WO1998041842A1 - Direct detection of bacteria-antibody complexes via uv resonance raman spectroscopy - Google Patents

Direct detection of bacteria-antibody complexes via uv resonance raman spectroscopy Download PDF

Info

Publication number
WO1998041842A1
WO1998041842A1 PCT/US1998/004623 US9804623W WO9841842A1 WO 1998041842 A1 WO1998041842 A1 WO 1998041842A1 US 9804623 W US9804623 W US 9804623W WO 9841842 A1 WO9841842 A1 WO 9841842A1
Authority
WO
WIPO (PCT)
Prior art keywords
medium
microorganism
bacteria
energy
antibody
Prior art date
Application number
PCT/US1998/004623
Other languages
French (fr)
Inventor
Wilfred H. Nelson
Jay F. Sperry
Original Assignee
The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations
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 Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations filed Critical The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations
Priority to EP98910272A priority Critical patent/EP0966662A4/en
Priority to CA002283814A priority patent/CA2283814A1/en
Priority to AU64555/98A priority patent/AU733691B2/en
Publication of WO1998041842A1 publication Critical patent/WO1998041842A1/en

Links

Classifications

    • 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
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • 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
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/804—Radioisotope, e.g. radioimmunoassay
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Definitions

  • Mass spectroscopy may be unequalled in identification of pure cultures and it is very rapid and sensitive. However, it is expensive to use, requires the destruction of samples, and is of questionable use in the analysis of complex mixtures. Flow cytometry is perhaps even more costly, requires extensive sample preparation, and in many aspects is limited in its scope of applicability. Luminescence techniques are of little use except in studies of pure cultures unless combined with immunological methods. Immunological methods are unequalled in specificity and speed, as well as sensitivity. Yet, they are often impractical to use unless very expensive and perishable materials are available in a state of constant readiness. Such methods are not practical for a wide range of organisms. Gas chromatography requires that cells be grown and, hence, this method is generally slow and of limited applicability.
  • the system and method of the invention avoids cumbersome separation steps and aids in the stabilization of the antigen- antibody complexes. This is especially true in those cases where it is necessary to detect small numbers of bacteria.
  • the invention is useful in environmental analysis for various consumer products, such as food products and liquid products and is useful for clinical analysis to provide rapid analysis of body fluids such as blood, spinal fluid or urine.
  • bacteria attached to antibody can be detected with resonance Raman spectroscopy.
  • the bacteria can be detected directly in a great numerical excess, e.g. 100 to 10,000, of antibody molecules. This discovery results in a system and method for the rapid and low cost detection of microorganisms .
  • the invention is based upon the formation and detection of the antigen-antibody complex. The detection of the complex is distinctly different from the prior art.
  • the invention embodies a system and method for detecting microorganisms.
  • a sample to be tested is placed in a medium, the medium containing antibodies attached to a surface for binding to a specific microorganism to form an antigen to antibody complex.
  • the medium is contacted with a beam of light energy, some of the energy is emitted from the medium as a lower resonance enhanced Raman backscattered energy.
  • the presence or absence of the microorganism is detected based on a characteristic spectral peak of said microorganism.
  • the figure illustrates a system of the invention.
  • Example Bacterium Escherichia coll, was grown in 50 ml of Trypticase soy broth (without glucose) in a shaking waterbath at 37°C overnight. The bacteria were pelleted by centrifugation (12,100 x g for 5 minutes at 4°C), washed once in 20 ml of 0.85% saline and resuspended in 5 ml of 0.025M sodium phosphate buffer pH 7 to which was added 2.25-25 ⁇ l of anti- Escherichia coli (rabbit anti E. coli all ag's - purified IgG fraction 4-5 mg/ml protein, purchased from Biodesign International, Kennebunk, Maine). This was put into a continuous cycle loop, feeding through a quartz flow cell positioned in the laser beam.
