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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.

We report on phase-dispersion optical tomography, a new imaging technique based on phase measurements using low-coherence interferometry. The technique simultaneously probes the target with fundamental and second-harmonic light and interferometrically measures the relative phase shift of the backscattered light fields. This phase change can arise either from reflection at an interface within a sample or from bulk refraction. We show that this highly sensitive (~5 degrees ) phase technique can complement optical coherence tomography, which measures electric field amplitude, by revealing otherwise undetectable dispersive variations in the sample.

We present a novel interferometer for measuring angular distributions of backscattered light. The new system exploits a low-coherence source in a modified Michelson interferometer to provide depth resolution, as in optical coherence tomography, but includes an imaging system that permits the angle of the reference field to be varied in the detector plane by simple translation of an optical element. We employ this system to examine the angular distribution of light scattered by polystyrene microspheres. The measured data indicate that size information can be recovered from angular-scattering distributions and that the coherence length of the source influences the applicability of Mie theory.

Ballistic light, i.e., radiation that propagates undeflected through a turbid medium, undergoes a small change in phase velocity and exhibits unusual dispersion because of its wave nature. We use a novel highly sensitive differential phase optical interferometer to study these previously unmeasurable phenomena. We find that ballistic propagation can be classified into three regimes based on the wavelength-to-size ratio. In the regime in which the scatterer size is comparable with the wavelength, there is an anomalous phase-velocity increase as a result of adding scatterers of higher refractive index. We also observe an anomaly in the relative phase velocity, where red light is slowed more than blue light even though the added scatterers are made of material with normal dispersion.

We describe a new scanning microscopy technique, phase-dispersion microscopy (PDM). The technique is based on measuring the phase difference between the fundamental and the second-harmonic light in a novel interferometer. PDM is highly sensitive to subtle refractive-index differences that are due to dispersion (differential optical path sensitivity, 5 nm). We apply PDM to measure minute amounts of DNA in solution and to study biological tissue sections. We demonstrate that PDM performs better than conventional phase-contrast microscopy in imaging dispersive and weakly scattering samples.

We present a method based on photon migration of extracting intrinsic fluorescence spectra from turbid media, using concomitantly measured fluorescence and reflectance. Intrinsic fluorescence is defined as fluorescence that is due only to fluorophores, without interference from the absorbers and scatterers that are present. Application to fluorescence spectra taken with tissue phantoms and human mucosal tissues demonstrates excellent agreement in both spectral line shape and intensity between the extracted and the directly measured intrinsic fluorescence spectra.

We present a multichannel detection technique for three-dimensional imaging of objects embedded in turbid media by using time-resolved fluorescence. By using a streak camera, we can obtain the experimental data in a single measurement. The data, analyzed by means of a triangulation algorithm, provide accurate localization of a fluorescent object for path lengths of up to 120 scattering mean free paths. The results demonstrate the feasibility of combining fluorescence spectroscopy with time-resolved optical tomography for localizing and identifying embedded objects.