Lab-on-a-Chip for Multiplexed Newborn Screening of Lysosomal Storage Disorders

描述（由申请人提供）：新生儿筛查目前是通过收集婴儿的干血点，然后将其送到实验室进行分析。它主要用于发现导致严重身体和精神残疾的疾病。有越来越多的必要筛选一些溶酶体储存疾病的治疗方法是可用的。串联质谱法是一种广泛应用于新生儿筛查的多重检测技术，但当应用于酶分析时，它是昂贵、耗时和劳动密集型的。需要一种廉价、快速和自动化的技术来进行新生儿筛查分析。一个数字微流体盒，本质上是一个液体处理系统操作的亚微升液滴，已经

DESCRIPTION (provided by applicant): 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.