Exploiting DNA polymerase as a sequencing engine requires single molecule detection. DNA polymerization is a stochastic process, where intervals between incorporation events typically vary. Thus a population of polymerases even acting on the same template would quickly become out of phase with each other. Existing single molecule detection techniques are limited to low nanomolar concentrations to reduce the background fluorescence of other nucleotides in solution. At higher concentrations, hundreds or thousands of labeled molecules flood the detection volumes of these microscope systems (Figure 1). This creates a high background noise level, against which it is not possible to detect individual fluorophores. However, polymerases require this high concentration level, without which the speed, accuracy, and processivity of the enzyme all suffer.   1 | 2 | 3 | 4 next »