Sequencing by Expansion: what’s next in NGS

The Evolution of Precision: The Journey to SBX

The history of genetic sequencing is a narrative of shrinking timelines and expanding possibilities. For decades, the scientific community operated under the constraints of traditional methods like Sanger sequencing, which, while revolutionary for its time, could only process one DNA fragment at a time. The completion of the Human Genome Project in 2003—a thirteen-year international effort—marked the end of one era and the beginning of another - NGS and the race for speed, scalability, and accessibility.

A Revolutionary Shift in Landscape

The emergence of Next-Generation Sequencing (NGS) fundamentally altered the genomic landscape. By enabling the simultaneous sequencing of millions of fragments—a process known as massively parallel sequencing—technology that once required decades of effort - transitioned into a task that could be completed in a single day. This shift moved the industry away from asking specific, narrow questions about single genes and toward a "hypothesis-free" approach, where researchers could sequence entire genomes or protein-coding regions to see the full picture of an organism’s genetic material.

Redefining the Approach: The Birth of SBX

Despite the massive leaps in NGS, spatial challenges and signal- to-noise limitations in technologies like traditional nanopore sequencing remained. This backdrop set the stage for a radical departure from conventional thinking: Sequencing by Expansion (SBX).

The core philosophy of SBX was born from a simple yet profound realization: to efficiently sequence DNA, the best approach might be to "not sequence DNA" directly. Instead of struggling to measure the compact, minute structures of a native DNA molecule, the vision was to biochemically convert that information into a larger, more easily measurable surrogate polymer. By converting DNA into an "Xpandomer" molecule, the technology rescaled the challenges of molecular measurement, enabling higher accuracy and incredibly high rates of speed. Today SBX opens a new chapter in the history of sequencing, moving beyond the limitations of the past to support the clinical research of the future.