Biosensors with porous dielectric surface for fluorescence enhancement and methods of manufacture

• US 7,869,032 B2
• Filed: 03/24/2008
• Issued: 01/11/2011
• Est. Priority Date: 04/05/2007
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Zhang, Wei, Cunningham, Brian T.
• Primary Examiner(s): Toatley; Gregory J
• Assistant Examiner(s): Ton; Tri T
• Application Number:
  US12/079,171
• Publication Number:
  US 20080246961A1
• Time in Patent Office: 1,023 Days
• Field of Search: 356/317, 356/328, 356/445, 356/364, 356/301, 356/311, 356/305, 156/60, 653/86, 422 8205- 8211, 385/12, 385/37, 435/7.9, 435/7.32, 435/287.2, 435/7.2, 435/5, 435/4, 435/7.1, 435/34, 435/288.7, 438/31, 438/32, 438/69, 438/71, 438/72, 438/87, 436/518, 436/164, 436/525, 436/527, 436/805, 977/924, 372/102, 372/7
• US Class Current: 356/317
• 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: G01N 2021/7726 Porous glass
• 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
• CPC Class Codes: G02B 6/1226 involving surface plasmon interaction

Abstract

Biosensors are disclosed which include a surface for binding to sample molecule to the biosensor in the form of a porous, thin film of dielectric material, e.g., TiO₂. In one example the porous, thin film is in the form of a multitude of sub-micron sized rod-like structures (“nanorods”) projecting therefrom. In one embodiment, the biosensor is in the form of a photonic crystal biosensor. The approach of depositing a thin film of dielectric nanorods may be applied to any enhanced fluorescence biosensor surface structure, including 1-dimensional photonic crystals, 2-dimensional photonic crystals, 3-dimensional photonic crystals, surface plasmon resonance surfaces, planar waveguides, and grating-coupled waveguides. The dielectric nanorod structures can be fabricated on the surface of a biosensor by the glancing angle deposition technique (GLAD).

Claims

1. In a photonic crystal biosensor adapted for detection of a sample labeled with a fluorescent label, the biosensor having a periodic surface grating structure and a dielectric material deposited on the periodic surface grating structure, the dielectric material providing a surface upon which the sample is deposited, the improvement comprising:

the surface of the biosensor comprising a porous dielectric structure in the form of a multitude of closely spaced raised structures made from a dielectric material, wherein the closely spaced raised structures are surrounded by adjacent spaces, and wherein the raised structures and adjacent spaces providing an enhanced surface area available for binding of the sample to the biosensor.

2. The improvement of claim 1, wherein the closely spaced raised structures comprises a multitude of nanorods having has a thickness t of between 25 and 300 nm.

3. The improvement of claim 1, wherein the photonic crystal biosensor further comprises a spacer layer comprising a layer of material deposited on the periodic surface grating structure, a high index of refraction layer comprising a layer of relatively high index of refraction material deposited on the spacer layer, and wherein the porous dielectric structure as recited in claim 1 is deposited on the high index of refraction layer.

4. The improvement of claim 1, wherein the porous dielectric structure comprises a multitude of nanorods.

5. In a surface Plasmon resonance biosensor, adapted for detection of a sample, the improvement comprising:

a porous dielectric structure deposited on the surface Plasmon resonance biosensor, the porous dielectric structure providing a surface upon which the sample is deposited, and wherein the porous dielectric structure comprises a multitude of nanorods made from a dielectric material surrounded by adjacent spaces, the dielectric nanorods and adjacent spaces providing an enhanced surface area available for binding of the sample to the biosensor.

6. In a planar waveguide, adapted for detection of a sample, the improvement comprising:

a porous dielectric structure deposited on the planar waveguide, the porous dielectric structure providing a surface upon which the sample is deposited, wherein the porous dielectric structure comprises a multitude of nanorods made from a dielectric material surrounded by adjacent spaces, the nanorods and adjacent spaces providing an enhanced surface area available for binding of the sample to the planar waveguide.

7. In a grating-coupled waveguide, adapted for detection of a sample, the improvement comprising:

a porous dielectric structure deposited on the grating-coupled waveguide, the porous dielectric structure providing a surface upon which the sample is deposited, and wherein the porous dielectric structure comprises a multitude of nanorods made from a dielectric material surrounded by adjacent spaces, the nanorods and adjacent spaces providing an enhanced surface area available for binding of the sample to the grating-coupled waveguide.

8. A photonic crystal biosensor comprising:

a substrate layer;

a periodic grating applied to the substrate layer;

a relatively high index of refraction layer deposited on or above the periodic grating layer; and

a porous dielectric structure comprising a dielectric material deposited on the relatively high index of refraction layer, the porous dielectric structure in the form of a multitude of closely spaced raised structures made from said dielectric material, the closely spaced raised structures surrounded by adjacent spaces, the raised structures and adjacent spaces providing an enhanced surface area available for binding of the sample to the biosensor.

9. The photonic crystal biosensor of claim 8, wherein the thickness t of the porous dielectric structure is between 25 and 300 nm.

10. The photonic crystal biosensor of claim 8, wherein the biosensor is incorporated into a sample handling device.

11. The photonic crystal biosensor of claim 8, wherein the raised structures comprise nanorods.

12. A method of detection of a sample comprising the steps of:

a) providing a sample having a fluorescent label bound to the sample;

b) placing the sample onto a biosensor as claimed in claim 8;

c) illuminating the biosensor with light in a manner to excite the fluorescent label and capturing the fluorescence emission from the biosensor with a detection instrument; and

d) determining the intensity of the fluorescent emission from the biosensor.

13. The method of claim 12, wherein the sample comprises a biological sample.

14. The method of claim 12, wherein the label comprises an organic fluorophore.

15. The method of claim 12, wherein the label comprises a quantum dot.

20. The photonic crystal biosensor of claim 8, wherein the dielectric material comprises a dielectric material having a low optical loss coefficient at a resonant wavelength of the photonic crystal.

21. The photonic crystal biosensor of claim 20, wherein the dielectric material is selected from the groups of materials consisting of TiO₂, Ta₂O₅, SiN, SiO₂, ZnS, MgF, VO and HfO₂.

16. A method of manufacturing a biosensor comprising the steps of:

providing a biosensor having an upper surface; and

depositing a dielectric material on the upper surface of the biosensor so as to form a porous dielectric structure, the porous dielectric structure forming a surface for receiving a sample deposited on the biosensor, the porous dielectric structure in the form of a multitude of closely spaced raised structures made from a dielectric material, the closely spaced raised structures surrounded by adjacent spaces, the raised structures and adjacent spaces providing an enhanced surface area available for binding of the sample to the biosensor.

17. The method of claim 16, wherein the depositing step is performed using a glanced angle deposition (GLAD) deposition technique.

18. The method of claim 16, wherein the biosensor comprises a substrate layer, a periodic grating applied to the substrate layer, a relatively high index of refraction layer deposited on the periodic grating layer and forming the said upper surface, and wherein in the depositing step further comprises the step of depositing the porous dielectric structure on the relatively high index of refraction layer.

19. The method of claim 16, wherein the raised structures comprise nanorods and wherein the porous dielectric structure has a thickness t of between 25 and 300 nm.