EP1216310A1 - Capteur d'affinite pour la detection d'especes biologiques et/ou chimiques, et son utilisation - Google Patents

Capteur d'affinite pour la detection d'especes biologiques et/ou chimiques, et son utilisation

Info

Publication number
EP1216310A1
EP1216310A1 EP00962399A EP00962399A EP1216310A1 EP 1216310 A1 EP1216310 A1 EP 1216310A1 EP 00962399 A EP00962399 A EP 00962399A EP 00962399 A EP00962399 A EP 00962399A EP 1216310 A1 EP1216310 A1 EP 1216310A1
Authority
EP
European Patent Office
Prior art keywords
nanoparticles
sensor according
affinity sensor
binding surfaces
affinity
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Withdrawn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
EP00962399A
Other languages
German (de)
English (en)
Inventor
Wolfgang Fritzsche
Andrea Czaki
Johann Michael KÖHLER
Jörg REICHERT
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.)
Institut fuer Physikalische Hochtechnologie eV
Original Assignee
Institut fuer Physikalische Hochtechnologie eV
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 Institut fuer Physikalische Hochtechnologie eV filed Critical Institut fuer Physikalische Hochtechnologie eV
Publication of EP1216310A1 publication Critical patent/EP1216310A1/fr
Withdrawn legal-status Critical Current

Links

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
    • G01N21/62—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
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • 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
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • 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
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B01J2219/00529—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00608—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00646—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports
    • B01J2219/00648—Making arrays on substantially continuous surfaces the compounds being bound to beads immobilised on the solid supports by the use of solid beads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof

