A simulation study of nanoparticle -based SERS biosensing platforms with application towards glioma detection

Abstract

Gliomas are the most commonly occurring primary brain tumour with poor prognosis and high mortality rate. Currently, the diagnostic and monitoring options for glioma mainly revolve around imaging techniques, which often provide limited information and require supervisory expertise. Liquid biopsy is a great alternative or complementary monitoring protocol that can be implemented along with other standard diagnosis protocols. However, standard detection schemes for sampling and monitoring biomarkers in different biological fluids lack the necessary sensitivity and ability for real-time analysis. Lately, biosensor-based diagnostic and monitoring technology has attracted significant attention due to several advantageous features, including high sensitivity and specificity, high-throughput analysis, minimally invasive, and multiplexing ability. In this thesis, we have focused our attention on glioma and presented a literature survey summarizing the diagnostic, prognostic, and predictive biomarkers associated with glioma. Further, we discussed different biosensory approaches reported to date for the detection of specific glioma biomarkers. Current biosensors demonstrate high sensitivity and specificity, which can be used for point-of-care devices or liquid biopsies. However, for real clinical applications, these biosensors lack high-throughput and multiplexed analysis, which can be achieved via integration with microfluidic systems. Design of surface-enhanced Raman scattering (SERS) based biosensing platforms for cancer detection require careful optimization of nanostructure size and interparticle gap to facilitate resonance of localised plasmons and thus maximize enhancement factor. In this thesis, we discussed a simple modeling strategy of nanoparticle-based SERS biosensing platform, which can even be extended to other complex nanostructures as per design requirement. A comprehensive simulation study has been conducted to understand the effects of polarization dependence on the enhancement factor of the system. A new phenomenon of local hotspot switching is observed in multiple nanosphere systems which hasn’t been reported in literatures yet. Finally, validation experiments were performed on a simple self-assembled gold nanoparticle substrate with methylene blue as Raman probe molecule.