This thesis is overarchingly concerned with optically detecting or monitoring two classes of nucleic
acids – G-Quadruplex and microRNA. G-quadruplexes are a structural arrangement of nucleic acid
which play key biological roles including regulating transcription and translation. Oncogenic Gquadruplexes
present attractive binding targets for small-molecule drugs, but these low-weight
interactions are challenging and costly to study, and no drugs have yet made it to market.
Circulating cell-free microRNA have recently emerged as clinically relevant and minimally invasive
cancer biomarkers (the ‘liquid biopsy’). However, they are difficult to detect accurately due to their
low concentrations, short lengths, and high sequence homology. Current technologies typically
rely on complex and costly procedures that are incompatible with miniaturized point-of-care
devices. This thesis presents the design, engineering, and validation of two optical platform
technologies for sensitive and specific detection of nucleic acid (microRNA) or monitoring of nucleic
acid interactions with binding partners (G-quadruplexes). These novel platforms are based on
microneedle patches and whispering gallery mode sensors. Both optical platforms demonstrate
specificity and sub-micromolar sensitivity. This was aided by careful selection of low-fouling
surfaces based on click-chemistry. Both platforms also incorporate or explore the use of clickengineered
hydrogels to enhance performance. Because of their versatility and small size, the
platforms may be developed in the future to offer multiplexing capabilities and may be integrated
into miniaturized lab-on-a-chip devices.
In summary, we engineer an entire whispering gallery mode sensor platform, from hardware to
software to surface chemistry (Chapter 2). The results from several applications are presented,
including validating small-molecule interactions with G-quadruplexes, and proof-of-concept
microRNA detection (Chapter 3). We also develop hydrogel-coated microneedle sensors as a
sampling, detecting and quantifying system for melanoma-associated microRNA. We validate this
second-generation microneedle array featuring a two-probe system – an advance on the previous
single-probe design (Chapter 4).