Aluminum Foil Substrates Support Solvent-Free Raman Analysis of Skin Lipids

Abstract Sebum, a lipid-rich biofluid secreted onto the skin surface, holds promise as a non-invasive biomarker source but poses analytical challenges due to its hydrophobicity. Here, we demonstrate that aluminum foil substrates enable direct, solvent-free sampling and Raman spectroscopic analysis of human sebum, preserving key vibrational signatures of lipids, proteins, and carotenoids. We compared unprocessed sebum with chloroform/methanol and diethyl ether extraction methods in three volunteers, finding that solvent-free sampling yields more intense and chemically rich Raman spectra, while solvent-based methods attenuate signals and introduce compositional bias. Differential spectral analysis revealed that solvent extraction modifies the carbonyl and hydrocarbon stretching regions in a solvent-dependent manner. Our technical note focuses specifically on how sample processing affects the Raman spectral signature of sebum, underscoring the importance of solvent-free approaches and providing a methodological baseline for standardized Raman-based sebum analysis.