Systems and methods enabling high-throughput, real time detection of analytes

• US 9,285,314 B2
• Filed: 10/12/2012
• Issued: 03/15/2016
• Est. Priority Date: 10/12/2011
• Status: Active Grant

• Current Assignee: Brown University
• Original Assignee: Brown University
• Inventors: Pacifici, Domenico, Lezec, Henri J., Siu, Vince, Mehta, Vihang, Roelke, Alec, Rhieu, Steve, Feng, Jing, Palmore, Tayhas G. r.
• Primary Examiner(s): Chowdhury, Tarifur
• Assistant Examiner(s): RAHMAN, MD M
• Application Number:
  US14/350,896
• Publication Number:
  US 20140327913A1
• Time in Patent Office: 1,250 Days
• Field of Search: 356/450
• US Class Current: 1/1
• CPC Class Codes: G01N 21/45 using interferometric methods; using Schlieren methods
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 21/554 detecting the surface plasmon resonance of nanostructured metals, e.g. localised surface plasmon resonance

Abstract

System and methods for detecting analytes are provided. The system includes a plasmonic interferometer with a first surface having a first and second scattering element and an aperture disposed between the first scattering element and the second scattering element. A first distance between the aperture and the first scattering element and a second distance between the aperture and the second scattering element are selected to provide interference of light at the slit. The system also includes a light source for illuminating the first surface of the plasmonic interferometer, a detector positioned for detecting light transmitted through the aperture, and a sample holder for disposing a sample to be analyzed onto the first surface of the plasmonic interferometer.

Claims

1. A system for detecting an analyte comprising:

a plasmonic interferometer, the plasmonic interferometer comprising a first surface and a second surface on an opposite side of the plasmonic interferometer than the first surface, the first surface having a first groove and a second groove and a slit disposed between the first groove and the second groove to define a first distance between the slit and the first groove and a second distance between the slit and the second groove, wherein the first and second distances are selected to provide interference of light at the slit;

a light source for illuminating the first surface of the plasmonic interferometer;

a detector for detecting light transmitted through the slit, the detector positioned proximate to the second surface of the plasmonic interferometer; and

a sample holder for disposing a sample to be analyzed onto the first surface of the plasmonic interferometer.

2. The system of claim 1, wherein the first and second scattering elements are surface plasmon polariton scattering elements.

3. The system of claim 1, wherein the aperture slit is designed to allow collection of a light property.

4. The system of claim 1, wherein the plasmonic interferometer comprises a conductive film.

5. The system of claim 4, wherein the plasmonic interferometer comprises one of gold (Au), silver (Ag), aluminum (Al), copper (Cu), or other noble metal, and a functional protective layer such as indium-tin oxide (ITO), or silicon dioxide, or other functional material.

6. The system of claim 1, wherein the sample holder comprises walls positioned to retain the sample on the first surface of the plasmonic interferometer.

7. The system of claim 1, wherein the sample holder comprises a microfluidic channel positioned to direct a sample over the first surface of the plasmonic interferometer.

8. The system of claim 1, wherein the first surface of the plasmonic interferometer is functionalized with an analyte capture agent selected to capture the analyte to be detected.

9. The system of claim 1, wherein the first surface of the plasmonic interferometer is coated with a dielectric material.

10. The system of claim 1, wherein the first surface of the plasmonic interferometer is coated with an analyte capture agent selected to capture the analyte to be detected.

11. The system of claim 1, wherein the analyte capture agent is selected to capture cytokines.

12. The system of claim 1, further comprising a power source.

13. The system of claim 1, wherein the detector is a CCD camera.

14. The system of claim 1, wherein the detector is a CMOS camera.

15. The system of claim 1, wherein the detector is external.

16. The system of claim 1, wherein the detector is internal.

17. The system of claim 1, wherein the first scattering element and the second scattering element have a length between 10 nm and 100 μ

m.

18. The system of claim 1, wherein the first scattering element and the second scattering element have a width between 10 nm and 500 nm.

19. The system of claim 1, wherein the first and the second scattering element have a depth between 1 nm and 300 nm.

20. The system of claim 1, wherein the aperture has a width between 50 nm and 500 nm.

21. The system of claim 1, wherein the second distance is greater than the first distance.

22. The system of claim 1, wherein the second distance is equal to the first distance.

23. The system of claim 1, wherein the light source is selected to provide light at optical frequencies.

24. The system of claim 1, further comprising a protective layer of a dielectric material, or a functional layer, or oxidative dye, or chromogenic dye disposed on the first surface.

