Wearable System for Real-Time Sensing of Biomarkers in Human Sweat

Wearable sweat sensing systems offer non-invasive and real-time bio-data streaming solutions. They open the possibility for continuous monitoring of biomarkers' concentrations as well as their variation in sweat, which is a complementary to current passive and discrete health check procedures. Sweat contains many biomarkers, ranging from electrolytes and small molecules, to peptides and proteins. Some of these biomarkers' concentrations have been demonstrated to be closely correlated to their concentrations in blood, while others show more complicated partitioning procedures related to re-adsorption to sweat gland, sweat rate, contamination from old skin and degradation due to exposure to ambient environment. Therefore, on-body sweat sensing is of utmost importance in both application-driven industry and clinical research. Yet, there are several challenges in the development of on-body sweat sensing systems. i. Reliable and scalable sensors that can be integrated within a miniaturized area, ii. Real-time sweat sampling and analysis that minimizes contamination and preserves maximum fidelity of bio-info from biomarker degradation. The goal of this thesis is to demonstrate a wearable sensing system for simultaneous monitoring of multiple analytes in sweat, with building blocks potentially solving the above mentioned challenges. This thesis reports the development and experimental validation of a wearable sensor system that allows multiplexed sensing and streaming of bio-data concerning electrolyte concentrations in sweat. The wearable sensor system comprises: I. Multi-analyte (pH, Na+, K+ and Ca2+) sensing chip that incorporates high performance, high yield, high robustness, ultra-low power (down to pico-Watt per sensor) ISFETs. High sensitivities close to the Nernstian limit for all the analytes are demonstrated. Simultaneous time-dependent recording of multiple analytes and dedicated tests with prepared samples containing many known analytes, demonstrate the high selectivity of the reported sensors. II. Bio-compatible skin interface (microfluidics) with drop-to-drop resolution, capable of sampling and analyzing sweat drops with volume as low as tens of nano-Liters. Continuous electronic readout of sweat rate is enabled with the implementation of microfluidics. III. Multiplexed readout circuits are implemented on bio-compatible substrates, in order to simultaneously readout the electrolyte concentrations and sweat rate in real-time, enabling bio-data streaming. We report integration of all the needed functions in a wearable patch that is developed to be tested on humans.