Label-free imaging of exosomes using depth scanning correlation (DSC) interferometric microscopy

Direct visualization and characterization of nanosized biological particles such as viruses, vesicles and protein aggregates are important for various applications in medicine. Specifically, exosomes (30-150 nm in diameter) gained huge interest due to their potential role as a biomarker in cancer diagnosis and prognosis, however direct detection of these particles is challenging due to their small size. Interferometric microscopy allows detection of these particles without using any labels. We show that visibility of nanoparticles can be enhanced in interferometric microscopy by utilizing defocused images. In this paper, with the proposed method Depth Scanning Correlation, we demonstrate label-free detection of individual exosomes isolated from breast cancer cell culture isolated by using Exosome Total Isolation Chip (ExoTIC). Proposed imaging system combined with an isolation tool, can be used in a wide range of applications, where label-free detection of single biological nanoparticles is needed.