Sequencing Template Runway Regions for Reliable Initial Base Reads

The patent applies preliminary action by incorporating a runway region into the nucleic acid template before the actual sequencing begins. This runway region allows the polymerase enzyme to traverse a known sequence first, which delays the sequencing of the insert region until the reaction has equilibrated. This preliminary traversal ensures that when the polymerase reaches the insert region, the sequencing conditions are optimal and reliable, thus resolving the contradiction between speed and reliability.

The patent applies segmentation by dividing the nucleic acid template into distinct functional regions: a runway region with known sequence and an insert region with the sequence of interest. The runway region is specifically designed to be traversed first to allow reaction equilibration, while the insert region contains the actual target sequence. This segmentation allows the system to sacrifice sequencing of a small portion (the runway) to ensure reliable sequencing of the important insert region, thereby managing the time-loss trade-off effectively.

The patent uses the runway region as an intermediary element between the primer binding site and the insert region. This intermediary runway sequence serves as a buffer that allows the sequencing reaction to establish proper kinetics and signal detection before the polymerase reaches the insert region. The known sequence of the runway acts as a mediator that ensures accurate base calling by providing a stable reference framework, thus improving measurement precision without significantly impacting overall productivity.