Label-free evanescent-field detection of biological and chemical agents

• US 7,368,281 B2
• Filed: 03/05/2004
• Issued: 05/06/2008
• Est. Priority Date: 03/27/2003
• Status: Expired due to Fees

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Quan, Frederic J-Y, Yuen, Po Ki, Mozdy, Eric J.
• Primary Examiner(s): Chin; Christopher L.
• Application Number:
  US10/794,937
• Publication Number:
  US 20040191765A1
• Time in Patent Office: 1,523 Days
• Field of Search: 385/12, 385/30, 422/82.05, 422/82.11, 435/6, 435/4, 435/5, 435/287.2, 435/287.9, 435/288.7, 435/808, 436/514, 436/524, 436/525, 436/527, 436/528, 436/529, 436/805
• US Class Current: 435/287.2
• 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: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

An evanescent-field sensor system and method of using the system to detect either liquid- or airborne biological pathogens, chemical agents, and other harmful or toxic species is provided. The sensor system involves 1) an evanescent-field sensor having a substrate surface with at least a partial bio- or chemo-responsive layer, which forms a part of a serially renewable sensing region; 2) an optical interrogation apparatus for monitoring the bio- or chemo-responsive layer; and 3) an air-fluid delivery system. The optical interrogation apparatus has a light source, an optical delivery system, and a detection instrument or device. The air-fluid delivery system includes either macro or micro-fluidic passages designed to convey biological or chemical analytes to a sensing region.

Claims

1. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises:

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part with a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument; and

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region, wherein said substrate having tensile strength and pliability can be supplied from a dispensing device as a single unit in a continuous fashion, and wherein said substrate being configurable to a fraction of its fully extended length along its longest dimension without breaking and can be retrieved from such configuration as a continuous body suitable for performing molecular interactive assays with the biological or chemical analytes to detect the biological pathogens, chemical agents, or other harmful or toxic species.

2. The sensor system according to claim 1, wherein said surface is modified with one or more materials, which enhance stable immobilization of said bio- or chemo-responsive layer.

3. The sensor system according to claim 1, wherein said surface has reactant and non-reactant regions.

4. The sensor system according to claim 1, wherein said evanescent-field sensor has a continuous substrate having thereon at least two or more contiguous sets of sensing regions, wherein each sensing region comprises a predetermined set of multiple regions for biological or chemical sensing.

5. The sensor system according to claim 4, wherein said contiguous sets of sensing regions are arranged longitudinally along the length of said substrate.

6. The sensor system according to claim 1, wherein said substrate is an optically transparent film of about 50 microns to about 2 mm thick.

7. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer in each sensing region in said serially renewable sensing region is specifically formulated to react with particular biological pathogens, chemical agents, or other harmful or toxic species.

8. The sensor system according to claim 7, wherein each sensing region in said serially renewable sensing region is formulated to react with one or more particular biological pathogens, chemical agents, or other harmful or toxic species.

9. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer includes a pathogen-specific antibody.

10. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer is designed to adsorb a chemical molecule of interest.

11. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer is designed to react with the biological pathogen, chemical agent, or other harmful or toxic species of interest resulting in either a change in mass or refractive index.

12. The sensor system according to claim 11, wherein said change in mass is due to either a binding of said biological pathogen, chemical agent, or other harmful or toxic species of interest, or a removal of an original chemistry from the surface.

13. The sensor system according to claim 1, wherein said evanescent-field sensor is able to detect biological toxins present in the biological or chemical analytes at levels of at least 1 femtomole per liter.

14. The sensor system according to claim 1, wherein said evanescent-field sensor is able to detect biological organism present in the biological or chemical analytes at levels of at least 1 organism per liter.

15. The sensor system according to claim 1, wherein said evanescent-field sensor is able to detect chemical toxins present in the biological or chemical analytes at levels of at least 50-70 attomoles per liter.

16. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer has probes including a polymer matrix, a biomembrane with a ligand-gated ion channel, or chemical compounds.

17. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer has probes including antibodies, or immuno-receptors.

18. The sensor system according to claim 1, wherein said evanescent-field sensor has the substrate coated with a metallic film capable of supporting surface plasmon modes.

19. The sensor system according to claim 1, wherein said substrate is made of either a ductile organic or inorganic material, or a combination of both.

20. The sensor system according to claim 19, wherein said ductile material is polymeric, amorphous, or metal.

21. The sensor system according to claim 1, wherein said pliable, continuous substrate takes a form like that of a ribbon, sheet, strip, tape, film, fiber, filament, or floss.

22. The sensor system according to claim 1, wherein said dispensing device includes a roll.

23. The sensor system according to claim 1, wherein said dispensing device is a reel.

24. The sensor system according to claim 1, wherein said pliable substrate has a plurality of perforations for engaging with sprockets.

