ISM-FLUX: single-step MINFLUX with an array detector

Abstract

Single-molecule localization based on the concept of MINFLUX allows for molecular resolution imaging and tracking. However, MINFLUX has a limited field-of-view and therefore requires a precise and photon-costly pre-localization step. We propose ISM-FLUX, a localization technique that combines structured illumination with structured detection. We show through simulations that replacing the point-detector with a small (e.g. 5 × 5 pixels) single-photon camera and sequentially exciting the sample with four spatially separated doughnut-shaped beams, a localization precision between 1 and 15 nm can be obtained over a field-of-view (FOV) of more than 800 nm with 100 photons. The large FOV, induced by the camera, makes the pre-localization step obsolete. We calculate the effect of different parameters, such as the position of the doughnut beams and the number of pixels, on the localization precision. We predict that the combination of a good localization precision and the experimental simplicity of ISM-FLUX will help the wide adoption of MINFLUX based microscopy.