Modulated Doppler phase microscopy for dynamic imaging with subcellular resolution.

Understanding cell-nanoparticle interaction is crucial for advancing nanoparticle-based medicine. Doppler imaging techniques, such as Doppler Optical Coherence Tomography (DOCT), have been widely used for dynamic imaging. However, conventional DOCT performs fast scanning along the depth direction and requires spatial domain oversampling, limiting its spatial and temporal resolution for motion imaging in the en face plane. To achieve high-resolution, high-sensitivity motion imaging, we developed the modulated Doppler phase microscopy (M-DPM) technology. M-DPM utilizes an innovative optical computation strategy to compute the Fourier transform of the interferometric spectrum, imposes temporal modulation to the interferometric signal, and applies time-domain filtering to the 3D data cube (x-y-t) to extract phase-resolved signals for high-resolution Doppler imaging in the en face plane. We validated the performance of M-DPM using samples that exhibited global motion. We further demonstrated M-DPM's capability to detect spatially resolved motion by imaging different magnetic particles interacting with cultured cells.