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 Cramér-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.

Updated to include Supplemental Material as ancillary file