+

WO1998052013A1 - Instrument pour la mesure du rayon hydrodynamique des molecules - Google Patents

Instrument pour la mesure du rayon hydrodynamique des molecules Download PDF

Info

Publication number
WO1998052013A1
WO1998052013A1 PCT/US1998/008879 US9808879W WO9852013A1 WO 1998052013 A1 WO1998052013 A1 WO 1998052013A1 US 9808879 W US9808879 W US 9808879W WO 9852013 A1 WO9852013 A1 WO 9852013A1
Authority
WO
WIPO (PCT)
Prior art keywords
avalanche photodetector
instrument
molecules
detector
light beam
Prior art date
Application number
PCT/US1998/008879
Other languages
English (en)
Inventor
Norman C. Ford, Jr.
Original Assignee
Precision Detectors, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Precision Detectors, Inc. filed Critical Precision Detectors, Inc.
Publication of WO1998052013A1 publication Critical patent/WO1998052013A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • G01J3/4412—Scattering spectrometry

Definitions

  • This invention relates to methods and apparatus for molecular characterization and, more particularly, to improved methods and apparatus for measuring the hydrodynamic radii of molecules.
  • the present invention is typically utilized with a liquid chromatography system, but is not limited to such use.
  • LC liquid chromatography
  • a flowing mixture of a solvent and the substances to be tested (a mixture of molecules with various molecular weights and other molecular characteristics) is passed through specifically selected chromatography columns which result in the component molecules being separated in time in the flowing solvent according to their size or according to some other molecular characteristic.
  • a laser beam is directed through the fluid, and the light scattered by molecules of the sample is analyzed to provide molecular characterization.
  • a detector of this type is disclosed in U.S. Patent No. 5,305,073 issued April 19, 1994 to Ford, Jr.
  • Examples of uses of liquid chromatography are the analyses of proteins, commercial resins, natural and synthetic polymers, nucleic acids, plasticizers, plant and animal metabolites, lubricants, dyes, petroleum residues, pharmaceuticals, amino acids, pigments, polysaccharides, pesticides, herbicides, fungicides, surfactants, lipids, explosives, and other materials.
  • hydrodynamic radius of a complex molecule is related to the force required to move the molecule through a liquid at a given speed and is defined as the radius of a sphere which requires the same force as the complex molecule to move at the same speed. It is known that hydrodynamic radius can be determined from a scattered light intensity fluctuation measurement of a sample containing the molecules of interest. In particular, hydrodynamic radius can be determined from fluctuations in scattered light intensity in a direction perpendicular to a light beam. The rate of such fluctuations is indicative of hydrodynamic radius.
  • Prior art techniques have involved passing a laser beam having a wavelength in the visible range through a sample and measuring the fluctuations in scattered light intensity with a photomultiplier. Suitable lasers in the visible wavelength range are typically complex and expensive. As a result, systems using a visible wavelength laser and a photomultiplier are complex and expensive. It is desirable to provide methods and apparatus for measuring the hydrodynamic radius of molecules which overcome the drawbacks of prior art systems.
  • an instrument for measuring hydrodynamic radius of molecules comprises a scattering cell, conduits for passing a liquid sample through the scattering cell, a semiconductor laser for directing a light beam through the scattering cell along an optical axis so that the light beam is scattered by the molecules of the sample and produces scattered light, and a detector assembly comprising an avalanche photodetector for detecting fluctuations in intensity of the scattered light in a direction perpendicular to the optical axis.
  • the instrument further comprises a correlator for determining a correlation function representative of a characteristic decay time of the fluctuations in scattered light intensity and a processor for determining hydrodynamic radius of the sample molecules from the correlation function.
  • the detector assembly preferably further includes an active quench circuit for operating the avalanche photodetector in a region of high quantum efficiency.
  • the active quench circuit includes means for pulsing the avalanche photodetector following detection of a photon, so that the avalanche photodetector is reset to a non-conducting state.
