Transmission mode direct analysis in real time mass spectrometry for fast untargeted metabolic fingerprinting

• Published in: Rapid communications in mass spectrometry Vol. 27; no. 12; pp. 1311 - 1318
• Main Authors: Jones, Christina M., Fernández, Facundo M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 30-06-2013; Wiley Subscription Services, Inc
• Subjects: Blood; Confidence intervals; Desorption; Fingerprinting; Human; Humans; Ionization; Mass spectrometry; Mass Spectrometry - instrumentation; Mass Spectrometry - methods; Metabolites; Metabolomics - instrumentation; Metabolomics - methods; Serum - chemistry
• ISSN: 0951-4198; 1097-0231
• DOI: 10.1002/rcm.6566

RATIONALE
Untargeted metabolic fingerprinting is a discovery tool to better understand biochemical processes involved in detecting and characterizing disease states and responses to environmental stressors. Although current mass spectrometric (MS) methods are very powerful, there is a clear need for more rapid, high‐throughput MS approaches for metabolomics studies.
METHODS
A rapid metabolic fingerprinting method for human blood sera that utilizes a new transmission mode direct analysis in real time (TM‐DART) sampling technique coupled with quadrupole time of flight mass spectrometry (QTOFMS) is presented. In this approach, the sample is deposited directly on a stainless steel mesh that is held in the ionization region by a custom‐built module. As a result, the DART plasma gas stream interacts with the sample in a flow‐through fashion, which maximizes the interaction between the sample and ionizing species and minimizes variance in sample positioning.
RESULTS
The optimization of TM‐DART parameters directly affecting metabolite desorption and ionization, such as sample position and ionizing gas desorption temperature, was critical in achieving high sensitivity and detecting a broad mass range of metabolites. Ramping the ionizing gas desorption temperature further enhanced analysis by adding a simple separation dimension to this ambient approach. In terms of reproducibility, TM‐DART compared favorably with traditional probe mode (PM‐) DART analysis, with coefficients of variation as low as 16%. The longer‐lasting TM‐DART signals enabled the acquisition of metabolite full scan and product ion accurate mass spectra in a single experiment, resulting in greater confidence in metabolite identification.
CONCLUSIONS
TM‐DART MS proved to be a powerful analytical technique for rapid metabolome analysis of human blood sera. Copyright © 2013 John Wiley & Sons, Ltd.