High-throughput single-cell whole-genome amplification through centrifugal emulsification and eMDA

Single-cell whole-genome sequencing (scWGS) is mainly used to probe intercellular genomic variations, focusing on the copy number variations or alternations (CNVs/CNAs) and the single nucleotide variations (SNVs) occurring inside single cells. Single-cell whole-genome amplification (scWGA) is necessary before scWGS and is challenging due to the low copy number of DNA. Besides, many genomic variations have low incidence among a population of cells, thus the throughput of currently available scWGA methods is far from satisfying. Here we integrate a one-step micro-capillary array (MiCA) based centrifugal droplet generation technique with emulsion multiple displacement amplification (eMDA) and demonstrate a high-throughput scWGA method, MiCA-eMDA. MiCA-eMDA increases the single-run throughput of scWGA to a few dozens, and enables CNVs/CNAs assessment at the resolution of 50 kb. Downstream target enrichment further enables the detection of SNV with 20% allele drop-out.