Rapid skin biomarker discovery using hydrogel-phase sampling followed by semi-automated liquid-phase re-extraction high-resolution mass spectrometry

A facile and rapid skin metabolomics protocol is proposed. The liquid microjunction-surface sampling probe system has been partly automated, and used in conjunction with hydrogel probes for skin metabolite analysis. A control device was built to precisely control the segmented solvent flow and analyte re-extraction into the liquid microjunction. This mode provides rapid online re-extraction of the analytes from hydrogel probes. Humectant was added to the hydrogel, and moist heat treatment was used to make the hydrogel probes rugged for sampling in the clinical setting. The developed method was validated for the analysis of choline – a putative biomarker of psoriasis. A linear relationship over six calibration levels from 3.18 × 10⁻⁵ to 3.18 × 10⁻⁴ mol m⁻² has been obtained. The limit of detection was 6.6 × 10⁻⁶ mol m⁻², while the recoveries range from 92 to 109%. The within-run and between-run precision were evaluated and the coefficients of variation range from 1.84 to 7.13%. Furthermore, the developed method has been used to screen patients (n = 10) and healthy participants (control group; n = 10) for psoriasis-related skin metabolites. Metabolomic profiling of the skin excretion-related signals identified potential biomarkers of psoriasis: choline, pipecolic acid, ornithine, urocanic acid, and methionine.