Aberration sensing in fluorescence microscopy using quantum correlations

Abstract

Widefield fluorescence microscopy is an essential biological imaging tool, yet its penetration depth is fundamentally restricted by tissue-induced aberrations. Correcting these requires precise characterization of the point spread function (PSF), but existing wavefront sensing techniques rely either on often-unavailable guide stars, or on computationally heavy indirect phase retrieval methods, that could struggle in low-contrast regions. Here, we show that the PSF can be mapped directly and non-invasively by exploiting quantum correlations between photons. Standard fluorophores inherently exhibit photon antibunching, effectively acting as sources of ``missing''photon pairs. By capturing these correlation statistics across a wide field of view using a single-photon avalanche diode (SPAD) array imager, we extract the local PSF autocorrelation directly from the fluorescence emission itself. This approach bypasses the limitations of classical intensity measurements, requiring no iterative or complex numerical optimization. We demonstrate widefield direct PSF retrieval in a second or less, paving the way for real-time operation. By translating quantum optical concepts to conventional fluorescent probes, this technique provides a robust, direct pathway to deep-tissue adaptive optics in life sciences.