Molecular Mapping of Sebaceous Squalene by Ambient Mass Spectrometry

Abstract

Squalene (SQ), a highly unsaturated sebaceous lipid, plays an important role in protecting human skin. To better understand the role of SQ in clinical medicine, an efficient analytical approach is needed to comprehensively study the distribution of SQ on different parts of the skin. In this study, sebaceous lipids were collected from different epidermal areas of a volunteer with sampling probes. Thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was then used to characterize the lipid species on the probes, and each TD-ESI/MS analysis was completed within a few seconds without any sample pretreatment. The molecular mapping of epidermal squalene on whole-body skin was rendered by scaling the peak area of the extracted ion current (EIC) of SQ based on a temperature color gradient, where colors were assigned to the 1357 sampling locations on a 3D map of the volunteer. The image showed a higher SQ distribution on the face than any other area of the body, indicating the role of SQ in protecting facial skin. The results were in agreement with previous studies using SQ as a marker to explore sebaceous activity. The novelty and significance of this work are concluded as two points: (1) direct and rapid detection of all major classes of sebaceous lipids, including the unsaturated hydrocarbons (SQ) and nonpolar lipids (e.g., cholesterol). The results are unique compared to other conventional and ambient ionization mass spectrometry methods and (2) this is the first study to analyze SQ distribution on the whole-body skin by a high-throughput approach.

No skin off your back: the sampling and extraction of sebum for metabolomics

“…An emerging area that avoids the sampling biases imposed by either the sebum sampling technique or the laborious sample pre-treatment mentioned above is ambient ionisation mass spectrometry (AIMS) with/without direct skin analysis. The use of AIMS directly after sample collection by media (Table 2 ), such as swabs (Bouslimani et al, 2015 ; Sarkar et al, 2021 ) or filter paper (Motoyama & Kihara, 2017 ), skips the need for solvent extraction; whereas, direct skin analysis, using a harmless ionisation technique for skin, allows real-time in-situ analysis of sebum, potentially capturing metabolites in their native, localised environments to low detection limits (Cho et al, 2021 ; Cooks et al, 2015 ; Huang et al, 2010 , 2011 ). Both AIMS approaches allow a high sample throughput (≤ 5 s from collection to data generation (Cho et al, 2021 ; Zhao et al, 2008 ) but do not allow molecular separation prior to detection.…”

“…The use of AIMS directly after sample collection by media (Table 2 ), such as swabs (Bouslimani et al, 2015 ; Sarkar et al, 2021 ) or filter paper (Motoyama & Kihara, 2017 ), skips the need for solvent extraction; whereas, direct skin analysis, using a harmless ionisation technique for skin, allows real-time in-situ analysis of sebum, potentially capturing metabolites in their native, localised environments to low detection limits (Cho et al, 2021 ; Cooks et al, 2015 ; Huang et al, 2010 , 2011 ). Both AIMS approaches allow a high sample throughput (≤ 5 s from collection to data generation (Cho et al, 2021 ; Zhao et al, 2008 ) but do not allow molecular separation prior to detection. Considering the successes of AIMS for biological skin analyses in forensic science (Justes et al, 2007 ; Zhao et al, 2008 ), drug development (Cho et al, 2022 ; Katona et al, 2011 ), and cosmetic science (Motoyama & Kihara 2017 ), as well as continuous developments regarding probes (Fatou et al, 2018 ; Meisenbichler et al, 2020 ; Shamraeva et al, 2022 ) and portable mass spectrometers (Burns et al, 2022 ; Hendricks et al, 2014 ; Li et al, 2014 ; Mulligan et al, 2006 ), this is an exciting area to watch.…”

The study of distribution of ingested terbinafine on skin with ambient ionization tandem mass spectrometry

“…Alternatively, AIMS has been demonstrated to be useful for rapidly characterizing samples from the skin [ 18 , 29 – 33 ]. Ambient ionization mass spectrometry (AIMS) encompasses the features of traditional mass spectrometric techniques but operates under ambient conditions and require minimal or no sample pretreatment, making AIMS highly applicable for in situ and real-time sample analysis [ 34 – 36 ].…”

“…In our previous study, TD-ESI/MS has been used to rapidly characterize sebaceous lipids [ 34 ]. Compared to the other AIMS approaches which were used to analyze skin surface lipids [ 30 – 33 ], the lipid profile of TD-ESI/MS is unique. All major classes of sebaceous lipids, including the unsaturated hydrocarbons (SQ) and nonpolar lipids (e.g.…”

“…cholesterol), can be directly and rapidly detected without any sample treatment [ 34 ]. It is likely due the high temperature makes charged electrospray droplets dry faster, gas-phase ion/molecule reactions play a role in TD-ESI source for the ionization of thermal desorbed analytes [ 33 ].…”