Optophysiology and calorimetry based on quantitative phase imaging (Conference Presentation)

Abstract

Nanometer-scale movements of the cell membrane associated with changes in cell potential can reveal the underlying electrical activity. Using wide-field quantitative phase imaging, we observed deformations of up to 3 nm (0.9 mrad) during the action potential in spiking HEK cells, and about 0.3 nm in neurons. The time course of the optically-recorded action potential is similar to intracellular recordings based on patch clamp, while time derivative of the rising edge of the optical spike matches the timing and duration of the extracellular electrical recording. Sufficiently fast QPI may enable non-invasive and label-free monitoring of cellular physiology. Imaging of the optical phase changes induced by transient heating provides a sensitive measure of material properties associated with refractive index dependence on temperature and thermal expansion. Using fast (50 kHz) QPI, we demonstrate the shot-noise limited sensitivity of about 3.4 mJ/cm2 in a single pulse. Phase-resolved OCT can detect energy deposition of 4.7 mJ/cm2 between two scattering interfaces producing signals with about 45 dB SNR. Integration of the phase changes along the beam path helps increase temperature sensitivity during perturbation. For example, temperature rise of about 0.8 C can be detected in a single cell layer, while hundred times lower heating produces the same phase change in 100-fold thicker tissue layer. Time course of thermal relaxation in QPI can reveal the size and shape of the hidden objects. Methods based on fast phase imaging may enable multiple applications, ranging from temperature control in retinal laser therapy to subsurface characterization of semiconductor devices.