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

• US 20040191765A1
• Filed: 03/05/2004
• Published: 09/30/2004
• Est. Priority Date: 03/27/2003
• Status: Active Grant

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Yuen, Po Ki, Mozdy, Eric J., Quan, Frederic J-Y
• Granted Patent: US 7,368,281 B2
• Time in Patent Office: Days
• US Class Current: 435/5
• 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 surface having at least in-part a bio- or chemo-responsive layer, which forms a serially renewable sensing region;

     2) an optical interrogation apparatus for monitoring 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 said sensing region.

2. The sensor system according to claim 1, wherein said substrate 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 substrate 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 sensor arrays, wherein each array comprises a predetermined set of multiple regions for biological or chemical sensing.

5. The sensor system according to claim 1, wherein said substrate having tensile strength and pliability can be supplied from a dispensing device as a single unit in a continuous fashion;

and

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 toxin targets.

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

7. The sensor system according to claim 1, wherein said evanescent-field sensor has a substrate in the form of a rotatable platform.

8. The sensor system according to claim 1, further comprising a collection of individual substrates, each having one or more sensing regions that can be optically interrogated in series.

9. The sensor system according to claim 8, wherein each substrate in said collection of substrates is a substrate according to any one of claims 2-8.

10. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer in said sensing region is specifically formulated to react with particular biological or chemical analytes.

11. The sensor system according to claim 10, wherein each array of sensors bio- or chemo-responsive layers specifically is formulated to react with one or more particular biological or chemical analyte.

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

13. The sensor system according to claim 10, wherein said has bio- or chemo-responsive layer includes a pathogen-specific ganglioside probe.

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

15. The sensor system according to claim 1, wherein said bio- or chemo-responsive layer is designed to react with a chemical molecule of interest resulting in either a change in mass or refractive index.

16. The sensor system according to claim 15, wherein said change in mass is due to either a binding of said chemical molecule of interest, or a removal of an original chemistry from the sensor surface.

17. The sensor system according to claim 1, wherein said sensor is able to detect biological toxins present in a sample at levels of at least 1 femtomole per liter.

18. The sensor system according to claim 1, wherein said sensor is able to detect biological organism present in a sample at levels of at least 1 organism per liter.

19. The sensor system according to claim 1, wherein said sensor is able to detect chemical toxins present in a sample at levels of at least 50-100 attomoles per liter.

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

21. The sensor system according to claim 1, wherein probes in said bio- or chemo-responsive layer include glycolipds, gangliosides, or lipid biomembranes.

22. The sensor system according to claim 1, wherein probes in said bio- or chemo-responsive layer include antibodies, or immuno-receptors.

23. The sensor system according to claim 1, wherein said substrate has immobilized antibodies against various different surface marker molecules of a particular pathogen.

24. The sensor system according to claim 23, wherein antibodies include 4-5 different antibodies for anthrax.

25. The sensor system according to claim 1, wherein said sensor is a a waveguiding structure formed by an effective index waveguiding region covering a 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

a bio- or chemo-responsive layer covering the waveguiding region, wherein said bio- or chemo-responsive layer is capable of interacting with the toxins of interest.

26. The sensor system according to claim 1, wherein said sensor is a substrate coated with a metallic film capable of supporting surface plasmon modes.

27. The sensor system according to claim 1, wherein said sensor is a substrate coated with multiple dielectric layers, having varying optical indices, in which the optical field has an evanescent tail extending beyond the layer immediately in contact with a medium to be sensed.

28. The sensor system according to claim 1, wherein said sensor is a patterned optical circuit.

29. The sensor system according to claim 1, wherein said sensor is an interferometer.

30. The sensor system according to claim 1, wherein said sensor is a Mach-Zehnder interferometer.

31. The sensor system according to claim 1, wherein 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 an evanescent sensing field.

32. The sensor system according to claim 1, wherein the optical delivery system utilizes optical fiber to either deliver or collect a light signal from said sensors.

33. The sensor system according to claim 32, wherein the optical delivery system includes a diffractive optic to generate multiple optical probe beams for multiplexed monitoring of multiple sensing regions.

34. The sensor system according to claim 33, wherein said substrate is made of either a ductile organic or inorganic material, or a combination of both.