25. The sensor system according to claim 1, wherein said substrate having a length that is at least about 5×

the width.

26. The sensor system according to claim 1, wherein said substrate having a length that is at least about 10×

the width.

27. The sensor system according to claim 1, wherein said substrate having a length that is at least about 100×

the width.

28. The sensor system according to claim 1, wherein said continuous substrate has an effective serial sensor up to 1 m long.

29. The sensor system according to claim 1, wherein said continuous substrate has an effective serial sensor length of up to 10 m long.

30. The sensor system according to claim 1, wherein said continuous substrate has an effective serial sensor length of at least 10 m long.

31. The sensor system according to claim 1, wherein said continuous substrate has an effective serial sensor length of at least 1 kilometer long.

32. The sensor system according to claim 1, wherein said evanescent-field sensor, said optical interrogation apparatus, said air-fluid delivery system, said dispensing device are deployed on a mobile platform and moved to or through a contaminated environment and sensor response signals are transmitted to a remote analysis location.

33. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises:

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region, wherein said substrate is in the form of a rotatable platform.

34. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises:

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region

     4) said bio- or chemo-responsive layer in said serially renewable sensing region is specifically formulated to react with particular biological or chemical analytes; and

     5) said bio- or chemo-responsive layer includes a pathogen-specific ganglioside probe.

35. The sensor system according to claim 34, wherein said evanescent-field sensor further comprising a collection of individual substrates, each having one or more sensing regions that can be optically interrogated in series.

36. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises:

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

(4) said bio- or chemo-responsive layer has probes including glycolipids, gangliosides, or lipid biomembranes.

37. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises:

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

     4) said substrate has immobilized antibodies against various different surface marker molecules of a particular pathogen.

38. The sensor system according to claim 37, wherein antibodies include 4-5 different antibodies for anthrax.

39. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region, wherein said evanescent-field sensor has a waveguiding structure formed by an effective index waveguiding region covering the substrate, wherein the waveguiding region has a refractive index at least 0.1% higher than the refractive index of the substrate;

a diffraction grating contained in or near the waveguiding structure; and

the bio- or chemo-responsive layer covering the waveguiding region, wherein said bio- or chemo-responsive layer is capable of interacting with the biological pathogen, chemical agent, or other harmful or toxic species of interest.

40. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

     4) said evanescent-field sensor has the substrate coated with multiple dielectric layers, having varying optical indices, in which an optical field has an evanescent tail extending beyond the layer immediately in contact with a medium to be sensed.

41. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

     4) said evanescent-field sensor is a patterned optical circuit.

42. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

     4) said evanescent-field sensor is an interferometer.

43. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

     4) said evanescent-field sensor is a Mach-Zehnder interferometer.

44. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

(4) the optical delivery system includes a diffraction grating, a prism, or a specifically tailored dielectric stack in order to couple in-coming and out-going optical probe beams to said evanescent-field sensor.

45. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

(4) the optical delivery system utilizes optical fiber to either deliver or collect a light signal from said evanescent-field sensor.

46. The sensor system according to claim 45, wherein the optical delivery system includes a diffractive optic to generate multiple optical probe beams for multiplexed monitoring of multiple sensing regions.

47. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region;

     4) said evanescent-field sensor has a continuous substrate having thereon at least two or more contiguous sets of sensor arrays, wherein each sensor array comprises a predetermined set of multiple regions for biological or chemical sensing; and

     5) said contiguous sets of sensor arrays comprise families of toxin probes.

48. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region;

     4) said surface has reactant and non-reactant regions; and

     5) said surface has contiguous set of arrays of toxin targets are repeating along the length of said substrate and each of said set of arrays of toxin targets is recognizably separated from one another.

49. The sensor system according to claim 48, wherein each of said arrays of toxin targets is indexed according to an identifier.

50. The sensor system according to claim 49, wherein said identifier may include a biological marker, a chemical marker, an alpha-numeric label, or a bar code.

51. The sensor system according to claim 50, wherein said bar code is optical, electronic, metallic, or magnetic.

52. A sensor system for detecting biological pathogens, chemical agents, or other harmful or toxic species, the sensor system comprises;

1) an evanescent-field sensor comprising a substrate with a surface covered at least in-part a bio- or chemo-responsive layer which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring at least a portion of said bio- or chemo-responsive layer, said optical interrogation apparatus comprising a light source, an optical delivery system, and a detection instrument;

     3) an air-fluid delivery system, comprising either macro or micro-fluidic passages designed to deliver biological or chemical analytes to at least a portion of said serially renewable sensing region; and

     4) said substrate has a length, width, and thickness compatible with commercial 35-mm photographic film technology.