Sub-micron resolution surface plasmon resonance microscopy of binding kinetics under active microfluidic mixing

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Research into miniaturized biosensing, whether in microarray or lab-on-chip formats, has seen explosive growth in recent years. Surface plasmon resonance (SPR), a powerful method for biosensing, is well established in both cases. Most SPR systems are based either on propagating plasmons in "macroscopic" (mm2 or cm2) thin-films, or on non-propagating localized surface plasmons (LSRP) in nanostructures. Though systems at both ends of the spectrum have been extensively studied, there exists a knowledge gap between the two where surface structure and its impact on chemical reactivity and optical properties of SPR-active metals are not fully understood. This gap is important to explore because, in the push to "go nano", scientists and engineers may not have all the elements in hand to make informed decisions about optimal levels of scale in biosensor design. This research aims to fill this gap by developing instrumentation & methods for observing SPR phenomena at the sub-µm scale linked to real-time measurements of surface chemistry kinetics and microfluidic mixing. The program will address these challenges with a novel imaging platform capable of producing high-resolution tomographic SPR microscopy images co-registered with that from a scanning electron microscope (SEM), and incorporating active on-chip microfluidic mixing. This system will enable the study of surface functionalization and assay kinetics in relation to metal thin-film properties, at the sub-µm level of scale, and allow direct measurement of Langmuir isotherms. The work will have wide-ranging repercussions in next-generation miniaturized biosensors in applications where SPR is prevalent such as rapid medical diagnostics, environmental monitoring, and the pharmaceutical and agri-food industries. The long term objective of this research is to enable microarray- and lab-on-chip-based SPR systems to achieve levels of density, miniaturization, and reliability of measurement not currently possible.