Improving the Speed and Selectivity of Newborn Screening Using Ion Mobility Spectrometry-Mass Spectrometry.
Anal Chem
; 93(51): 17094-17102, 2021 12 28.
Article
em En
| MEDLINE
| ID: mdl-34851605
ABSTRACT
Detection 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 â¼400 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 â¼10 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triagem Neonatal
/
Espectrometria de Mobilidade Iônica
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
/
Newborn
Idioma:
En
Revista:
Anal Chem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos