A Combinatorial Electrochemical Biosensor for Sweat Biomarker Benchmarking

Abstract

Misclassification of an acute disease condition as chronic and vice versa by electrochemical sweat biomarker sensors can cause significant psychological, emotional, and financial stress among patients. To achieve higher accuracy in distinguishing between a chronic condition and an acute condition, there is a need to establish a reference biomarker to index the actual chronic disease biomarker of interest by combinatorial sensing. This work provides the first technological proof of leveraging the chloride ion content in sweat for a combinatorial sweat biomarker benchmarking scheme. In this scheme, the sweat chloride ion has been demonstrated as the reference/indexing biomarker, while sweat cortisol has been studied as the disease biomarker of interest. Label-free affinity biosensing is achieved by using a two-electrode electrochemical system on a flexible substrate suitable for wearable applications. The electrochemical stability of the fabricated electrodes for biosensing applications was studied by open-circuit potential measurements. Attenuated total reflectance–Fourier transform infrared spectroscopy spectra validate the crosslinker–antibody binding chemistry. Concentration-dependent analyte–capture probe binding induces a modulation in the electrical properties (charge transfer resistance and double-layer capacitance) at the electrode–sweat buffer interface, which are transduced by nonfaradaic electrochemical impedance spectroscopy (EIS). Calibration dose responses for the sensor for cortisol (5–200 ng/mL) and chloride (10–100 mM) detection were evaluated in synthetic (pH 6) and pooled human sweat ( R2 > 0.95). The variation in the cortisol sensor response due to fluctuations in sweat chloride levels and the significance of reporting normalized biomarker levels were demonstrated to further emphasize the need for biomarker benchmarking in electrochemical sensors.

Identification of Suitable Biomarkers for Stress and Emotion Detection for Future Personal Affective Wearable Sensors

“…Several methods have been utilized to detect cortisol, the main stress biomarker. In this regard, the antibody-based technique is the most common tool used to detect cortisol in sweat [37,[39][40][41]55], while less commonly used techniques include the aptamer [43], e-nose [44,56], and MIP [45,46] techniques. In terms of sensitivity, all of the above-mentioned studies succeeded in detecting cortisol in its targeted range.…”

“…Antibody recognition methods including immunoassay and electrochemical immune sensing were utilized in five out of eight studies to detect cortisol [37,[39][40][41]55]. These methods were effective in terms of specificity to cortisol molecules because of the nature of antibody-antigen immunochemistry [55]. CortiWatch [39], a cortisol wristband sensor, presents the antibody technique as an advanced step in this field.…”

Evidence-Based Point-of-care Technology Development During the COVID-19 Pandemic

“…Minimally invasive sample collection methods and the manufacturability of POC tests will decide their successful integration into device form factors that can be used in various POC settings. Our lab is equipped to address the needs of COVID-19 diagnostics because of our expertise in developing biosensors toward identifying relevant biomarkers from various body fluids such as blood [ 37 ], sweat [ 38 , 39 ], saliva, blood and exhaled breath condensate. For example, robust sensing platforms include a rapid electrochemical device using a single drop of sample (<40 μl blood) for point-of-use parathyroid hormone screening, a portable biosensor for cortisol monitoring in a low volume (1–5 μl) of human sweat and a screen-printed graphene oxide textile biosensor for point-of-exposure detection of influenza for at-risk populations [ 40 ].…”

Development Perspective of Bioelectrocatalysis-Based Biosensors

“…The water content in sweat is easily varied. The suggested internal standards in sweat are chloride ion [ 114 ] and sodium ion [ 115 ]. Because it is difficult to incorporate those ions into the redox reaction, potentiometry is suitable to detect these ions.…”