Definitions

  • Affinity sensor for the detection of biological and or chemical species and its use
  • the invention relates to an affinity sensor for the detection of biological and / or chemical species, which is particularly suitable for tasks in combinatorial chemistry, for diagnostic tasks, such as in medicine or for the development of new active substances, e.g. for medication or selective pesticides.
  • Binding events on biochips are usually measured using
  • Fluorescence measurement is time consuming and only with expensive optical ones Establish reading facilities. The longer exposure and exposure times required for quantitative measurements
  • Accumulation times also cause a photochemical degradation of the dyes, which worsens the signal in the course of the measurement and makes quantification difficult.
  • the intensity of the fluorescent light per excitation light quantity and binding event also depends on the specific chemical environment of the chromophores used for labeling. Therefore, from batch to batch and from test to test and even within a sample, there are considerable deviations in the measurement signals, which considerably impair the actually required quantification of the measurement signals.
  • a slow photo- and thermochemical degradation of the chromophores also leads to the fact that measurement samples cannot be stored for a longer period, i.e. they cannot be archived and used for comparative measurements at a later date.
  • US Pat. No. 5,556,756 describes a gold sol that can be used in analytical test kits. Since the analysis is based on a color change of the surface, particles between 1 nm and 5 nm are preferably used.
  • the method described there has the disadvantage that, on the one hand, relatively large test areas have to be used and, on the other hand, permeable membranes have to be used in order to be able to carry out rinsing processes. This solution is not suitable for marking small binding areas in the middle and lower micrometer range.
  • WO 98/57148 AI describes a method and an arrangement in which the changes in the angle of the surface plasmon resonance associated with the addition of such small particles to a thin metal film can be determined. This process requires a complex SPR arrangement and is also dependent on the existence of a metal layer on an otherwise transparent substrate that prevents the passage of light.
  • the invention is based on the object of specifying an affinity sensor which enables rapid, quantitative and low-cost detection of the presence of biological and / or chemical species, in particular on areas in the lower to medium micrometer range.
  • Reliable detection of binding events on surfaces in the lower to medium ⁇ m range is achieved in the context of the invention by the production of nanoparticle layers which are formed by markers, the density of which is particularly by absorption but also by reflection or scattering light measurements or by plasmon resonance measurements. measurements is quantifiable.
  • the size-specific absorption of light can advantageously be used, as a result of which multiple markings are also possible using several monodisperse groups of nanoparticles with different diameters.
  • the selective labeling of immobilized biomolecules has been surprising proven unproblematic. Gold particles have proven to be particularly favorable for marking. When using gold particles, such an affinity sensor can also be integrated in a device for determining the plasmon resonance. A selective binding can also be demonstrated in the case of relatively large particle diameters which already provide quite comfortable scattered light signals.
  • the readout of binding events on biochips can be carried out particularly advantageously by the areal marking provided in the present invention with in particular metallic nanoparticles.
  • Fig. 2 shows a partial area of the AfBnticianssensor according to Fig. 1 in a side view
  • Fig. 3 is a scanning force microscope image of a nanoparticle layer, which is formed by a coating with 30 nm gold particles
  • Fig. 4 shows a high-microscopic image of an individual
  • FIG. 1 shows an example of an affinity sensor for the detection of biological and / or chemical species consisting of an optically transparent substrate 1, which is provided with a plurality of microstructured binding surfaces 2 spaced apart from one another.
  • the type and design of the binding surfaces depends on the specification of the binding events to be determined and can be implemented as such by customary professional action, which is why no further explanations are required here.
  • the bonding surfaces 2 are spaced apart by free-structured areas 11 of the substrate 1.
  • the dimensioning of the side lengths of the individual bonding surfaces 2, which are square here takes place in such a way that it is set above the light-optical diffraction limit; in the example 2 ⁇ m, in any case> 0.5 ⁇ m.
  • the side length of the optically transparent substrate 1 should be 3 mm, with the active surface area 22, namely the surface of the substrate 1, which is provided with the binding surfaces 2, only being of the order of 1 mm 2 for certain applications (e.g. rapid diagnostics) can also easily take up areas below 0.01 mm 2 , the only important thing is that the individual binding surfaces 2 are given a surface that lies above the light-optical diffraction limit, with the active surface area 22 occupied by all binding surfaces 2 from common lenses a numerical aperture between 0.1 ... 0.9, preferably 0.2, optical microscopes should be detectable. If one omits this advantage created by the invention, it is also possible to use expensive lenses with a larger aperture, in which case larger active surface areas 22 can also be used.
  • FIG. 2 shows a partial area of the affinity sensor according to FIG. 1 in a side view, the same parts being designated with the same reference symbols as in FIG. 1.
  • the nanoparticles 3 used in the context of the invention are provided with coupling partners 4 which have a high selective affinity for the binding surfaces 2 or, as shown in the example according to FIG. 2, sequences (DNA) specifically bound thereon.
  • the following example is intended to explain:
  • Oligonucleotides with, for example, 20 base pairs are immobilized on the mils-patterned areas of the substrate 1 and thus form the binding areas 2 described above.
  • the affinity sensor thus prepared is mixed with a solution to be tested which contains DNA of unknown composition. This only binds to the binding surfaces 2, which carry oligonucleotides complementary to sections of the DNA.
  • the surface of the nanoparticles is provided with a coupling partner 4, in the example an oligonucleotide, the sequence of which is such that it is not complementary to one of the binding surfaces 2 on the substrate 1 but is complementary to a conservative nucleotide sequence of the target molecules to be examined, which occurs in the same way in all target molecules in question (bound DNA).
  • a coupling partner 4 in the example an oligonucleotide, the sequence of which is such that it is not complementary to one of the binding surfaces 2 on the substrate 1 but is complementary to a conservative nucleotide sequence of the target molecules to be examined, which occurs in the same way in all target molecules in question (bound DNA).
