Reflectively coated optical waveguide and fluidics cell integration

• US 6,192,168 B1
• Filed: 04/09/1999
• Issued: 02/20/2001
• Est. Priority Date: 04/09/1999
• Status: Active Grant

• Current Assignee: the united states of america as represented by the secretary of the navy
• Original Assignee: the united states of america as represented by the secretary of the navy
• Inventors: Golden, Joel P., Feldstein, Mark J., Rowe, Chris A., Ligler, Frances S.
• Primary Examiner(s): Font, Frank G.
• Assistant Examiner(s): Rodriguez, Armando
• Application Number:
  US09/288,957
• Time in Patent Office: 683 Days
• Field of Search: 385/12, 385/30
• US Class Current: 385/12
• CPC Class Codes: G01N 2021/7709 Distributed reagent, e.g. over length of guide
• CPC Class Codes: G01N 2021/7776 Index
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 2021/7793 Sensor comprising plural indicators
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 2201/024 Modular construction
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: G02B 6/10 of the optical waveguide type G02B6/02, G02B6/24 take precedence; devices or arrangements for the control of light by electric, magnetic, electro-magnetic or acoustic means G02F1/00; transferring the modulation of modulated light G02F2/00; optical logic elements G02F3/00; optical analogue/digital converters G02F7/00
• CPC Class Codes: G02B 6/4206 Optical features G02B6/4207, G02B6/421 take precedence

Abstract

A multimode waveguide device for assays includes a multimode waveguide with a patterned, reflective surface coating. The exposed portion or portions of the reflectively coated waveguide surface are for analyte recognition. A fluidics cell is attached to the waveguide so that the channel or channels of the fluidics cell match with the exposed portion or portions of the waveguide surface. The channel or channels direct one or more sample fluids over the exposed portion or portions of the waveguide surface. The reflective coating minimizes loss and scattering of excitation and fluorescence light during a fluorescence assay.

Claims

1. A waveguide device for surface-sensitive optical detection of a first analyte in a first fluid sample, comprising:

a multimode waveguide having a surface bearing patterned, reflective coating, said patterned reflective coating defining a reflectively coated region and a first optically exposed region on said surface;

said first optically exposed region being sensitive to said first analyte so as to produce an alteration of said first optically exposed region indicative of the presence of said first analyte in said sample, said alteration being detectable by launching a light wave into said waveguide to generate an evanescent field at said patterned surface, and then detecting an interaction of said first optically exposed region with said evanescent wave.

2. The waveguide device of claim 1, wherein said first optically exposed region includes a first area and a second area, said first area being sensitive to said first analyte so as to produce said alteration of said first area, said second are being sensitive to a second analyte so as to produce said alteration of said second area.

3. The waveguide device of claim 1, wherein said first optically exposed region physically or chemically interacts with said first analyte.

4. The waveguide device of claim 3, wherein said first optically exposed region is coated with an analyte-responsive material, selected from the group consisting of a doped polymer, an undoped polymer, a doped sol-gel, an undoped sol-gel, and mixtures thereof, that exhibits a differential optical response upon exposure to said first analyte or upon exposure to said first analyte and an optically labeled molecule that recognizes said first analyte bound to said material on said first optically exposed region.

5. The waveguide device of claim 1, wherein said first optically exposed region comprises attached biomolecular recognition species.

6. The waveguide device of claim 5, wherein said biomolecular recognition species is a protein, a cell, a cell fragment, or a nucleic acid that recognizes said first analyte.

7. The waveguide device of claim 6, wherein said protein is an antibody.

8. The waveguide device of claim 1, further comprising a light source optically coupled into said waveguide so as to produce an evanescent wave at said first optically exposed region.

9. The waveguide device of claim 8, wherein said reflective coating comprises a reflective layer comprising silver, aluminum, platinum, rhodium, a dielectric, chromium, or a mixture thereof.

10. The waveguide device of claim 9, wherein said reflective layer is a dichroic multilayer reflector including said dielectric.

11. The waveguide device of claim 8, wherein said reflective coating comprises reflective layer and a bonding layer between said reflective layer and said waveguide.

12. The waveguide of claim 11, wherein said bonding layer is chromium, platinum, rhodium, a dielectric, a thiol silane, a cyanoacrylate, a polymer, or a mixture thereof.

13. The waveguide of claim 8, wherein said reflective coating comprises a reflective layer and a protective layer on an outer surface of said reflective layer.

14. The waveguide of claim 13, wherein said protective layer comprises chromium, platinum, rhodium, a dielectric, a polymer, or a mixture thereof.

15. The waveguide device of claim 8, further comprising a detector that detects a first signal generated by said first optically exposed region in response to said evanescent wave.

16. The waveguide device of claim 1, further comprising a mechanical, optical, or electronic component attached to said reflectively coated region of said surface of said waveguide.

17. The waveguide device of claim 1, further comprising:

a fluidics cell including;

a first surface having a portion thereof sealed to said coated region, said first surface including a depression therein defining a first fluid channel bounded at least in part by said first optically exposed region;

a first sample introduction port for the introduction of a sample into said first fluid channel.

18. The waveguide device of claim 17, wherein said patterned surface of said waveguide is planar.

19. The waveguide device of claim 17, wherein said patterned reflective coating includes a second optically exposed region sensitive to said first analyte and first surface includes:

a second depression therein defining a second fluid channel bounded at least in part by said second optically exposed region of said patterned reflective coating; and

a second sample introduction port for the introduction of a sample into said second fluid channel.

