Quanta microscopy enables fluorescence imaging at the native bit-plane rate

Abstract

Live-cell fluorescence microscopy remains constrained by limited photon budgets and exposure-integrated detection, imposing a fundamental trade-off between temporal sampling and image quality. Here we present quanta microscopy (QM), an optical-computational framework that integrates high-speed single-photon acquisition with self-supervised spatiotemporal reconstruction. QM transforms highly sparse binary photon-detection maps, or bit planes, into multibit grayscale fluorescence image sequences, generating one output frame per bit plane at the native 50 kHz sensor cadence without temporal binning. We demonstrate QM across biological specimens spanning diverse spatial and temporal characteristics, including subcellular organelles with distinct morphologies, rapid contractile dynamics in beating hiPSC-derived cardiomyocytes, and electrically stimulated calcium-response transients in primary cortical neurons. By uniting quanta-level acquisition with data-driven image formation, QM broadens the scope of live-cell fluorescence microscopy for quantitative analysis of rapid cellular physiology under photon-limited conditions.