Figure 8.

Microfluidic tools and operations are used to enhance observation and analysis of interactions involving single nucleic acid molecules. Stable concentration gradients, generated by diffusion across flow streams in a microchannel, enable analysis of protein/DNA interactions on a DNA curtain over a continuous range of protein concentrations in a single experiment (picture reprinted from ref. ¹⁹⁸ copyright 2013, with permission from Elsevier). Rapid mixing at a channel constriction coupled with convective flow can be used to observe fast kinetics through spatial separation (figure reprinted by permission from Macmillan Publishers Ltd: Nature Protocols ref. ²⁰³, copyright 2013). Rapid pump mixing can also be used for high throughput combinatorial screening separation (figure reprinted by permission from Macmillan Publishers Ltd: Nature Methods ref.²⁰⁴, copyright 2011). Microchannel constrictions can also be used to enhance detection efficiency by matching the microfluidic chamber dimensions to the optical detection volume. This has been demonstrated in both z-dimension with compression of channel height (figure reprinted by permission from Macmillan Publishers Ltd: Nature Methods ref. ²⁰⁵, copyright 2014), and x-dimension through microfabricated cross-section constriction (figure reproduced from ref. ²⁰⁶).