EP0266370A1 - Dispositif et procede pour determiner la resistance microbienne a des agents microbicides - Google Patents

Dispositif et procede pour determiner la resistance microbienne a des agents microbicides

Info

Publication number
EP0266370A1
EP0266370A1 EP87902269A EP87902269A EP0266370A1 EP 0266370 A1 EP0266370 A1 EP 0266370A1 EP 87902269 A EP87902269 A EP 87902269A EP 87902269 A EP87902269 A EP 87902269A EP 0266370 A1 EP0266370 A1 EP 0266370A1
Authority
EP
European Patent Office
Prior art keywords
antibodies
specimen
entity
antimicrobic
enzymes
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP87902269A
Other languages
German (de)
English (en)
Inventor
Miles G. Hossom
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Murex Corp
Original Assignee
Murex Corp
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 Murex Corp filed Critical Murex Corp
Publication of EP0266370A1 publication Critical patent/EP0266370A1/fr
Withdrawn legal-status Critical Current

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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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54306—Solid-phase reaction mechanisms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/18—Testing for antimicrobial activity of a material
    • 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
    • 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
    • G01N33/54386—Analytical elements
    • 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
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • 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
    • G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • 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
    • G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
    • G01N33/9446—Antibacterials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • Beta-lactam antibiotics bind to primary receptors, known as membrane associated penicillin-binding proteins (PBP's), which play a central role in the cell cycle-related, morphogenetic synthesis of cell wall peptidoglycan. Inactivation of PBP's by antibiotics has an immediate impact on the. bacterial cell.
  • PBP's membrane associated penicillin-binding proteins
  • microorganisms such as bacteria may express enzymes which structurally alter or inactivate certain antibiotics or other antimicrobic agents which are used to treat infections caused by such bacteria.
  • antibiotic modifying enzymes are the beta-lactamases which can hydrolyze the lactam ring of beta-lactam antibiotics, such as the penicillins and cephalosporins and render them ineffective.
  • beta-lactam drugs have been developed with structures intended to be resistant to the action of the commonly produced beta-lactamases.
  • Some bacteria have responded with new forms of beta-! ac a ase which are capable of hydrolysing even the most defensively structured beta-lactam antibiotics.
  • These enzymes are largely responsible for bacterial resistance to the penicillin and cephalosporin family of antibiotics.
  • aminoglycoside-aminocyclitols such as Neamine, Neomycin, Genta icin, Tobramycin, Streptomycin and Sorbistin are also subject to inactivation by the bacteria-produced plas id encoded enzymes which may phosphor late, adenylate, or acetylate the drug's structure, and eliminate or reduce the antimicrobic activity of this important class of antibiotics.
  • other antimicrobic agents such as polypeptides
  • Bacitracin which inhibits peptidogycan synthesis by inhibiting the dephosphorylation of used pyrophosphate to lipid phosphate, a step essential to the regeneration of the lipid carrier
  • Other classes of antimicrobics which may be inactivated include acrolides (e.g., Erythromycin, Clinda ycin and Lincomycin), quinolones (e.g., Ciprofloxacin, Norfloxacin and nalidixic acid), thienamycins (e.g., Imipenem) and the like.
  • bacteria may express proteins which appear to block or bind to an antibiotic agent and sterically hinder their mode of action.
  • Present testing methods include culturing the bacteria in the presence of the antibiotic for a period of time, normally 4-18 hours, and observing the bacteria's ability to reproduce and multiply in the presence of the antibiotic. In these culture tests, the exact mode of antibiotic resistance is seldom known.
  • U.S. Patent No. 4,383,032 issued 10 May 1983 to Stahl et al., discloses a reagent and process for the determination of beta-lactamase using 7-cyanoacetylaminocephalosporanic acid and a mixture of ammonium ions, phosphate ions and oxygen-splitting agents. A red color forms where beta-lactamases are present.
  • U.S. Patent No. 4,381,343, issued 26 April 1983 to Citri describes a technique for the determination of antibacterial agents wherein a sample containing a beta-lactum antibiotic is applied to a site on a nutrient medium that has been seeded with beta-lactamase generating bacteria or spores; incubating the medium to promote the generation of beta-lactamase; and, assaying the beta-lactamase produced. Since the induction of beta-lactamase production is specific to beta-lactam antibiotics, the test provides an indication of the presence or amount of beta-lactam antibiotics in the sample. The invention is limited in the sensitivity obtainable, which appears to be substantially less than for typical fluorescent enzyme immunoassay techniques.
  • beta-lactamase test can sensitively detect all beta-lactamases produced by bacteria; no practical tests are available for the detection of the aminoglycosi de-modifying enzymes; and no practical tests are available to detect other proteins which block, bind, or otherwise inhibit the antimicrobial activity of antimicrobic agents. Also, and most importantly, no single test exists which can utilize a single specimen to detect icrobial resistance regardless of the nature of the antimicrobic agent or of the nature of any inactivating enzymes or other proteins.
  • the present invention provides a test device and method employing a series of monoclonal or polyclonal antibodies in an immunoassay to detect and identify antimicrobic agent modifying enzymes and antimicrobic agent blocking or binding proteins as are produced by pathogenic microorganisms.
