Ultrasensitive detection of nanometer sized metal particles in living cells.

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The ability to visualize, track and quantify molecules and events directly inside living cells with high spatial and temporal resolution is essential for understanding biological systems. Gold nano-particles are very attractive as optical labels because they offer unlimited observation time and can be easily linked to (bio-)molecules via well-established procedures. The challenge undertaken in this project is to detect and follow metal nanoparticles smaller than 5 nm at ambient conditions directly inside a living cell with optical methods. The challenge in detecting small single nanoparticles lies in the fact that only a small fraction of the incident light will impinge on the particle leading to very weaks signals. We aim to detect these weak signals by amplifying the signal from the nanoparticle by interference with a strong optical reference. We will compare a method relying on photo-induced changes of the local refractive index of the environment of the particle to a method relying on the intrinsic scattering properties of the nano-particle. Combining these methods for detecting small metal nanoparticles in combination with the three-dimensional imaging ability of a confocal microscopy would result in a powerful detection system to monitor biochemical process inside living cells under biological relevant conditions on fast time-scales.