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

• US 6,870,630 B2
• Filed: 10/09/2003
• Issued: 03/22/2005
• Est. Priority Date: 07/05/1999
• Status: Expired due to Fees

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Budach, Wolfgang Ernst Gustav, Neuschaefer, Dieter
• Primary Examiner(s): Toatley, Jr., Gregory J.
• Assistant Examiner(s): CONNOLLY, PATRICK J
• Application Number:
  US10/684,070
• Publication Number:
  US 20040115825A1
• Time in Patent Office: 530 Days
• Field of Search: 356/491, 356/521, 356/517, 422/82.09, 422/82.11
• 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 platform for use in sample analysis, said platform having one or more sensing areas or regions, each for receiving a capture element or elements which when the platform is irradiated with coherent light can interact to provide an indication of an affinity reaction, wherein each capture element includes two or more types of capture molecule, the platform further 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 the one or multiple sensing areas or regions, said grooves being so profiled, dimensioned and oriented that 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 a surface of the one or more sensing areas.

2. The platform of claim 1, wherein the enhanced evanescent field interacts with luminescent material on or in the vicinity of one of the sensing areas or regions so as to produce a detectable luminescent signal.

5. The platform of claim 2 or 4, wherein the luminescent material comprises a fluorophore, and wherein the luminescent signal comprises a fluorescent signal.

6. The platform of claim 1 or 3, wherein the center-to-center spacing between each of the one or more sensing areas or regions is between about 1 μ

m and about 1 mm.

7. The platform of claim 1 or 3, wherein said light incident on the platform is incident on the side of the substrate having the optically transparent layer formed thereon.

8. The platform of claim 1 or 3, wherein the grooves of at least one of said corrugated structures are profiled, dimensioned and oriented such that the radiation loss coefficient of the incident light within the at least one corrugated structure is on the order of 2000/cm or greater.

9. The platform of claim 1 or 3, wherein the grooves of at least one of said corrugated structures are profiled, dimensioned and oriented such that the propagation distance of the incident light within the at least one corrugated structure is less than about 100 μ

m.

10. The platform of claim 1 or 3, wherein the grooves of at least one of said corrugated structures are profiled, dimensioned and oriented such that the propagation distance of the incident light within the at least one corrugated structure is less than about 10 μ

m.

11. The platform of claim 1 or 3, wherein the depth of the grooves is in the range of about 50 nm to the thickness of the optically transparent layer.

12. The platform of claim 1 or 3, wherein

the depth of the grooves is in the range of about 30 nm to the thickness of the optically transparent layer,

the thickness of the optically transparent layer is in the range of 30 to 1000 nm,

the period of the corrugated structure is in the range of 200 to 1000 nm,

the ratio of groove depth to the thickness of the optically transparent layer is in the range of 0.02 to 1, and

the ratio of grove width to the period of the grooves is in the range of 0.2 to 0.8.

13. Apparatus for analyzing samples comprising a platform according to claim 1 or 3, and further including means for generating a light beam and for directing the beam so that it is incident upon the platform on the side of the substrate having the optically transparent layer disposed thereon at an angle which causes evanescent resonance to occur in at least one sensing area of the platform to thereby create an enhanced resonant field in the at least one sensing area of the platform, and means for detecting a characteristic of an affinity reaction occurring on or in the vicinity of, or a characteristic of a material disposed on or in the vicinity of, the at least one sensing area of the platform.

14. The platform of claim 1 or 3, wherein each type of capture molecule includes a molecule selected from the group consisting of a nucleotide, an oglionucleotide, DNA, RNA, PNA, an antibody, an antigen, a protein, an antibiotic, a drug, an enzyme, a ligand, a peptide, a polymer, a molecular probe, a receptor, an indicator and a tissue sample.

3. A platform for use in sample analysis, said platform having one or more sensing areas or regions, each for receiving a capture element or elements which when the platform is irradiated with coherent light can interact to provide an indication of an affinity reaction, wherein each capture element includes two or more types of capture molecule, the platform further 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 the one or multiple sensing areas or regions, said grooves being so profiled, dimensioned and oriented that 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 a surface of the one or more sensing areas.

4. The platform of claim 3, wherein the enhanced evanescent field interacts with luminescent material on or in the vicinity of one of the sensing areas or regions so as to produce a detectable luminescent signal.