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    SOFI-based spatial superresolution in nanosensing with blinking emitters

    Alexander Mikhalychev1,2,* and Alex Ulyanenkov2

    • 1Atomicus Sp. z o.o., Ul. Aleja Grunwaldzka 163, Gdansk, 80-266 Poland
    • 2Atomicus GmbH, Amalienbadstraße 41C, Karlsruhe, 76227, Germany

    • *Contact author: alexander.mikhalychev@atomicus-software.com

    Phys. Rev. Applied 26, 034073 – Published 30 September, 2026

    DOI: https://doi.org/10.1103/gh34-zt9d

    Abstract

    We propose a method of spatial resolution enhancement in metrology (thermometry, magnetometry, pH estimation, and similar methods) using blinking fluorescent nanosensors by combining sensing with superresolution optical fluctuation imaging. By utilizing the idea of quantum superresolution imaging by photon statistics, the applicability of the proposed methodology is extended to the low-brightness regime. The efficiency of the approach is demonstrated by numerical simulations performed for several model configurations, representing steplike and continuous variation of the sensed parameter, high- and low-brightness regimes, and one- and two-dimensional structures. The second- and fourth-order cumulant images provide improvement of the contrast and enable successful reconstruction of smaller features of the modeled parameter distribution relatively to the intensity-based approach. We believe that blinking fluorescent sensing agents, when complemented with the developed image analysis technique, could be routinely utilized in the life science sector to recognize the local changes in the spectral response of blinking fluorophores, such as those delivered targetly to a specific cell or even organelle. It is extremely useful for the local measurements of changes in living cells’ physical parameters due to applying any external “forces,” including disease effects, aging, healing, or response to treatment.

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