Nanophotonic Metasurface Biosensing Chip for Fluorescence Imaging

Nano-sized bioparticles such as exosomes are gaining increased attention, emerging as important biomarkers in disease diagnosis and treatment efficiency, including cancers, neurodegenerative diseases, metabolic disorders, pathogenic infections, etc. Molecular profiling of exosomes aims to improve early-stage disease diagnosis, understand the biological pathways of disease and conduct treatment efficacy studies. On the other hand, understanding the infectivity of different virus strains or epitope variations and the effect of drugs is the key to developing diagnostic, therapeutic and preventive measures for future outbreaks. Fluorescence molecular imaging is a powerful tool to identify multiple potential biomarkers with high specificity and high sensitivity. However, the main bottlenecks in multiplexed fluorescence molecular imaging covering the whole visible light range are (1) lowconcentration biomarkers in such nano-sized bioparticles, and (2) limited sensitivity for fluorescence imaging in the red and far-red ranges (>600 nm) due to low irradiance light source or low quantum yield of the imaging sensor.This proposed project aims to tackle these bottlenecks by exploiting several state-of-theart techniques (metasurface, silicon nanophotonics, immunofluorescence, and microfluidics) to develop next-generation fluorescence enhanced molecular imaging technology that is ultrasensitive in red and far-red ranges based on surface lattice resonance effect in nanophotonic metasurfaces. First, we will design and fabricate a novel nanophotonic metasurface consisting of a nanoantenna array to enhance fluorescence signals (>50-fold signal amplification) via surface lattice resonances. Second, we will improve the specificity of nano-sized bioparticles (e.g., exosomes, viruses, bacteria) immunolabelling, reduce background noise, and optimize ultra-sensitive multiplexed fluorescence analysis. Third, we will design a microfluidic chip to handle volumes below a milliliter, for automation and improved efficiency and uniformity. An innovative nanophotonic metasurface biosensing platform will be developed, using the available nanophotonic fabrication infrastructure and expertise at the City University of Hong Kong to ensure the successful delivery of this project. As a case demonstration, we will employ the developed nanophotonic metasurface biosensing platform for multiplexed fluorescence molecular imaging of exosomes collected from laboratory-grown breast cancer cells, demonstrating enhanced fluorescence detection at red and far-red ranges and illustrating a significant milestone in exosome–based disease diagnosis. The nanophotonic metasurface platform can be applied for other nano-sized bioparticles such as viruses and bacteria and will help promote Hong Kong as a leading international research hub in biomedical engineering and translational biomedical devices, while benefiting medical industries, professionals, and patients, and reducing the financial burden of medical treatments in the Greater Bay Area.