  • Laser light 242 nm was directed into the flow cell.
  • the emitted light energy (resonance enhanced Raman scattering) was sensed with a Raman detector.
  • the spectrum was read and the prominent peak at 1485 cm -1 was easily detected.
  • the tests confirmed that the spectral characteristics of the antibody are relatively weak and do not affect the spectra of the emitted light energy from the bacteria. Detection of about 50 complexes in the presence of great excess (200-1000 fold) of antibody molecules was achieved.
  • the number of complexes was estimated based on laser beam geometry and known bacterial densities in the culture studied.
  • the figure illustrates a flow cell 10, a laser 12, a Raman detector 14 and a display 16.
  • a sample of the egg yolk would be taken and placed in a fluid medium such as 0.025 M phosphate buffer pH 7.2.
  • Antibody e.g. rabbit anti- salmonella antibodies attached to glass beads or another solid surface would then be mixed in the fluid medium.
  • the medium would then be rinsed to remove other bacteria and contaminants and to isolate any bound antibody/salmonella complex.
  • the isolate preferably in aqueous medium, is placed in the cell 10. This isolate would then be scanned by the laser 12 as described above. The backscattered energy would be read by the detector 14. If the characteristic spectral peak of the bacterium were detected then the display 16 would indicate (actuate a light) the presence of salmonella in the source of the original sample.
  • Sensitive detection is possible because a prominent peak at 1485 cm -1 associated with nucleic acids of bacteria can be selectively and sensitively detected in the presence of proportionately very much larger numbers of antibody if irradiation is with laser light in the range 242-257.
  • the system and method also embodies microorganism/antibodies immobilized on various surfaces, i.e. magnetic beads, which allows for the application of simple "dip-stick” or immunomagnetic processes where antibody can be directly scanned by machine methods for the presence of bacteria.
  • analyses can be accomplished in full daylight. Since only a single peak, e.g. at 1485 cm -1 , needs to be detected, inexpensive detection methods normally used in UV filter fluorimetry can be used. This allows inexpensive optical components and simple detectors to be used. The ability to sensitively detect bacteria in a great numerical excess of antibody results in an inexpensive means of scanning the surfaces containing immobilized antibody rapidly, sensitively and relatively inexpensively.
  • the suitable wavelength ranges for microorganisms and other cells are in the ultraviolet region (242-257 nm) which excites nucleotide bases of deoxyribonucleic and ribonucleic acids (DNA and RNA) , as well as the aromatic amino acids of proteins (to a lesser extent).
  • the invention has been described with reference to the detection of a particular bacterium, it is equally applicable to the detection of any microorganisms or other cells that contain nucleic acids (DNA and/or RNA). Potentially, any cell that one can produce specific antibodies against for specific attachment could be detected using this detection system.
  • the common characteristics of the detection of the microorganisms is the presence of specific chemicals in their macromolecules, which when struck with an incident beam of light energy, particularly ultraviolet energy, emits very characteristic spectra.

Abstract

A system for the detection of bacteria antibody complexes. A sample to be tested for the presence of a bacteria is placed in a medium which medium contains antibodies attached to a surface for binding to a specific bacteria to form an antigen to antibody complex. The medium is contacted with an incident beam of light energy. Some of the energy is emitted from the medium as a lower resonance enhanced Raman backscattered energy. The presence or absence of the microorganism is detected based on the characteristic spectral peak of said microorganism.

