Newborn screening is currently performed by collecting dried bloodspots from infants and then sending them to a lab for analysis. It is primarily performed to detect disorders which lead to severe physical and mental disabilities. There is an increasing necessity to screen for a number of lysosomal storage disorders for which therapies are becoming available. Tandem mass spectrometry is a multiplex detection technology widely utilized in newborn screening, but when applied to enzyme assays it is expensive, time consuming, and labor intensive. There is a need for an inexpensive, rapid, and automated technology for performing newborn screening assays. A digital microfluidic cartridge, which is essentially a liquid handling system operating on sub- microliter droplets, has been developed for performing fluorometric enzymatic assays for screening lysosomal storage disorders using dried blood spots. This system is configured to enable walkaway automation and multiplex several assays inexpensively. In phase II, we have successfully demonstrated assays for Pompe, Fabry, Gaucher, Hunter and Hurler disorders using a single punch from a dried blood spot. The digital microfluidic method compared favorably with a "gold standard" fluorometric enzymatic method performed in microtiter plates at Duke University for all the 5 disorders. The digital microfluidic system is currently under a pilot trial in the Illinois Newborn Screening Laboratory. Over 6,000 dried blood spots have been screened for Pompe, Fabry, and Gaucher during the ongoing pilot study. Following a positive results on this platform, 4 infants were further confirmed with Fabry disease and 1 infant with Gaucher disease. Phase IIB continuation will focus on addressing several user issues that were identified during the pilot trial, submission of a 510(k) application to the FDA, and expansion of the newborn screening assay panel to include other LSDs which are mandated or which have therapies available/under development.

Public Health Relevance

Newborn screening is performed on almost every infant born in the US. Due to the availability of therapies, there is a growing interest in adding lysosomal storage disorders (LSDs) to the panel of tests. In this project, a cost-effective microfluidic platform will be developed and validated for newborn screening of LSDs. Illinois, Missouri and New Mexico have mandated laws requiring screening all the babies for LSDs and availability of this inexpensive platform will make it affordable for cash-strapped states. During a limited pilot trial of this platform in Illinois, some babies with LSDs were already identified.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44HD057713-04
Application #
8252254
Study Section
Special Emphasis Panel (ZRG1-IMST-A (12))
Program Officer
Urv, Tiina K
Project Start
2007-09-30
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$997,329
Indirect Cost
Name
Advanced Liquid Logic
Department
Type
DUNS #
140695474
City
Research Triangle Park
State
NC
Country
United States
Zip Code
27709
Sista, Ramakrishna S; Wang, Tong; Wu, Ning et al. (2013) Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platform. Clin Chim Acta 424:12-8
Graham, Carrie; Sista, Ramakrishna S; Kleinert, Jairus et al. (2013) Novel application of digital microfluidics for the detection of biotinidase deficiency in newborns. Clin Biochem 46:1889-91
Sista, Ramakrishna S; Wang, Tong; Wu, Ning et al. (2013) Rapid assays for Gaucher and Hurler diseases in dried blood spots using digital microfluidics. Mol Genet Metab 109:218-20
Sista, Ramakrishna S; Eckhardt, Allen E; Wang, Tong et al. (2011) Digital microfluidic platform for multiplexing enzyme assays: implications for lysosomal storage disease screening in newborns. Clin Chem 57:1444-51
Millington, David S; Sista, Ramakrishna; Eckhardt, Allen et al. (2010) Digital microfluidics: a future technology in the newborn screening laboratory? Semin Perinatol 34:163-9