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Area of Science:

  • Analytical Chemistry
  • Spectrometry
  • Biomarker Discovery

Background:

  • Ion mobility mass spectrometry (IM-MS) is a powerful analytical technique.
  • Existing IM-MS instruments face challenges in sensitivity and resolving power, especially at ambient pressures.
  • There is a need for improved instrumentation for complex sample analysis, including biological fluids.

Purpose of the Study:

  • To present the design and performance of a novel ambient-pressure ion mobility mass spectrometer (IM-MS).
  • To evaluate the analytical figures of merit of the prototype instrument for standard and complex samples.
  • To demonstrate the capability of the instrument for metabolite identification in human blood.

Main Methods:

  • Development of a new IM-MS design featuring an ambient-pressure resistive glass ion mobility drift tube (RGIMS).
  • Coupling the RGIMS to a high-resolution time-of-flight mass spectrometer (TOFMS) via an enhanced interface with segmented quadrupoles.
  • Evaluation of instrument performance using standard solutions (e.g., caffeine) and complex biological samples (human blood).

Main Results:

  • The enhanced interface increased sensitivity while maintaining high resolving power.
  • A detection limit of 300 nM for caffeine was achieved.
  • Over 300 tentative metabolites and 80 isomers/isobars were detected in human blood.
  • High separation power was demonstrated for both IMS (resolving power 85) and MS (mass resolving power 7000).

Conclusions:

  • The new IM-MS design offers significant improvements in sensitivity and resolving power for ambient-pressure measurements.
  • The instrument is capable of analyzing complex biological samples, facilitating metabolite and isomer identification.
  • Developed software enhances instrument control, data evaluation, and visualization for comprehensive analysis.