Description

Title
Direct Detection of Bacteria-Antibody Complexes Via UV Resonance Raman Spectroscopy
Field of the Invention The detection and identification of microorganisms using Raman spectroscopy.
Background and Brief Summary of the Invention
There are many effective methods for the detection of microorganisms. At present, rapid, sensitive tests include fluorescent (fluorescence iitimunoassay or FIA), or radioactive labels (radio immunoassay or RIA) on the antibody attached in the antigen-antibody complex. Enzymes can be attached to the antibody to produce products which are more easily detected (ELISA) . However, such processes (ELISA, RIA and FIA) tend to be labor intensive and not easily adapted to automation. The fluorescence method suffers from background interference and the RIA method is hampered by policies which discourage the use of radioisotopes in routine processes. If only small numbers of bacteria are present separation of the complex from the labelled antibody can be very difficult.
Among the most highly developed of the new rapid detection techniques is mass spectroscopy and its various combinations with gas chromatography (bacterial byproducts from cultures) and pyrolysis methods. Gas chromatography is highly effective in detecting characteristic bacterial metabolic products. Flow cytometry provides for the rapid detection, identification, and separation of cells. Total luminescence spectroscopy can detect organisms very rapidly. The various immunological methods also can be very specific and very rapid. All of these methods have their distinct advantages and disadvantages.
Mass spectroscopy may be unequalled in identification of pure cultures and it is very rapid and sensitive. However, it is expensive to use, requires the destruction of samples, and is of questionable use in the analysis of complex mixtures. Flow cytometry is perhaps even more costly, requires extensive sample preparation, and in many aspects is limited in its scope of applicability. Luminescence techniques are of little use except in studies of pure cultures unless combined with immunological methods. Immunological methods are unequalled in specificity and speed, as well as sensitivity. Yet, they are often impractical to use unless very expensive and perishable materials are available in a state of constant readiness. Such methods are not practical for a wide range of organisms. Gas chromatography requires that cells be grown and, hence, this method is generally slow and of limited applicability.
In bacterial analysis normally the cost effective means of analysis involves isolating organisms and then growing them in controlled cultures. This process is very slow and relatively labor intensive.
It is known to detect and identify microorganisms based on resonance Raman spectra, U.S. Pat. No. 4,847,198. A beam of visible or ultraviolet light energy contacts a microorganism under investigation. A portion of the light energy is absorbed by the microorganism and a portion of the light energy is 'emitted' from the microorganism at a lower energy level. The emitted light energy (resonance enhanced Raman scattering) can be correlated to a specific microorganism. The present invention is directed to a system and method for detecting microorganisms with greater speed, sensitivity and specitivity than prior art methods. The need for growth of cultures is essentially eliminated. The sensitivity is much higher than rapid methods in current use (other than PCR and RIA) comparable to or better than RIA and better than FIA or ELISA since there is very little background interference and no need to purify or separate the complex.
The system and method of the invention avoids cumbersome separation steps and aids in the stabilization of the antigen- antibody complexes. This is especially true in those cases where it is necessary to detect small numbers of bacteria.
The invention is useful in environmental analysis for various consumer products, such as food products and liquid products and is useful for clinical analysis to provide rapid analysis of body fluids such as blood, spinal fluid or urine. We have unexpectedly discovered that bacteria attached to antibody can be detected with resonance Raman spectroscopy. The bacteria can be detected directly in a great numerical excess, e.g. 100 to 10,000, of antibody molecules. This discovery results in a system and method for the rapid and low cost detection of microorganisms . The invention is based upon the formation and detection of the antigen-antibody complex. The detection of the complex is distinctly different from the prior art.
Broadly, the invention embodies a system and method for detecting microorganisms. A sample to be tested is placed in a medium, the medium containing antibodies attached to a surface for binding to a specific microorganism to form an antigen to antibody complex. The medium is contacted with a beam of light energy, some of the energy is emitted from the medium as a lower resonance enhanced Raman backscattered energy. The presence or absence of the microorganism is detected based on a characteristic spectral peak of said microorganism.
In the preferred embodiment, there is a rinse step before spectral analysis to isolate the antigen to antibody complex.
Brief Description of the Drawings
