Molecular contrast on phase-contrast microscope

Abstract

An optical microscope enables image-based findings and diagnosis on microscopic targets, which is indispensable in many scientific, industrial and medical settings. A standard benchtop microscope platform, equipped with e.g., bright-field and phase-contrast modes, is of importance and convenience for various users because the wide-field and label-free properties allow for morphological imaging without the need for specific sample preparation. However, these microscopes never have capability of acquiring molecular contrast in a label-free manner. Here, we develop a simple add-on optical unit, comprising of an amplitude-modulated mid-infrared semiconductor laser, that is attached to a standard microscope platform to deliver the additional molecular contrast of the specimen on top of its conventional microscopic image, based on the principle of photothermal effect. We attach this unit, termed molecular-contrast unit, to a standard phase-contrast microscope, and demonstrate high-speed label-free molecular-contrast phase-contrast imaging of silica-polystyrene microbeads mixture and molecular-vibrational spectroscopic imaging of HeLa cells. Our simple molecular-contrast unit can empower existing standard microscopes and deliver a convenient accessibility to the molecular world.