Single-Cell Genomics By Digital Microfluidics

Single-cell whole-genome sequencing (WGS) is essential for identifying dynamic intercellular DNA changes. Single-cell genomics sample preparation technologies are complex, expensive, and plagued by high amplification bias and errors.

The researchers describe Digital-WGS, a sample preparation platform that automates high-performance single-cell WGS with digital microfluidics. They use a wetted hydrodynamic structure to provide high single-cell capture efficiency for any number and type of cells.

The digital control of droplets in a closed hydrophobic interface allows for the complete removal of exogenous DNA, adequate cell lysis, and lossless amplicon recovery, with a low coefficient of variation and high coverage at multiple scales. Single-cell genomics variations profiling detects copy number variants with the smallest bin of 150 kb and single-nucleotide variants with an allele dropout rate of 5.2%, holding great promise for broader single-cell genomics applications.

Single-cell genomics has enabled the investigation of genomic variations of numerous biological processes at the single-cell level by revealing genomic heterogeneity hidden in conventional bulk characterization. Single-cell genomic sequencing technology is widely used to resolve early embryonic development, tumor heterogeneity, and neural somatic mosaicism. It is especially important in the case of highly valued and rare samples, such as prenatal testing samples and circulating tumor cells. However, single-cell genomics has relied on whole-genome amplification (WGA) to generate enough replicates for sequencing, potentially introducing amplification bias and loss of coverage.

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