High Mass Accuracy and High Mass Resolving Power FT-ICR Secondary Ion Mass Spectrometry for Biological Tissue Imaging

TL;DR

This paper demonstrates the application of high mass accuracy and ultra-high mass resolving power FT-ICR secondary ion mass spectrometry for detailed biological tissue imaging, achieving unprecedented resolution and accuracy.

Contribution

It introduces a novel FT-ICR MS platform for SIMS imaging with significantly enhanced mass resolving power and accuracy, enabling detailed chemical mapping of biological tissues.

Findings

Achieved mass resolving power of 67,500 at m/z 750

Demonstrated ultra-high resolving power >3,000,000

Measured rat brain tissue with 75 μm spatial resolution

Abstract

Biological tissue imaging by secondary ion mass spectrometry has seen rapid development with the commercial availability of polyatomic primary ion sources. Endogenous lipids and other small bio-molecules can now be routinely mapped on the sub-micrometer scale. Such experiments are typically performed on time-of-flight mass spectrometers for high sensitivity and high repetition rate imaging. However, such mass analyzers lack the mass resolving power to ensure separation of isobaric ions and the mass accuracy for elemental formula assignment based on exact mass measurement. We have recently reported a secondary ion mass spectrometer with the combination of a C60 primary ion gun with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for high mass resolving power, high mass measurement accuracy and tandem mass spectrometry capabilities. In this work, high specificity and high sensitivity secondary ion FT-ICR MS was applied to chemical imaging of biological tissue. An entire rat brain tissue was measured with 150 um spatial resolution (75 um primary ion spot size) with mass resolving power (m/{\Delta}m50%) of 67,500 (at m/z 750) and root-mean-square measurement accuracy less than two parts-per-million for intact phospholipids, small molecules and fragments. For the first time, ultra-high mass resolving power SIMS has been demonstrated, with m/{\Delta}m50% > 3,000,000. Higher spatial resolution capabilities of the platform were tested at a spatial resolution of 20 um. The results represent order of magnitude improvements in mass resolving power and mass measurement accuracy for SIMS imaging and the promise of the platform for ultra-high mass resolving power and high spatial resolution imaging.