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

• US 6,867,869 B2
• Filed: 10/09/2003
• Issued: 03/15/2005
• 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:
  US10/684,071
• Publication Number:
  US 20040115826A1
• Time in Patent Office: 523 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 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, each comprising substantially parallel periodic grooves which define one or multiple sensing regions, said grooves being configured such that

coherent and linearly polarized 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 regions;

wherein the enhanced evanescent field interacts with luminescent material on or in the vicinity of one or more of the sensing regions so as to produce a luminescent signal.

2. The platform of claim 1, wherein for each corrugated structure:

(a) the depth of the grooves is in the range of 3 nm to the thickness of the optically transparent layer,

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

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

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

(e) the ratio of groove width to the period of the grooves is in the range of 0.2 to 0.8.

3. A platform according to claim 1 wherein the substrate of the platform is formed from inorganic material.

4. A platform according to claim 1, wherein the substrate is formed from organic material.

5. A platform according to claim 1, wherein the optically transparent layer is formed from inorganic material.

6. A platform according to claim 1, wherein the optically transparent layer is formed from organic material.

7. A platform according to claim 1, wherein the surface of the optically transparent layer includes one or a plurality of sensing regions, each of which carries one or plurality of capture elements.

8. A platform according to claim 7, wherein each capture element contains one or more capture molecules which are capable of affinity reactions.

9. A platform according to claim 7, including an adhesion promoting layer disposed at the surface of the optically transparent layer in order to enable immobilisation of capture molecules.

10. A platform according to claim 1, wherein the platform is formed with a plurality of sensing regions, each having its own diffractive grooves or multiple, superimposed grooves suitable for multicolor excitation and detection of samples.

11. The platform of claim 1, wherein the grooves of at least one of said corrugated structures are configured 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.

12. The platform of claim 1, wherein the grooves of at least one of said corrugated structures are configured such that the propagation distance of the incident light within the at least one corrugated structure is less than about 100μ

m.

13. The platform of claim 1, wherein the grooves of at least one of said corrugated structures are configured such that the propagation distance of the incident light within the at least one corrugated structure is less than about 10μ

m.

14. The platform of claim 1, wherein the luminescent signal is one of a fluorescent signal, a phosphorescent signal, a chemi-luminescent signal and an electro-luminescent signal.

15. The platform of claim 1, wherein the luminescent material includes one of a fluorescent material, a phosphorescent material, and two or more materials which interact to produce a luminescent signal.

16. Apparatus for analysing samples comprising a platform including 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 regions, said grooves being configured such 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 regions;

or

b) coherent and linearly polarized 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 regions,

wherein the enhanced evanescent field interacts with luminescent material on or in the vicinity of one or more of the sensing regions so as to produce a detectable luminescent signal;

said apparatus 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 region of the platform to thereby create an enhanced resonant field in the at least one sensing region 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 region of the platform.

17. Apparatus according to claim 16, wherein the light generating means comprises a laser for emitting a coherent laser beam.

18. Apparatus according to claim 17, wherein the means for directing the beam includes optical elements for directing the laser beam so that it is incident on the platform at an angle θ

, the angle θ

being defined by the expression sin θ

=n−

λ

/Λ

where Λ

is a period of the diffractive grooves, λ

is the wavelength of the light and n is the effective refractive index of the optically transmitting layer.

19. Apparatus according to claim 16, wherein the detecting means is arranged to detect luminescence such as fluorescence, phosphorescence, chemi-luminescence, and electro-luminescence.