Hydrogel Micropatches for Sampling and Profiling Skin Metabolites

Abstract

Metabolites excreted by skin have a huge potential as disease biomarkers. However, due to the shortage of convenient sampling/analysis methods, the analysis of sweat has not become very popular in the clinical setting (pilocarpine iontophoresis being a prominent exception). In this report, a facile method for sampling and rapid chemical profiling of skin metabolites excreted with sweat is proposed. Metabolites released by skin (primarily the constituents of sweat) are collected into hydrogel (agarose) micropatches. Subsequently, they are extracted in an online analytical setup incorporating nanospray desorption electrospray ionization and an ion trap mass spectrometer. In a series of reference measurements, using bulk sampling and electrospray ionization mass spectrometry, various low-molecular-weight metabolites are detected in the micropatches exposed to skin. The sampling time is as short as 10 min, while the desorption time is 2 min. Technical precision of micropatch analysis varies within the range of 3-42%, depending on the sample and the method of data treatment; the best technical precision (≤10%) has been achieved while using an isotopically labeled internal standard. The limits of detection range from 7 to 278 pmol. Differences in the quantities of extracted metabolites are observed for the samples obtained from healthy individuals (intersubject variabilities: 30-89%; n = 9), which suggests that this method may have the potential to become a semiquantitative assay in clinical analysis and forensics.

Hydrogel Micropatch and Mass Spectrometry–Assisted Screening for Psoriasis-Related Skin Metabolites

“…Several methods for collecting small amounts of skin excretions have been proposed (cotton swab, wipe, skinpatch, and syringe), but all of them involve major inconveniences (13 ). Therefore, it would be helpful to develop and implement analytical methods for sampling and analyzing skin excretions that circumvent chromatographic separations (14,15 ). We hypothesized that the recently developed hydrogel micropatch method (14 ) could enable the sampling of tiny amounts of skin excretions from the metabolically dysregulated skin of psoriatic patients.…”

“…The hydrogel micropatch sampling probes (14 ) were adapted to the requirements of the current study. A 16 ϫ 16 -mm chip was cut from a 2-mm thick sheet of polytetrafluoroethylene (All-Fluoro).…”

Micropatch‐arrayed pads for non‐invasive spatial and temporal profiling of topical drugs on skin surface

“…The proposed method of skin surface analysis encompasses selective sampling of molecules from skin surface onto structured MAPA probes and subsequent scans by MS. We assume that the method is selective to polar metabolites because of two reasons: (1) the hydrophilic nature of the agarose hydrogel, and (2) the ionization capabilities of the nanoDESI source. Contrary to the previous report, the current method preserved spatial information on the distribution of the target analytes on skin surface. However, scanning large number of hydrogel micropatches by MS operated at atmospheric pressure incurred technical problems that had to be addressed.…”

Electrospray Modifications for Advancing Mass Spectrometric Analysis

“…[128][129][130] Furthermore, it has been applied in pro ling sweat metabolites using hydrogel micropatches as sampling substrates. 131,132) Electrospray for post-ionization e interaction of neutral species using electrospray as the post-ionization source for MS analysis has been investigated for some time. [133][134][135][136] Post-ionization based on the use of electrospray is highly e cient for transferring charges from electrospray to neutral species.…”