WO1989001620A1 - Systemes d'analyses optoelectriques d'echantillons electrophoretiques - Google Patents

Systemes d'analyses optoelectriques d'echantillons electrophoretiques Download PDF

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Publication number
WO1989001620A1
WO1989001620A1 PCT/US1988/002679 US8802679W WO8901620A1 WO 1989001620 A1 WO1989001620 A1 WO 1989001620A1 US 8802679 W US8802679 W US 8802679W WO 8901620 A1 WO8901620 A1 WO 8901620A1
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WO
WIPO (PCT)
Prior art keywords
molecules
sample
detecting
light
electrophoresis
Prior art date
Application number
PCT/US1988/002679
Other languages
English (en)
Inventor
Michael D. Morris
Reed A. Shick
Konan Peck
Stephen J. Parus
Original Assignee
The Regents Of The University Of Michigan
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 The Regents Of The University Of Michigan filed Critical The Regents Of The University Of Michigan
Publication of WO1989001620A1 publication Critical patent/WO1989001620A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21—Polarisation-affecting properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416—Systems
    • G01N27/447—Systems using electrophoresis
    • G01N27/44704—Details; Accessories
    • G01N27/44717—Arrangements for investigating the separated zones, e.g. localising zones
    • G01N27/44721—Arrangements for investigating the separated zones, e.g. localising zones by optical means
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N2021/1738—Optionally different kinds of measurements; Method being valid for different kinds of measurement
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N2021/4792—Polarisation of scatter light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/19—Dichroism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/21—Polarisation-affecting properties
    • G01N21/23—Bi-refringence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6445—Measuring fluorescence polarisation

