Handheld, quantitative phase imaging probe for skin evaluation at subcellular resolution in vivo, in real-time, and in 3D

Skin cancer is the most common malignancy in the United States. The gold standard for diagnosis of skin cancer is histopathological analysis via tissue biopsy. However, identifying which lesions to biopsy remains a significant clinical challenge, particularly at early stages of disease. In this work, we present a volumetric quantitative oblique back-illumination microscopy (qOBM) probe, a highly maneuverable, handheld imaging system capable of providing high-resolution, 3D visualization of the skin microstructure. We show the probe is capable of visualizing the dynamic, layered microstructure of the epidermis and the top of the dermis across all Fitzpatrick skin types in human skin in vivo. The easy maneuverability of the probe is highlighted by imaging anatomically challenging areas typically hard to reach for bulkier systems. Finally, we present additional case studies in ex vivo murine models and in vivo human nevi that further illustrate the potential clinical applications of the volumetric handheld probe. These results establish a low-cost, easy to use, high-resolution, compact system that combines the strengths of its predecessors -- the excellent maneuverability of the widely-used dermatoscopes and 3D, high-resolution imaging of prior bulkier systems -- to improve screening of dermatological lesions at the bedside.