20. The waveguide device of claim 1, wherein said patterned surface of said waveguide is planar.

21. A method of preparing a waveguide for use in an assay, comprising the steps of:

providing a multimode waveguide having a surface bearing patterned, reflective coating, said patterned reflective coating defining a reflectively coated region and a first optically exposed region on said surface;

attaching a first biomolecular recognition species to said first optically exposed region by physically contacting a first area of said first optically exposed region with a deposition liquid including said first biomolecular recognition species and having a salt concentration of no more than about 75 mM for a time sufficient to attach said first biomolecular recognition species to said first area of said first optically exposed region, but for less than an amount of time that results in significant delamination of said reflective coating.

22. The method of claim 21, further comprising the step of attaching a second biomolecular recognition species for a second analyte to a second area of said first optically exposed region by physically contacting said second area of said first optically exposed region with a deposition liquid including said second biomolecular recognition species and having a salt concentration of no more than about 75 mM for a time sufficient to attach said second biomolecular recognition species to said first optically exposed region, but for less than an amount of time that results in significant delamination of said reflective coating.

23. The method of claim 22, further comprising the step of attaching said first and second biomolecular recognition species to a second optically exposed region by:

physically contacting a first area of said second optically exposed region with said deposition liquid including said first molecular species for a time sufficient to attach said first biomolecular recognition species to said first area of said second optically exposed region, but for less than an amount of time that results in significant delamination of said reflective coating; and

physically contacting a second area if said second optically exposed region with said deposition liquid including said second molecular species for a time sufficient to attach said second biomolecular recognition species to said second area of said optically exposed region, but for less than an amount of time that results in significant delamination of said reflective coating.

24. A method of performing an assay, comprising the steps of:

providing a multimode waveguide having a surface bearing a patterned, reflective coating, said patterned reflective coating defining a reflectively coated region and a first area of a first optically exposed region on said surface, said first area of said first optically exposed region generating an optical signal, indicative of the presence of said first analyte in said sample, in response to an evanescent wave at said surface;

fixing a fluidics cell to said multimode waveguide, said fluidics cell including;

a first surface having a portion thereof sealed to said coated region, said first surface including a depression therein defining a fluid channel bounded at least in part by said first optically exposed region; and

a first sample introduction port for the introduction of a first sample into fluid channel;

introducing said first sample into said fluid channel via said first sample introduction port so that said first sample physically contacts said first optically exposed region;

optically coupling light into said waveguide so as to produce an evanescent wave at said first optically exposed region that has been physically contacted with said first sample;

detecting a first signal generated by said first area of said first optically exposed region in response to said evanescent wave, wherein said first signal is correlated with the presence of said first analyte in said sample.

25. The method of claim 24, wherein said first optically exposed region is coated with a first analyte-responsive material, selected from the group consisting of a doped polymer, an undoped polymer, a doped sol-gel, an undoped sol-gel, and mixtures thereof, that exhibits a differential optical response upon exposure to said first analyte or upon exposure to said first analyte and an optically labeled molecule that recognizes said first analyte bound to said material on said first optically exposed region.

26. The method of claim 25, wherein said first optically exposed region is coated with a second analyte-responsive material, selected from the group consisting of a doped polymer, an undoped polymer, a doped sol-gel, an undoped sol-gel, and mixtures thereof, that exhibits a differential optical response upon exposure to said second analyte or upon exposure to said second analyte and an optically labeled molecule that recognizes said second analyte bound to said material on said first optically exposed region;

and further comprising the step of;

detecting a second signal generated by said second analyte-responsive material in response to said evanescent wave, wherein said second signal is correlated with the presence of said second analyte in said sample.

27. The method of claim 24, further comprising the step of:

attaching a first biomolecular recognition species for a first analyte to said first area of said first optically exposed region by physically contacting said first area of said first optically exposed region with a deposition liquid including said first biomolecular recognition species and having a salt concentration of no more than about 75 mM for a time sufficient to attach said first biomolecular recognition species to said first area of said first optically exposed region, but for less than an amount of time that results in significant delamination of said reflective coating.

28. The method of claim 27, comprising the step of preparing said multimode waveguide by attaching a second biomolecular recognition species for a second analyte to a second area of said first optically exposed region by physically contacting said second area of said first optically exposed region with a deposition liquid including said second biomolecular recognition species and having a salt concentration of no more than about 75 mM for a time sufficient to attach said second biomolecular recognition species to said second area of said first optically exposed region, but for less than an amount of time that results in significant delamination of said reflective coating;

detecting a second signal generated by said second area of said first optically exposed region in response to said evanescent wave, wherein said second signal is correlated with the presence of said second analyte in said sample.

29. The method of claim 27, wherein said first biomolecular recognition species and said second biomolecular species are different from each other and are selected from the group consisting of proteins, cells, cell fragments, and nucleic acids that recognizes said first analyte or said second analyte.

30. The method of claim 24, wherein said first sample includes an optically labeled analog of said first analyte.

31. The method of claim 24, wherein said introducing step results in any said first analyte in said first sample binding to said first optically exposed region, and further comprising the step of introducing, into said first sample introduction port after said binding of first analyte to said attached first optically exposed region, an optically labeled molecule that recognizes said first analyte bound to said first attached optically exposed region.