Membrane isolation of repeated-use sweat stimulants for mitigating both direct dermal contact and sweat dilution.

With the device integration of sweat stimulation, sweat becomes a stronger candidate for non-invasive continuous biochemical sensing. However, sweat stimulants are cholinergenic agents and non-selective to just the sweat glands, and so, direct placement of sweat stimulants poses additional challenges in the possibility for uncontrollable transport of the stimulant into the body and challenges in contamination of the sweat sample. Reported here is membrane isolation of repeated-use sweat stimulants for mitigating direct dermal contact, dilution of the sweat stimulant, and contamination of the sweat sample. The membrane dramatically reduces passive diffusion of the sweat stimulant carbachol by roughly two orders of magnitude, while still allowing repeated sweat stimulation by iontophoretic delivery of the carbachol through the membrane and into the skin. Both in-vivo and in-vitro validation reveal feasibility for reliable integration of sweat stimulants within a wearable device for use periods of 24 h or more. In addition, advanced topics and confounding issues such as stimulant gel design, osmotic pressure, and ionic impurities are speculatively and theoretically discussed.

A new oil/membrane approach for integrated sweat sampling and sensing: sample volumes reduced from µL's to nL's and reduction of analyte contamination from skin.

Wearable sweat biosensensing technology has dominantly relied on techniques which place planar-sensors or fluid-capture materials directly onto the skin surface. This 'on-skin' approach can result in sample volumes in the µL regime, due to the roughness of skin and/or due to the presence of hair. Not only does this increase the required sampling time to 10's of minutes or more, but it also increases the time that sweat spends on skin and therefore increases the amount of analyte contamination coming from the skin surface. Reported here is a first demonstration of a new paradigm in sweat sampling and sensing, where sample volumes are reduced from the µL's to nL's regime, and where analyte contamination from skin is reduced or even eliminated. A micro-porous membrane is constructed such that it is porous to sweat only. To complete a working device, first placed onto skin is a cosmetic-grade oil, secondly this membrane, and thirdly the sensors. As a result, spreading of sweat is isolated to only regions above the sweat glands before it reaches the sensors. Best case sampling intervals are on the order of several minutes, and the majority of hydrophilic (low oil solubility) contaminants from the skin surface are blocked. In vitro validation of this new approach is performed with an improved artificial skin including human hair. In vivo tests show strikingly consistent results, and reveal that the oil/membrane is robust enough to even allow horizontal sliding of a sensor.

The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications.

Non-invasive and accurate access of biomarkers remains a holy grail of the biomedical community. Human eccrine sweat is a surprisingly biomarker-rich fluid which is gaining increasing attention. This is especially true in applications of continuous bio-monitoring where other biofluids prove more challenging, if not impossible. However, much confusion on the topic exists as the microfluidics of the eccrine sweat gland has never been comprehensively presented and models of biomarker partitioning into sweat are either underdeveloped and/or highly scattered across literature. Reported here are microfluidic models for eccrine sweat generation and flow which are coupled with review of blood-to-sweat biomarker partition pathways, therefore providing insights such as how biomarker concentration changes with sweat flow rate. Additionally, it is shown that both flow rate and biomarker diffusion determine the effective sampling rate of biomarkers at the skin surface (chronological resolution). The discussion covers a broad class of biomarkers including ions (Na(+), Cl(-), K(+), NH4 (+)), small molecules (ethanol, cortisol, urea, and lactate), and even peptides or small proteins (neuropeptides and cytokines). The models are not meant to be exhaustive for all biomarkers, yet collectively serve as a foundational guide for further development of sweat-based diagnostics and for those beginning exploration of new biomarker opportunities in sweat.