  • the active quench circuit may further include means for sensing a conducting state of the avalanche photodetector and means responsive to the conducting state for pulsing the avalanche photodetector until it returns to the non-conducting state.
  • the detector assembly may further comprise a mask defining a slit having a long dimension perpendicular to the optical axis and optics for focusing an image of a coherence region of the light beam on the slit.
  • the detector assembly may further comprise an optical fiber for coupling light passing through the slit to the avalanche photodetector.
  • the semiconductor laser preferably has an output wavelength greater than about 650 nanometers and, in a preferred embodiment, has an output wavelength of about 800 nanometers.
  • the semiconductor laser preferably has an output power level of about 100 milliwatts or greater.
  • the scattering cell is preferably configured to produce a substantially laminar flow of the liquid sample in the coherence region. This avoids the effects of turbulence on the measurement of hydrodynamic radius.
  • a molecular characterization detector for detecting fluctuations in scattered light intensity from molecules in a liquid sample.
  • the molecular characterization detector comprises a scattering cell, conduits for passing a liquid sample through the scattering cell, a semiconductor laser for directing a light beam through the scattering cell along an optical axis so that the light beam is scattered by molecules of the sample and produces scattered light, and a detector assembly comprising an avalanche photodetector for detecting fluctuations in intensity of the scattered light in a direction perpendicular to the optical axis.
  • a method for detecting fluctuations in scattered light intensity from molecules in a liquid sample.
  • a liquid sample is passed through a scattering cell.
  • a light beam from a semiconductor laser is directed through the scattering cell along an optical axis, so that the light beam is scattered by molecules of the sample and produces scattered light. Fluctuations in scattered light intensity in a direction perpendicular to the optical axis are detected with a detector assembly comprising an avalanche photodetector.
  • Fig. 1 is a block diagram of an instrument for measuring hydrodynamic radius of molecules in accordance with an embodiment of the invention
  • Fig. 2 is an enlarged end view of the scattering cell of Fig. 1 ;
  • Fig. 3 illustrates a coherence region viewed by the detector assembly of Fig. 1 ;
  • Fig. 4 is a schematic diagram of an example of the active quench circuit of Fig. 1 ;
  • Fig. 5 is a graph of avalanche photodetector voltage as a function of time.
  • Fig. 6 is a graph of received photons as a function of time.
  • a scattering cell 10 contains a sample for measurement of hydrodynamic radius.
  • the sample is in liquid form and flows continuously through an enclosed chamber 11 of scattering cell 10 from an inlet conduit 12 to an outlet conduit 14.
  • the liquid sample is typically received from a liquid chromatography column.
  • the liquid sample is typically a solvent containing a group of complex molecules to be measured.
  • the scattering cell 10 includes a transparent window/lens 16 at one end and a transparent window/lens 18 or a window at the other end.
  • the chamber 11 of scattering cell 10 preferably has a small volume, on the order of about 10 microliters, and may be cylindrical in shape. In a preferred embodiment, the chamber 1 1 of scattering cell
  • 10 has a length of about 3 millimeters and a diameter of about 2 millimeters.
  • a laser 20 directs a laser beam 22 along an optical axis 24 through the chamber 11 of scattering cell 10.
  • the laser beam 22 passes through window/lens 16, through the liquid sample, and through window/lens 18.
  • the laser beam output from the scattering cell 10 may be detected for other measurements, as described in the aforementioned Patent No. 5,305,073, and is preferably intercepted by a beam dump 26 that is constructed to minimize reflections.
  • the laser 20 is preferably a semiconductor laser having an output wavelength greater than about 650 nanometers and a power level in the range of about 100 to 500 milliwatts.
  • the laser 20 comprises a type SDL-5311-G1 having a typical output wavelength of 800 nanometers.
  • the liquid sample must be substantially transparent to the laser wavelength.
  • the laser beam 22 that passes through the scattering cell 10 is preferably polarized, but is not required to be polarized.
  • the laser 20 generates a polarized beam.
