Common-path interferometer for digital holographic Doppler spectroscopy of living biological tissues

Significance: Common-path interferometers have the advantage of producing ultrastable interferometric fringes compared with conventional interferometers, such as Michelson or Mach–Zehnder that are sensitive to environmental instabilities. Isolating interferometric measurements from mechanical disturbances is important in biodynamic imaging because Doppler spectroscopy of intracellular dynamics requires extreme stability for phase-sensitive interferometric detection to capture fluctuation frequencies down to 10 mHz. Aim: The aim of this study was to demonstrate that Doppler spectra produced from a common-path interferometer using a grating and a spatial filter (SF) are comparable to, and more stable than, spectra from conventional biodynamic imaging. Approach: A common-path interferometer using a holographic diffraction grating and an SF was employed with a low-coherence source. Simulations evaluated the spatial resolution. DLD-1 (human colon adenocarcinoma) spheroids were used as living target tissue samples. Power spectra under external vibrations and drug-response spectrograms were compared between common-path and Fourier-domain holographic systems. Results: The common-path holography configuration shows enhanced interferometric stability against mechanical vibrations through common-mode rejection while maintaining sensitivity to Doppler frequency fluctuations caused by intracellular motions. Conclusions: A common-path interferometer using a grating and an SF can provide enhanced interferometric stability in tissue-dynamics spectroscopy for drug screening assays.