25. The system of claim 1, wherein the first scattering element and the second scattering element are linear.

26. The system of claim 1, wherein the first scattering element and the second scattering element are arcs.

27. The system of claim 1, wherein the aperture is a hole.

28. The system of claim 1, wherein the first scattering element and the second scattering elements are curvilinear.

29. The system of claim 1, further comprising inlet and outlets positioned to permit inflow and outflow of a second fluid in the sample holder.

30. The system of claim 1, wherein the first and second scattering elements comprise a plurality of scattering elements of different sizes, shapes and/or dimensions, and the aperture comprises several slits of different sizes, shapes and/or dimensions.

31. A method of real-time detection of an analyte comprising:

providing a plasmonic interferometer according to claim 1 applying a sample to be analyzed on the first surface of the plasmonic interferometer;

illuminating the plasmonic interferometer with the light source;

measuring a light property of a composite light transmitted through the aperture; and

determining a characteristic of an analyte of interest based on the measured light intensity;

wherein the composite light is generated through interference at the aperture of the incident light and scattered light from the first and second scattering elements.

32. The method of claim 31, wherein the step of measuring a light property includes measuring a light intensity of the composite light transmitted through the aperture.

33. The method of claim 31, wherein a first wave of scattered light propagates from the first scattering element to the aperture;

a second wave propagates from the second scattering element to the aperture; and

wherein the first and second distances are selected to provide constructive interference of the first and second light.

34. A method of real-time detection of an analyte comprising:

providing a plasmonic interferometer according to claim 1;

applying a sample to be analyzed on the first surface of the plasmonic interferometer, wherein the sample comprises an oxidative or chromogenic dye selected to absorb particular light frequencies;

illuminating the plasmonic interferometer with the light source;

measuring a light property of a composite light transmitted through the aperture; and

determining a characteristic of an analyte of interest based on the measured light intensity;

wherein the composite light is generated through interference at the slit of the incident light and scattered light from the first and second scattering elements.

35. A method of spectroscopic measurements of the dispersion relation and optical constants of dielectric materials in gaseous, liquid, or solid form, the method comprising:

providing a plasmonic interferometer according to claim 1;

applying a sample to be analyzed on the first surface of the plasmonic interferometer, wherein the sample comprises at least one of a dielectric material and a mixture of dielectric material;

illuminating the plasmonic interferometer with a light source;

measuring a light property of a composite light transmitted through the aperture; and

determining a characteristic of an analyte in the sample based on the measured light property;

wherein the composite light is generated at the aperture through interference of incident light from the source and scattered light from the first and second scattering elements.

36. A system for detecting a plurality of analytes comprising:

a plurality of plasmonic interferometers, each plasmonic interferometer comprising;

a first surface and a second surface on an opposite side of the plasmonic interferometer than the first surface, the first surface having a first groove and a second groove; and

a slit disposed between the first groove and the second groove to define a first distance between the slit and the first groove and a second distance between the slit and the second groove;

wherein the first and second distances are selected to provide controlled interference of light at the aperture slit;

a light source for illuminating the first surface of each of the plurality of plasmonic interferometers;

a plurality of detectors for detecting light transmitted through the slit of each plasmonic interferometer, each detector positioned proximate to the second surface of a corresponding plasmonic interferometer; and

a plurality of sample holders, each sample holder disposing a sample to be analyzed onto the first surface of each plasmonic interferometer.

37. The system of claim 36, wherein the number of plasmonic interferometers varies between 1 and 10,000,000,000.

38. The system of claim 36, wherein the plasmonic interferometers are etched over an area that varies between 1E-6 mm² and 1E4 mm².

39. The system of claim 36, wherein two neighboring plasmonic interferometers are separated by a distance of at least two propagation lengths.

40. The system of claim 36, wherein two neighboring plasmonic interferometers are separated by a thin film of platinum or chromium.

41. The system of claim 36, wherein neighboring plasmonic interferometers are optimally staggered to minimize cross-talk along the plane.

42. A system for detecting an analyte comprising:

a plasmonic interferometer, the plasmonic interferometer comprising a first surface and a second surface on an opposite side of the plasmonic interferometer than the first surface, the first surface having a first groove and a second groove and a slit disposed between the first groove and the second groove to define a first distance between the slit and the first groove and a second distance between the slit and the second groove, wherein the first and second distances are selected to provide interference of light at the slit;

a light source for illuminating the first surface of the plasmonic interferometer;

a detector for detecting light transmitted through the slit, the detector positioned proximate to the second surface of the plasmonic interferometer; and

a sample holder for disposing a sample to be analyzed onto the first surface of the plasmonic interferometer;

wherein the sample comprises an oxidative or chromogenic dye selected to absorb particular light frequencies.