Dual Source Ion Mobility-Mass Spectrometer - Project Summary/Abstract:
The Bruker timsTOF fleX includes a liquid chromatograph (LC), matrix assisted laser desorption ionization
(MALDI-2) and electrospray ionization (ESI) sources, trapped ion mobility spectrometer (tims), and quadrupole-
time-of-flight (QTOF) mass spectrometer combined into an instrument that can analyze metabolites, lipids, and
proteins with high content or high throughput. Most importantly, the gap between these two experiments can
be bridged easily when both are conducted on the same instrument; for example, metabolomics data can be
effectively integrated with mass spectrometry imaging. To describe the individual components, the liquid
chromatograph provides separation of analytes to increase depth of proteome and metabolome sampling. The
two ion sources enable analysis of liquid samples (ESI) or arrays of samples co-crystallized with matrix
(MALDI). The trapped ion mobility spectrometer (tims) provides data for collision cross section (CCS)
calculations to further define each analyte as well as gas phase enrichment of molecules into packets with
similar CCS-to-charge ratios for mass analysis. The QTOF provides mass spectrometry and tandem mass
spectrometry with high resolution and accurate mass measurement. Vendor software provides support for
data analysis in both metabolomics and proteomics as well as visualization and analysis of mass spectrometry
imaging. The addition of this instrument to our Proteomics & Metabolomics Core (P&MC) complements our
existing LC-MS resources, provides novel capability for ion mobility-mass spectrometry, replaces a MALDI
instrument that was decommissioned last year, and enhances resources available for mass spectrometry
imaging. As tumor heterogeneity, the tumor-immune interface, and spatial distribution of analytes in tumors
now have increasing importance, existing analytical platforms must be modified to meet these needs and
additional investments in instrumentation are needed. The Bruker timsTOF fleX complements existing LC-MS
instruments and optimizes the value of investment in new technology by lowering sample input requirements,
creating capability for spatial omics of tissues, supporting high throughput screening with MALDI-tims-MS, and
ion mobility separation of isomeric lipids, metabolites, and post-translationally modified or chemically labeled
peptides. Examples provided by Bruker have been confirmed by demonstration data from our own samples.
This device also can be used to improve biomarker discovery and integrate molecular measurements with
traditional pathology workflows. The placement in a core facility with highly trained staff and extensive
institutional support will maximize both the availability to the user group and their benefit from access to the
instrument. Together, these advantages are expected to significantly advance cancer metabolomics and
proteomics applications at Moffitt Cancer Center to support existing and planned NIH/NCI-funded research and
fuel the development of a Cancer Metabolism Program to develop strategies to target tumor vulnerabilities.
