High-throughput automated microfluidic sample preparation for accurate microbial genomics

Research output: Contribution to journalArticleScientificpeer-review

Details

Original languageEnglish
Article number13919
Pages (from-to)1-10
JournalNature Communications
Volume8
Publication statusPublished - 27 Jan 2017
MoE publication typeA1 Journal article-refereed

Researchers

  • Soohong Kim
  • Joachim De Jonghe
  • Anthony B. Kulesa
  • David Feldman
  • Tommi Vatanen

  • Roby P. Bhattacharyya
  • Brittany Berdy
  • James Gomez
  • Jill Nolan
  • Slava Epstein
  • Paul C. Blainey

Research units

  • University of Cambridge
  • Massachusetts General Hospital
  • Northeastern University
  • Broad Institute
  • Massachusetts Institute of Technology

Abstract

Low-cost shotgun DNA sequencing is transforming the microbial sciences. Sequencing instruments are so effective that sample preparation is now the key limiting factor. Here, we introduce a microfluidic sample preparation platform that integrates the key steps in cells to sequence library sample preparation for up to 96 samples and reduces DNA input requirements 100-fold while maintaining or improving data quality. The general-purpose microarchitecture we demonstrate supports workflows with arbitrary numbers of reaction and clean-up or capture steps. By reducing the sample quantity requirements, we enabled low-input (∼ 10,000 cells) whole-genome shotgun (WGS) sequencing of Mycobacterium tuberculosis and soil micro-colonies with superior results. We also leveraged the enhanced throughput to sequence ∼400 clinical Pseudomonas aeruginosa libraries and demonstrate excellent single-nucleotide polymorphism detection performance that explained phenotypically observed antibiotic resistance. Fully-integrated lab-on-chip sample preparation overcomes technical barriers to enable broader deployment of genomics across many basic research and translational applications.

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