Interferometric Mass Photometry at the Quantum Limit of Sensitivity

We present an innovative optical imaging system for measuring parameters of a small particle such as a macromolecule or nanoparticle at the quantum limit of sensitivity. In comparison to the conventional confocal interferometric scattering (iSCAT) approach, our setup adds a second arm to form a Michelson interferometer that allows us to tune a relative phase. We evaluate the quantum Cramér-Rao bound (QCRB) for different quantum states, including single-mode coherent states, multi-frequency coherent states, and phase-averaged coherent states. Our results show that the proposed setup can achieve the QCRB of sensitivity and outperform iSCAT for all considered quantum states for mass and phase estimation of a particle.