A DNA sequencing technology that combines speed with high sensitivity is reported online this week in Nature Methods.
High-throughput sequencing has contributed to enormous advances in biology and medicine, but there is still room for improvement. Current methods emphasize either speed, or high capacity and sensitivity.
Sunney Xie and colleagues now combine all of the above in a strategy they call fluorogenic sequencing. The authors trap the target DNA to be sequenced in microwells arranged in a microfluidic device. They then serially add the four nucleotides, each labeled with the same dye that is not fluorescent as long as it is part of the nucleotide. If the nucleotide is incorporated into the growing DNA strand, the dye is cleaved and starts to fluoresce making it easy to detect.
Although still at the proof-of-principle stage, fluorogenic sequencing shows many promising features: its capacity can be scaled up by including more microwells in the microfluidic platform, its speed can be increased by using faster fluorescence scanning techniques, and its cost can be lowered by reducing the microwell volume.