Optical phase changes induced by transient perturbations provide a sensitive measure of material properties. One such measure is associated with the change in refractive index with temperature. Another - with thermal expansion. We demonstrate the high sensitivity and speed of such methods using two interferometric techniques: Quantitative Phase Imaging (QPI) in transmission, and phase-resolved Optical Coherence Tomography (OCT) in reflection. Camera frame rate in QPI varied from 10 to 50 kHz, exposure from 1 to 10 µs, and heating pulse – from 0.02 to 1 ms in duration. The phase-stabilized swept-source OCT was operating at 100 kHz repetition rate. Shot-noise limited QPI can resolve energy deposition of about 3.4 mJ/cm^2 in a single pulse, which corresponds to 0.8 ℃ temperature rise in a single cell. OCT can detect deposition of 24 mJ/cm^2 energy between two scattering interfaces producing about 30 dB SNR signals and 4.7 mJ/cm^2 with 45 dB. Finite element modeling of the phase changes in materials heated by laser and by electric current matched the experimental results very well. These techniques can be used for mapping absorption coefficients, electric current density, doping depth in semiconductors, and many other properties. Integration of the phase changes along the penetrating beam path helps increase sensitivity and reveals the size of the hidden objects by looking at the signal relaxation time. These methods may enable multiple applications, ranging from temperature control in retinal laser therapy and in gene expression to characterization of semiconductor devices.
Beating heart cells, cardiomyocytes, are used in drug testing and have the potential for regenerative medicine. Currently their classification into atrial, nodal and ventricular subtypes is performed using destructive and tedious patch clamp measurements. We present a method for analyzing cardiomyocyte contraction cycles using diffraction phase microscopy, a fast quantitative phase imaging method based on off-axis common-path interferometry. The phase variation during the beating cycle can exceed 300 mrad in the most active regions, and is about 40 mrad on average. The phase noise is about 2 mrad per pixel, and it can be reduced by temporal averaging over multiple frames and spatial averaging over the cell. With a maximum acquisition rate exceeding 25,000 fps and with approximately 100 fps required for the characterization of cardiomyocyte motion, 250 frames can be averaged per step, reducing the temporally white noise by a factor of 16. Additional improvements can be obtained by averaging over multiple contraction cycles. Averaging over space does not reduce noise to the same extent due to low-pass spatial filtering during the phase extraction procedure. Low-pass filtering by the pinhole in the reference arm, resulting in high-pass filtering of the image, and low-pass filtering during the phase reconstruction highlight the dynamics of redistribution of dry mass within the cell during a beat cycle. Quantitative phase imaging is a promising approach for rapid, non-invasive, high-throughput characterization of human stem cell-derived cardiomyocytes in culture, with applications to modeling of diseases with patients' specific genes, drug development, and repair of damaged heart tissue.
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