  • the present invention comprises a method for detecting and identifying antimicrobic agent modifying enzymes or antimicrobic agent blocking or binding proteins in a specimen comprising contacting a specimen with at least two antibodies selected from monoclonal antibodies, polyclonal antibodies, or mixtures thereof arranged in a spaced relationship to each other and determining when a reaction has taken place between any of said at least two antibodies and an antimicrobic agent modifying agent or antimicrobic agent blocking or binding protein in said specimen by means of any immunoassay suitable for use with said antibodies.
  • test device that is also the subject of the present invention is described more fully below.
  • a panel of immunoassays to detect the presence of antibiotic modifying enzymes and other antibiotic reactive proteins, as are expressed by bacteria and perhaps other microorganisms, can accurately and quickly predict resistance and thereby infer susceptibility of microorganisms to antimicrobic therapy.
  • the time necessary to perform such assays is a matter of minutes, compared to many hours as required of the currently employed antimicrobic susceptibility tests using bacterial culture methods.
  • the microorganism being tested are exposed to antibodies to the antimicrobic modifying enzymes or proteins, and the presence of such enzymes or proteins is detected by the resulting immunochemical reaction.
  • the immunochemical reaction employs conventional methods, including, but not limited to, fluorescence, luminescence, radioisotope emission and spectral absorbence, and enzyme amplified variations of such methods.
  • the icroorgansm will be exposed to sublethal concentrations of antimicrobics, prior to or during testing for the antimicrobic modifying enzyme or protein, to induce the microorganism to produce such enzyme or protein if it possesses the genetic coding or capability to do so.
  • the immunoassay may employ any conventional heteroge ⁇ ous technique wherein an antibody to the antibiotic modifying enzyme or protein is bound to a solid support, such as plastic, latex or cellulose materials, or the like, and the test organism or a specimen containing the metabolites is exposed to the solid-bound antibody.
  • a solid support such as plastic, latex or cellulose materials, or the like
  • the microbial material contains the enzyme or protein to which the antibody is active, such enzyme or protein will be bound by the antibody. Extraneous, unreacted microbial material and metabolite is then washed off or otherwise removed from the solid support and the antibody/enzyme and antibody/protein complexes bound to the solid support.
  • a second antibody to the same enzyme or protein which is labelled or tagged with a compound or molecule or isotope and is detectable by visual or instrumented observations, is added and exposed to the solid bound antibody/enzyme or antibody/protein complex and will, in turn, react with and bind to the enzyme or protein.
  • Unbound second antibody is then washed off or otherwise removed from the resulting solid bound antibod /enzyme labelled antibody or antibody/protein/labelled antibody complexes.
  • the labelling compound or molecule or isotope is then detected by the analytical method for which it was intended, and the detectable presence of the labelling substance is indicative of the presence of the antibiotic modifying enzyme or protein.
  • the amount of labelling substance bound to the solid support is quantitatively proportional to the amount of enzyme or protein in the test organism or metabolite solution.
  • An example of a heterogeneous assay employs a set or series of devices whereby a specimen is contacted with insolubilized antibody and a labelled second antibody, both of which are directed against the modifying entity.
  • the reaction mixture is performed on or within or is subsequently added to a filter means and washed to effect a separation of bound from unbound material.
  • an enzyme label an appropriate substrate is added to develop a colored product, if a complex has formed, indicating the presence of antibmicrobic agent modifying enzyme or protein.
  • a panel of discrete reactions can be achieved using either a number of single reaction filter devices or one device adapted for multiple reactions. Several such assay systems are commercially available.
  • kits can be used incorporating reagents for a test, such as a heterogeneous assay, using insolubilized antibody, labelled second antibody conjugate, wash solution, and a multicavity filter device.
  • a test such as a heterogeneous assay
  • Another kit assembly that can be used comprises a conventional microtiter tray with a first antibody captured thereon with a different first antibody in each well, thereby forming a panel of different tests, a labelled second antibody and wash solution.
  • each reaction zone could have a different monoclonal antibody conta- ⁇ -ned OR-O ⁇ within it, and after adding specimen, would have a labelled polyclonal antibody solution added.
  • the invention is flexible so as to permit these, as well as other procedural steps to be chosen as warranted for the circumstances.
  • the immunoassay may also employ any conventional homogenous technique in which the test organism or metabolite specimen is mixed with labelled antibody to the antibiotic modifying enzyme or protein, and the resulting immunochemical reaction is detected by a change in the chemical or photometric activity of the labelling compound, which, change is induced by the presence or absence of antibiotic modifying enzyme or protein.
  • the amount of change in the chemical or photometric activity of the labelling compound is quantitatively proportional to the amount of enzyme or protein in the test organism or metabolite solution.
  • the particular immunoassay procedure used depends mainly on that which is most effective with any specific antibody or antibodies in giving rapid and accurate results.
  • the most suitable immunoassay can be easily determined by routine testing using the antibody or antibodies with various known immunoassay procedures against standard antigens (enzymes and blocking or binding proteins) and choosing that which is most effective.
  • test organism or metabolite solution is either contained in the specimen (urine, blood, wound exudate, cerebral spinal fluid, serum or plasma, saliva, feces, sputum, mucus, pus, or other body fluid or tissue) which is collected from or near the site of infection, or which is subsequently isolated or extracted from such material by additional processing.
  • specimen urine, blood, wound exudate, cerebral spinal fluid, serum or plasma, saliva, feces, sputum, mucus, pus, or other body fluid or tissue
