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We report a highly sensitive means of measuring cellular dynamics with a novel interferometer that can measure motional phase changes. The system is based on a modified Michelson interferometer with a composite laser beam of 1550-nm low-coherence light and 775-nm CW light. The sample is prepared on a coverslip that is highly reflective at 775 nm. By referencing the heterodyne phase of the 1550-nm light reflected from the sample to that of the 775-nm light reflected from the coverslip, small motions in the sample are detected, and motional artifacts from vibrations in the interferometer are completely eliminated. We demonstrate that the system is sensitive to motions as small as 3.6 nm and velocities as small as 1 nm/s. Using the instrument, we study transient volume changes of a few (approximately three) cells in a monolayer immersed in weakly hypotonic and hypertonic solutions.

Phase-referenced interferometer with subwavelength and subhertz sensitivity applied to the study of cell membrane dynamics