Theoretical minimum uncertainty of single-molecule localizations using a single-photon avalanche diode array

Journal article (2021)

Authors

D. Kalisvaart Team Carlas Smith - Mechanical, Maritime and Materials Engineering
S. Hung Team Carlas Smith - Mechanical, Maritime and Materials Engineering
J.P. Cnossen Team Carlas Smith - Mechanical, Maritime and Materials Engineering
D. Fan Team Carlas Smith - Mechanical, Maritime and Materials Engineering
Paul Mos EPFL Neuchâtel
Arin C. Ulku EPFL Neuchâtel
Claudio Bruschini EPFL Neuchâtel
C.S. Smith Team Carlas Smith - Mechanical, Maritime and Materials Engineering
Research Group
Team Carlas Smith (Mechanical, Maritime and Materials Engineering) (TU Delft)
Copyright: © 2021 Quint Houwink, D. Kalisvaart, S. Hung, J.P. Cnossen, D. Fan, Paul Mos, Arin Can Ülkü, Claudio Bruschini, E. Charbon-Iwasaki-Charbon, C.S. Smith
DOI: https://doi.org/10.1364/OE.439340
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Published Date

2021

Language

English

Reuse Rights

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Faculty

Mechanical, Maritime and Materials Engineering

Department

Delft Center for Systems and Control

Research Group

Team Carlas Smith

Abstract

Single-photon avalanche diode (SPAD) arrays can be used for single-molecule localization microscopy (SMLM) because of their high frame rate and lack of readout noise. SPAD arrays have a binary frame output, which means photon arrivals should be described as a binomial process rather than a Poissonian process. Consequentially, the theoretical minimum uncertainty of the localizations is not accurately predicted by the Poissonian Cramér-Rao lower bound (CRLB). Here, we derive a binomial CRLB and benchmark it using simulated and experimental data. We show that if the expected photon count is larger than one for all pixels within one standard deviation of a Gaussian point spread function, the binomial CRLB gives a 46% higher theoretical uncertainty than the Poissonian CRLB. For typical SMLM photon fluxes, where no saturation occurs, the binomial CRLB predicts the same uncertainty as the Poissonian CRLB. Therefore, the binomial CRLB can be used to predict and benchmark localization uncertainty for SMLM with SPAD arrays for all practical emitter intensities.

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