  • the window/lens 16 focuses the laser beam 22 to its smallest diameter at a coherence region 30 in the scattering cell 10.
  • the laser beam 22 may be focused by window/lens 16, by laser optics, or by combinations thereof as known in the art.
  • liquid flow through chamber 1 1 of scattering cell 10 should be relatively free of turbulence, at least in coherence region 30.
  • the coherence region 30 is a small volume along optical axis 24 where the measurement of fluctuations in scattered light intensity is made.
  • a view of one end of scattering cell 10 along optical axis 24 is shown in Fig. 2.
  • the scattering cell 10 may be provided with a circular passage 40 connected to inlet conduit 12. Passages 42, 43 and 44 extend radially inwardly from circular passage 40 to one end of chamber 1 1. This ensures that the liquid sample is introduced into chamber 1 1 relatively uniformly.
  • the outlet end of the scattering cell 10 may have a similar configuration, so that the liquid sample is exhausted from chamber 1 1 relatively uniformly.
  • three radial passages are used at the inlet, and three radial passages are used at the outlet. It will be understood that different inlet and outlet configurations and different numbers of inlet and outlet passages may be utilized.
  • the scattering cell 10 is designed to achieve a laminar flow in coherence region 30 that is relatively free of turbulence. Typically, coherence region 30 is located at or near the midpoint of the axis of chamber 1 1.
  • the flow rate through scattering cell 10 is preferably less than about 2 milliliters per minute to provide measurements of hydrodynamic radius that are independent of flow rate.
  • the instrument for measuring hydrodynamic radius includes a detector assembly 50 for detecting fluctuations in intensity of scattered light from the liquid sample in a direction perpendicular to optical axis 24 and perpendicular to the direction of polarization of laser beam 22.
  • the detector assembly 50 detects light scattered from molecules in the liquid sample in the coherence region 30.
  • the detector assembly 50 provides an output to a correlator 200.
  • Optics which may include a lens 52 and a lens 54, focuses an image of coherence region 30 on a slit 58 formed in a mask 60.
  • the mask 60 may, for example, be fabricated of 302 stainless steel 0.0005 inch thick.
  • slit 58 has a long dimension perpendicular to optical axis 24 and is oriented such that light scattered from molecules in coherence region 30 in a direction perpendicular to optical axis 24 is incident on slit 58.
  • slit 58 has a width w of 18 micrometers.
  • light beam 22 has a diameter of about 18 micrometers in coherence region 30.
  • the coherence region 30 from which scattered light is detected has a length of 18 micrometers and a diameter of 18 micrometers.
  • the width of slit 58 and the diameter of light beam 22 in the coherence region 30 are approximately equal.
  • the width of slit 58 and the diameter of light beam 28 should be as small as is practical in order to permit use of a relatively large area detector, so as to collect a relatively large amount of scattered light and obtain a large signal-to-noise ratio.
  • the detector assembly 50 further includes an optical fiber 70 having one end 72 positioned to intercept scattered light passing through slit 58.
  • optical fiber 70 is an Amphenol type 907-11025-10001 having a core diameter of 62.5 micrometers and a cladding of 125 micrometers.
  • End 72 of optical fiber 70 is preferably spaced from slit 58 by a distance d of about 2 millimeters. In a preferred embodiment, the distance d is adjustable.
  • the scattered light collected by optical fiber 70 is output through a lens 76 and is focused on an avalanche photodetector 80.
  • the avalanche photodetector 80 is controlled by an active quench circuit 82.
  • the avalanche photodetector and its operation are selected to provide high quantum efficiency at the wavelength of laser 20.
  • the avalanche photodetector is a highly sensitive device in which one photon results in multiple electrons at the output.
  • the avalanche photodetector is biased beyond breakdown, such that a single received photon initiates conduction.
  • the avalanche photodetector is operated in the Geiger mode as a single photon detector.
  • the active quench circuit 82 applies a voltage pulse that temporarily biases the avalanche photodetector below breakdown and stops conduction, effectively resetting the device for reception of another photon.
  • FIG. 4 A schematic diagram of an example of the avalanche photodetector 80 and the active quench circuit 82 is shown in Fig. 4.
