A dual-modality fluorescence correlation microscope with single molecule sensitivity for the study of soft and biological systems

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We propose to build a microscope allowing to acquire background-free fluorescence images at a very high frame rate, while still maintaining low noise and high sensitivity. This microscope will integrate two different methods for suppressing out-of-focus background, each useful in different situations: 1) lightsheet illumination to image deep within cells or tissues and 2) convex lens-induced confinement for soft media. This instrument will allow applying single particle and correlation techniques to the study of soft and biological systems. Specific applications will include the study of anomalous diffusion in complex media, and the spatio-temporal trafficking and activity of morphogens in the early fly embryo. By pushing the limit of what is currently possible to observe in these systems in terms of dynamics, we will gain access to yet unobserved phenomena. The process of building a state-of-the-art instrument will give trainees in my group the opportunity to gain a first-hand and in-depth knowledge in biophotonics, furthering their employment perspectives.