Digital-WGS: automated, highly efficient whole-genome sequencing of single cells by digital microfluidics
Single-cell whole-genome sequencing (WGS) is critical for characterizing dynamic intercellular changes in DNA. Current sample preparation technologies for single cells are operationally complex, expensive, and suffer from high amplification bias and errors. Here we describe Digital-WGS, a single-cell sample preparation platform that streamlines high-performance whole genome amplification with automatic processing based on digital microfluidics. Using the method, we provide high single cell capture efficiency (100%) for any amount and types of cells by combining hydrodynamic trap with surface wettability. The addressable control of droplet enables the complete removal of exogenous DNA, sufficient cell lysis and lossless amplicons recovery, achieving lowest CV and highest coverage on all scales. The single-cell genomic variations profiling performs the excellent detection of copy number variants (CNVs) with smallest bin of 150 kb and single-nucleotide variants (SNVs) with alleles drop out (ADO) rate of 5.2%, holding great promise for broader applications for single cell genomics.