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

• US 6,707,561 B1
• Filed: 07/05/2000
• Issued: 03/16/2004
• 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
• Application Number:
  US09/609,846
• Time in Patent Office: 1,350 Days
• Field of Search: 356/521, 356/517, 356/491, 356/FOR.116, 356/FOR.123
• US Class Current: 356/521
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• 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 anormal 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 is an apparatus incorporating the platform and a method of using the platform.

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 comprising periodic grooves which define one or multiple sensing areas of 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 anormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing area;

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 anormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing areas,

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

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

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

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

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

6. A platform according to claim 1, wherein the depth of the diffraction grooves is in the range 3 nm to the thickness of the optically transparent layer, preferably 10 nm to the thickness of the optically layer.

7. A platform according to claim 6, wherein the thickness of the optically transparent layer is in the range 30 to 1000 nm, the period of the diffraction grooves is in the range 200 to 1000 nm, the ratio of the groove depth to the thickness of the optically transparent layer lies in the range 0.02 to 1 and the ratio of the grooves width to the period of the grooves lies in the range 0.2 to 0.8 resulting in an extremely short propagation distance.

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

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

12. Apparatus for analyzing samples comprising a platform according to claim 1, 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 resortant field in the sensing area of the platform, and means for detecting a characteristic of a material disposed on or in the vicinity of the sensing area of the platform.

13. Apparatus according to claim 12, wherein the light generating means comprises a laser for emitting a coherent laser beam.

14. Apparatus according to claim 13, including 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.

15. Apparatus according to claim 13, wherein the detecting means is arranged to detect luminescence such as fluorescence, phosphorescence, chemi-luminescence, and electroluminescence.

16. The platform of claim 1, wherein the luminescent material comprises a fluorophore, and wherein the luminescent signal comprises a fluorescent signal.

17. The platform of claim 1, wherein the center-to-center spacing between each of said one or multiple sensing areas or regions is between about 1 μ

m and about 1 mm.

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

19. The platform of claim 1, wherein the grooves of at least one of said corrugated structures are profiled, dimensional 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.

20. The platform of claim 1, 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.

21. The platform of claim 1, 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.

10. A platform according to claim 10, including an adhesion promoting layer disposed at the surface of the optically transparent layer in order to enable immobilisation of capture molecules.

9. A platform according to claim 10, wherein each capture element contains individual and/or mixtures of capture molecules which are capable of affinity reactions.

22. A 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 in the transparent layer a corrugated structure substantially over the entire platform, or multiple separate corrugated structures arranged on the platform, said structures comprising substantially parallel periodic grooves which are mono- or multi-diffractional which grooves represent one or multiple sensing areas or regions, wherein

(a) the depth of the grooves is in the range of about 30 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 grooves depth to the thickness of the optically transparent layer is in the range of 0.02 to 1, and

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

23. A platform as claimed in claim 22, the arrangement being such that, in use, the grooves are so profiled, dimensioned and oriented that either

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

24. The platform of claim 22, wherein the depth of the grooves is in the range of about 50 nm to thickness of the optically transparent layer.

25. The platform of claim 22, 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.

26. The platform of claim 22, 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.

27. The platform of claim 22, 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.

28. The platform of claim 22, wherein the center-to-center spacing between each of said one or multiple sensing areas or regions is between about 1 μ

and about 1 mm.

29. 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 periodic grooves which define one or multiple sensing areas, wherein for each corrugated structure said grooves are profiled, dimensioned and oriented such that either:

a) coherent light incident on said corrugated structure is diffracted into individual beams or diffraction orders which interfere resulting n reduction of the transmitted beam and an anormal 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 polarized light incident on said corrugated structures is diffracted into individual beams or diffraction orders which interfere resulting in almost total extinction of the transmitted beam and an anormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing areas;

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

30. The platform of claim 29, 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.

31. The platform of claim 29, 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.

32. The platform of claim 29, 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.

33. The platform of claim 29, wherein the center-to-center spacing between each of said one or multiple sensing areas is between about 1 μ

m and about 1 mm.

34. A sample analysis system, comprising:

a platform having 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, dimensional 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 anormal 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 anormal high reflection of the incident light thereby generating an enhanced evanescent field at the surface of the one or multiple sensing areas,

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

a light source configured and arranged to illuminate at least a portion of the platform with coherent or coherent and linearly polarized light; and

a detector configured to detect the luminescent signal.