  • a density of approx. 40 particles / ⁇ m 2 was obtained in the example, the diameter of 30 nm being given to the gold nanoparticles 3 used in the example.
  • nanoparticle layers with a nanoparticle coating 31 of approx. 3% are obtained, which are immediately and clearly visible in the light microscope. These structures correspond to the pre-stabilized binding areas 2.
  • the diameter ranges of the nanoparticles 3 can be defined within wide limits depending on the test assay to be designed in each case.
  • the diameters of the nanoparticles can be set in the order of 2 ... 600 nm.
  • a diameter range of 15 ... 60 nm is preferably selected.
  • Metallic nanoparticles are preferably used in the context of the invention since they absorb light in a very effective manner, as a result of which nanoparticle occupations of the order of magnitude of 0.1% can be detected in transmitted light in the light microscope. This makes it possible to work just above the diffraction limit (1 ⁇ m .. 10 ⁇ m) even when the individual binding surfaces 2 are extended. In this way, 100 binding surfaces 2 can be placed on active surfaces 22 of significantly less than 0.1 mm in side length, 10,000 binding surfaces 2 on less than 1 mm 2 . Even for highly integrated affinity sensors with 100,000 binding areas 2, a total area of less than 1 mm 2 appears to be feasible.
  • nanoparticles 3 also to contain metal-containing composite particles in the size range mentioned also use nanoparticles made of a semiconductor material, such as CdSe, InP, as well as coated nanoparticles, for example with ZnSe. It is also within the scope of the invention to use nanoparticles made of plastic, which preferably contain inclusions made of an absorbent dye, metal or semiconductors.
  • nanoparticle coatings 31 formed by them with lenses of conventional light-optical microscopes for the purpose of determining the optical absorption, reflection or scattering caused by the nanoparticle coating 31, also in the case of the above-described ones low densities of the nanoparticles per binding surface 2 can be detected when the entire active surface 22 is recorded.
  • the arrangement of the binding surfaces 2, which accommodate the aforementioned nanoparticle coatings 31, can be provided on the surface of a prism in the manner described above, as a result of which such an affinity sensor is accessible to a device for detecting the plasmon resonance.
  • the size of the nanoparticles should be selected so that, on the one hand, they make a very effective contribution to signal generation even with a few binding molecules, whereby they must not be too small, but on the other hand, in order to specifically couple , must not be too large, a cooperative measurement effect being achieved by coupling several nanoparticles 3 to a single binding surface 2.
  • the measurement signal With decreasing particle size, the measurement signal becomes worse, with increasing particle size the specificity of the binding decreases. The former leads to a reduction in the absolute signal, the latter to an increase in the background signal.
  • the specific selection of the particles in question lies within a reasonable range for the person skilled in the art. For the use described above.
  • FIG. 3 shows a scanning force microscope image of a nanoparticle coating 31 on a 5 ⁇ 5 ⁇ m surface, which is covered by a coating of 30 nm Gold particles is formed, wherein in FIG. 4 a highly microscopic transmitted light image of an individual binding surface, which illustrates the absorption caused by the nanoparticle coating 31 with respect to the substrate 1 carrying it.
  • the proposed affinity sensor offers the following advantages over the fluorescent dye marking and reading customary in the prior art:
  • the signal is independent of the chemical environment, which is why the affinity sensor can be used for quantitative measurements.
  • the proposed structure of the affinity sensor provides a favorable signal-to-noise ratio, as a result of which short measuring times can be achieved.
  • the affinity sensors which are provided with the nanoparticle assignments, have a long-term storage stability, since the particle assignments do not undergo any changes of their own accord, which enables their archiving, which is important in medicine, in particular forensic medicine, environmental technology, and the
  • the proposed affinity sensor is also suitable for fast assays and for small sample quantities and up to approximately 10 6 binding areas 22 in an area of 1 mm 2 can have, which is particularly advantageous for tests with molecular library chips, such as biochips, DNA chips, etc.
  • the proposed affinity sensor can thus be used in particular for tasks in combinatorial chemistry, for diagnostic tasks in medicine, for the development of new active substances, for the development of new medicinal substances or for the development of selectively acting pesticides.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Hematology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Biotechnology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un capteur d'affinité pour la détection d'espèces biologiques et/ou chimiques, qui permet de détecter rapidement, quantitativement et de façon peu complexe la présence d'espèces biologiques et/ou chimiques, en particulier sur des surfaces dans la gamme des valeurs basses à moyennes, de l'ordre du micromètre. A cet effet, ledit capteur est constitué, selon le type de lecture, d'un substrat (1) optiquement transparent ou partiellement réfléchissant qui est pourvu de plusieurs faces de liaison (2) microstructurées, espacées les unes des autres, dont la surface est fixée, par rapport au diamètre de nanoparticules (3) et de façon à être supérieure à la limite de diffraction optique, cette surface étant d'une grandeur telle que les nanoparticules (3) sont pourvues de partenaires de couplage (4) qui présentent, vis-à-vis des faces de liaison (2) ou de séquences (ADN) liées spécifiquement à ces faces, une telle affinité sélective qu'ils se lient de façon permanente aux faces de liaison (2) ou aux séquences (ADN) liées spécifiquement à ces faces. Ainsi, sur au moins une face de liaison (2) peut se fixer un nombre de nanoparticules (3), qui forment une couche de nanoparticules (31), tel que la surface occupée par la couche de nanoparticules (31) peut correspondre à au moins 0,1 % de la surface d'une face de liaison (2). Toutes les faces de liaison (2) sont disposées dans une zone de faces active telle qu'elles peuvent être observées ensemble par l'intermédiaire de l'objectif d'un microscope optique classique avec une ouverture numérique comprise entre 0,1...0,9, pour permettre la détermination de l'absorption, de la réflexion ou de la dispersion dues aux couches de nanoparticules (31), ou bien à l'aide d'un dispositif servant à la détermination de la résonance des plasmons.
EP00962399A 1999-09-08 2000-08-28 Capteur d'affinite pour la detection d'especes biologiques et/ou chimiques, et son utilisation Withdrawn EP1216310A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19943704 1999-09-08
DE19943704A DE19943704C1 (de) 1999-09-08 1999-09-08 Affinitätssensor zum Nachweis biologischer und/oder chemischer Spezies und dessen Verwendung
PCT/EP2000/008360 WO2001018242A1 (fr) 1999-09-08 2000-08-28 Capteur d'affinite pour la detection d'especes biologiques et/ou chimiques, et son utilisation

