In this project, we will (click on the link to see a movie)

• construct prototypes of a next-generation fluorescence super-resolution microscopy platform for biomedical research and development, offering one order of magnitude higher spatial resolution than current state-of-the-art super-resolution microscopes.

• develop new single-photon detector arrays with enhanced sensitivity.

• develop a pulsed, narrow-linewidth, multi-line laser for cellular imaging based on label-free inelastic light scattering.

• integrate the developed lasers and detector arrays into the prototypes of the super- resolution microscopy platform, offering a broadened wavelength range for imaging, faster image acquisition, lower background, and allowing correlative super-resolution fluorescence and label-free imaging of cells.

• as a lead demonstration for this platform, resolve nanometer scale localization patterns of specific proteins in bacteria and host cells, providing overlaid morphological and chemical images of the bacteria, representing key information on the mechanisms underlying virulence and invasiveness of the bacteria.

With the developed microscope platform and by this lead application, we expect to take a decisive step towards better diagnostics, effective treatments and prevention of severe bacterial infections causing significant morbidity and mortality world-wide. We also expect that the ability to resolve nano-scale localization patterns in cells, correlated to their morphology and sub-cellular environments, will open new means to understand, diagnose and prevent other diseases. At the end of the project, we will therefore offer access to one of the developed microscope systems to biomedical researchers outside of the project, to promote this development and such applications.

Background and Objectives

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