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WO1991004489A1 - Systeme d'immuno-analyse interferometrique homogene - Google Patents

Systeme d'immuno-analyse interferometrique homogene Download PDF

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Publication number
WO1991004489A1
WO1991004489A1 PCT/CA1990/000309 CA9000309W WO9104489A1 WO 1991004489 A1 WO1991004489 A1 WO 1991004489A1 CA 9000309 W CA9000309 W CA 9000309W WO 9104489 A1 WO9104489 A1 WO 9104489A1
Authority
WO
WIPO (PCT)
Prior art keywords
antigen
waveguide
antibody
bsa
homogeneous immunoassay
Prior art date
Application number
PCT/CA1990/000309
Other languages
English (en)
Inventor
Ashraf A. Ismail
Original Assignee
The Royal Institution For The Advancement Of Learning (Mcgill University)
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 Royal Institution For The Advancement Of Learning (Mcgill University) filed Critical The Royal Institution For The Advancement Of Learning (Mcgill University)
Publication of WO1991004489A1 publication Critical patent/WO1991004489A1/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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • 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
    • G01J3/45—Interferometric spectrometry
    • G01J3/453—Interferometric spectrometry by correlation of the amplitudes
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7769—Measurement method of reaction-produced change in sensor
    • G01N2021/7779—Measurement method of reaction-produced change in sensor interferometric
    • 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
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection

Definitions

  • Fellgett's or the multiplex, advantage, which gives rise to improvements in signal-to- noise ratio (S/N) and reduction in measurement time for FT spectral acquisition, compared to the time required to obtain spectra with a grating instrument.
  • Fellgett's advantage originates in the fact that information for all wavelengths emitted from the source reaches the detector at the same time in FTOS measurements, whereas in a grating instrument each spectral element ( ⁇ cm -1 -, corresponding to the resolution) is detected separately. This results in a dramatic decrease in measurement time if information from a large spectral region is required. This is an important consideration if multiple components absorbing in different regions of the spectrum are to be detected.
  • an homogeneous immunoassay system for the determination of the presence of an antibody or an antigen in a sample which comprises of:
  • Figure 1 shows an interferometrically coded signal
  • FIG. 2 shows a schematic representation of the homogeneous immunoassay system made in accordance with the present invention
  • Figure 5 shows a homogeneous immunoassay system according to the present invention for the detection of an antibody (ab) in which antigens are bound onto the waveguide, and a known amount of labeled antibodies (ab*) competes for the antigen with the unlabeled antibody;
  • Figure 8 shows 2 curves representing intensities of the ⁇ (CO) absorptions of the X(CO) 3 label in the ATR spectrum measured from the surface of a waveguide immersed in a solution containing anti- BSA-X(CO) 3 (0.3 mg/ml), (a) with a bare waveguide and (b) with a
  • Figure 9 shows superposition of ATR spectra recorded from the surface of a waveguide coated with (a) BSA-Z(CO)g and (b) BSA- X(CO) 3 .
  • FIG. 2 An embodiment of the homogeneous immunoassay system according to the present invention is shown in Figure 2 and is generally denoted 1. It mainly consists in coupling of an optical fiber waveguide-based measurement cell to an optoelectronic detector assembly in which there are: a lens or beam condenser 3, an optical fiber waveguide 5, an aluminum sample boat 7, a stainless steel optical fiber coupler 9, a detector element 11, and a detector housing 13.
  • a beam condenser 3 to focus the interferometric signal onto the waveguide 5 aids in increasing the throughput of the signal reaching the detector 11.
  • a variety of beam condensers are commercially available, and simple lens systems can be assembled.
  • a detector design based on optical fiber technology has been implemented to enhance signal detection from optical fiber waveguides.
  • the homogeneous immunoassay system of the present invention is an immunoassay where no separation step is required.
  • an optical waveguide coated with an antigen (or antibody) is immersed in a solution containing the corresponding antibody (or antigen).
  • Introduction of the interferometrically coded signal ( Figure 1) to the waveguide at such an angle that it is internally reflected through the waveguide establishes an evanescent wave at the waveguide- solution interface.
  • the evanescent wave a the waveguide-solution interface has a depth of penetration proportional to the wavelength of the radiation propagating through the waveguide:
  • An homogeneous interferometric immunoassay system for the detection of an antigen (ag) has the antibodies bound onto the waveguide, and a known amount of labeled antigen (ag*) in the surrounding solution competes for the antibody binding sites with the unlabeled antigen ( Figure 4).
  • An homogeneous interferometric immunoassay system for the detection of an antibody (ab) has the antigen molecules bound onto the waveguide and a known amount of labeled antibody (ab*) in the surrounding solution competes for the antigen with the unlabeleld antibody ( Figure 5).
  • a sandwich-type homogeneous interferometric immunoassay for total antibody content is also possible using the system of the present invention.
  • Antigens are coated onto the surface of the waveguide, and antibodies specific to these antigens are introduced in the solution surrounding the waveguide. Following an incubation period, the solution is replaced with a solution containing labeled protein A molecules.
  • Protein A is a substance that binds to the Fc fragment of antibodies. Accordingly, the amount of labeled protein
  • a bound at the surface of the waveguide provides a measure of the total antibody content of the initial solution.
  • This invention also deals with the first application of a waveguide transmitting radiation in the mid-infrared region of the electromagnetic spectrum for the development of a homogeneous "mid-infrared" immunoassay.
  • the waveguide utilized was a ZnSe rod (8 X 0.5 X 0.5 cm) transmitting radiation in the frequency range between 5000 and 650 c ⁇ r
  • the coated waveguide was washed 3 times with distilled water and then immersed in 4 ml of a phosphate buffer (0.01 M, pH 7.4) solution containing bovine serum albumin (BSA) (1 mg/ml) and water-soluble carbodiimide [WSC; l-(3-Dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride] (1 mg/ml).
  • BSA bovine serum albumin
  • WSC water-soluble carbodiimide
  • HOOCC 6 H 5 Cr(CO) 3 (100 mg) in 20 ml of phosphate buffer in the presence of WSC (100 mg) at 4°C.
  • the solution was dialyzed (molecular weight cutoff, 20,000) twice against phosphate buffer and once against water, and the dialysate was evaporated under reduced pressure to yield a yellow solid, anti-BSA-[Lys- ⁇ -NHCOC 6 H 5 Cr(CO) 3 l n ' henceforth denoted as anti-BSA-X(CO) 3 .
  • IR in KBr: ⁇ (CO) 1975, 1910 cm -1 .
  • Protein A-[Lys- ⁇ -NHCOC 6 H 5 Cr(CO) 3 ] n ' henceforth denoted as Protein A-X(CO) 3 was synthesized by the above procedure.
  • a waveguide coated with CML to which BSA had been covalently bound was immersed in phosphate buffer (0.01 M, pH 7.4).
  • the ATR spectrum from the surface of the waveguide was recorded as the reference spectrum.
  • the buffer was then decanted, and 4 ml of a buffer solution containing labeled anti-BSA-X(CO) 3 (0.05 mg/ml) was introduced.
  • Spectral acquisition was commenced immediately upon addition of the antibody solution.
  • the formation of the BSA-[anti- BSA-X(CO) 3 ] complex with time was monitored by the growth of the peaks in the ATR spectrum due to the v(CO) absorptions of the X(CO) 3 label ( Figure 7, curve 1).
  • BSA-X(CO) 3 not bound to the BSA on the surface of the waveguide.
  • the background signal can arise in two ways: (1) penetration of the evanescent wave beyond the bound fraction into the solution surrounding the waveguide, and (2) nonspecific binding of anti-BSA-
  • BSA was complexed to two different labels having distinct absorptions.
  • a phosphate buffer solution containing BSA-X(CO) 3 and BSA-Z(CO)g was deposited onto the surface of an anti-BSA/CML-coated waveguide.
  • the absorptions of the X(CO) 3 and Z(CO)g labels can be distinguished and their intensities measured independently.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Plasma & Fusion (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention se rapporte à un système d'immuno-analyse homogène qui permet de déterminer la présence d'un anticorps ou d'un antigène dans un échantillon et qui utilise un signal interférométrique provenant d'une source optique, un guide d'ondes recouvert d'un anticorps ou d'un antigène et comportant au moins une région immergée dans une solution contenant un échantillon, de sorte que l'antigène ou l'anticorps correspondant puisse être amené à former un complexe sur le guide d'ondes, un capteur destiné à mesurer le signal interférométrique après sa propagation à travers le guide d'ondes, ainsi qu'un dispositif de mesure permettant d'obtenir la transformée de Fourier du signal interférométrique en vue de déterminer le degré d'atténuation du signal interférométrique à une longueur d'onde correspondant à une caractéristique d'absorption du complexe antigène/anticorps ou d'une marque incorporée dans le complexe antigène/anticorps, ce qui permet de déterminer la quantité d'antigènes ou d'anticorps contenue dans l'échantillon.
PCT/CA1990/000309 1989-09-20 1990-09-20 Systeme d'immuno-analyse interferometrique homogene WO1991004489A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US40978889A 1989-09-20 1989-09-20
US409,788 1989-09-20

