title: Transmission mode direct analysis in real time mass spectrometry for fast untargeted metabolic fingerprinting.
abstract: BACKGROUND
  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.
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive NW, Atlanta, GA 30332, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Jones
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
mesh_terms: D006801:Humans; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D055432:Metabolomics / Q000295:instrumentation / Q000379:methods*; D044967:Serum / Q000737:chemistry*