The figure illustrates a system of the invention.
Description of the Preferred Embodiment( s )
Example Bacterium, Escherichia coll, was grown in 50 ml of Trypticase soy broth (without glucose) in a shaking waterbath at 37°C overnight. The bacteria were pelleted by centrifugation (12,100 x g for 5 minutes at 4°C), washed once in 20 ml of 0.85% saline and resuspended in 5 ml of 0.025M sodium phosphate buffer pH 7 to which was added 2.25-25μl of anti- Escherichia coli (rabbit anti E. coli all ag's - purified IgG fraction 4-5 mg/ml protein, purchased from Biodesign International, Kennebunk, Maine). This was put into a continuous cycle loop, feeding through a quartz flow cell positioned in the laser beam.
Laser light 242 nm was directed into the flow cell. The emitted light energy (resonance enhanced Raman scattering) was sensed with a Raman detector. The spectrum was read and the prominent peak at 1485 cm-1 was easily detected. The tests confirmed that the spectral characteristics of the antibody are relatively weak and do not affect the spectra of the emitted light energy from the bacteria. Detection of about 50 complexes in the presence of great excess (200-1000 fold) of antibody molecules was achieved.
The number of complexes was estimated based on laser beam geometry and known bacterial densities in the culture studied.
The formation of a single wavelength in the ultraviolet range, the use of that wavelength to create spectral information about a specimen and the control and output of that information in various graphic or tabular forms is within the scope of those skilled in the art.
The figure illustrates a flow cell 10, a laser 12, a Raman detector 14 and a display 16.
If testing for salmonella in egg yolks, a sample of the egg yolk would be taken and placed in a fluid medium such as 0.025 M phosphate buffer pH 7.2. Antibody, e.g. rabbit anti- salmonella antibodies attached to glass beads or another solid surface would then be mixed in the fluid medium. The medium would then be rinsed to remove other bacteria and contaminants and to isolate any bound antibody/salmonella complex. The isolate, preferably in aqueous medium, is placed in the cell 10. This isolate would then be scanned by the laser 12 as described above. The backscattered energy would be read by the detector 14. If the characteristic spectral peak of the bacterium were detected then the display 16 would indicate (actuate a light) the presence of salmonella in the source of the original sample. Sensitive detection is possible because a prominent peak at 1485 cm-1 associated with nucleic acids of bacteria can be selectively and sensitively detected in the presence of proportionately very much larger numbers of antibody if irradiation is with laser light in the range 242-257.
Previous UV spectral studies of bacteria and protein support that, if the bacteria-antibody complex can be detected using 242 nm light, that the approach will work for various wavelengths in the vicinity of 242-257 nm for which there is little protein fluorescence interference in the Raman fingerprint region, and specifically at 1485 cm-1.
The system and method also embodies microorganism/antibodies immobilized on various surfaces, i.e. magnetic beads, which allows for the application of simple "dip-stick" or immunomagnetic processes where antibody can be directly scanned by machine methods for the presence of bacteria.
In an alternative embodiment, through use of inexpensive solar-blind coatings, analyses can be accomplished in full daylight. Since only a single peak, e.g. at 1485 cm-1, needs to be detected, inexpensive detection methods normally used in UV filter fluorimetry can be used. This allows inexpensive optical components and simple detectors to be used. The ability to sensitively detect bacteria in a great numerical excess of antibody results in an inexpensive means of scanning the surfaces containing immobilized antibody rapidly, sensitively and relatively inexpensively.
The suitable wavelength ranges for microorganisms and other cells are in the ultraviolet region (242-257 nm) which excites nucleotide bases of deoxyribonucleic and ribonucleic acids (DNA and RNA) , as well as the aromatic amino acids of proteins (to a lesser extent).
Although the invention has been described with reference to the detection of a particular bacterium, it is equally applicable to the detection of any microorganisms or other cells that contain nucleic acids (DNA and/or RNA). Potentially, any cell that one can produce specific antibodies against for specific attachment could be detected using this detection system. In general, the common characteristics of the detection of the microorganisms is the presence of specific chemicals in their macromolecules, which when struck with an incident beam of light energy, particularly ultraviolet energy, emits very characteristic spectra.
The foregoing description has been limited to a specific embodiment of the invention. It will be apparent, however, that variations and modifications can be made to the invention, with the attainment of some or all of the advantages of the invention. Therefore, it is the object of the appended claims to cover all such variations and modifications as come within the true spirit and scope of the invention. Having described our invention, what we now claim is:

