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

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.

The Space Dimension at the Micro Level: Mass Spectrometry Imaging of Drugs in Tissues

“…In SIMS a primary ion beam is focused directly on the tissue section to produce and desorb secondary ions, which are then channeled to the time‐of‐flight (TOF) mass analyzer. SIMS gives the best spatial resolution among MSI techniques, up to 250 nm (50 nm in NanoSIMS) and the use of gas cluster ions has expanded the applicability from only elemental analysis to biological molecules (Yoon & Lee, 2018). In addition, the technique is matrix‐free, avoiding complications such as matrix selection, optimization of matrix deposition, matrix interference in spectra.…”

Obtaining molecular imagings of pesticide residues on strawberry surfaces with probe sampling followed by ambient ionization mass spectrometric analysis

“…MSI's two most commonly used ionization methods are matrix-assisted laser desorption/ionization (MALDI) and secondary ionization mass spectrometry (SIMS). [6][7][8] SIMS can detect organic and inorganic compounds under a very high spatial resolution (sub-micrometer), but the masses of the detectable molecules or elements are relatively low, 9 whereas MALDI can detect large biological molecules and is the most commonly used ionization method for MSI but has a low spatial resolution (10-50 μm). MALDI-MSI is performed in microprobe mode in a vacuum, and thus, the signals of the molecules in each laser desorption spot are recorded individually.…”

“…Recently, the development of the combination of thermal desorption-electrospray ionization mass spectrometry (TD-ESI/MS) with a probe allows for direct surface sample analysis without sample preparation. 1,[7][8][9][10] Analytes, such as pesticides on fruit surfaces, are collected simply by sweeping a metallic probe along the fruit's surface for approximately 1 cm. The probe is then inserted in a thermal desorption unit to desorb the analytes on the probe's tip, with a nitrogen gas stream subsequently delivering the desorbed analytes to an electrospray plume that was generated from a methanol solution flowing out of a capillary.…”

“…The molecular information obtained from mass spectrometry and visualized in a thin tissue section makes MSI a valuable analytical technique to ascertain the distribution of thousands of biomolecules such as metabolites, lipids, peptides, and proteins in samples. MSI's two most commonly used ionization methods are matrix‐assisted laser desorption/ionization (MALDI) and secondary ionization mass spectrometry (SIMS) 6–8 . SIMS can detect organic and inorganic compounds under a very high spatial resolution (sub‐micrometer), but the masses of the detectable molecules or elements are relatively low, 9 whereas MALDI can detect large biological molecules and is the most commonly used ionization method for MSI but has a low spatial resolution (10–50 μm).…”

“…Recently, the development of the combination of thermal desorption‐electrospray ionization mass spectrometry (TD‐ESI/MS) with a probe allows for direct surface sample analysis without sample preparation 1,7–10 . Analytes, such as pesticides on fruit surfaces, are collected simply by sweeping a metallic probe along the fruit's surface for approximately 1 cm.…”