Label free optical transmission tomography for biosystems: Intracellular structures and dynamics

TL;DR

This paper introduces a novel label-free optical tomography method, FF-OTT, capable of revealing intracellular structures and dynamics in living cells by measuring forward scattering signals and metabolic activity.

Contribution

The development of a new full-field optical transmission tomography technique that uses common-path interferometry and phase modulation to image intracellular structures without labels.

Findings

Successfully imaged single-cell diatoms and biological samples.

Revealed metabolic dynamic contrast through intracellular motion detection.

Demonstrated robustness and ease of implementation of the method.

Abstract

There is an increasing need for label free methods that could reveal intracellular structures and dynamics. In this context, we develop a new optical tomography method working in transmission - Full-field optical transmission tomography (FF-OTT). The method can measure the forward scattering signals and reveal the metabolic time-dependent signals in living cells. FF-OTT is a common path interferometer taking advantage of the Gouy phase shift - a {\pi} phase shift that the light wave experiences around the focus. By modulating position of the focus one can alter the phase of the scattered light. Demodulation of images with different phases rejects the background and enhances the light from the depth-of-focus, thus producing an optical section. We test FF-OTT by imaging single-cell diatoms and ex vivo biological samples. In fresh samples, we show that the intracellular motions create visible intensity fluctuations in FF-OTT so that the method is able to reveal a metabolic dynamic contrast. FF-OTT was found to be an efficient label free technique that can be readily implemented thanks to a robust common-path speckle-free interferometer design using an incoherent light source.