Abstract
Non-invasive wearable biosensors provide real-time, continuous, and actionable health information. However, difficulties detecting diluted biomarkers in excreted biofluids limit practical applications. Most biomarkers of interest are transported paracellularly into excreted biofluids from biomarker-rich blood and interstitial fluid during normal modulation of cellular tight junctions. Calcium chelators are reversible tight junction modulators that have been shown to increase absorption across the intestinal epithelium. However, calcium chelators have not yet been shown to improve the extraction of biomarkers. Here we show that for glucose, a paracellularly transported biomarker, the flux into sweat can be increased by >10x using citrate, a calcium chelator, in combination with electroosmosis. Our results demonstrate a method of increasing glucose flux through the sweat gland epithelium, thereby increasing the concentration in sweat. Future work should examine if this method enhances flux for other paracellularly transported biomarkers to make it possible to detect more biomarkers with currently available biosensors.
Highlights
Sweat is separated from the surrounding biomarker-rich blood and ISF by a one- to twocell thick epithelium [1]
The cellular lipid bilayers form a barrier for transcellular diffusion, while the tight junctions between the cells form a barrier for paracellular diffusion
The treatment consisted of reverse iontophoresis (RI) of either acetate, which should induce only electroosmotic flow, or citrate, which should induce both paracellular permeability enhancement and electroosmotic flow
Summary
Sweat is separated from the surrounding biomarker-rich blood and ISF by a one- to twocell thick epithelium [1]. This leaves only two routes of entry for biomarkers—transcellular (through the cells) or paracellular (between the cells). Larger, uncharged, polar molecules (e.g., glucose) and charged molecules (e.g., ions or proteins) must move through the space between the cells.
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