Introduction: Digital microfluidics (DMF) is an emerging technology with the appropriate metrics for application to newborn and high-risk screening for inherited metabolic disease and other conditions that benefit from early treatment. Areas covered: This review traces the development of electrowetting-based DMF technology toward the fulfillment of its promise to provide an inexpensive platform to conduct enzymatic assays and targeted biomarker assays at the bedside. The high-throughput DMF platform, referred to as SEEKER®, was recently authorized by the United States Food and Drug Administration to screen newborns for four lysosomal storage disorders (LSDs) and is deployed in newborn screening programs in the United States. The development of reagents and methods for LSD screening and results from screening centers are reviewed. Preliminary results from a more compact DMF device, to perform disease-specific test panels from small volumes of blood, are also reviewed. Literature for this review was sourced using principal author and subject searches in PubMed. Expert commentary: Newborn screening is a vital and highly successful public health program. DMF technology adds value to the current testing platforms that will benefit apparently healthy newborns with underlying genetic disorders and infants at-risk for conditions that present with symptoms in the newborn period.

Studies to assess glucose metabolism such as the isotope-labeled intravenous glucose tolerance test (IVGTT) or the primed, constant infusion of stable isotope-labeled glucose to estimate fasting hepatic glucose output (HGO) generally involve the use of either 2H2-labeled or 13C1-labeled D-glucose as a tracer with gas chromatography-mass spectrometry (GC-MS) for the analysis of glucose derivatives. These techniques are both technically and financially challenging. We describe here a novel method that involves the use of 13C6-D-glucose as a tracer with ultra performance liquid chromatography-electrospray ionization mass spectrometry (UPLC-ESIMS). Aliquots of plasma are prepared by protein precipitation and incubation with butyl p-aminobenzoate and sodium cyanoborohydride to form a stable derivative of glucose. Isotope signals from the protonated glucose derivative corresponding to A+2, A+3 and A+6 are collected by selected ion recording during UPLC-ESIMS, where A is the most abundant isotope, and used in the mathematical computations. Here we describe the application of this method in pilot studies of labeled IVGTT and HGO estimation. The results are similar to those obtained using previously published methods. We conclude that the new method is robust, convenient, accurate, and cost-efficient, and thereby will facilitate studies of glucose kinetics in large subject cohorts.