Near ultraviolet-wavelength photonic-crystal biosensor with enhanced surface to bulk sensitivity ratio

• US 20080014632A1
• Filed: 07/02/2007
• Published: 01/17/2008
• Est. Priority Date: 07/07/2006
• Status: Active Grant

• Current Assignee: X-Body Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Board of Trustees of The University of Illinois, Sru Biosystems Incorporated
• Inventors: Ganesh, Nikhil, Cunningham, Brian, Block, Ian
• Granted Patent: US 7,756,365 B2
• Time in Patent Office: Days
• US Class Current: 435/288.7
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 20/00 Nanooptics, e.g. quantum optics or photonic crystals
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/33 using ultraviolet light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/551 the carrier being inorganic
• CPC Class Codes: G01N 33/552 Glass or silica
• CPC Class Codes: G02B 1/005 made of photonic crystals or photonic band gap materials photonic band-gap structures or photonic lattices in integrated optics G02B6/1225; photonic band-gap structures or photonic lattices in optical fibres G02B6/02295

Abstract

Biosensors are disclosed based on one- or two-dimensional photonic-crystal reflectance filters operating at near-ultraviolet wavelengths. Rigorous Coupled-Wave Analysis simulations predict a more tightly confined resonant electric field at the surface of this biosensor as compared to previously fabricated near-infrared photonic-crystal biosensors. This change in the resonant electric field provides an improvement of over 4.5 times in the surface-sensitivity to bulk-sensitivity ratio, and therefore enables enhanced detection resolution for biomolecules adsorbed on the biosensor surface. These new biosensors can be fabricated in mass by replica molding. They are especially well suited for applications requiring the detection of small molecules or ultra-low analyte concentrations.

Claims

1. A photonic crystal biosensor comprising:

an optically transparent substrate,

a relatively low index of refraction material formed in a periodic grating structure applied to the substrate, the low index of refraction material comprising a porous dielectric material;

a relatively high index of refraction material deposited onto the low index of refraction grating structure;

wherein the grating structure period and high and low index of refraction materials are selected such that the sensor produces a substantial confinement of the electric field intensity due to light directed to the biosensor substantially at the plane of the periodic surface grating of the biosensor and wherein a reflection maximum at a resonant wavelength of the biosensor occurs in the near-ultraviolet portion of the spectrum;

and further wherein the sensor grating structure period and high and low index of refraction materials are selected to result in a biosensor which has a relatively high surface to bulk sensitivity ratio thereby improving the ability of the device to detect low concentrations of biomolecules, analytes, and/or and small molecules deposited on the surface of the biosensor.

2. The biosensor of claim 1, wherein the biosensor has a surface to bulk sensitivity ratio of approximately 0.060 or higher.

3. The biosensor of claim 1, wherein the biosensor has a bulk shift coefficient of approximately 100 nm/refractive index units (RIU) or less and has a sensitivity to surface-absorbed material of PPL (poly-phe-lysine) of approximately 3 nm or greater;

where the bulk shift coefficient is defined as the Δ

PWV/Δ

n, where Δ

PWV is change in the resonance wavelength due to placement of a bulk medium on the surface of the biosensor, and where Δ

n is the change in the refractive index due to the bulk medium applied to the surface of the biosensor.

4. The biosensor of claim 1, wherein the grating structure comprises a one dimensional surface structure and wherein the low index of refraction material comprises a porous dielectric material.

5. The biosensor of claim 4, wherein the one-dimensional surface grating structure has a period of approximately 250 nm.

6. The biosensor of claim 1, wherein the grating structure comprises a two-dimensional surface grating structure.

7. The biosensor of claim 6, wherein the two-dimensional surface grating structure comprises a two-dimensional array of posts or holes.

16. A system for detection of low concentrations of biomolecules, analytes, and/or and small molecules, comprising in combination:

a biosensor according to claim 1, wherein the biomolecules, analytes and/or small molecules are deposited on the surface of the biosensor, and

a detection instrument for illuminating the biosensor and measuring a shift in the peak wavelength value of reflected light from the surface of the biosensor, the shift in peak wavelength value due to the presence of the low concentration of the biomolecules, analytes and/or small molecules deposited on the surface of the biosensor.

8. A method of fabricating a highly sensitive biosensor comprising the steps of:

a) conducting a nanoreplication process by which a relatively low index of refraction material is patterned on an optically transparent substrate as a periodic surface grating structure;

b) depositing a relatively high index of refraction material onto the periodic surface grating structure;

c) wherein the grating structure period and high and low index of refraction materials are selected such that the sensor produces a substantial confinement of the electric field intensity due to light directed to the biosensor substantially at the plane of the periodic surface grating of the biosensor and wherein a reflection maximum at a resonant wavelength occurs in the near-ultraviolet portion of the spectrum,

d) and further wherein the sensor grating structure period and high and low index of refraction materials are selected to result in a biosensor which has a relatively high surface to bulk sensitivity ratio thereby improving the ability of the device to detect low concentrations of biomolecules, analytes, and/or and small molecules deposited on the surface of the biosensor.

9. The method of claim 8, wherein step a) comprises the step of coating the substrate with a relatively low refractive index porous glass, and patterning the glass into a periodic grating structure with the aid of a stamp.

10. The method of claim 8, wherein the biosensor has a surface to bulk sensitivity ratio of approximately 0.060 or higher.

11. The method of claim 8, wherein the biosensor has a bulk shift coefficient of approximately 100 nm/refractive index units (RIU) or less and has a sensitivity to surface-absorbed material of PPL (poly-phe-lysine) of approximately 3 nm or greater;

where the bulk shift coefficient is defined as the Δ

PWV/Δ

n, where Δ

PWV is change in the resonance wavelength due to placement of a bulk medium on the surface of the biosensor, and where Δ

n is the change in the refractive index due to the bulk medium applied to the surface of the biosensor.

12. The method of claim 8, wherein the grating structure comprises a one dimensional surface structure and wherein the low index of refraction material comprises a porous dielectric material.

13. The method of claim 12, wherein the one-dimensional surface grating structure has a period of approximately 250 nm.

14. The method of claim 8, wherein the grating structure comprises a two-dimensional surface grating structure.

15. The method of claim 8, wherein the two-dimensional surface grating structure comprises a two-dimensional array of posts or holes.