Publications (1)

Publication Number Publication Date
EP1216310A1 true EP1216310A1 (fr) 2002-06-26

Family

ID=7921775

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00962399A Withdrawn EP1216310A1 (fr) 1999-09-08 2000-08-28 Capteur d'affinite pour la detection d'especes biologiques et/ou chimiques, et son utilisation

Country Status (3)

Country Link
EP (1) EP1216310A1 (fr)
DE (1) DE19943704C1 (fr)
WO (1) WO2001018242A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10109777A1 (de) * 2001-03-01 2002-09-19 Infineon Technologies Ag Verfahren zum Erfassen von makromolekularen Biopolymeren mittels mindestens einer Einheit zum Immobilisieren von makromolekularen Biopolymeren
DE10113712A1 (de) * 2001-03-16 2002-09-26 Lifebits Ag Verfahren zum Aufbringen chemischer Substanzen
US6867275B2 (en) 2001-03-30 2005-03-15 Rohm And Haas Company Solid media
DE10116315A1 (de) * 2001-04-02 2002-10-10 Giesecke & Devrient Gmbh Farbcodierung zur Kennzeichnung von Gegentänden
DE10164309A1 (de) * 2001-12-28 2003-07-10 Fraunhofer Ges Forschung Verbesserte strukturiert-funktionale Bindematrices für Biomoleküle
DE102004033586A1 (de) * 2004-07-06 2006-01-26 Imtec Immundiagnostika Gmbh Verfahren zur Auswertung von Biochips
RU2537267C1 (ru) * 2013-07-03 2014-12-27 Закрытое акционерное общество "Центр перспективных технологий" Устройство для идентификации последовательностей нуклеотидов
DE102018133037B4 (de) 2018-12-20 2021-02-25 Leibniz-Institut für Photonische Technologien e. V. Anordnung und Verfahren zur Erfassung von optischen Eigenschaften einer Probe, insbesondere zum selektiven Nachweis von biologischen Molekülen und zum Auslesen einer Molekülbelegung

