abstract |
A system for determining nucleic acid sequences, including (a) an array of nucleic acid features; (b) a fluidic apparatus configured to deliver sequencing reagents, including polymerases and nucleotides, to the array; (c) a detector configured to obtain pre-equilibrium kinetic measurements from the array at a resolution that distinguishes individual nucleic acid features; (d) a control module having instructions for (i) directing the fluidic apparatus to deliver the sequencing reagents to the array, and (ii) directing the detection apparatus to obtain the kinetic measurements; and (e) an analysis module having instructions for (i) processing the kinetic measurements to determine binding of the polymerase molecules to the nucleic acid features at several pre-equilibrium time points, thereby determining a transient state of the polymerase molecules at the nucleic acid features, and (ii) identifying nucleic acid features that correctly incorporate the nucleotide molecules based on the transient state of the polymerase molecules. |