The workflow eliminates separate qPCR quantification and manual normalization steps, preparing sequencing-ready libraries in approximately 2.5 hours.
Watchmaker Genomics has introduced Expanse Whole Genome Sequencing, a PCR-free workflow that integrates library preparation and normalization into a single process. The company announced the technology and opened an early access program ahead of a preview at the American Society of Human Genetics (ASHG) 2026 Annual Meeting.
While PCR-free whole genome sequencing (WGS) provides data quality advantages, scaling the method has historically been hindered by the need for labor-intensive qPCR quantification and manual dilution steps to achieve uniform coverage depth. In addition, conventional approaches frequently face barriers including high DNA input requirements and limited compatibility with challenging sample types.
Eliminating qPCR and Manual Normalization
Expanse addresses these operational bottlenecks by integrating the company’s EquiPlex Cas9-mediated normalization technology directly into an automatable library preparation workflow. By removing the need for manual normalization and qPCR assays, the method is designed to provide balanced library representation alongside more uniform sequencing coverage.
Beyond simplifying workflow steps, the Cas9-mediated normalization mechanism enriches for sequencing-competent molecules, while the library preparation chemistry maintains consistent insert sizes across variable DNA inputs. Together, these features improve flow cell utilization and overall sequencing efficiency.
The integrated protocol converts sample DNA into a normalized, sequencing-ready pool in approximately 2.5 hours, accommodates inputs as low as 75 ng, and supports difficult sample types, including formalin-fixed paraffin-embedded (FFPE) tissue.
“Sequencing capacity has advanced dramatically, but the workflows used to prepare samples haven’t kept pace,” says Trey Foskett, CEO of Watchmaker Genomics, in a release. “With Expanse, we’re not simply making individual steps faster. We’re fundamentally changing how libraries are prepared and normalized to make high-quality PCR-free WGS more practical at scale.”
Technology Origins and Performance Data
The workflow builds on technology Watchmaker established earlier in the year. In February, the company entered into a licensing agreement with Caribou Biosciences to utilize CRISPR-Cas9 as a molecular binding tool for normalization rather than as a cutting enzyme. That mechanism previously supported the launch of the EquiPlex Normalization Kit at ESHG 2026, which targeted applications such as PCR-free cell-free DNA sequencing. Expanse incorporates this normalization chemistry directly into the core WGS workflow.
Watchmaker presented initial performance metrics for the platform at ASHG 2026. The data evaluate coverage uniformity, sequencing efficiency, and variant-calling performance across reference DNA, blood, saliva, and FFPE samples.
The company is currently accepting select laboratories into its early access program prior to full commercial release.
