Cystic Fibrosis Breathomics by Transmission-Mode Direct Analysis in Real Time-Traveling Wave Ion Mobility-Mass Spectrometry

FACUNDO M. FERNÁNDEZ; JOSÉ J. PÉREZ; CHRISTINA M. JONES; MARÍA EUGENIA MONGE; NAEL A. MCCARTY; ARLENE A. STECENKO

Atlanta

Conferencia; Pittcon 2016 Conference & Expo; 2016

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene affecting many organs, and particularly damaging effects to the lungs. To better understand CF pathology and pathogenesis at the systems biology level, breath discovery metabolomics (breathomics) investigations are gaining remarkable importance. In particular, investigation of simple-to-collect biofluids such as exhaled breath condensate (EBC) provide a non-invasive way of studying metabolic alterations associated with lung inflammatory processes.In this study, we evaluated the applicability of positive and negative-ion transmission-mode direct analysis in real time-traveling wave ion mobility spectrometry-time-of-flight mass spectrometry (TM-DART-TWIMS-TOF MS) for rapid, high-throughput discovery CF breathomics investigations. The EBC metabolome coverage yielded by DART was compared with equivalent direct-infusion electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) techniques based on sensitivity, m/z and drift time range, type of ionic species detected, and metabolome coverage. Using TM-DART-TWIMS-TOF MS in combination with multivariate analysis, EBC samples from CF patients and healthy subjects were screened for metabolic differences. Nine salient spectral features selected by a genetic algorithm were used to build a classification model via orthogonal projections to latent structures-discriminant analysis (oPLS-DA), which successfully discriminated between sample classes with 100% cross-validated accuracy, sensitivity, and specificity.