Development of nanophotonic biosensor platform towards on-chip liquid biopsy

Abstract

<p>Liquid biopsy has the potential to enable diagnosis, prognosis, and monitoring of some diseases at an early stage using body fluids from patients. This minimally invasive, label-free detection method is less likely to harm the cell’s viability through binding to the surface protein. Smart integration of liquid biopsy designs with microfluidics on a single chip will lead to a considerable reduction in the detection time (due to controlled diffusion length), and the volumes of sample, agent and reagent, and the limit of detection.</p> <p>Optical label-free biosensors are a powerful tool to analyze biomolecular interactions and have been widely studied in the field of biomedical and biological science and engineering. Label-free detection enables direct measurement of key characteristic properties of the chemical compound, DNA molecule, peptide, protein, virus, or cell, while eliminating experimental uncertainty induced by the effect of the label on molecular conformation, thus reducing the time and effort required for bioassay. Existing optical label-free biosensors suffer from three limitations, including low detection sensitivity, slow molecules mass transfer, and poor throughput. The goal of this dissertation is to overcome these limitations through the development of a novel and efficient modality towards liquid biopsy-based bioassay with increased detection sensitivity, speed, and throughput.</p> <p>To increase the detection sensitivity, we investigate the optical bound states in the continuum (BIC) of slotted high-contrast grating (sHCG) structures. We demonstrate that the sHCG support BICs and high-Q resonant modes, and the slot position can be utilized to tune and optimize the linewidth of the high-Q resonances. To overcome the mass-transfer limitation and reduce the assay time, we propose a lateral flow-through optical biosensor integrating high-contrast gratings and microfluidics on a silicon-on-insulator platform. The biosensor design allows reducing the diffusion length to a submicron scale and enhancing direct interactions between the analytes and sensing structures. Finally, we develop a high-throughput, label-free exosome vesicles (EVs) detection microarray formed on a photonic crystal (PC) biosensor surface. We design and implement a hyperspectral imaging approach to quantify the antibody and EV absorptions on the PC-based microarray consisting of a panel of seven antibodies specific to multiple membrane receptors of the target EVs. We validate that the EV microarray by adopting it to detect EVs released by macrophages for the analysis of immune responses.</p>