A new paradigm in sweat based wearable diagnostics biosensors using Room Temperature Ionic Liquids (RTILs).

Successful commercialization of wearable diagnostic sensors necessitates stability in detection of analytes over prolonged and continuous exposure to sweat. Challenges are primarily in ensuring target disease specific small analytes (i.e. metabolites, proteins, etc.) stability in complex sweat buffer with varying pH levels and composition over time. We present a facile approach to address these challenges using RTILs with antibody functionalized sensors on nanoporous, flexible polymer membranes. Temporal studies were performed using both infrared spectroscopic, dynamic light scattering, and impedimetric spectroscopy to demonstrate stability in detection of analytes, Interleukin-6 (IL-6) and Cortisol, from human sweat in RTILs. Temporal stability in sensor performance was performed as follows: (a) detection of target analytes after 0, 24, 48, 96, and 168 hours post-antibody sensor functionalization; and (b) continuous detection of target analytes post-antibody sensor functionalization. Limit of detection of IL-6 in human sweat was 0.2 pg/mL for 0-24 hours and 2 pg/mL for 24-48 hours post-antibody sensor functionalization. Continuous detection of IL-6 over 0.2-200 pg/mL in human sweat was demonstrated for a period of 10 hours post-antibody sensor functionalization. Furthermore, combinatorial detection of IL-6 and Cortisol in human sweat was established with minimal cross-talk for 0-48 hours post-antibody sensor functionalization.

Flexible nanoporous tunable electrical double layer biosensors for sweat diagnostics.

An ultra-sensitive and highly specific electrical double layer (EDL) modulated biosensor, using nanoporous flexible substrates for wearable diagnostics is demonstrated with the detection of the stress biomarker cortisol in synthetic and human sweat. Zinc oxide thin film was used as active region in contact with the liquid i.e. synthetic and human sweat containing the biomolecules. Cortisol detection in sweat was accomplished by measuring and quantifying impedance changes due to modulation of the double layer capacitance within the electrical double layer through the application of a low orthogonally directed alternating current (AC) electric field. The EDL formed at the liquid-semiconductor interface was amplified in the presence of the nanoporous flexible substrate allowing for measuring the changes in the alternating current impedance signal due to the antibody-hormone interactions at diagnostically relevant concentrations. High sensitivity of detection of 1 pg/mL or 2.75 pmol cortisol in synthetic sweat and 1 ng/mL in human sweat is demonstrated with these novel biosensors. Specificity in synthetic sweat was demonstrated using a cytokine IL-1ß. Cortisol detection in human sweat was demonstrated over a concentration range from 10-200 ng/mL.