Towards digital photon counting cameras for single-molecule optical nanoscopy

Abstract

Background: Optical nanoscopy based on separation of single molecules by stochastic switching and subsequent localization allows surpassing the diffraction limit of light. The growing pursuit towards live-cell imaging using nanoscopy demands advancements in both science and technology. Results: In this article, we provide an overview of the technological advancements in the development of scientific cameras used for nanoscopy. We discuss the prospects of novel digital photon counting cameras based on a single-photon avalanche diode (SPAD) array camera for optical nanoscopy. Numerical simulations are used to evaluate and compare different scientific cameras for their performance towards single-molecule identification and localization. Conclusion: A SPAD array camera with single-photon sensitivity and zero read-out noise allows for the detection of extremely weak signals at ultra-fast imaging speeds. With temporal resolution in the order of micro-seconds, a SPAD array camera offers great potential for live-cell imaging with super-resolution. © 2014 Krishnaswami et al.