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High Performance Molecular Imaging with MALDI Trapped Ion Mobility Time-of-Flight (timsTOF) Mass Spectrometry

preprint
revised on 30.09.2019 and posted on 02.10.2019 by Jeffrey Spraggins, Katerina Djambazova, Emilio Rivera, Lukasz Migas, Elizabeth Neumann, Arne Fuetterer, Juergen Suetering, Niels Goedecke, Alice Ly, Raf Van de Plas, Richard Caprioli
Imaging mass spectrometry (IMS) enables the spatially targeted molecular assessment of biological tissues at cellular resolutions. New developments and technologies are essential for uncovering the molecular drivers of native physiological function and disease. Instrumentation must maximize spatial resolution, throughput, sensitivity, and specificity, because tissue imaging experiments consist of thousands to millions of pixels. Here, we report the development and application of a matrix-assisted laser desorption/ionization (MALDI) trapped ion mobility spectrometry imaging platform. This prototype MALDI timsTOF instrument is capable of 10 µm spatial resolutions and 20 pixels/s throughput molecular imaging. The MALDI source utilizes a Bruker SmartBeam 3-D laser system that can generate a square burn pattern of <10 x 10 µm at the sample surface. General image performance was assessed using murine kidney and brain tissues and demonstrate that high spatial resolution imaging data can be generated rapidly with mass measurement errors < 5 ppm and ~40,000 resolving power. Initial TIMS-based imaging experiments were performed on whole body mouse pup tissue demonstrating the separation of closely isobaric [PC(32:0)+Na]+and [PC(34:3)+H]+(3 mDa mass difference) in the gas-phase. We have shown that the MALDI timsTOF platform can maintain reasonable data acquisition rates (>2 pixels/s) while providing the specificity necessary to differentiate components in complex mixtures of lipid adducts. The combination of high spatial resolution and throughput imaging capabilities with high-performance TIMS separations provides a uniquely tunable platform to address many challenges associated with advanced molecular imaging applications.

Funding

MRI: Development of a next-generation MALDI ion mobility mass spectrometry platform for molecular imaging and training

Directorate for Engineering

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15 Tesla Bruker SolariX FT-ICR mass spectrometer

Office of the Director

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Vanderbilt University Biomolecular Multimodal Imaging Center for 3-Dimensional Tissue Mapping

National Institute of Diabetes and Digestive and Kidney Diseases

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Imaging Mass Spectrometry Research Resource at Vanderbilt University

National Institute of General Medical Sciences

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Molecular mapping of microbial communities at the host-pathogen interface by multi-modal 3-dimensional imaging mass spectrometry

National Institute of Allergy and Infectious Diseases

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History

Email Address of Submitting Author

jeff.spraggins@vanderbilt.edu

Institution

Vanderbilt University

Country

United States of America

ORCID For Submitting Author

0000-0001-9198-5498

Declaration of Conflict of Interest

A. Fuetterer, J. Suetering, N. Goedecke, and A. Ly were employees of Bruker Daltonik GmbH for the duration of this study.

Version Notes

Version 1.0

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