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Two main bottlenecks prevent time-domain diffuse optics instruments to reach their maximum performances, namely the limited light harvesting capability of the detection chain and the bounded data throughput of the timing electronics. In this work, for the first time to our knowledge, we overcome both those limitations using a probe-hosted large area silicon photomultiplier detector coupled to high-throughput timing electronics. The system performances were assessed based on international protocols for diffuse optical imagers showing better figures with respect to a state-of-the-art device. As a first step towards applications, proof-of-principle in-vivo brain activation measurements demonstrated superior signal-to-noise ratio as compared to current technologies.

By use of low-temperature (20 K) confocal microscopy, fluorescence spectra of isolated single CdS nanocrystals have been recorded. The narrowest measured line width of the main fluorescence band has been determined to be about 5 meV at the lowest excitation intensities. At higher intensities at least three additional observations are made:  the main fluorescence band broadens, a line to the blue of the main peak evolves, and a peak due to the coupling to a longitudinal optical phonon appears.

Time-resolved confocal microscopy is well established to image spectral and spatial properties of samples in biology and material science. Atomic Force Microscopy (AFM) in addition enables to investigate properties which are not optically addressable or are hidden by the diffraction limited optical resolution. We present a straight forward combination of single molecule sensitive time-resolved confocal microscopy with different commercially available AFMs. Besides an extra of information about for example a cell surface, the AFM tip can also be used to manipulate the sample on a nanometer scale down to the single molecule level.

The combination of simultaneous spectral detection together with Fluorescence Lifetime Imaging (sFLIM) allows collecting the complete information inherent to the fluorescence signal. Their fingerprint of lifetime and spectral properties identify the fluorescent labels unambiguously. Multiple labels can be investigated in parallel and separated from inherent auto-fluorescence of the sample. In addition, spectral FLIM FRET has the prospect to allow simultaneous detection of multiple FRET signals with quantitative analysis of FRET-efficiency and degree of binding. Spectral FLIM measurements generate huge amount of data. Suitable analysis procedures must be found to condense the inherent information to answer the scientific questions in a straightforward way. Different analysis techniques have been evaluated for a diversity of applications as multiplex labeling, quantitative determination of environmental parameters and distance measurements via FLIM FRET. In order to reach highest sensitivity in single photon detection, different detector types are investigated and developed. SPAD arrays equipped with micro-lenses promise superior detection efficiency while the integration of a spectrograph with a PMT array is easier to realize and allows for a higher number of detection channels. High detection speed can be realized through parallel TCSPC channels. In order to overcome the limits of the USB 2.0 interface, new interface solutions have been realized for the multichannel TCSPC unit HydraHarp 400.

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