Definitions

  • This invention relates to systems for analyzing electrophoresis samples and particularly to such systems which detect the presence of molecules by inducing orientation of the molecules by an external electrical or magnetic field and detecting the oriented molecules by optical means.
  • Nucleic acids, proteins and other biological macromolecules are commonly separated by electrophoresis in which the molecules are caused to migrate within a media such as agarose or polyacrylamide gels.
  • a media such as agarose or polyacrylamide gels.
  • Molecule characteristics determine their mobility and thus molecules become separated by type during migration. Depending on the complexity of the sample, the separation process may take as little as forty-five minutes or as long as twelve hours.
  • Nucleic acid electrophoresis must be performed in a low DC field and is therefore slow. The reason is that the molecules become elongated in high electric fields. When this happens, molecules of different sizes tend to migrate at similar rates, causing a loss in resolution.
  • Ethidium bromide The components separated by electrophoresis are visualized by staining them.
  • the most co ⁇ ton stain is ethidium bromide.
  • Color stains and silver staining are occasionally employed, but are less convenient and sensitive than ethidium.
  • Ethidium staining is a fairly rapid procedure, requiring only about twenty minutes of operator time if carried out manually.
  • Ethidium bromide is, however, a known potent carcinogen, and must be used carefully.
  • proteins or nucleic acids are reacted with fluorescent molecules or molecules containing radioisotopes before separation, thus making the separated macromolecules fluorescent or radioactive.
  • Gene sequencing procedures involve such fluorescent or radioactivity labelling of nucleic acids, with molecules which are specific for the base which terminates one end of the chain.
  • Protein electrophoresis itself is generally faster than nucleic acid separation. Times of thirty minutes to several hours are co ⁇ mon. The staining procedures are, however, time consuming. An automated procedure for staining with Coo assie stain takes about an hour. An automated silver staining procedure takes about three hours. Accordingly, present electrophoresis evaluation techniques are both time consuming in that a significant time period must elapse to enable adequate separation of molecules to occur, and also since staining procedures are often complex and time consuming. A technique to examine molecules separated by electrophoresis without staining would be welcome, even if some sensitivity were sacrificed. In addition, procedures for detecting molecule mobility in various media without separation would also be desirable.
  • characterization of electrophoresis samples after molecule separation is carried out without staining using optical systems for detecting orientation of the molecules caused by exposure to an external electromagnetic or other field.
  • the birefringence characteristics of the sample can be used to detect orientation.
  • molecules become oriented within an electrophoresis sample they cause the sample to become birefringent in the area in which they are present.
  • a linearly polarized light ray passing through the sample in the area of the oriented molecules will become circularly or elliptically polarized as it exits the sample.
  • Linear and/or circular polarizers are used to detect polarization changes in the sample caused by birefringence.
  • This birefringence characteristic can be used to detect the presence of molecules at particular regions of the sample after molecule separation without staining, which is ordinarily necessary for evaluation by visual inspection or by conventional densitometers.
  • optical systems can be used to detect molecular orientation for unseparated samples.
  • the molecules become oriented in the presence of an electric or magnetic field which is periodically relaxed or reversed.
  • Molecule length, configuration, charge and other characteristics determine their mobility within the medium. This mobility is related to the time necessary for the molecules to move from an oriented state within the medium to random orientation (or vice versa) .
  • the change from orientation to randomness is detected by an optical system. For example, birefringence change in the sample with respect to time can be evaluated. Highly mobile molecules will return to randomness or become oriented in a very short time, whereas longer, less mobile molecules will have a longer characteristic change 5 " of state time period.
  • a distribution of change of state times can be generated which is characteristic of the constituents of the sample.
  • Change of state time can be measured by observing birefringence changes after the external field is removed, 10 or as a function of light transmission through a range of applied AC signal frequencies.
  • optical properties or oriented molecule can be used to detect molecular orientation. For example, if the wavelength of the light source is absorbed by the sample molecules, then orientation in 15 an electromagnetic field causes a difference in the absorption of light polarized at different angles. The time or frequency dependence of circular dichroism may also be used to characterize the orientation of the molecules. The techniques are similar to those used to monitor birefringence changes, except for the wavelength of the light source. 20 If wavelengths characteristic of different classes of molecules can be found, then electric dichroism at several wavelengths may be monitored at the same time, thus increasing the resolving power of the technique.
  • Another optical technique for evaluating molecular 25o orientation employs fluorescence. If a molecule is itself fluorescent or has been labelled with a fluorescent reagent, then the fluorescence of the oriented molecule will be polarized. As the molecule returns to random orientation or becomes oriented, the change of this fluorescence polarization is monitored by techniques similar to those 30. used to monitor birefringence decay.
  • Figure 1 is a diagrammatic view showing an electrophoresis analysis system in accordance with a first embodiment of this invention adapted for characterizing separated gel samples using a pair of linear polarizers for detecting birefringence changes in the sample.
  • Figure 2 is a diagrammatic view showing an electrophoresis analysis system in accordance with a second embodiment of this invention adapted for characterizing separated gel samples using a pair of linear polarizers and a quarter-wave plate which detect birefringence changes in the sample.
  • Figure 3 is a diagra ⁇ iatic view showing an electrophoresis analysis system in accordance with a third embodment of this invention for detecting birefringence changes having a translating stage for scanning a gel sample particularly suited for use with samples previously subjected to electrophoresis migration.
  • Figure 4 is a diagra ⁇ iatic view showing an electrophoresis analysis system in accordance with a fourth embodiment of this invention for detecting birefringence changes particularly adapted for column electrophoresis.
  • Figure 5 is a diagrammatic view of an electrophoresis analysis system for detecting birefringence changes in accordance with a fifth embodiment of this invention adapted for relaxation time measurements of unseparated samples.
  • Figure 6 is a diagra ⁇ atic view of an electrophoresis analysis system according to a sixth embodiment of this invention adapted for measuring orientation time or relaxation time, or frequency of samples based on changes in non-linear optical properties of the sample.
  • Figure 7 is a diagrammatic view of an electrophoresis analysis system in accordance with a seventh embodiment of this invention which detects molecular orientation by changes in electric dichroism.
  • Figure 8 is a diagrairmatic view of an electrophoresis analysis system in accordance with an eighth e ⁇ bodiment of this invention which detects molecular orientation by fluorescence polarization.
  • Figure 9 is a diagrai iatic view of an electrophoresis analysis system in accordance with a ninth embodiment of this invention vfaich detects molecular orientation by light scattering.
  • Figure 10 is a diagrammatic view of an electrophoresis
  • System 10 includes low power laser 12 as a light source which may be a helium-neon lazer
  • the light output from laser 12 needs to be linearly polarized for this system since it is based on measuring birefringence. This is achieved in accordance with the embodiment of Figure 1 by using a laser 12 of a ' type which inherently provides a polarized output and further increasing the