Claims

1. A method for detecting microorganisms comprising: placing a sample to be tested in a medium, the medium containing antibodies specific for binding to a microorganism to form an antigen to antibody complex; contacting the medium with a beam of light energy, some of the energy emitted from the medium as a lower resonance enhanced Raman backscattered energy; and detecting the presence or absence of the microorganism based on a characteristic spectral peak of said microorganism.
2. The method of claim 1 wherein the medium is a fluid medium and the microorganism is a bacterium.
3. The method of claim 2 wherein the light energy is ultraviolet light.
4. The method of claim 3 wherein the ultraviolet light is in the range of 242 to 257 nm.
5. The method of claims 3 or 4 wherein the medium is a liquid medium further comprising: removing the antigen antibody complex from the liquid medium; and detecting subsequently the presence or absence of the microorganism.
6. A system for detecting the presence or absence of a microorganism comprising: contacting a medium containing antibodies specific for binding to a microorganism with a beam of light energy; and means for detecting the presence or absence of the microorganism in the presence of an excess of antibodies.
PCT/US1998/004623 1997-03-14 1998-03-10 Direct detection of bacteria-antibody complexes via uv resonance raman spectroscopy WO1998041842A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP98910272A EP0966662A4 (en) 1997-03-14 1998-03-10 Direct detection of bacteria-antibody complexes via uv resonance raman spectroscopy
CA002283814A CA2283814A1 (en) 1997-03-14 1998-03-10 Direct detection of bacteria-antibody complexes via uv resonance raman spectroscopy
AU64555/98A AU733691B2 (en) 1997-03-14 1998-03-10 Direct detection of bacteria-antibody complexes via UV resonance raman spectroscopy

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US08/818,534 US6844199B1 (en) 1997-03-14 1997-03-14 Direct detection of bacteria-antibody complexes via UV resonance Raman spectroscopy
US08/818,534 1997-03-14

Publications (1)

Publication Number Publication Date
WO1998041842A1 true WO1998041842A1 (en) 1998-09-24

Family

ID=25225770

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/004623 WO1998041842A1 (en) 1997-03-14 1998-03-10 Direct detection of bacteria-antibody complexes via uv resonance raman spectroscopy

Country Status (5)

Country Link
US (1) US6844199B1 (en)
EP (1) EP0966662A4 (en)
AU (1) AU733691B2 (en)
CA (1) CA2283814A1 (en)
WO (1) WO1998041842A1 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6379920B1 (en) 1999-07-24 2002-04-30 Georgia Tech Research Corp. Spectroscopic diagnostics for bacteria in biologic sample
WO2007018556A2 (en) * 2004-09-30 2007-02-15 Nano Science Diagnostics, Inc. Method for detection and decontamination of antigens by nanoparticle-raman spectroscopy
US7411671B2 (en) 2005-09-15 2008-08-12 Flowgene Sa Technique for analyzing biological compounds in a non-destructive mode
WO2008122975A2 (en) 2007-04-04 2008-10-16 Opticul Diagnostics Ltd. Means and methods for detecting bacteria in a sample
WO2010076801A1 (en) 2009-01-05 2010-07-08 Opticul Diagnostics Ltd. Means and methods for rapid droplet, aerosols and swab infection analysis
US9365883B2 (en) 2011-12-19 2016-06-14 Opticul Diagnostics Ltd. Spectroscopic means and methods for identifying microorganisms in culture

