Sequencing by Avidity Enables High Accuracy With Low Reagent Consumption

Abstract We present a novel sequencing chemistry implemented as part of the AVITI system. Relying on the proximal DNA binding sites created through DNA amplification on a solid support, avidity sequencing uses multivalent nucleotide ligands on dye-labeled cores to simultaneously form polymerase-polymer nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides by 100x and yield a negligible dissociation rate. We demonstrate the use of avidites within a novel sequencing technology that surpasses Q40 accuracy and enables a diversity of applications that include single cell RNA-seq and whole human genome sequencing.