  • the avalanche photodetector 80 is a silicon avalanche photodiode, type C30902S-TC, supplied by EG&G. This device has a nominal breakdown voltage at a temperature of 0°C of about 170 to 230 volts and is biased at a voltage about 20 volts above the breakdown voltage when in a non-conducting state. At this bias voltage, the avalanche photodetector has a quantum efficiency of about 30% to 50%.
  • the anode of avalanche photodetector 80 is coupled through a resistor 100 and a capacitor 102 to an inverting input of a high speed comparator 104.
  • the avalanche photodetector 80 begins to conduct, which raises the voltage on the non-inverting input of comparator 104.
  • a transistor 110 coupled to the inverting input of comparator 104 limits the voltage rise.
  • the output of comparator 104 falls, causing a transistor 112 to conduct and raising the anode voltage of avalanche photodetector 80 to about 24 volts, so that the voltage across the avalanche photodetector no longer sustains an avalanche current.
  • comparator 104 causes a comparator 120 to generate a negative pulse starting on the falling voltage at its input.
  • a comparator 124 coupled to the output of comparator 120 generates a positive pulse starting on the rising edge of the output of comparator 120.
  • the output of comparator 124 turns on a transistor 130 and a transistor 132, thereby returning the input of comparator 104 and the anode of the avalanche photodetector
  • the avalanche photodetector is ready to detect another photon. The entire process requires about 0.2 microseconds. If the avalanche photodetector is not fully quenched after one pulse, a second pulse is generated by comparator 120.
  • a comparator 140 coupled to the output of comparator 120 and a line driver 142 generate an output pulse to drive a coaxial line connected to correlator 200.
  • a graph of avalanche photodetector voltage as a function of time is shown in Fig. 5.
  • the avalanche photodetector is biased at a photon detection voltage V PD that is sufficiently above the breakdown voltage V BD to achieve high quantum efficiency.
  • V PD is about 230 volts and V BD is about 212 volts.
  • a reset pulse 144 is approximately 50 nanoseconds in duration and is of sufficient amplitude (approximately 24 volts) to return the avalanche photodetector voltage to its non-conducting state.
  • two or more reset pulses may be applied to the avalanche photodetector in the event that it continues to conduct.
  • the correlator 200 receives pulses representative of received photons from the output of active quench circuit 82 and determines a correlation function that is representative of a characteristic decay time of the fluctuations in scattered light intensity.
  • the correlator 200 may be implemented as a digital signal processor programmed to perform a correlation operation.
  • a FIFO buffer may be used to buffer the pulses received from the active quench circuit 82.
  • a graph of received photons as a function of time is shown in Fig. 6.
  • Pulses 210 represent received photons.
  • the correlator 200 first determines the number of photons received in each time interval ⁇ T, where ⁇ T is typically 5 microseconds. Thus, for example, with reference to Fig. 6, two photons were received in the first time interval, one photon was received in the second time interval, no photons were received in the third time interval, etc.
  • the correlation function is determined from the statistics as follows:
  • g is the correlation function
  • k ⁇ T is the separation between two time intervals ⁇ T labeled i and i + k
  • n, and n, + are the numbers of received pulses in intervals i and i + k, respectively.
  • the correlation function representative of fluctuations in scattered intensity
  • a computer 240 which may, for example, be a personal computer (PC).
  • the computer 240 is programmed to determine the hydrodynamic radius of molecules in the liquid sample in scattering cell 10 from the correlation function.
  • the correlation function of the fluctuations in scattered light intensity in scattering cell 10 may be expressed as follows:
  • D is the diffusion constant
  • n is the index of refraction of the fluid
  • ⁇ is the wavelength of laser 20
  • ⁇ is the scattering angle. Since the correlation function g is measured and all other quantities in equation (2) except the diffusion constant D are known, the diffusion constant D may be calculated from equation (2).
  • the diffusion constant D is used to determine the hydrodynamic radius from the following equation:

Landscapes

  • Physics & Mathematics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • General Physics & Mathematics (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un détecteur de caractérisation moléculaire permettant de détecter les fluctuations de l'intensité lumineuse diffusée par les molécules dans un échantillon liquide, qui comprend une cellule à diffusion (10), un laser à semiconducteur (20) pour orienter un faisceau lumineux (22) à travers ladite cellule (10) le long d'un axe optique (24), de sorte que la lumière soit diffusée par les molécules de l'échantillon et produise une lumière diffusée, et un ensemble détecteur équipé d'un photodétecteur à avalanche (80) pour déceler les fluctuations de l'intensité de la lumière diffusée dans une direction perpendiculaire à l'axe optique (24). Le détecteur de caractérisation moléculaire peut être intégré à un instrument de mesure du rayon hydrodynamique des molécules. L'instrument comprend ledit détecteur, un corrélateur (200) pour déterminer une fonction de corrélation représentative d'un temps de décroissance des fluctuations de l'intensité lumineuse diffusée, et un processeur (240) pour déterminer le rayon hydrodynamique des molécules de l'échantillon à partir de la fonction de corrélation.
PCT/US1998/008879 1997-05-13 1998-05-01 Instrument pour la mesure du rayon hydrodynamique des molecules WO1998052013A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US85499897A 1997-05-13 1997-05-13
US08/854,998 1997-05-13

Publications (1)

Publication Number Publication Date
WO1998052013A1 true WO1998052013A1 (fr) 1998-11-19

Family

ID=25320082

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/008879 WO1998052013A1 (fr) 1997-05-13 1998-05-01 Instrument pour la mesure du rayon hydrodynamique des molecules

Country Status (1)

Country Link
WO (1) WO1998052013A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2906032A1 (fr) * 2006-09-15 2008-03-21 Centre Nat Rech Scient Determination des rayons hydrodynamiques des constituants d'un melange par analyse d'une dispersion de taylor effectuee suite a une separation par electrophese capillaire.
EP2335079A2 (fr) 2008-09-25 2011-06-22 Varian, Inc Dispositif de cellule à écoulement diffusant la lumière
DE202011107342U1 (de) 2011-10-18 2012-07-18 Postnova Analytics Gmbh Blendensystem für Vielwinkellichtstreudetektoren
US8760652B2 (en) 2011-10-18 2014-06-24 Postnova Analytics Gmbh Aperture system for multi-angle light scattering detectors
DE202014102634U1 (de) 2014-06-05 2014-07-01 Postnova Analytics Gmbh Zweiteilige Messzelle für die statische Lichtstreuung
CN109883650A (zh) * 2019-03-28 2019-06-14 哈尔滨工业大学 基于激光干涉的感知海洋湍流和海洋颗粒的装置

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4303861A (en) * 1980-03-28 1981-12-01 Battelle Development Corporation Photon detector system
US4975237A (en) * 1987-03-12 1990-12-04 The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland Dynamic light scattering apparatus
US5030843A (en) * 1989-02-13 1991-07-09 Kowa Company Ltd. Apparatus for measuring particles in liquid having a laminar flow condition
US5113083A (en) * 1988-07-25 1992-05-12 Otsuka Electronics Co., Ltd. Light scattering measuring apparatus utilizing a photodetector mounted on a rotary stand
US5581349A (en) * 1995-03-27 1996-12-03 Halaka; Folim G. Method for biological cell and particulate analysis

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4303861A (en) * 1980-03-28 1981-12-01 Battelle Development Corporation Photon detector system
US4975237A (en) * 1987-03-12 1990-12-04 The Secretary Of State For Defence In Her Britannic Majesty's Government Of The United Kingdom Of Great Britain And Northern Ireland Dynamic light scattering apparatus
US5113083A (en) * 1988-07-25 1992-05-12 Otsuka Electronics Co., Ltd. Light scattering measuring apparatus utilizing a photodetector mounted on a rotary stand
US5030843A (en) * 1989-02-13 1991-07-09 Kowa Company Ltd. Apparatus for measuring particles in liquid having a laminar flow condition
US5581349A (en) * 1995-03-27 1996-12-03 Halaka; Folim G. Method for biological cell and particulate analysis

