Table 2.

Strategies to break the “concentration barrier”

Approach	Applicable to	Comments	References
Confinement in vesicles	smFRET	Enzymes must survive vesicle encapsulation procedure	[41–45]
Confinement in microfluidic channels	smFRET	Microfabrication required	[46]
Convex lens-induced confinement	Long DNA molecules	Simple implementation	[47]
Zero-mode waveguides	smFRET, long DNA molecules	Nanolithography required	[48–50]
Fluorophore photoactivation	smFRET, particle tracking	Used in concert with TIRF microscopy	[54]
Plasmonic nanostructures	smFRET	Nanolithography required	[51,52]