  • the antimicrobic modifying enzymes or protein may also be detected directly in the body fluid or tissue of the infected patient, without collection or isolation of the infection organism.
  • the patient's urine, blood, wound exudate, spinal fluid, or other body fluid or tissue is tested by the immunoassay for the presence of antimicrobic agent modifying enzymes or proteins, without regard to the presence of the infecting organism in the test material.
  • the absence or presence of such antimicrobic agent modifying enzymes or proteins is the information required by a physician to determine which antibiotic to utilize in treating the patient.
  • the labelling material can be any material capable of emitting a detectable signal, such as, but not limited to a radioactive isotope, an enzyme, fluorescent, bioluminescent, chemiluminescent material or ferromagnetic atom or particle.
  • a detectable signal such as, but not limited to a radioactive isotope, an enzyme, fluorescent, bioluminescent, chemiluminescent material or ferromagnetic atom or particle.
  • This antibody is prepared according to the general procedure disclosed by Milstein & Kohler in NATURE 256:495-497, 1975.
  • the monoclonal antibodies of the present invention are prepared by fusing spleen cells, from a mammal which has been immunized against penicillinase, with an appropriate myeloma cell line such as NS-0. The resultant product is then cultured in a standard HAT (hypoxanthine, aminopterin, and thymidine) medium. Screening tests for the specific monoclonal antibodies are employed utilizing immunoassay techniques which will be described below.
  • the immune spleen cells may be derived from any mammal, such as primates, humans, rodents (i.e., mice, rats, and rabbits), bovine, ovine, canine, or the like, but the present invention will be described in connection with mice.
  • the mouse is first immunized by injection of the antigen chosen generally for a period of eleven weeks. When the mouse shows sufficient antibody production against the antigen, as determined by conventional assay, it is given a booster injection of the antigen, and then killed so that the spleen may be removed. The fusion can then be carried out utilizing immune spleen cells and an appropriate myeloma cell line.
  • the fused cells yielding an antibody which give a positive response to the presence of the antigen are removed and cloned utilizing any of the standard methods.
  • the monoclonal antibodies from the clones are then tested against standard antigens to determine their specificity for the particular antigen.
  • the monoclonal antibody selected, which is specific for the antigen or species, is then bound to an appropriate label.
  • Amounts of antibody sufficient for labelling and subsequent commercial production are produced by the known techniques, such as by batch or continuous tissue culture or culture iji vivo in mammals, such as mice.
  • the monoclonal antibodies may be labelled with a multitude of different labels, such enzymes, _.flu_pre,s..cent compounds, luminescent compounds, radioactive compounds, ferromagnetic labels, and the like.
  • Some of the enzymes utilized as labels are alkaline phosphatase, glucose oxidase, galactosidase, peroxidase, urease, and the like.
  • Such linkage with enzymes can be accomplished by any one of the conventional and known methods, such as the Staphylococcal Protein A method, the glutaraldehyde method, the benzoquinone method, or the periodate method.
  • Clindamycin, Lincomycin, Ciprofloxacin, Norfloxacin, nalidixic acid and Imipenem such that each well contains a different monoclonal antibody for each modifying enzyme or protein.
  • the tray is incubated for 1 hour at 37C or 24 hours at 4C. The incubated material is removed and the tray washed with 0.05M Tris buffered saline, pH 7.4,
  • a blocking agent bovine serum albumin in
  • step A To each coated well of the microtiter tray of step A is added an aliquot of specimen, such as a blood or urine sample, and allowed to incubate for 1 hour at 37C.
  • specimen such as a blood or urine sample
  • The- tray is washed with Tris buffered saline with BSA solution to remove unbound specimen.
  • the tray is washed with Tris buffered saline with BSA solution to remove unbound labelled monoclonal antibody.
  • To each well is added lOOul of indoxyl phosphate substrate. A visible blue color will appear in each well where the particular antimicrobic agent modifying enzyme or protein is present.
  • EXAMPLE 2 A. Procedure for preparing monoclonal antibodies to antimicrobic agent modifying enzymes or proteins: The procedure according to Example 1, Step A is followed wherein substituted for penicillinase is an enzyme or protein listed in Example 1, Step B.
  • Procedure for assay in a filter device To a ulticavity or multichamber filter device such as that described in co-pending Application No. 740,100 is added 1 drop (50ul) of each monoclonal antibody prepared in Step A above, which have been coated on latex particles (0.5% in glycine buffer) such that each distinct reaction zone receives one distinct type of monoclonal antibody. 1.0 ml of specimen is added to each reaction zone of the filter device.
  • Example 2 The procedure according to Example 2 is followed, wherein the respective and corresponding first and labelled monoclonal antibodies are combined together with the specimen and allowed to react, and then added to the filter device to each respective reaction zone. While the invention has been described in connection with a preferred embodiment, it is not intended to limit the scope of the invention to the particular form set forth, but, on the contrary, it is intended to cover such alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Un dispositif et un procédé, servant à détecter et à identifier une substance altérant des agents microbicides choisie parmi des enzymes ou des protéines de blocage et de liaison, comprend un moyen pour retenir au moins deux anticorps choisis parmi des anticorps monoclonaux, des anticorps polyclonaux ou leurs mélanges espacés les uns des autres, mettre en contact un spécimen soupçonné de contenir une substance microbicide avec les deux anticorps et, déterminer le moment où a lieu une réaction entre les anticorps et, la substance à l'aide d'une technique d'immuno-analyse quelconque apte à être utilisée avec les deux anticorps.
EP87902269A 1986-03-26 1987-03-19 Dispositif et procede pour determiner la resistance microbienne a des agents microbicides Withdrawn EP0266370A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US84407186A 1986-03-26 1986-03-26
US844071 1986-03-26