  • linear polarizer 14 which may be a sheet or prism polarizer.
  • Sample 16 would typically be an agarose or polyacrylamide gel in which macromolecules are present and have been separated by electrophoresis migration.
  • Power supply 18 applies an electric field to sample 16 in a manner which orients molecules within
  • the direction of the electric field within sample 16 is oriented 45 degrees frcm the plane of polarization of the light from laser 12. This orientation maximizes the sensitivity to birefringence change.
  • Analyzing polarizer 20 is interposed within the ray emitted
  • Detector 22 senses the intensity of light transmitted through analyzing polarizer 20.
  • the light from laser 12 is made well polarized after passing through polarizer 14. Induced birefringence within sample 16 causes linearly polarized light passing through the sample
  • Analyzing polarizer 20 may be oriented to normally extinguish the light where there is no birefringence such that induced circular or elliptical polarization will cause some light to be transmitted through polarizer 20 and sensed by detector 22 since birefringence causes the plane of polarization of some of the light to change.
  • polarizer 20 may be oriented to normally permit light to pass which would be reduced in intensity upon birefringence through sample 16.
  • system 10 can be used to detect the presence of molecules in selected areas of sample 16 which where separated by electrophoresis, or may be used to characterize unseparated samples, as explained in greater detail below.
  • System 30 varies from the embodiment shown in Figure 1 in that quarter-wave plate 32 is added. Quarter-wave plate 32 causes linearly polarized light passing through it to become circularly polarized. Therefore, absent birefringence being induced within sample 16, the light will be circularly polarized as it passes through quarter-wave plate 32. In the event of induced birefringence, quarter-wave plate 32 partly reverses the elliptical polarization to make it more closely approach linear polarization. The degree of linear polarization is evaluated by analyzing polarizer 20 and detector 22.
  • FIG. 3 illustrates an electrophoresis analysis system in accordance with a third embodiment of this invention which functions as a scanning densitometer to detect birefringence changes and is designated by reference number 40.
  • Light transmitted through polarizer 14 is directed through sample 16 by mirror 42.
  • Sample 16 is immersed in a bath 44 of electrophoresis buffer.
  • Bath 44 contains two electrodes 46 which are conventionally platinum wire and run along the sides of the gel sample.
  • the bottom of bath 44 is transparent glass
  • Sample 16 is scanned by translating it through the fixed optical path (as shown in phantom lines) , most conveniently with a motor driven X-Y translation stage.
  • molecules are deposited on a gel sample and subjected to an electromagnetic field to cause molecular migration and separation.
  • Light from laser 12 passes through selected areas of sample 16 to detect the presence of the molecules of interest.
  • Signal generator 50 produces an AC signal with a frequency range, for example, of 4 to 16 Hz. The AC signal is used to prevent net movement of molecules which occurs When they are exposed to DC fields.
  • the signal from detector 22 is processed through lock-in amplifier 52 which provides synchronous demodulation.
  • FIG. 4 An electrophoresis analysis system according to a fourth embodiment of this invention is shown in Figure 4 and is generally designated by reference number 60.
  • This embodiment is similar in configuration to that shown in Figure 3 except that it is adapted for use with column electrophoresis procedures.
  • Power supply 18 and signal generator 50 are operated so that the sample receives a voltage with a net DC component, which causes migration, and an AC component, which can be detected by synchronous demodulation or other techniques.
  • macromolecules within column 62 are detected as they cross the optical path of the analyzer.
  • Column 62 is typically a length of glass tubing filled with a gel media or with a fluid buffer only with buffer reservoirs 64 and 66 at both ends. Power connections are made to each of reservoirs 64 and 66.
  • Column 62 is preferably made of tubing having a rectangular cross section to minimize distortion of the probing laser beam as it passes through the column.
  • Figure 5 illustrates an electrophoresis analysis system in accordance with a fifth embodiment designated by reference number 80.
  • a sample of molecules is provided which is mixed with a gel such as agarose or polyacrylamide.
  • the mixture is poured - 8 - into sample chamber 82 which preferably has a light path length on the order of one to ten millimeters.
  • Chamber 82 is constructed from Lucite (Trademark) or other material which is both electrically insulating and waterproof and fitted with glass windows 86.
  • a field 3 is presented to the sample by platinum foil electrodes 84. In operation, voltage is applied, and when it is turned off, molecular mobility is measured as a change in birefringence as the oriented molecules returning to random orientation or change frcm randomness to orientation. It is convenient to repeat the measurement many times,
  • Detector 22 generates data which are collected by an analog-to-digital converter and stored.
  • the frequency of applied voltage to sample chamber 82 can be varied, for example, between about 1 Hz to 1 MHz.
  • the relaxation times are observed as the
  • the embodiment illustrated in Figure 6 designated by reference number 90 utilizes the phenomenon of electric birefringence in which a second harmonic of the fundamental frequency of light from laser 12 is generated when the sample molecules are oriented.
  • laser 12 is pulsed.
  • the light at the optical second harmonic frequency is separated from the unconverted laser light (at the fundamental frequency) by interference filter 92.
  • the second harmonic light is then sensed by detector 22 and the signal is processed through waveform analyzer 54. This means for detecting molecular orientation can be used in systems for use with separated or unseparated samples.
  • Figure 7 shows a system for detection of molecular orientation by electric dichroism which is designated by reference number 110.
  • the dichroism is measured as the change in absorption of laser light, which need not be laser light, as the electromagnetic field applied to the sample is varied. If an incoherent source is used, then filters such as 112 or a monochro at ⁇ r may be used to isolate several characteristic wavelengths.
  • Figure 8 shows a system for measurement of fluorescence polarization which is designated by reference number 120.
  • the sample is illuminated with a light source and the fluorescence is measured through lens 122 and polarizer 124.
  • the fluorescence component which is passed by polarizer 124 will change.
  • a laser 12 is the preferred light source, because the fluorescence intensity is proportional to the source light intensity.
  • filters 12 and detectors, or a monochrcanator may be used to monitor fluorescence at several wavelengths simultaneously.
  • Figure 9 shows a system according to this invention for measurement of molecule orientation by detecting changes in light scattering.
  • Sample chamber 82 is illuminated with a light source 12 designated by reference number 130 and light scattering is measured through analyzing polarizer 20 by detector 22. The measurement is made at an angle to the illuminating beam, preferably 90 degrees, to discriminate against transmitted light.
  • the scattering component which is passed by polarizer 20 will change.
  • Laser 12 is the preferred light source, because the scattering intensity is proportional to the source light intensity.
  • Figure 10 shows a system designated by reference number 140 for measurement of birefringence, dichroism, fluorescence polarization or scattering by formation of the image of an extended region of a gel or of an entire gel.
  • Sample 82 is illuminated with a light source 12 through lenses 142 and 144, and polarizer 14 and the birefringence or
  • Iff dichroism is measured through analyzing polarizer 20 by . means of focusing the beam by lens 148 onto a two dimensional imagery device such as a photographic camera or a video camera 146. Two measurements are required. The dichroism or birefringence is measured with the external field applied. A background measurement is made in the
  • the induced birefringence or dichroism is then calculated as the difference between these measurements.
  • the fluorescence polarization or light scattering can be measured.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