Publications (1)

Publication Number Publication Date
WO1991004489A1 true WO1991004489A1 (fr) 1991-04-04

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AU (1) AU6426490A (fr)
WO (1) WO1991004489A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5413939A (en) * 1993-06-29 1995-05-09 First Medical, Inc. Solid-phase binding assay system for interferometrically measuring analytes bound to an active receptor
EP1496361A1 (fr) * 2003-07-07 2005-01-12 Matsushita Electric Industrial Co., Ltd. Assay et système immunologique, utilisant une transformation Fourier, pour évaluer la survenue des phénomènes zonales.
US7405831B2 (en) 2005-02-01 2008-07-29 Purdue Research Foundation Laser scanning interferometric surface metrology
WO2008118934A1 (fr) * 2007-03-26 2008-10-02 Purdue Research Foundation Procédé et dispositif pour conjuguer la détection interférométrique en quadrature d'un immuno-essai
US7522282B2 (en) 2006-11-30 2009-04-21 Purdue Research Foundation Molecular interferometric imaging process and apparatus
US20220091031A1 (en) * 2020-09-18 2022-03-24 Salvus, Llc Interferometric Detection and Quantification System and Methods of Use in Chemical Processing

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61173138A (ja) * 1985-01-28 1986-08-04 Olympus Optical Co Ltd 光強度ゆらぎによる免疫反応測定方法
DE3623265A1 (de) * 1986-07-10 1988-01-21 Siemens Ag Verfahren und anordnung zur faseroptischen messung einer weglaenge oder einer weglaengenaenderung
WO1989007756A1 (fr) * 1988-02-14 1989-08-24 Walter Lukosz Procede optique integre d'interference

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61173138A (ja) * 1985-01-28 1986-08-04 Olympus Optical Co Ltd 光強度ゆらぎによる免疫反応測定方法
DE3623265A1 (de) * 1986-07-10 1988-01-21 Siemens Ag Verfahren und anordnung zur faseroptischen messung einer weglaenge oder einer weglaengenaenderung
WO1989007756A1 (fr) * 1988-02-14 1989-08-24 Walter Lukosz Procede optique integre d'interference

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Dialog Informational Services, File 351: WPI, Acc No: 4239549, WPI Acc No: 86-242938/37 & JP, A, 61173138 (OLYMPUS OPTICAL KK) 4 August 1986, abstract *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5413939A (en) * 1993-06-29 1995-05-09 First Medical, Inc. Solid-phase binding assay system for interferometrically measuring analytes bound to an active receptor
EP1496361A1 (fr) * 2003-07-07 2005-01-12 Matsushita Electric Industrial Co., Ltd. Assay et système immunologique, utilisant une transformation Fourier, pour évaluer la survenue des phénomènes zonales.
US7405831B2 (en) 2005-02-01 2008-07-29 Purdue Research Foundation Laser scanning interferometric surface metrology
US7522282B2 (en) 2006-11-30 2009-04-21 Purdue Research Foundation Molecular interferometric imaging process and apparatus
WO2008118934A1 (fr) * 2007-03-26 2008-10-02 Purdue Research Foundation Procédé et dispositif pour conjuguer la détection interférométrique en quadrature d'un immuno-essai
US20220091031A1 (en) * 2020-09-18 2022-03-24 Salvus, Llc Interferometric Detection and Quantification System and Methods of Use in Chemical Processing

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Publication number Publication date
AU6426490A (en) 1991-04-18

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