Sensor platform, apparatus incorporating the platform, and process using the platform

• US 6,771,376 B2
• Filed: 01/10/2002
• Issued: 08/03/2004
• Est. Priority Date: 07/05/1999
• Status: Expired due to Term

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Budach, Wolfgang Ernst Gustav, Neuschaefer, Dieter
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): CONNOLLY, PATRICK J
• Application Number:
  US10/043,629
• Publication Number:
  US 20020135780A1
• Time in Patent Office: 936 Days
• Field of Search: 356/521, 356/517, 356/491, 422/82.09, 422/82.11, 422/82.08
• US Class Current: 356/521
• CPC Class Codes: B82Y 10/00 Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 20/00 Nanooptics, e.g. quantum optics or photonic crystals
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide

Abstract

A sensor platform for use in sample analysis comprises a substrate (30) of refractive index (n₁) and a thin, optically transparent layer (32) of refractive index (n₂) on the substrate, (n₂) is greater than (n₁). The platform incorporates one or multiple corrugated structures in the form of periodic grooves (31), (33), which defines one or more sensing areas each for one or more capture elements. The grooves are so profiled, dimensioned and oriented that when coherent light is incident on the platform it is diffracted into individual beams or diffraction order resulting in reduction of the transmitted beam and an abnormal high reflection of the incident light thereby creates an enhanced evanescent field at the surface of the or each sensing area. The amplitude of this field at the resonant condition is greater by an order of approximately 100 than the field of prior art platforms so that the luminescence intensity created from samples on the platform is also increased by a factor of 100. Also disclosed are an apparatus incorporating the platform and a method of using the platform. Further increases of amplitude have been detected by using light having a linear component which gives rise to TM excitation and/or irradiating the platform from the substrate side.

Claims

1. A process for analysing a sample or samples, the process comprising:

bringing the sample into contact with a first sensing area of a platform, said platform comprising an optically transparent substrate having a refractive index n₁, a thin, optically transparent layer, formed on one surface of the substrate, said layer having a refractive index n₂ which is greater than n₁, said platform incorporating therein one or multiple corrugated structures comprising periodic grooves which define one or multiple sensing areas or regions, each for one or multiple capture elements, said grooves being so profiled, dimensioned and oriented that either

a) coherent light incident on said platform is diffracted into individual beams or diffraction orders which interfere resulting in reduction of the transmitted beam and an abnormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing areas;

or

b) coherent and linearly polarised light incident on said platform is diffracted into individual beams or diffraction orders which interfere resulting in almost total extinction of the transmitted beam and an abnormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing areas;

irradiating the platform with a light beam such that evanescent resonance is caused to occur within the first sensing area of the platform and

detecting radiation emanating from the first sensing area.

2. A process according to claim 1, including adding fluorescent inducing material to the samples under investigation and sensing fluorescence induced in said samples by excitation of the samples by the enhanced evanescent field.

3. A process according to claim 2 wherein the fluorescent inducing material comprises a luminescent marker.

4. A process according to claim 3, wherein the luminescent marker comprises luminescent compound or compounds having luminescence in the range of from 400 nn to 1200 nm which are functionalised or modified in order to be attached to one or more of the affinity partners, including derivatives of one or more of the following:

polyphenyl and heteroaromatic compounds

stilbenes,

coumarines,

xanthene dyes,

methine dyes,

oxazine dyes,

rhodamines,

fluoresceines,

coumarines, stilbenes,

pyrenes, perylenes,

cyanines, oxacyanines, phthalocyanines, porphyrines, naphthalopcyanines, azobenzene derivatives, distyryl biphenyls,

transition metal complexes e.g. polypyridyl/ruthenium complexes, tris(2,2′

-bipyridyl)ruthenium chloride, tris(1,10-phenanthroline)rutheniu- m chloride, tris(4,7-diphenyl-1,10-phenanthroline) ruthenium chloride and polypyridyl/phenazine/ruthenium complexes, such as octaethyl-platinum-porphyrin, Europium and Terbium complexes quantum dot particles/beads or derivatives thereof.

5. A process as claimed in claim 1 wherein the light beam is configured so as to give rise to TM excitation.

6. A process according to claim 1 wherein the light beam is incident onto the substrate side of the platform.

7. A process according to claim 1 wherein the light beam is incident onto the corrugated high refractive index side of the platform.

8. A process according to claim 5 wherein the light beam is incident onto the substrate side of the platform.

9. A process according to claim 5 wherein the light beam is incident onto the corrugated high refractive index side of the platform.

10. The process of claim 1 wherein the enhanced evanescent field interacts with luminescent material on or in the vicinity of the first sensing area so as to produce a detectable luminescent signal, and wherein detecting radiation includes detecting the luminescent signal.

11. A method of analysing a sample, the method comprising:

bringing the sample into contact with a first sensing area of a platform, said platform comprising an optically transparent substrate having a refractive index n₁, a thin, optically transparent layer, formed on one surface of the substrate, said layer having a refractive index n₂ which is greater than n₁, said platform incorporating therein one or multiple corrugated structures comprising periodic grooves which define one or multiple sensing areas, each for one or multiple capture elements, said grooves being so profiled, dimensioned and oriented that either

a) coherent light incident on said platform is diffracted into individual beams or diffraction orders which interfere resulting in reduction of the transmitted beam and an abnormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing areas;

or

b) coherent and linearly polarised light incident on said platform is diffracted into individual beams or diffraction orders which interfere resulting in a substantially total extinction of the transmitted beam and an abnormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing areas;

irradiating the platform with a light beam such that evanescent resonance is caused to occur within the first sensing area of the platform and

detecting radiation emanating from the first sensing area.

12. The method of claim 11, wherein the light beam is incident onto the substrate side of the platform.

13. The method of claim 11, wherein the light beam is incident onto the corrugated high refractive index side of the platform.

14. The method of claim 11, wherein the light beam is configured so as to give rise to TM excitation.

15. A method according to claim 11, including adding fluorescent inducing material to the sample, and wherein detecting includes sensing fluorescence induced in said sample by excitation of the sample by the enhanced evanescent field.

16. The method of claim 11, wherein the enhanced evanescent field interacts with luminescent material on or in the vicinity of the first sensing area so as to produce a detectable luminescent signal, and wherein detecting radiation includes detecting the luminescent signal.