This single-molecule sequencing method allows a number of innovations that are not possible with bulk sequencing by synthesis (5, 8). Most of these are related to the principle of asynchronous synthesis; that is, because each template molecule is monitored individually, there is no need to keep each step of synthesis in phase. Thus, it is not necessary to drive each enzymatic incorporation step to completion. The principal benefit is that mis-incorporations are rare; their slow kinetics do not compete appreciably with the time to incorporate 80 to 90% of the correct base. A corollary is that this allows greater flexibility in the choice of reagents and synthesis chemistries, because the requirements on incorporation kinetics are relaxed. Asynchronicity is also used to facilitate reading of base-repeat sequences, homopolymers.