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9494581B2 (en) 2004-08-24 2016-11-15 University Of Wyoming System and method for Raman spectroscopy assay using paramagnetic particles
US20060199209A1 (en) * 2005-03-03 2006-09-07 Neal Arthur Siegel Enhanced detection of biological and bioactive components by resonance Raman spectroscopy
US7450228B2 (en) * 2005-11-09 2008-11-11 Chemimage Corporation Spectral imaging of biofilms
US9150900B2 (en) * 2009-05-15 2015-10-06 Biomerieux, Inc. Automated transfer mechanism for microbial detection apparatus
CA2760982C (en) 2009-05-15 2019-01-15 Biomerieux, Inc. System and methods for rapid identification and/or characterization of a microbial agent in a sample
CN108827936B (en) * 2018-06-15 2024-03-08 何坚 Blood culture positive reporting detection device and method

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4483929A (en) * 1982-05-03 1984-11-20 Liposome Technology Incorporated Liposomes with glycolipid-linked antibodies
US4822566A (en) * 1985-11-19 1989-04-18 The Johns Hopkins University Optimized capacitive sensor for chemical analysis and measurement
US4847198A (en) * 1987-10-07 1989-07-11 The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations Detection and indentification of bacteria by means of ultra-violet excited resonance Raman spectra
US5266498A (en) * 1989-10-27 1993-11-30 Abbott Laboratories Ligand binding assay for an analyte using surface-enhanced scattering (SERS) signal
US5468606A (en) * 1989-09-18 1995-11-21 Biostar, Inc. Devices for detection of an analyte based upon light interference
US5492840A (en) * 1988-11-10 1996-02-20 Pharmacia Biosensor Ab Surface plasmon resonance sensor unit and its use in biosensor systems

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0322549A3 (en) * 1987-11-27 1991-05-08 F. Hoffmann-La Roche Ag Method for the immunological determination of polysaccharide antigens from bacteria or fungi in a biological sample
US5512492A (en) * 1993-05-18 1996-04-30 University Of Utah Research Foundation Waveguide immunosensor with coating chemistry providing enhanced sensitivity

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4483929A (en) * 1982-05-03 1984-11-20 Liposome Technology Incorporated Liposomes with glycolipid-linked antibodies
US4822566A (en) * 1985-11-19 1989-04-18 The Johns Hopkins University Optimized capacitive sensor for chemical analysis and measurement
US4847198A (en) * 1987-10-07 1989-07-11 The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations Detection and indentification of bacteria by means of ultra-violet excited resonance Raman spectra
US5492840A (en) * 1988-11-10 1996-02-20 Pharmacia Biosensor Ab Surface plasmon resonance sensor unit and its use in biosensor systems
US5468606A (en) * 1989-09-18 1995-11-21 Biostar, Inc. Devices for detection of an analyte based upon light interference
US5266498A (en) * 1989-10-27 1993-11-30 Abbott Laboratories Ligand binding assay for an analyte using surface-enhanced scattering (SERS) signal

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHADHA S., ET AL.: "ULTRAVIOLET MICRO-RAMAN SPECTROGRAPH FOR THE DETECTION OF SMALL NUMBERS OF BACTERIAL CELLS.", REVIEW OF SCIENTIFIC INSTRUMENTS., AIP, MELVILLE, NY., US, vol. 64., no. 11., 1 November 1993 (1993-11-01), US, pages 3088 - 3093., XP002911027, ISSN: 0034-6748, DOI: 10.1063/1.1144313 *
NELSON W. H., ET AL.: "UV RESONANCE RAMAN STUDIES OF BACTERIA.", APPLIED SPECTROSCOPY REVIEWS., MARCEL DEKKER INC.270 MADISON AVENUE. NEW YORK., US, vol. 27., no. 01., 1 January 1992 (1992-01-01), US, pages 67 - 124., XP002911026, ISSN: 0570-4928 *
See also references of EP0966662A4 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6379920B1 (en) 1999-07-24 2002-04-30 Georgia Tech Research Corp. Spectroscopic diagnostics for bacteria in biologic sample
WO2007018556A2 (en) * 2004-09-30 2007-02-15 Nano Science Diagnostics, Inc. Method for detection and decontamination of antigens by nanoparticle-raman spectroscopy
WO2007018556A3 (en) * 2004-09-30 2007-11-15 Nano Science Diagnostics Inc Method for detection and decontamination of antigens by nanoparticle-raman spectroscopy
US7411671B2 (en) 2005-09-15 2008-08-12 Flowgene Sa Technique for analyzing biological compounds in a non-destructive mode
WO2008122975A2 (en) 2007-04-04 2008-10-16 Opticul Diagnostics Ltd. Means and methods for detecting bacteria in a sample
US9102975B2 (en) 2007-04-04 2015-08-11 Opticul Diagnostics Ltd. Means and methods for detecting bacteria in a sample
WO2010076801A1 (en) 2009-01-05 2010-07-08 Opticul Diagnostics Ltd. Means and methods for rapid droplet, aerosols and swab infection analysis
US9365883B2 (en) 2011-12-19 2016-06-14 Opticul Diagnostics Ltd. Spectroscopic means and methods for identifying microorganisms in culture

