Point-of-Care, Cable Type Electrochemical Sensor with Ultrahigh Sensitivity for Detection of Metabolites in Human Perspiration
Authors: Mondal Sudeshna , Subramaniam Chandramouli 
Published: May 2020

Wearable sensors with a non-invasive platform have garnered significant interest over the recent years in the area of personalised healthcare monitoring. Extensive research is being carried out in this field as it utilizes recent technology for the fabrication of smart sensors which aims in addressing the demands of epidermal sensing where durability, lightweight, and intimated skin conformance are core requirements. Yet, further progress in this area has been hindered due to the lack of efficient chemical sensors and biosensors, able to monitor the chemical constituents residing on the epidermis of the wearer’s body. In this context, electrochemical sensors offer promise as wearable chemical sensors due to their high performance, inherent miniaturization and low cost. A wide range of electrochemical sensors and biosensors have been developed for real-time non-invasive monitoring of electrolytes and metabolites in sweat, tears, saliva as indicator of wearer’s health status. Substantial progress in this field of electrochemical sensors has led to the development of commercial hand analysers such as ACCU-CHECK (Roche Diagnostics, Inc.), iSTAT (Abbot, Inc.), or Lactate Scout (Sports Resource Group, Inc.), for detecting metabolites and electrolytes.
The present work demonstrates the fabrication and characterization of a wearable sensor which can help in real-time, non-invasive monitoring of metal ion levels (K+, Zn2+) in perspiration directly from human epidermis. Potassium, one of the major constituents in sweat after sodium is important for the normal functioning of the human body in regulating blood pressure, normal water balance, muscle contractions and maintain pH balance of the body. It is also an important electrolyte present in the human body. Deficiency in potassium can lead to high blood pressure, muscle paralysis, breathing problems, irregular heart rhythms and constipation. Zinc, another metal present in trace levels in human perspiration; is a primary biomarker for muscular stress and fatigue. It is an important trace metal ion as it is involved in functioning of biochemical processes relevant to enzymes, hormones, and transcription related factors. Perspiration represents an efficient pathway for the release of potassium and zinc which leads to its deficiency in the body. Thus, monitoring of these metal ions in the body from perspiration becomes essential for athletes and for persons engaged in strenuous physical activity for the detection of wide ranging physiological states. Changes of potassium concentration in perspiration beyond optimal concentration (0.2 g/l) and zinc (1.56 µg/ml) can be used as indicators for physiological state of human body, such as low blood pressure and muscular stress and fatigue. While identifying the loss of these metal ions during physical activity is very important, currently very few tools exist for real-time detection of metal ion levels in perspiration. Electrochemical techniques such as stripping voltammetry have also been employed extensively for qualitative and quantitative detection of metal ions from the body. In-situ measurements have been demonstrated using micro-fabricated three-electrode assemblies utilizing expensive and laborious lithographic techniques. Although miniaturized and portable, such systems are not reusable and therefore are expensive and not scalable. Besides, their integration for real-time monitoring has been a challenge. Thus, the need of the hour is a detection system that combines ease of handling, real-time, in-situ analysis and specific detection of these metal ions in perspiration without compromising on the sensitivity reusability and cost-effectiveness.
In order to achieve this, we have utilized novel molecular nanomaterials as transducers onto which the ion-selective receptors were immobilized. Specifically, the detection assembly consisted of cellulose fibres that were conformally coated with single wall carbon nanotubes (SWNTs). This resulted in a synergistic relation with the cellulose matrix providing the porosity and SWNTs providing the high specific surface area and electrical conduction pathway for signal transduction resulting in the fabrication of CNT-thread. Achieving ultrahigh sensitivity over a wide concentration range of analyte has been a persistent, mutually exclusive challenge for real-time analytical detection and diagnostics. To this end, we demonstrate a miniaturized, coaxial, cable-type electrochemical sensor comprised of a carbon nanotube immobilized cellulose yarn (CNT-thread) to achieve ultrahigh sensitivity (<1 ppm) across a wide dynamic range (0.1−500 ppm) for the rapid (∼60 s) detection of K+ and Zn2+. The sensor comprises of two cables of CNT-thread, one coated with a polymeric, ion-receptor (tetrakis(p-aminophenyl) porphyrin for Zn2+) and Valinomycin for K+ acting as the working electrode and the other being a reference electrode of pristine CNT-thread. The sensor is extremely tolerant to interference (selectivity coefficient 10−3−10−5) from a wide range of cations (Na+, Mg2+, Cd2+, Ca2+, Fe2+, and Cu2+) and anions (Cl−, NO3
−, PO4
3−, and CH3COO−) enabling real-time detection of K+ and Zn2+. Importantly, excellent signal consistency (<5% deviation) across multiple electrochemical techniques such as cyclic voltammetry, differential pulse voltammetry, and chronoamperometry is demonstrated. Minimal deviation (<6%) between the analyte concentrations estimated from the sensor and those estimated from atomic-absorption techniques is observed. Finally, the lifetime and mechanical sturdiness of the sensing platform is illustrated through elaborate experiments involving bending and seamless interfacing with human skin for noninvasive point-of-care analysis. Thus, this portable electrochemical platform enables the real-time analysis of metal ions in human perspiration without compromising on its sensitivity, reusability and cost-effectiveness.

References

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Figure 1