Un système permet d'évaluer des échantillons d'électrophorèse en utilisant des moyens optiques pour détecter l'orientation des macromolécules suspendues dans le gel ou fluide. Un échantillon d'électrophorèse (16) est positionné de sorte qu'un rayon d'une sonde passe au travers de l'échantillon. Des éléments optiques (14, 16) et des détecteurs (22) sont utilisés pour détecter les variations du faisceau ou rayon de la sonde provoquées par l'orientation des molécules dans l'échantillon. Les systèmes optiques peuvent se baser sur la biréfringence induite dans l'échantillon, le dichroïsme électrique, la fluorescence, la dispersion de lumière etc. Des systèmes selon cette invention peuvent être utilisés pour déterminer des zones dans un échantillon de gel électrophorétique où la séparation s'est produite pour déterminer la présence des molécules de l'échantillon. Dans une variante, des échantillons non séparés peuvent être analysés en chronométrant le temps d'orientation ou de relaxation caractéristique de diverses molécules lorsque celles-ci passent d'un état d'orientation dans le fluide ou gel de l'échantillon vers un état d'orientation au hasard après suppression du champ externe ou inversion de sa polarité, ou lorsque celles-ci passent d'une orientation au hasard vers un état orienté après application d'un champ externe ou inversion de polarité de ce champ.
PCT/US1988/002679 1987-08-13 1988-08-11 Systemes d'analyses optoelectriques d'echantillons electrophoretiques WO1989001620A1 (fr)

