Advanced tools and technologies for liquid biopsy

Nanotechnology holds immense promise in revolutionising healthcare, offering opportunities in diagnostics, drug delivery, cancer therapy, and combating infectious diseases. The capacity to manipulate light-matter interactions at the nanoscale has opened new avenues for the development of integrated biomedical platforms, addressing pressing clinical needs for rapid, minimally invasive and patient-tailored solutions. Within this framework, this thesis explores two clinically relevant frontiers where nanophotonic technologies can exert transformative impact: the development of integrable photonic biosensors for precision oncology applications and the optical manipulation of viral bio-objects for infectious-disease management. In the field of oncology, Liquid Biopsy (LB) has emerged as a promising alternative to conventional tissue biopsy, driven by the need for diagnostic methods that are less invasive, faster, and capable of providing real-time molecular insights. By enabling the molecular profiling of circulating biomarkers in body fluids, LB overcomes key limitations of traditional approaches, including invasiveness, sampling bias, and the inability to capture tumour heterogeneity in real time. Nevertheless, its widespread clinical adoption critically depends on the development of highly sensitive, reproducible, and integrable platforms capable of meeting the stringent requirements of precision medicine and Point-of-Care (PoC) diagnostics. Translating LB into routine practice requires not only highly sensitive and reproducible assays but also their seamless integration into miniaturised and automated platforms. Lab-On-Chip (LoC) systems provide this framework by combining precise microfluidic handling with high selective sensing platforms. In this framework, photonic biosensors emerge as a particularly attractive solution, enabling label-free and real-time detection with high sensitivity while remaining fully compatible with LoC system and PoC diagnostics. Accordingly, this thesis focuses on the design and assessment of two nanophotonic sensing devices tailored for the detection of tumour-associated biomarkers, with particular emphasis on Immunoglobulin G (IgG) proteins at diagnostically relevant concentrations. This first solution is a 1D photonic crystal waveguide incorporating engineered defects to generate a box-like resonance profile, thereby enhancing spectral interrogation, improving linearity, and mitigating noise in refractometric measurements. The second is a slot-assisted dielectric metasurface that provides strong electromagnetic field confinement and high Q-factor within a compact, wafer-scalable footprint, ensuring compatibility with LoC integration and large-scale fabrication. Together, these proposed platforms highlight complementary strategies for advancing liquid biopsy towards robust, label-free, and clinically deployable photonic diagnostics. i Complementing the focus on cancer research, the thesis further explores infectious diseases, where conventional diagnostic approaches, including culture-based assays, molecular analyses, and imaging techniques, are often limited by long turnaround times, operational complexity, and insufficient single-particle resolution, which in turn hampers timely outbreak management and effective antimicrobial resistance surveillance. To address these challenges, this doctoral thesis introduces a hybrid dielectric-plasmonic nanobowtie cavity as a multifunctional nanophotonic platform for viral-scale trapping and manipulation. Numerical analyses combining electromagnetic and thermal modelling demonstrate the stable confinement of ~ 100 nm particles under physiological conditions, enabled by enhanced near- field localisation through the integration of a thin metallic layer within a dielectric cavity. Moreover, controlled modulation of the optical power enables localised thermal inactivation, thereby merging trapping and selective deactivation within a single device and paving the way for compact nanophotonic tools for pathogen and rapid viral phenotyping.