Quantitative phase imaging with molecular vibrational sensitivity

TL;DR

This paper introduces a wide-field molecular-vibrational microscopy technique integrated with quantitative phase imaging, enabling chemical sensitivity and high-speed, label-free molecular imaging with minimal sample damage.

Contribution

It presents a novel mid-infrared photothermal QPI method that achieves spectroscopic performance comparable to traditional IR spectrometers and allows rapid, wide-field molecular imaging with low photodamage.

Findings

Achieves mid-infrared spectroscopic performance similar to conventional spectrometers.

Enables wide-field molecular imaging at 1 fps with 430 nm resolution.

Reduces photodamage by 2-3 orders of magnitude compared to existing methods.

Abstract

Quantitative phase imaging (QPI) quantifies the sample-specific optical-phase-delay enabling objective studies of optically-transparent specimens such as biological samples, but lacks chemical sensitivity limiting its application to morphology-based diagnosis. We present wide-field molecular-vibrational microscopy realized in the framework of QPI utilizing mid-infrared photothermal effect. Our technique provides mid-infrared spectroscopic performance comparable to that of a conventional infrared spectrometer in the molecular fingerprint region of 1,450 - 1,600 cm-1 and realizes wide-field molecular imaging of silica-polystyrene beads mixture over 100 {\mu}m x 100 {\mu}m area at 1 frame per second with the spatial resolution of 430 nm and 2 - 3 orders of magnitude lower fluence of ~10 pJ/{\mu}m2 compared to other high-speed label-free molecular imaging methods, reducing photodamages to the sample. With a high-energy mid-infrared pulse source, our technique could enable high-speed, label-free, simultaneous and in-situ acquisition of quantitative morphology and molecular-vibrational contrast, providing new insights for studies of optically-transparent complex dynamics.