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Download fileImproving the Speed and Selectivity of Newborn Screening Using Ion Mobility Spectrometry–Mass Spectrometry
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posted on 2021-12-01, 18:40 authored by James
N. Dodds, Erin S. BakerDetection and diagnosis of congenital
disorders is the principal
aim of newborn screening (NBS) programs worldwide. Mass spectrometry
(MS) has become the preferred primary testing method for high-throughput
NBS sampling because of its speed and selectivity. However, the ever-increasing
list of NBS biomarkers included in expanding panels creates unique
analytical challenges for multiplexed MS assays due to isobaric/isomeric
overlap and chimeric fragmentation spectra. Since isobaric and isomeric
systems limit the diagnostic power of current methods and require
costly follow-up exams due to many false-positive results, here, we
explore the utility of ion mobility spectrometry (IMS) to enhance
the accuracy of MS assays for primary (tier 1) screening. Our results
suggest that ∼400 IMS resolving power would be required to
confidently assess most NBS biomarkers of interest in dried blood
spots (DBSs) that currently require follow-up testing. While this
level of selectivity is unobtainable with most commercially available
platforms, the separations detailed here for a commercially available
drift tube IMS (Agilent 6560 with high-resolution demultiplexing,
HRdm) illustrate the unique capabilities of IMS to separate many diagnostic
NBS biomarkers from interferences. Furthermore, to address the need
for increased speed of NBS analyses, we utilized an automated solid-phase
extraction (SPE) system for ∼10 s sampling of simulated NBS
samples prior to IMS-MS. This proof-of-concept work demonstrates the
unique capabilities of SPE-IMS-MS for high-throughput sample introduction
and enhanced separation capacity conducive for increasing speed and
accuracy for NBS.
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throughput sample introductionrequire costly followdried blood spotscurrently require followconcept work demonstratescommercially available platformschimeric fragmentation spectraisomeric systems limition mobility spectrometrynbs biomarkers includedthroughput nbs samplingnbs biomarkersmass spectrometryisomeric overlapnbs analyses∼ 10unique capabilitiestier 1separations detailedresults suggestresolution demultiplexingprograms worldwideprincipal aimpositive resultsphase extractionmany falseincreasing listexams duediagnostic powercurrent methodscongenital disordersconfidently assessautomated solidagilent 6560