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU593151B2 (en) * 1986-11-12 1990-02-01 Molecular Diagnostics, Inc. Method for the detection of nucleic acid hybrids
GB8800702D0 (en) * 1988-01-13 1988-02-10 Nycomed As Test method & reagent kit therefor
US5599668A (en) * 1994-09-22 1997-02-04 Abbott Laboratories Light scattering optical waveguide method for detecting specific binding events
US6180415B1 (en) * 1997-02-20 2001-01-30 The Regents Of The University Of California Plasmon resonant particles, methods and apparatus
GB2326229A (en) * 1997-06-13 1998-12-16 Robert Jeffrey Geddes Carr Detecting and analysing submicron particles
US6294327B1 (en) * 1997-09-08 2001-09-25 Affymetrix, Inc. Apparatus and method for detecting samples labeled with material having strong light scattering properties, using reflection mode light and diffuse scattering

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0118242A1 *

Also Published As

Publication number Publication date
DE19943704C1 (de) 2001-05-10
WO2001018242A1 (fr) 2001-03-15

Similar Documents

Publication Publication Date Title
DE69819916T2 (de) Vorrichtung und verfahren zur abbildung von mit lichtstreuendem stoff markierten proben
EP1248948B1 (fr) Procede et dispositif pour la determination de parametres dependant de la temperature, tels que les parametres d'association/dissociation et/ou la constante d'equilibre de complexes constitues d'au moins deux composants
AT403961B (de) Optochemisches messsystem mit einem fluoreszenzsensor
DE19725050C2 (de) Anordnung zur Detektion biochemischer oder chemischer Substanzen mittels Fluoreszenzlichtanregung und Verfahren zu deren Herstellung
EP1556695B1 (fr) Plate-forme analytique et procede d'identification par des analytes a deceler dans un echantillon eventuellement apres fractionnement et se presentant sous forme de partenaires de liaison specifiques
EP0126450A2 (fr) Particule et méthode de détection d'antigènes et/ou anticorps utilisant cette particule
DE2509215C2 (de) Fluorometer
WO2002097405A2 (fr) Procede d'ellipsometrie a resolution spatiale pour la determination quantitative et/ou qualitative de modifications d'echantillons, biopuce et systeme de mesure
DE10142691A1 (de) Verfahren zum Nachweis biochemischer Reaktionen sowie eine Vorrichtung hierfür
WO2002046756A1 (fr) Kit et procede de detection d'analytes multiples comprenant des mesures de referenciation a resolution locale d'une intensite de lumiere d'excitation
DE10023423B4 (de) Direkter Nachweis von Einzelmolekülen
DE19943704C1 (de) Affinitätssensor zum Nachweis biologischer und/oder chemischer Spezies und dessen Verwendung
WO2004023142A1 (fr) Plate-forme analytique et procede d'identification avec des substances d'analyse a identifier dans un echantillon, se presentant sous forme de partenaires de liaison specifiques immobilises
EP1872127A1 (fr) Systeme de detection micro-optique et procede pour determiner des parametres d'analytes variables avec la temperature
DE4301005A1 (de) Verfahren und Vorrichtung zur Bewertung der Fitness von Biopolymeren
EP0920625B1 (fr) Procede de criblage de substances actives
DE69829182T2 (de) Modulare anordnung zur reagenzlosen affinitätsseparation und detektion von analyten
EP3899494B1 (fr) Arrangement et procédé pour l'acquisition de propriétés optiques d'un échantillon, notamment pour la détection sélective de molécules biologiques et pour la lecture de l'occupation d'une molécule
WO2001025759A1 (fr) Procede et dispositif permettant de determiner des substances, comme les sequences d'adn, dans un echantillon
WO2000046600A2 (fr) Procede de detection d'analytes dans un echantillon pour essai et support de mesure y relatif
AT413058B (de) Optischer sensor mit nanopartikel transfer sowie verfahren zur identifizierung von molekülen und objekten
DE102004038163A1 (de) Fluoreszenz-basierte Assays zur schnellen, quantitativen Analyse von Biomolekülen (Proteine und Nukleinsäuren) durch Anreicherung auf Zellen oder Beads
DE4435727A1 (de) Bindematrix und Analyseelement zur Simultananalyse verschiedener Analyte
DE102007018356A1 (de) Mikrokapsel

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20020326

AK Designated contracting states

Kind code of ref document: A1

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

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: INSTITUT FUER PHYSIKALISCHE HOCHTECHNOLOGIE E.V.

17Q First examination report despatched

Effective date: 20030807

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20031218