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US8553887A 1987-08-13 1987-08-13
US085,538 1987-08-13

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996025660A2 (fr) * 1995-02-13 1996-08-22 Visible Genetics Inc. Procede et appareil pour une electrophorese automatisee utilisant un detecteur de polarisation de la lumiere
US6150089A (en) * 1988-09-15 2000-11-21 New York University Method and characterizing polymer molecules or the like
US6412123B1 (en) * 2000-11-01 2002-07-02 Pleasure Time Products (Hong Kong) Limited Portable spa
US7797770B2 (en) 2005-05-23 2010-09-21 Ideal Time Consultants. Limited Portable spa
US7818825B2 (en) 2005-05-23 2010-10-26 Ideal Time Consultants Limited Portable spa
US8095998B2 (en) 2005-05-23 2012-01-17 Ideal Time Consultants Limited Portable spa
CZ306860B6 (cs) * 2008-05-30 2017-08-16 Masarykova Univerzita Způsob a zařízení k provádění elektroforézy

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4101220A (en) * 1977-03-31 1978-07-18 General Electric Company Laser Doppler spectroscopy with smoothened spectra line shapes
US4154669A (en) * 1977-02-11 1979-05-15 Pen Kem, Inc. Automatic electrophoresis apparatus
US4320415A (en) * 1979-06-14 1982-03-16 National Research Development Corporation Method of and apparatus for measuring electrophoretic mobility of cells

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4154669A (en) * 1977-02-11 1979-05-15 Pen Kem, Inc. Automatic electrophoresis apparatus
US4101220A (en) * 1977-03-31 1978-07-18 General Electric Company Laser Doppler spectroscopy with smoothened spectra line shapes
US4320415A (en) * 1979-06-14 1982-03-16 National Research Development Corporation Method of and apparatus for measuring electrophoretic mobility of cells

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
ANNUAL REVIEW OF PHYSICAL CHEMISTRY, Vol. 36, issued 1985, D. PORSCHKE, "Effects of Electric Fields on Biopolymers", see pages 170 and 175. *
JAPANESE JOURNAL OF APPLIED PHYSICS, Vol. 19, No. 11, issued November 1974, N. OOKUBO et al., "A New Method of Dynamic Electric Birefringence Measurement Using a Sinusoidal Digital Lack-In System", see entire document, especially page 2274. *
JOURNAL OF COLLOID AND INTERFACE SCIENCE, Vol. 108, No. 2, issued December 1985, (London), R. ISHERWOOD AND B.R. JENNINGS, "Electrooptical Characteristics of Chrysotile Asbestos Sols", see page 464, col. 2, lines 12-21; page 466, col. 2, lines 10-33; and page 467, col. 1, first full paragraph. *
M. ROSS, ed., "Laser Applications", Volume 2, published 1974 by Academic Press (New York and London), see pages 21, 305 and 306. See also pages 122-125. *
METHODS IN ENZYMOLOGY, Volume 117, issued 1985, P. HAGERMANN, "Application of Transient Electric Birefringence to the study of Biopolymer Structure", see pp. 201 and 202, Optical Configuration; p. 213, first sentence under Data Acquisition. *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6150089A (en) * 1988-09-15 2000-11-21 New York University Method and characterizing polymer molecules or the like
US6448012B1 (en) 1988-09-15 2002-09-10 Wisconsin Alumni Research Foundation Method for mapping a nucleic acid
US6713263B2 (en) 1988-09-15 2004-03-30 Wisconsin Alumni Research Foundation Method for mapping a nucleic acid
WO1996025660A2 (fr) * 1995-02-13 1996-08-22 Visible Genetics Inc. Procede et appareil pour une electrophorese automatisee utilisant un detecteur de polarisation de la lumiere
WO1996025660A3 (fr) * 1995-02-13 1996-10-17 Visible Genetics Inc Procede et appareil pour une electrophorese automatisee utilisant un detecteur de polarisation de la lumiere
US5900131A (en) * 1995-02-13 1999-05-04 Visible Genetics, Inc. Method and apparatus for automated electrophoresis using light polarization detector
US6412123B1 (en) * 2000-11-01 2002-07-02 Pleasure Time Products (Hong Kong) Limited Portable spa
US7797770B2 (en) 2005-05-23 2010-09-21 Ideal Time Consultants. Limited Portable spa
US7818825B2 (en) 2005-05-23 2010-10-26 Ideal Time Consultants Limited Portable spa
US8095998B2 (en) 2005-05-23 2012-01-17 Ideal Time Consultants Limited Portable spa
US8108954B2 (en) 2005-05-23 2012-02-07 Ideal Time Consultants Limited Portable spa
CZ306860B6 (cs) * 2008-05-30 2017-08-16 Masarykova Univerzita Způsob a zařízení k provádění elektroforézy

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