Integrated Addressable Dynamic Droplet Array (aDDA) as Sub-Nanoliter Reactors for High-Coverage Genome Sequencing of Single Yeast Cells

Small. 2021 Sep;17(37):e2100325. doi: 10.1002/smll.202100325. Epub 2021 Jul 23.

Abstract

An addressable dynamic droplet array (aDDA) is presented that combines the advantages of static droplet arrays and continuous-flow droplet platforms. Modular fabrication is employed to create a self-contained integrated aDDA. All the sample preparation steps, including single-cell isolation, cell lysis, amplification, and product retrieval, are performed in sequence within a sub-nanoliter (≈300 pL) droplet. Sequencing-based validation suggests that aDDA reduces the amplification bias of multiple displacement amplification (MDA) and elevates the percentage of one-yeast-cell genome recovery to 91%, as compared to the average of 26% using conventional, 20 µL volume MDA reactions. Thus, aDDA is a valuable addition to the toolbox for high-genome-coverage sequencing of single microbial cells.

Keywords: droplet; microfluidics; multiple displacement amplification; sample preparation; single-cell genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Count
  • Saccharomyces cerevisiae* / genetics