Single molecule FRET measurements are typically performed on fluorescence microscopes, either using wide field or confocal geometries.
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Recently, the technique has been expanded by the development of confocal microscopy, which allows for the imaging and testing of live tissue samples with techniques such as Second-Harmonic Generation (SHG) and Multi-Photon Fluorescence Imaging.
Fluorescence signal is detected either using ultra sensitive CCD or CMOS cameras for wide field microscopy or avalanche photodiodes for confocal microscopy.
A long-term, concurrent confocal microscopy and electrophysiology investigation conducted on cortical rat in-vitro neural networks (age > 3 weeks in-vitro) growing on Multi Electrode Arrays examined the correlation between network activity levels and changes in the sizes of individual synapses.