Interferometric Microscopy for Detection and Visualization of Biological Nanoparticles

The sensitive detection and quantitative measurement of biological nanoparticles, such as viruses and exosomes, is of growing importance in biology and medicine since these structures are implicated in many biological processes and diseases. However, optical characterization of biological nanoparticles, especially in liquid media, has proven extremely difficult due to their very small size and low refractive index contrast. We present a label-free optical biosensing method based on interferometric reflectance imaging that can directly detect and characterize individual biological nanoparticles captured on a surface. We describe rigorous analysis and experimental methods to accurately characterize biological nanoparticles as well as contrast enhancement by pupil function engineering.