35. The sensor system according to claim 4, wherein said contiguous sets of arrays of sensors are arranged longitudinally along the length of said substrate.

36. The sensor system according to claim 4, wherein said contiguous sets of arrays of sensors comprise families of toxin probes.

37. The sensor system according to claim 3, wherein said ductile material is polymeric, amorphous, or metal.

38. The sensor system according to claim 3, wherein each contiguous set of arrays of toxin targets are repeating along the length of said substrate and each of said set of arrays is recognizably separated from one another.

39. The sensor system according to claim 38, wherein each of said arrays is indexed according to an identifier.

40. The sensor system according to claim 39, wherein said identifier may include a biological marker, a chemical marker, an alpha-numeric label, or a bar code.

41. The sensor system according to claim 3, wherein said bar code is optical, electronic, metallic, or magnetic.

42. The sensor system according to claim 3, wherein said pliable, continuous substrate takes a form like that of a ribbon, sheet, strip, tape, film, fiber, filament, or floss.

43. The sensor system according to claim 3, wherein said substrate has a length, width, and thickness compatible with commercial 35-mm photographic film technology.

44. The sensor system according to claim 3, wherein said dispensing device includes a roll.

45. The sensor system according to claim 3, wherein said dispensing device is a reel.

46. The sensor system according to claim 3, wherein said pliable substrate has a plurality of perforations for engaging with sprockets.

47. The sensor system according to claim 3, wherein said substrate having a length that is at least about 5×

the width.

48. The sensor system according to claim 3, wherein said substrate having a length that is at least about 10×

the width.

49. The sensor system according to claim 3, wherein said substrate having a length that is at least about 100×

the width.

50. The sensor system according to claim 3, wherein said continuous substrate has an effective serial sensor up to 1 m long.

51. The sensor system according to claim 3, wherein said continuous substrate has an effective serial sensor length of up to 10 m long.

52. The sensor system according to claim 3, wherein said continuous substrate has an effective serial sensor length of at least 10 m long.

53. The sensor system according to claim 3, wherein said continuous substrate has an effective serial sensor length of at least 1 kilometer long.

54. A method of using the evanescent-field sensors for detecting airborne biological pathogens, chemical agents, or other harmful or toxic species, the method comprises:

providing a sensor system having an evanescent-field sensor comprising a substrate surface having at least in-part a bio- or chemo-responsive layer, which forms a serially renewable sensing region;

exposing an individual sensor array to an environment with unknown hazardous contaminants; and

monitoring a response from said sensor system to determine a contamination level.

55. The method according to claim 54, wherein said substrate is modified with one or more materials, which enhance stable immobilization of said bio- or chemo-responsive layer.

56. The method according to claim 54, wherein said substrate has reactant and non-reactant regions.

57. The method according to claim 54, wherein said evanescent-field sensor has a continuous substrate having thereon at least two or more contiguous sets of sensor arrays, wherein each array comprises a predetermined set of multiple regions for biological or chemical sensing.

58. The method according to claim 54, wherein said sensor system is deployed on a mobile platform to be moved through said contaminated environment.

59. The method according to claim 58, wherein said mobile platform is an unmanned vehicle.

60. The method according to claim 54, wherein said sensor response is transmitted to a remote analysis location.

61. The method according to claim 54, wherein said bio- or chemo-responsive layer is designed to adsorb a chemical molecule of interest.

62. The method according to claim 54, wherein said bio- or chemo-responsive layer is designed to react with a chemical molecule of interest resulting in either a change in mass or refractive index.

63. The method according to claim 62, wherein said change in mass is due to either a binding of said chemical molecule of interest, or a removal of an original chemistry from the sensor surface.

64. The method according to claim 54, wherein said bio- or chemo-responsive layer has a set of probes.

65. The method according to claim 64, wherein said probes include a polymer matrix, a biomembrane with a ligand-gated ion channel, or chemical compounds.

66. The method according to claim 64, wherein said probes include glycolipds, gangliosides, or lipid biomembranes.

67. The method according to claim 64, wherein said probes include antibodies, or immuno-receptors.

68. The method according to claim 54, wherein said substrate has an effective serial sensor length of at least about 1 m long.