Method and apparatus for conjugate quadrature interferometric detection of an immunoassay

• US 20080304073A1
• Filed: 03/26/2008
• Published: 12/11/2008
• Est. Priority Date: 03/26/2007
• Status: Active Grant

• Current Assignee: Purdue Research Foundation (Purdue University)
• Original Assignee: Purdue Research Foundation (Purdue University)
• Inventors: Nolte, David D., Wang, Xuefeng
• Granted Patent: US 7,787,126 B2
• Time in Patent Office: Days
• US Class Current: 356/450
• CPC Class Codes: G01N 2021/7776 Index
• CPC Class Codes: G01N 2021/7779 interferometric
• CPC Class Codes: G01N 21/45 using interferometric methods; using Schlieren methods

Abstract

A detection system for detecting target material is provided. The system comprises a photonic structure having a reflectance-band and associated side bands; an illumination source for illuminating at a wavelength in at least one of an edge of the reflectance-band and the side bands of the photonic structure and for generating a return beam; a detector system having an intensity-sensitive channel configured to detect an in-line signal from the return beam and a phase-sensitive channel configured to detect a differential phase contrast signal from the return beam; and a processing system for receiving and adding in quadrature the in-line signal and the differential phase contrast signal to generate a joint signal, and for determining one of the presence or the absence of the target material on the photonic structure using the joint signal.

Claims

1. A detection system for detecting target material comprising:

a photonic structure having a reflectance-band and associated side bands;

an illumination source for illuminating at a wavelength in at least one of an edge of the reflectance-band and the side bands of the photonic structure and for generating a return beam;

a detector system having an intensity-sensitive channel configured to detect an in-line signal from the return beam and a phase-sensitive channel configured to detect a differential phase contrast signal from the return beam; and

a processing system for receiving and adding in quadrature the in-line signal and the differential phase contrast signal to generate a joint signal, and for determining one of the presence or the absence of the target material on the photonic structure using the joint signal.

2. The detection system of claim 1, wherein the joint signal is the sum of the squares of the in-line signal and the differential phase contrast signal.

3. The detection system of claim 1, wherein the photonic structure is a half-cavity structure comprising a substrate with a biolayer immobilized thereon.

4. The detection system of claim 3, wherein the substrate includes a multilayer dielectric stack.

5. The detection system of claim 3, wherein the half-cavity structure further comprises an absorbing layer.

6. The detection system of claim 1, wherein the photonic structure is a resonant-cavity structure comprising a first portion including a first substrate with a biolayer immobilized thereon, and a second portion including a second substrate with separation posts positioned thereon, the first portion being combined with the second portion such that the biolayer rests on the separation posts to form a cavity between the first substrate and the second substrate.

7. The detection system of claim 6, wherein at least one of the first and second substrates includes a multilayer dielectric stack.

8. The detection system of claim 6, wherein the cavity is about 5-10 microns in height.

9. The detection system of claim 6, wherein the separation posts are formed on the second substrate by spinning photoresist on the second substrate at high angular velocity.

10. The detection system of claim 1, wherein the photonic structure is immobilized on a biological compact disk.

11. The detection system of claim 10, further comprising:

a spin motor upon which the biological compact disk can be mounted, the spin motor being configured to rotate the biological compact disk.

12. The detection system of claim 11, further comprising:

a linear stage for translating the biological compact disk relative to the illumination source;

wherein the rotation of the biological compact disk by the spin motor and the translation of the biological compact disk relative to the illumination source by the linear stage creates a polar coordinate system that can be used for referencing any point on the biological compact disk.

13. The detection system of claim 1, wherein the detector system includes a segmented photodetector configured to simultaneously measure differential phase and in-line intensity of a resonant response modulus.

14. The detection system of claim 13, wherein the segmented photodetector is configured to detect the resonant response modulus by separately detecting the in-line signal and the differential phase contrast signal.

15. A method for detecting the presence of an antigen on a photonic structure, the method comprising:

exposing the photonic structure to a sample that may contain the antigen, the photonic structure having a reflectance-band and side bands;

illuminating at a wavelength in at least one of an edge of the reflectance-band and the side bands of the photonic structure with an illumination source to create a return beam;

detecting the return beam with a detector system having an intensity-sensitive detection function and a phase-sensitive detection function;

detecting an in-line quadrature signal from the return beam using the intensity-sensitive detection function of the detector system;

detecting a differential phase contrast quadrature signal from the return beam using the phase-sensitive detection function of the detector system;

receiving the in-line quadrature signal and the differential phase contrast quadrature signal;

combining the in-line quadrature signal and the differential phase contrast quadrature signal to generate a joint signal, and

determining one of the presence or the absence of the target material on the photonic structure using the joint signal.

16. The method of claim 15, wherein the combining step includes taking the sum of the squares of the in-line quadrature signal and the differential phase contrast quadrature signal to form the joint signal.

17. The method of claim 15, wherein the detecting step includes:

determining a detection wavelength in the side bands, the detection wavelength having approximately the maximum gain; and

detecting the in-line quadrature signal and the differential phase contrast quadrature signal at the detection wavelength.

18. The method of claim 15, wherein the photonic structure is a resonant-cavity structure and the exposing step includes flowing the sample through the resonant-cavity structure.

19. A method of using a resonant response modulus to provide a signal robust against operating system drift, the method comprising:

providing a substrate including a plurality of target molecules distributed about the substrate;

illuminating the substrate with a illumination source to produce a reflected beam and cause a resonant response;

detecting the modulus of the resonant response with a photodetector by separately detecting an in-phase intensity resonant response and a conjugate phase resonant response; and

combining the in-phase intensity resonant response and the conjugate phase resonant response to provide a signal robust against operating system drift, the signal being representative of the detected modulus of the combined responses.

20. The method of claim 19, further comprising generating a large electric field at the location of the plurality of target molecules by illuminating a photonic structure immobilized on the substrate.