Fundamental precision bounds for three-dimensional optical localization microscopy with Poisson statistics

Abstract

Point source localization is a problem of persistent interest in optical imaging. In particular, a number of widely used biological microscopy techniques rely on precise three-dimensional localization of single fluorophores. As emitter depth localization is more challenging than lateral localization, considerable effort has been spent on engineering the response of the microscope in a way that reveals increased depth information. Here we consider the theoretical limits of such approaches by deriving the quantum Cram\'{e}r-Rao bound (QCRB). We show that existing methods for depth localization with single-objective detection exceed the QCRB by a factor $>\sqrt{2}$, and propose an interferometer arrangement that approaches the bound. We also show that for detection with two opposed objectives, established interferometric measurement techniques globally reach the QCRB.