Publications (1)

Publication Number Publication Date
EP0266370A1 true EP0266370A1 (fr) 1988-05-11

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ID=25291725

Family Applications (1)

Application Number Title Priority Date Filing Date
EP87902269A Withdrawn EP0266370A1 (fr) 1986-03-26 1987-03-19 Dispositif et procede pour determiner la resistance microbienne a des agents microbicides

Country Status (3)

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EP (1) EP0266370A1 (fr)
AU (1) AU7202887A (fr)
WO (1) WO1987006004A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3929119A1 (de) * 1989-09-01 1991-03-07 Boehringer Mannheim Gmbh Verfahren zum nachweis von analyten

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1582956A (en) * 1976-07-30 1981-01-21 Ici Ltd Composite magnetic particles
US4234683A (en) * 1978-11-24 1980-11-18 Mcmillan William A Beta-lactamase diagnostic product and method
IL59723A (en) * 1980-03-27 1983-05-15 Teva Pharma Determination of antibacterial agents
DE3019451A1 (de) * 1980-05-21 1981-11-26 Boehringer Mannheim Gmbh, 6800 Mannheim Verfahren und reagens zur bestimmung von (beta) -lactamasen
US4361647A (en) * 1980-05-22 1982-11-30 Palo Alto Medical Research Foundation Sandwich immunoassay and compositions for use therein
US4376110A (en) * 1980-08-04 1983-03-08 Hybritech, Incorporated Immunometric assays using monoclonal antibodies
US4443549A (en) * 1981-10-19 1984-04-17 Molecular Genetics, Inc. Production of monoclonal antibodies against bacterial adhesins
US4514505A (en) * 1982-05-21 1985-04-30 The Trustees Of Columbia University In The City Of New York Monoclonal antibody mixtures and use thereof for enhanced sensitivity immunoassays
US4474892A (en) * 1983-02-16 1984-10-02 Board Of Trustees Of The Leland Stanford Junior University Two-site immunoassays using monoclonal antibodies of different classes or subclasses and test kits for performing same
US4596769A (en) * 1984-03-05 1986-06-24 Temple University Monoclonal antibodies to peptidoglycan and methods of preparing same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8706004A1 *

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AU7202887A (en) 1987-10-20
WO1987006004A1 (fr) 1987-10-08

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