Cavity-Enhanced Microscopy (CEMIC)

Intra-Cavity Image
Intracavity phase-contrast images: a) of a 100 nm thick step, note that the step is visible both in absorption and as a displacement of the fringes (indicated by dotted white line) between the top and bottom of the image; b) of an irregular transparent bio film with a maximum thickness of 1.4 μm. The width of both images is about 1 mm.

Background: Much of the knowledge that we have from our world stems from the analysis of images. Using optics and cameras, we can map how much light a sample absorbs or how by how quickly the light propagates in a medium (both together are described by the complex refractive index). From these spectral properties, we can then deduce the chemical compo- sition and/or physical makeup of the sample. Examples are many and wide-reaching, from astronomy to trace chemicals in the atmosphere, from monolayers on semiconductor sur- faces, to biological cells and their inner workings. Absorption or refractive index measurements are used in cancer detection, as cell morphology and growth in cell biology, malaria and anaemia disease diagnosis in haematology, and cancer cell and circulating tumour cell detection in pathology.

The main objective of CEMIC is to develop a novel ultra-sensitive method to image extremely small spatial variations in refractive index or tiny absorptions and scattering losses. This will result in a novel label-free non-phototoxic microscopy method, which is capable of observing the inner workings of lining cells. The second objective is to apply this novel method to imag- ing the organelles of live cells without having to label them first.

The breakthrough of CEMIC is that we have found a novel cavity configuration using specially shaped mirrors, which — by allowing the light to pass many times through the sample – en- hances any tiny changes in refractive index or absorption and scattering. The special shape of the mirrors preserves the image inside the cavity during an unlimited number of round tripsand allows this image to be transferred to a camera without requiring any additional compu- tation. This will result in a very high-resolution optical microscope, which is capable of measur- ing directly and simultaneously extremely small absorptions and phase shifts due to miniscule differences in refractive index. This will enable to us for example to directly image the orga- nelles of cells using their refractive index and/or very small absorptions.

This will hopefully represent a step-change in optical microscopy since there is currently no method available that provides high spatial resolution and simultaneously extremely high sensitivity in phase and absorption.