Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Genome sequencing in microfabricated high-density picolitre reactors.

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.

Pubmed ID: 16056220


  • Margulies M
  • Egholm M
  • Altman WE
  • Attiya S
  • Bader JS
  • Bemben LA
  • Berka J
  • Braverman MS
  • Chen YJ
  • Chen Z
  • Dewell SB
  • Du L
  • Fierro JM
  • Gomes XV
  • Godwin BC
  • He W
  • Helgesen S
  • Ho CH
  • Ho CH
  • Irzyk GP
  • Jando SC
  • Alenquer ML
  • Jarvie TP
  • Jirage KB
  • Kim JB
  • Knight JR
  • Lanza JR
  • Leamon JH
  • Lefkowitz SM
  • Lei M
  • Li J
  • Lohman KL
  • Lu H
  • Makhijani VB
  • McDade KE
  • McKenna MP
  • Myers EW
  • Nickerson E
  • Nobile JR
  • Plant R
  • Puc BP
  • Ronan MT
  • Roth GT
  • Sarkis GJ
  • Simons JF
  • Simpson JW
  • Srinivasan M
  • Tartaro KR
  • Tomasz A
  • Vogt KA
  • Volkmer GA
  • Wang SH
  • Wang Y
  • Weiner MP
  • Yu P
  • Begley RF
  • Rothberg JM



Publication Data

September 15, 2005

Associated Grants

  • Agency: NHGRI NIH HHS, Id: P01 HG003022-020002
  • Agency: NHGRI NIH HHS, Id: R01 HG003562-02

Mesh Terms

  • Electrophoresis, Capillary
  • Emulsions
  • Fiber Optic Technology
  • Genome, Bacterial
  • Genomics
  • Microchemistry
  • Mycoplasma genitalium
  • Polymerase Chain Reaction
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Analysis, DNA
  • Time Factors