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Title: SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here in this article, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV ≤ 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. Lastly, this SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.
Authors:
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  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Earth and Biological Sciences Division
  2. Agilent Technologies, Santa Clara, CA (United States)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Earth and Biological Sciences Division ; Oregon State Univ., Corvallis, OR (United States). Department of Environmental and Molecular Toxicology
Publication Date:
Report Number(s):
PNNL-SA-117436
Journal ID: ISSN 2376-9998; PII: S2376999816300150
Grant/Contract Number:
AC05-76RL01830
Type:
Accepted Manuscript
Journal Name:
Clinical Mass Spectrometry
Additional Journal Information:
Journal Volume: 2; Journal ID: ISSN 2376-9998
Publisher:
Elsevier - Association for Mass Spectrometry
Research Org:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ion mobility spectrometry; mass spectrometry; metabolomics; exposomics
OSTI Identifier:
1341744