Waveguide-based biosensors for pathogen detection

Abstract

Optical phenomena such as fluorescence, phosphorescence, polarization, interference and non-linearity have been extensively used for biosensing applications. Optical waveguides (both planar and fiber-optic) are comprised of a material with high permittivity/high refractive index surrounded on all sides by materials with lower refractive indices, such as a substrate and the media to be sensed. This arrangement allows coupled light to propagate through the high refractive index waveguide by total internal reflection and generates an electromagnetic wave-the evanescent field-whose amplitude decreases exponentially as the distance from the surface increases. Excitation of fluorophores within the evanescent wave allows for sensitive detection while minimizing background fluorescence from complex, "dirty" biological samples. In this review, we will describe the basic principles, advantages and disadvantages of planar optical waveguide-based biodetection technologies. This discussion will include already commercialized technologies (e.g., Corning's EPIC(®) Ô, SRU Biosystems' BIND(™), Zeptosense(®), etc.) and new technologies that are under research and development. We will also review differing assay approaches for the detection of various biomolecules, as well as the thin-film coatings that are often required for waveguide functionalization and effective detection. Finally, we will discuss reverse-symmetry waveguides, resonant waveguide grating sensors and metal-clad leaky waveguides as alternative signal transducers in optical biosensing.

Keywords: biosensors; fluorescence; immunoassay; pathogen sensor; planar optical waveguides; thin film.

Figure 1.

Waveguide cross-section illustrating zig-zag ray model for optical propagation.

Figure 2.

Grating coupler for efficient input/output.

Figure 3.

Physical Configuration for efficient input/output coupling.

Figure 4.

Electric field distribution for a low-contrast waveguide system.

Figure 5.

Electric field distribution of a high-contrast waveguide-system.

Figure 6.

Relative Detection sensitivity for a high contrast waveguide materials system.

Figure 7.

Chemistry of the Silane-based self-assembled monolayers used for waveguide functionalization (left) and a schematic representation of a waveguide-based sandwich immunoassay for biomarker detection used at LANL.

Figure 8.

Interferometer Response with exposure to water solutions containing E. coli O1:H57 at 3 × 10³ cells/mL.

Figure 9.

Multichannel interferometer response with exposure to water solution containing E. coli O1: H57 at ∼ 10⁷ cells/mL.

Figure 10.

Comparison of the evanescent field decay in different waveguide platforms. Details in Section 6 of the text.

Figure 11.

A photograph of the waveguide-based optical biosensor developed at LANL.

Figure 12.

The output of a typical assay on the waveguide-based biosensor is shown. Waveguide-associated background and non-specific binding associated with control sample and the fluorescence reporter are measured in each experiment. Standard measurement of a known concentration of the biomarker of interest is then made (in this case, 10 pM of carcinoembryonic antigen, a breast cancer biomarker), followed by measurement of the biomarker concentration in an unknown patient sample (in this case, HS4). The signal measured is extrapolated against the internal standard to determine the accurate concentration of the biomarker in the patient.