Method for SOFI-based spatial super-resolution in nanosensing with blinking emitters

We propose a method of spatial resolution enhancement in metrology (thermometry, magnetometry, pH estimation, and similar methods) with blinking fluorescent nanosensors by combining sensing with super-resolution optical fluctuation imaging (SOFI). By utilizing the idea of quantum super-resolution imaging by photon statistics (QSIPS), the applicability of the proposed methodology is extended to low-brightness regime. Efficiency of the approach is demonstrated by numerical simulations performed for several model configurations, representing step-like and continuous variation of the sensed parameter, high and low brightness regimes, 1- and 2-dimensional structures. The 2nd and 4th 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 being complemented with the developed image analysis technique could be utilized routinely in the life science sector for recognizing the local changes in the spectral response of blinking fluorophores, e.g. delivered targetly to the specific cell or even organelle. It is extremely useful for the local measurements of living cells' physical parameters changes due to applying any external "forces", including disease effect, aging, healing, or response to the treatment.