B ackscattering interferometry (BSI), which uses a simple optical train comprising a HeeNe laser, a microfluidic channel, and a position sensor, has now enabled the measurement of both tethered and freesolution, label-free, molecular interactions within just nanoliters of sample. The simple macro-to-micro interface allows for a highly efficient assay work flow, which has been used to interrogate molecular binding interactions between proteins, ions and protein, and small molecules and proteins, with a high dynamic range of dissociation constants (K D ) and unmatched sensitivity. With this technique, the equilibrium K D for several different binding partners was determined, typically using just picomoleemicromole quantities of the binding pair at physiologically relevant concentrations.