A non-faradaic label-free cortisol biosensor was demonstrated using MoS₂ nanosheets integrated into a nanoporous flexible electrode system. Low volume (1–5 μL) sensing was achieved through use of a novel sensor stack design comprised of vertically aligned metal electrodes confining semi-conductive MoS₂ nanosheets. The MoS₂ nanosheets were surface functionalized with cortisol antibodies towards developing an affinity biosensor specific to the physiological relevant range of cortisol (8.16 to 141.7 ng/mL) in perspired human sweat. Sensing was achieved by measuring impedance changes associated with cortisol binding along the MoS₂ nanosheet interface using electrochemical impedance spectroscopy. The sensor demonstrated a dynamic range from 1–500 ng/mL with a limit of detection of 1 ng/mL. A specificity study was conducted using a metabolite expressed in human sweat, Ethyl Glucuronide. Continuous dosing studies were performed during which the sensor was able to discriminate between four cortisol concentration ranges (0.5, 5, 50, 500 ng/mL) for a 3+ hour duration. Translatability of the sensor was shown with a portable form factor device, demonstrating a comparable dynamic range and limit of detection for the sensor. The device demonstrated a R² correlation value of 0.998 when comparing measurements to the reported impedance values of the benchtop instrumentation.

Zinc imidazole framework-8, abbreviated as ZIF-8, is a member of the metal organic framework (MOF) family. The chemical architecture of ZIF-8 consists of zinc metal duly coordinated with an organic ligand/fragment, resulting in a cagelike three-dimensional network with unique porosity. Because of such a unique architecture and physicochemical property, ZIF-8 has recently been explored in various applications such as gas storage, catalysis, electrochemical sensing, drug delivery, etc. Electrochemical sensors are currently a hot topic in scientific advances, where small, portable, Internet of Things (IoT)-enabled devices powered by electrochemical output show a newer path toward chemo and biosensor applications. The unique electrochemical property of ZIF-8 is hence explored widely for possible electrochemical sensor applications. The application and synthesis of the bare ZIF-8 have been widely reported for more than a decade. However, new scientific advancements depict tailoring the bare ZIF-8 structure to achieve smart hybrid ZIF-8 materials that show more advanced properties compared to bare ZIF-8. The framework is formed by joining inorganic (metal-containing) units with organic linkers by reticular synthesis, which results in the formation of a cross-linked crystalline network with permanent porosity. This unique porosity of ZIF-8 has recently been utilized for the encapsulation of suitable guest species to enhance the native physicochemical activity of ZIF-8. These engineered ZIF-8 materials show excellent results, especially for electrochemical sensing application. This review is intended to describe the research, including the one done by our group, where the ZIF-8 pore size is used for encapsulating nanoparticles, enzymes, and organic compounds to avail suitable sensor applications.

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.

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-1β. Cortisol detection in human sweat was demonstrated over a concentration range from 10–200 ng/mL.