Also Published As

Publication number Publication date
CA2283814A1 (en) 1998-09-24
AU6455598A (en) 1998-10-12
AU733691B2 (en) 2001-05-24
US6844199B1 (en) 2005-01-18
EP0966662A1 (en) 1999-12-29
EP0966662A4 (en) 2001-05-09

Similar Documents

Publication Publication Date Title
US5496700A (en) Optical immunoassay for microbial analytes using non-specific dyes
US6254830B1 (en) Magnetic focusing immunosensor for the detection of pathogens
Maragos Emerging technologies for mycotoxin detection
González-Martı́nez et al. On-line immunoanalysis for environmental pollutants: from batch assays to automated sensors
Rasooly et al. Real time biosensor analysis of Staphylococcal enterotoxin A in food
Dill et al. Detection of salmonella in poultry using a silicon chip-based biosensor
US6844199B1 (en) Direct detection of bacteria-antibody complexes via UV resonance Raman spectroscopy
US5543329A (en) Sensor for antigen-antibody reactions
Bilitewski Peer reviewed: Can affinity sensors be used to detect food contaminants?
Anis et al. Reusable fiber optic immunosensor for rapid detection of imazethapyr herbicide
US20030054569A1 (en) Particle based homogeneous assays using capillary electrophoresis with laser-induced fluorescence detection
US20100285522A1 (en) Versatile Multichannel Capillary Biosensor System
US7220596B2 (en) Real time detection of antigens
US20070218500A1 (en) Method and Apparatus for Detection of Live Bacterium Within Test Subject Through Specifically labeling Thereof
Strachan et al. Application of a rapid automated immunosensor for the detection of Staphylococcus aureus enterotoxin B in cream
CN107505459A (en) Quantitatively detect people H FABP time-resolved fluoroimmunoassay chromatograph test strip, kit and preparation method thereof
Starodub et al. Construction and biomedical application of immunosensors based on fiber optics and enhanced chemiluminescence
Oh Immunosensors for food safety
Contreras-Medina et al. Characteristics of mycotoxin analysis tools for tomorrow
Hartman et al. Rapid response biosensor for detection and identification of common foodborne pathogens
RU2197732C1 (en) Method for detecting and identifying microorganism cells and viruses
Taitt et al. Total internal reflection fluorescence (TIRF) array biosensors for biothreat agents for food safety and food defense
Yu Enhancing immunoassay possibilities using magnetic carriers in biological fluids
CA1197186A (en) Method of enumerating serologically selected cell populations
Kim et al. An automated fiber-optic biosensor based binding inhibition assay for the detection of Listeria monocytogenes

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA JP

AL Designated countries for regional patents

Kind code of ref document: A1

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

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2283814

Country of ref document: CA

Ref country code: CA

Ref document number: 2283814

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 64555/98

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 1998910272

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1998910272

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 1998540577

Format of ref document f/p: F

WWG Wipo information: grant in national office

Ref document number: 64555/98

Country of ref document: AU

WWW Wipo information: withdrawn in national office

Ref document number: 1998910272

Country of ref document: EP