温度が-20℃~160℃である、請求項1から11のいずれか一項に記載の方法。 said step of temperature conditioning said container over time at a first temperature at at least a first time point and a second temperature at a second time point at a tempering rate of from 0.01° C. per minute to 30° C. per minute; 12. The method according to any one of claims 1 to 11 , comprising the step of temperature conditioning the container at . 前記容器が、毛細管および/またはマルチウェルプレートである、請求項1から12のいずれか一項に記載の方法。 13. The method according to any one of claims 1 to 12 , wherein the container is a capillary tube and/or a multiwell plate. 溶液中の粒子の特徴を検出するデバイスであって、
- 溶液中の前記粒子のサンプルを含む少なくとも1つの容器収容する手段と、
- 単色光源および光検出器と、
- DSL測定を実行する手段と、
前記サンプルに含まれる溶液中の前記粒子および/または前記容器の材料の、蛍光を測定する手段と、
- 制御手段とを備え、前記制御手段が、
少なくとも1つの容器を収容する前記手段を制御し、
前記単色光源からの光を前記少なくとも1つの容器へ伝送するように前記単色光源を制御し、
前記少なくとも1つの容器からの信号を検出するように前記光検出器を制御し、
前記蛍光を測定する前記手段を制御し、
DSL測定を実行する前記手段を制御し、
前記測定された蛍光に基づいて、前記容器の位置を判定する手段を制御するように適合される、デバイス。
A device for detecting characteristics of particles in a solution, the device comprising:
- means for containing at least one container containing a sample of said particles in solution;
- a monochromatic light source and a photodetector;
- means for performing DSL measurements;
- means for measuring the fluorescence of the particles in the solution contained in the sample and/or the material of the container;
- control means, the control means comprising:
controlling said means for containing at least one container;
controlling the monochromatic light source to transmit light from the monochromatic light source to the at least one container;
controlling the photodetector to detect a signal from the at least one container;
controlling the means for measuring the fluorescence;
controlling said means for performing DSL measurements ;
A device adapted to control means for determining the position of the container based on the measured fluorescence .
- 溶液中の前記粒子の前記サンプルを収容する前記手段を位置決めする位置決め手段をさらに備え、前記制御手段が、前記サンプルを収容する前記位置決め手段を制御するようにさらに適合される、
請求項14に記載のデバイス。
- further comprising positioning means for positioning said means containing said sample of said particles in solution, said control means further adapted to control said positioning means containing said sample;
15. A device according to claim 14 .
- ナノDSF測定を実行する手段および/または後方反射を測定する手段をさらに備え、前記制御手段が、ナノDSF測定を実行する前記手段および/または後方反射を測定する前記手段を制御するようにさらに適合される、
請求項14または15に記載のデバイス。
- further comprising means for performing nano-DSF measurements and/or means for measuring back-reflections, further comprising: said control means controlling said means for performing nano-DSF measurements and/or said means for measuring back-reflections; adapted,
16. A device according to claim 14 or 15 .
- 単一モードファイバと、
- 前記単一モードファイバを介して前記単色光源からの単色光を送達する手段とをさらに備え、前記制御手段が、前記単一モードファイバを介して前記単色光源からの単色光を送達する前記手段を制御するようにさらに適合される、
請求項14から16のいずれか一項に記載のデバイス。
- single mode fiber;
- means for delivering monochromatic light from the monochromatic light source via the single mode fiber, the control means further comprising: means for delivering monochromatic light from the monochromatic light source via the single mode fiber; further adapted to control the
17. A device according to any one of claims 14 to 16 .
- 前記DLS測定のための前記少なくとも1つの単色光源と
- 前記蛍光測定のためのLED光源と
- 前記後方反射測定のためのさらなるLEDと
- 前記動的光散乱(DLS)測定のための少なくとも1つの光検出器と、
- 前記蛍光測定のための少なくとも1つの追加の光検出器と、
- 前記後方反射測定のための1つの追加の光検出器と
を備える、請求項14から17のいずれか一項に記載のデバイス。
- the at least one monochromatic light source for the DLS measurement ;
- an LED light source for said fluorescence measurement ;
- a further LED for said back reflection measurement ;
- at least one photodetector for said dynamic light scattering (DLS) measurements;
- at least one additional photodetector for said fluorescence measurement;
- one additional photodetector for said back reflection measurement;
18. A device according to any one of claims 14 to 17 , comprising:
JP2022525257A 2019-11-08 2020-11-06 Characterization of particles in solution Pending JP2023501942A (en)

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PCT/EP2020/081378 WO2021089841A1 (en) 2019-11-08 2020-11-06 Characterization of particles in solution

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US5328822A (en) * 1990-04-23 1994-07-12 Solid State Farms, Inc. Apparatus and method for sedimentation based blood analysis
US5973779A (en) * 1996-03-29 1999-10-26 Ansari; Rafat R. Fiber-optic imaging probe
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EP4242304A3 (en) * 2015-10-01 2024-02-07 Revolution Medicines, Inc. Methods and reagents for analyzing protein-protein interfaces
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US10473591B2 (en) * 2017-05-01 2019-11-12 Wyatt Technology Corporation High throughput method and apparatus for measuring multiple optical properties of a liquid sample
WO2019166650A1 (en) * 2018-03-02 2019-09-06 Cdr-Life Ag Trispecific antigen binding proteins
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