Solution-based single-molecule fluorescence spectroscopy is a powerful
experimental tool with applications in cell biology, biochemistry and biophysics. The
basic feature of this technique is to excite and collect light from a very small volume
and work in a low concentration regime resulting in rare burst-like events corresponding
to the transit of a single molecule. Detecting photon bursts is a challenging task: the
small number of emitted photons in each burst calls for high detector sensitivity. Bursts
are very brief, requiring detectors with fast response time and capable of sustaining high
count rates. Finally, many bursts need to be accumulated to achieve proper statistical
accuracy, resulting in long measurement time unless parallelization strategies are
implemented to speed up data acquisition. In this paper we will show that silicon
single-photon avalanche diodes (SPADs) best meet the needs of single-molecule detection.
We will review the key SPAD parameters and highlight the issues to be addressed in their
design, fabrication and operation. After surveying the state-of-the-art SPAD technologies,
we will describe our recent progress towards increasing the throughput of single-molecule
fluorescence spectroscopy in solution using parallel arrays of SPADs. The potential of
this approach is illustrated with single-molecule Förster resonance energy
transfer measurements.