(<i>Invited</i>) Innovative Biosensing Approaches for the Detection of Tuberculosis and Glioma

The talk aims to address critical public health challenges by developing innovative biosensing technologies for the detection of tuberculosis and glioma. Tuberculosis remains a deadly disease, particularly in low-resource communities, due to the limitations of current diagnostic tools. This study focuses on creating a low-cost, user-friendly diagnostic device with high sensitivity for detecting tuberculosis. The approach includes developing a paper-based lateral flow assay utilizing an anti-lipoarabinomannan DNA aptamer sequence for detecting the tuberculosis antigen lipoarabinomannan. Despite the assay's inability to successfully detect the antigen, valuable insights were gained regarding the challenges and potential solutions for developing such sensors. Parallel experimental work explored the potential of horse spleen ferritin, loaded with synthetic ferrihydrite cores, as a cost-effective and stable alternative to peroxidase enzymes common in biosensing. The ferritin was biotinylated and tested for catalyzing peroxidase-like reactions, showing promise with some additional optimization. In silico studies, including docking and molecular dynamics simulations, analyzed the aptamer's interaction with lipoarabinomannan, revealing potential binding sites but also highlighting discrepancies between computational and experimental results. Further computational work proposed a novel, multiplexable sensor architecture optimized for in vitro implementation. In another effort, the study addresses the limitations of glioma diagnostics, traditionally reliant on imaging techniques requiring expert interpretation. Liquid biopsy offers a complementary approach, but current detection methods lack real-time analysis and necessary sensitivity. The research presents a comprehensive literature review of glioma biomarkers and biosensor technologies, focusing on their diagnostic, prognostic, and predictive capabilities. Biosensors demonstrate high sensitivity and specificity suitable for point-of-care and liquid biopsy applications, yet their clinical utility is hindered by the need for high-throughput and multiplexed analysis, achievable through microfluidic integration. Additionally, the talk delves into the design of surface-enhanced Raman scattering (SERS) platforms for cancer detection. Optimal nanostructure size and interparticle gaps are crucial for enhancing localised plasmons' resonance. The study models nanoparticle-based SERS biosensing platforms and conducts simulations to understand polarization dependence effects on enhancement factors. A novel phenomenon of local hotspot switching in multiple nanosphere systems is observed, unreported in existing literature. Validation experiments on self-assembled gold nanoparticle substrates with methylene blue confirm the modeling strategy's efficacy. In summary, this talk contributes to the advancement of biosensing technologies for tuberculosis and glioma detection, emphasizing low-cost, high-sensitivity solutions integrated with computational and experimental insights to overcome existing diagnostic limitations.