Precise mass measurement of individual macromolecules and nanoparticles is essential for advancing biophysics and nanotechnology. Mass photometry achieves this by analyzing light scattered from particles, where the signal scales with particle size. A widely used approach, interferometric scattering microscopy (iSCAT), enhances this signal through interference, but uncontrolled phase relationships limit its precision. We present a novel optical system that integrates iSCAT into a Michelson interferometer, allowing active phase tuning. This design enables measurements that approach the quantum Cramér-Rao bound (the ultimate limit of sensitivity) surpassing conventional iSCAT in both mass estimation and phase resolved scattering. Our results demonstrate a pathway toward quantum-limited optical sensing for single-particle analysis.

References

[1] Fabian Müller, Emre Köse, Alfred J. Meixner, Erik Schäffer, and Daniel Braun, Phys. Rev. A 111, 043501 (2025)