Advanced Nanophotonic Biosensors for Ultrasensitive Biomedical Detection

This thesis presents the development of advanced photonic platforms for biosensing, integrating nanostructured optical architectures, functional materials, and tailored surface chemistries to achieve high sensitivity and selectivity in biomolecular detection. The research bridges fundamental photonic principles with practical diagnostic applications, advancing the field of integrated photonic biosensors both conceptually and technologically. The first part establishes the theoretical foundations of photonic crystals, exploring light–matter interactions, photonic band structures, and the phenomenon of bound states in the continuum (BIC), which enables ultra-high-Q resonances and extreme light confinement. Building on these principles, the thesis further investigates their implementation in biosensing architectures, supported by an in-depth analysis of optical transduction mechanisms and surface functionalization strategies essential for specific biochemical recognition. Experimentally, the work demonstrates three major photonic sensing platforms. The first one is a molecularly imprinted polymer (MIP) sensor integrated with a BIC-based nanostructure for the selective, label-free detection of Transforming Growth Factor Beta (TGF-β), achieving femtomolar detection limits and robust performance in complex media. The second sensing platform involves a microfluidic-integrated photonic crystal slab used to investigate the interaction between Secreted Protein Acidic and Rich in Cysteine (SPARC) and Human Serum Albumin (HSA), providing precise real-time kinetic analysis with nanomolar accuracy. These activities were carried out at the Istituto di Scienze Applicate e Sistemi Intelligenti “Eduardo Caianiello” (ISASI) of the Consiglio Nazionale delle Ricerche (CNR) in Naples that also provided the funding for the PhD scholarship. The final platform employs bimodal waveguide interferometry for small-molecule sensing, as shown by ibuprofen detection with optimized surface chemistries and competitive immunoassays. This activity was carried out during an exchange period at the Institut Català de Nanociència i Nanotecnologia (ICN2) in Barcelona. Together, these devices illustrate how resonance phenomena and biochemical functionalization can be effectively combined to achieve both sensitivity and specificity across a broad range of analytes. The thesis is structured to follow a logical progression from the illustration of the theoretical background up to the experimental results obtained. Chapter 1 introduces the fundamental principles of photonic crystals, describing their underlying physical mechanisms, classification schemes, and the role of bound states in the continuum in achieving high-Q optical resonances. Chapter 2 then examines the main classes of optical biosensors and discusses the essential aspects of surface functionalization, thus providing the theoretical and practical foundation for subsequent device development. Based on this foundation, Chapter 3 presents the design and realization of a BIC-based molecularly imprinted polymer sensor for the detection of TGF-β, whereas Chapter 4 investigates dynamic protein–protein interactions through a photonic crystal slab integrated with microfluidic handling. The final experimental chapter, Chapter 5, explores the potential of bimodal waveguide interferometry in small-molecule sensing, highlighting its prospective relevance for pharmaceutical applications. The thesis concludes with perspectives on the future development of integrated photonic biosensing systems toward multiplexed, portable, and clinically relevant applications.