Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platform.

Journal Article (Journal Article)

PURPOSE: New therapies for lysosomal storage diseases (LSDs) have generated interest in screening newborns for these conditions. We present performance validation data on a digital microfluidic platform that performs multiplex enzymatic assays for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases. METHODS: We developed an investigational disposable digital microfluidic cartridge that uses a single dried blood spot (DBS) punch for performing a 5-plex fluorometric enzymatic assay on up to 44 DBS samples. Precision and linearity of the assays were determined by analyzing quality control DBS samples; clinical performance was determined by analyzing 600 presumed normal and known affected samples (12 for Pompe, 7 for Fabry and 10 each for Hunter, Gaucher and Hurler). RESULTS: Overall coefficient of variation (CV) values between cartridges, days, instruments, and operators ranged from 2 to 21%; linearity correlation coefficients were ≥0.98 for all assays. The multiplex enzymatic assay performed from a single DBS punch was able to discriminate presumed normal from known affected samples for 5 LSDs. CONCLUSIONS: Digital microfluidic technology shows potential for rapid, high-throughput screening for 5 LSDs in a newborn screening laboratory environment. Sample preparation to enzymatic activity on each cartridge is less than 3h.

Full Text

Duke Authors

Cited Authors

  • Sista, RS; Wang, T; Wu, N; Graham, C; Eckhardt, A; Winger, T; Srinivasan, V; Bali, D; Millington, DS; Pamula, VK

Published Date

  • September 23, 2013

Published In

Volume / Issue

  • 424 /

Start / End Page

  • 12 - 18

PubMed ID

  • 23660237

Pubmed Central ID

  • PMC3926752

Electronic International Standard Serial Number (EISSN)

  • 1873-3492

Digital Object Identifier (DOI)

  • 10.1016/j.cca.2013.05.001


  • eng

Conference Location

  • Netherlands