Biological tissue sample preparation for time-of-flight secondary ion mass spectrometry (ToF\u2013SIMS) imaging

Tae Geol Lee,Sohee Yoon

doi:10.1186/s40580-018-0157-y

Tae Geol Lee, Sohee Yoon

Open Access

https://doi.org/10.1186/s40580-018-0157-y

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Abstract

Time-of-flight secondary ion mass spectrometry (ToF–SIMS) imaging is an analytical technique rapidly expanding in use in biological studies. This technique is based on high spatial resolution (50–100 nm), high surface sensitivity (1–2 nm top-layer), and statistical analytic power. In mass spectrometry imaging (MSI), sample preparation is a crucial step to maintaining the natural state of the biomolecules and providing accurate spatial information. However, a number of problems associated with temperature changes in tissue samples such as loss of original distribution due to undesired molecular migration during the sample preparation or reduced ionization efficiency make it difficult to accurately perform MSI. Although frozen hydrate analysis is the ideal sample preparation method to eliminate the effects of temperature, this approach is hindered by mechanical limitations. Alternatively, an adhesive-tape-supported mounting and freeze-drying preparation has been proposed. This paper provides a concise review of the sample preparation procedures, a review of current issues, and proposes efficacious solutions for ToF–SIMS imaging in biological research.

Highlights

Mass spectrometry imaging (MSI) provides information on the spatial distribution and chemical composition of analyte molecules on complex surfaces by irradiating the sample with an ionized beam and recording the ion signal at different locations [1–3]
Based on the high spatial resolution, sample surface sensitivity, and statistical analysis, the application of ToF–SIMS imaging to biological studies is on the rise
This review summarizes the preparation procedures of tissue samples to determine the accuracy of ToF–SIMS imaging, recent trends in the field, and discusses different approaches for improving or resolving issues associated with the technique

Summary

Introduction

Mass spectrometry imaging (MSI) provides information on the spatial distribution and chemical composition of analyte molecules on complex surfaces by irradiating the sample with an ionized beam and recording the ion signal at different locations [1–3]. Given the importance of sample preparation, ToF– SIMS is advantageous in that samples can be analyzed directly without applying additional organic molecules to the tissue to facilitate ionization, and enable labelfree detection [26–28]. This technology is emerging as a biological MSI because ToF–SIMS imaging achieves high spatial resolution (50–100 nm) using focused ion beams [29–32]. The frozen or frozen embedded tissue sample is placed in a chamber set

Mounting

Sample temperature during mounting and drying

Measurement temperature

Optimization of sample preparation for ToF– SIMS imaging

Enhancement of ionization efficiency—TFA and ammonia treatments

Frozen‐hydrated analysis—signal enhancements

Tape‐supported mounting and freeze drying

Findings

Conclusion