Design of a novel photonic biosensor based on whispering-gallery modes of dielectric microspheres for high-throughput immunoassays

Our goal is to develop a new generation of label-free biosensor using a simple, versatile, and highly sensitive optical method. During the last decade, label-free optical biosensors have become valuable tools for clinical and military use as well as drug discovery. They are important devices for a range of applications going from detection of infectious agents, toxins, proteins and DNA to investigation of whole cell behaviour (e.g. attachment, spreading and proliferation of animal cells on solid surfaces), to quantitative determination of binding affinities and interactions kinetics between molecules. Modern label-free optical biosensors, like the widely utilised surface plasmon resonance (SPR) method, are based on an evanescent light field travelling along a planar surface, probing the target material deposited on the surface. A more sensitive type of biosensor based on evanescent field coupling can be realized by exploiting narrow-linewidth photonic resonances of dielectric microspheres, the so called whispering-gallery modes (WGMs), where the field is confined close to the inner surface of the sphere and is travelling around the sphere via total internal reflection. The light can orbit many thousand times before escaping the resonator, giving rise to an effective interaction length between the evanescent light field and the target molecules many orders of magnitude longer than the physical length on the sphere surface where molecules are deposited (its SPR analogous would correspond to a planar chip of more than one meter length!). This method should show unprecedented sensitivity but to fully explore the range of possible applications a proper theoretical model is still missing. We have recently commenced the construction and experimental study of a prototype WGM biosensor for immunosensing based on antibody-antigen interaction where many microspheres coated with different antibodies can be addressed in parallel via their evanescent coupling to planar waveguide modes propagating near a substrate surface. With the present project we want to develop a theoretical modelling to assess the applicability of this optical biosensor toward sensitive detection not only of proteins but also of viruses and bacteria. By combining this rigorous theoretical study with the experiments already ongoing we aim to realize the design of an optimum label-free biosensor for high-throughput immunoassays.

The exploration of the advantages and applications of whispering-gallery mode (WGM) optical biosensors is at a relatively early stage. As a matter of fact, WGM biosensors reported in literature up to now where used only for detection of a uniformly deposited layer of proteins while detection and recognition of viruses or bigger disordered objects like bacterial cells has not yet been explored. To achieve this implementation, the ability to interpret the effect of the target particles not only on the resonance frequency of the WGMs but also on their width via a proper scattering theory is of crucial importance. This effect is significant to distinguish between the uniform deposition of small biomolecules forming a thin layer, which can be described with an effective medium approach, and the deposition of a single virus acting as a strong localized scatterer, or the disordered case of a large micro-particle such a whole bacterial cell attaching to the biosensor surface. The ability to distinguish analytes of different sizes via their scattering properties would render these WGM biosensors not only very sensitive but also very selective tools to be used without the need of pre-filtering and separation procedures. The aim of the present project is to develop a theoretical modelling based on scattering theory using both a numerical and a semi-analytical approach to assess the applicability of this WGM optical biosensor toward sensitive detection not only of proteins but also of viruses and bacteria. By combining this rigorous theoretical study with experiments already ongoing we aim to realize a realistic design of an optimum label-free biosensor for high-throughput immunoassays.