Imaging mass spectrometry at isomeric chemical resolution using gas phase ion/ion reactions

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Boone M. Prentice
Organization: UNIVERSITY OF FLORIDA
Fiscal Year: 2024
Award: $152,324
Funding agency: National Institute of General Medical Sciences

PROJECT SUMMARY
Molecular imaging plays a pivotal role in biomedical research. By enabling the visualization of biological
processes directly in tissue, in situ assessments of cellular function can be recorded with spatial context. The
use of mass spectrometry as a molecular imaging modality combines the high level of molecular specificity
provided by the mass spectrometer with the spatial fidelity of a microscopic imaging approach. By this, imaging
mass spectrometry (IMS) provides for the label-free mapping of a wide array of biomolecules in tissue
specimens. Accurate identification of the biochemical pathways altered during development and dysfunction is
a key step in designing novel treatment strategies for a variety of applications, such as in studies of diabetes,
infectious disease, drug pharmacology, and cancer. However, severe deficiencies remain in the differentiation
and structural identification of molecules detected during imaging mass spectrometry experiments due to the
enormous chemical complexity of tissue samples. The failure to adequately separate and identify these
compounds results in ion images consisting of multiple different compounds with overlapping masses. This
distorted picture of molecular distributions clouds the interpretation of the biochemical maps produced by imaging
mass spectrometry and prevents a complete and accurate understanding of cellular compositions and functions.
This proposal aims to develop methods and instrumentation that will enable tissue imaging at unparalleled levels
of sensitivity, separation, and identification. This will be achieved through the discovery and development of
novel gas-phase ion/ion reactions that target specific chemical functional groups in lipids and metabolites
(Specific Aim 1). These reactions offer rapid and flexible means for molecular transformations without
manipulating the tissue sample and can result in improved detection limits and more extensive chemical
structural information. Developing reproducible and quantitative ion/ion reaction methodologies will enable
reliable measurements to be made from tissue (Specific Aim 2). The development of instrumentation that can
perform gas-phase ion/ion reactions with high throughput will enable these transformations to be performed
directly during imaging mass spectrometry experiments (Specific Aim 3). These ‘reactive’ images are anticipated
to reveal spatial biochemical detail unobtainable by conventional imaging modalities. The continual development
of new analytical technologies such as those proposed herein is crucial in order to address increasingly
complicated biological and clinical questions.

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