Feasibility study of semiconductor sequencing for noninvasive prenatal detection of fetal aneuploidy

Clin Chem. 2013 May;59(5):846-9. doi: 10.1373/clinchem.2012.196725. Epub 2013 Jan 30.


Background: Noninvasive prenatal detection of common fetal aneuploidies with cell-free DNA from maternal plasma has been achieved with high-throughput next-generation sequencing platforms. Turnaround times for previously tested platforms are still unsatisfactory for clinical applications, however, because of the time spent on sequencing. The development of semiconductor sequencing technology has provided a way to shorten overall run times. We studied the feasibility of using semiconductor sequencing technology for the noninvasive detection of fetal aneuploidy.

Methods: Maternal plasma DNA from 13 pregnant women, corresponding to 4 euploid, 6 trisomy 21 (T21), 2 trisomy 18 (T18), and 1 trisomy 13 (T13) pregnancies, were sequenced on the Ion Torrent Personal Genome Machine sequencer platform with 318 chips. The data were analyzed with the T statistic method after correcting for GC bias, and the T value was calculated as an indicator of fetal aneuploidy.

Results: We obtained a mean of 3 524 401 high-quality reads per sample, with an efficiency rate of 77.9%. All of the T21, T13, and T18 fetuses could be clearly distinguished from euploid fetuses, and the time spent on library preparation and sequencing was 24 h.

Conclusions: Semiconductor sequencing represents a suitable technology for the noninvasive prenatal detection of fetal aneuploidy. With this platform, sequencing times can be substantially reduced; however, a further larger-scale study is needed to determine the imprecision of noninvasive fetal aneuploidy detection with this system.

MeSH terms

  • Chromosome Disorders / blood*
  • Chromosome Disorders / embryology
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 21 / genetics
  • DNA / blood
  • DNA / chemistry*
  • DNA / genetics
  • Feasibility Studies
  • Female
  • Fetus / pathology*
  • Humans
  • Maternal Serum Screening Tests / instrumentation
  • Maternal Serum Screening Tests / methods*
  • Pregnancy
  • Semiconductors*
  • Sequence Analysis, DNA / instrumentation
  • Sequence Analysis, DNA / methods*
  • Trisomy / genetics*
  • Trisomy / pathology


  • DNA