Enhancing glucose flux into sweat by increasing paracellular permeability of the sweat gland

<div><p>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.</p></div

Glucose flux under electroosmotic flow and paracellular permeability enhancement with electroosmotic flow.

<p>Total glucose flux measured before, during, and after treatments: iontophoresis of either acetate (black) which should induce only electroosmosis, or citrate (blue) which should induce both paracellular permeability enhancement and electroosmosis (<i>n</i> = 4).</p

Glucose flux under normal conditions.

<p>Sweat glucose concentration and sweat rates measured at various time points following artificial sweat stimulation. Sweat glucose concentration is inversely proportional to sweat rate. The average glucose flux for all participants is roughly 100 fmol/(min-gland) (<i>n</i> = 6).</p