Table 1.

High-throughput single-molecule methods

Approach	Applications	Comments	References
smFRET	Observing protein conformations, protein-nucleic acid binding and short-distance translocation	Used for short-distance (1–5nm) interactions	[15–19]
Microfluidic DNA Curtains	Observing micron-length protein-DNA interactions	1000’s of molecules in single field-of-view, defined DNA orientation	[26,27,32]
Random Surface Tethering		Tens of molecules in single field-of-view. DNA orientation unknown.	[1–3]
DNA Tightropes		Tens of molecules in single field-of-view. Tension and orientation unknown	[9,92]
Tethered Particle Motion	Monitors changes in DNA length, which can be used as an indirect probe of enzyme activity.	100’s of molecules in single field-of-view	[20]
Multiplexed Magnetic Tweezers	Force spectroscopy of protein-DNA interactions. Torsional control possible.	10’s to 100’s of molecules in single field-of-view	[70,71,93]
Multiplexed Optical Tweezers	Observing mechanical properties of DNA and protein-DNA interactions.	Offers 3D control of captured particles	[78,79]
Centrifugal Force Microscopy	Applies uniform centrifugal force on all molecules within an orbiting flowcell.	Imaging must occur out on a rotating stage.	[65]