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2906032A1 (fr) * 2006-09-15 2008-03-21 Centre Nat Rech Scient Determination des rayons hydrodynamiques des constituants d'un melange par analyse d'une dispersion de taylor effectuee suite a une separation par electrophese capillaire.
WO2008031958A3 (fr) * 2006-09-15 2008-05-15 Centre Nat Rech Scient Determination des rayons hydrodynamiques des constituants d'un melange par analyse d'une dispersion de taylor effectuee suite a une separation par electrophorese capillaire
US8118986B2 (en) 2006-09-15 2012-02-21 Centre National De La Recherche Scientifique (C.N.R.S.) Determination of the hydrodynamic radii of the constituents of an admixture by means of analysis of a taylor dispersion carried out following a separation by means of capillary electrophoresis
EP2335079A2 (fr) 2008-09-25 2011-06-22 Varian, Inc Dispositif de cellule à écoulement diffusant la lumière
EP2335079B1 (fr) * 2008-09-25 2015-07-01 Agilent Technologies, Inc. Dispositif de cellule à écoulement diffusant la lumière
US9222876B2 (en) 2008-09-25 2015-12-29 Agilent Technologies, Inc. Light scattering flow cell device
DE202011107342U1 (de) 2011-10-18 2012-07-18 Postnova Analytics Gmbh Blendensystem für Vielwinkellichtstreudetektoren
US8760652B2 (en) 2011-10-18 2014-06-24 Postnova Analytics Gmbh Aperture system for multi-angle light scattering detectors
DE202014102634U1 (de) 2014-06-05 2014-07-01 Postnova Analytics Gmbh Zweiteilige Messzelle für die statische Lichtstreuung
CN109883650A (zh) * 2019-03-28 2019-06-14 哈尔滨工业大学 基于激光干涉的感知海洋湍流和海洋颗粒的装置
CN109883650B (zh) * 2019-03-28 2020-07-24 哈尔滨工业大学 基于激光干涉的感知海洋湍流和海洋颗粒的装置

Similar Documents

Publication Publication Date Title
EP0626064B1 (fr) Procedes et appareil de caracterisation moleculaire
EP0899548B1 (fr) Procédé de corrélation croisée et appareil pour supprimer les effets de diffusion multiple
US3850525A (en) Simultaneous multiple measurements in laser photometers
US5292483A (en) Detecting a radiation signal
US3770351A (en) Optical analyzer for microparticles
US4172227A (en) Flow microfluorometer
US7440101B2 (en) System and method for multiple laser triggering
US3819270A (en) Blood cell analyzer
US3624835A (en) Microparticle analyzer employing a spherical detector array
US5074658A (en) Laser capillary spectrophotometric acquisition of bivariate drop size and concentration data for liquid-liquid dispersion
EP2388569A1 (fr) Capteurs et procede de comptage et de mesure de la grosseur des particules optiques de haute sensibilite
JP4201058B2 (ja) 中間統計データに基づいて試料を特徴付けする方法
JP2007501414A (ja) 混合物の迅速かつ高度に鋭敏に定量分析するための多次元蛍光装置及び方法
US10473591B2 (en) High throughput method and apparatus for measuring multiple optical properties of a liquid sample
EP0160568B1 (fr) Procédé et appareil l'analyse de particules ou cellules
WO2001014858A1 (fr) Systeme et procede de detection par interferometrie
JP6895463B2 (ja) 流体中の浮遊粒子を検出および／または特性評価するための装置と方法
Sabo et al. On-line high-performance liquid chromatography/Fourier tranform infrared spectrometry with normal and reverse phases using an attenuated total reflectance flow cell
US6361672B1 (en) Multiple laser diode electromagnetic radiation source in multiple electrophoresis channel systems
US3999857A (en) Refractive index detector
WO1998052013A1 (fr) Instrument pour la mesure du rayon hydrodynamique des molecules
US5572321A (en) Detector for measuring the luminous intensity scattered by thin films of colloidal media
Zarrin et al. Particle counting by laser light scatter for capillary hydrodynamic chromatography
US5231466A (en) Capillary fluid stream concentration measuring apparatus and method
Kurosu et al. Fluorescence detection with an immersed flow cell in capillary electrophoresis

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 1998549262

Format of ref document f/p: F

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载