(Invited) Breath and Skin Gas Sensing for Rapid POC Medical Diagnostics

Abstract

Antiquity’s first known physician, Hippocrates of Cos (460–370 BC), smelled his patients’ breath to diagnose disease and recommend the appropriate remedy. Some medical terms coined then survive today, such as “fetor hepaticus,” which describes the sweet, ketone- and ammonia- rich scent that indicates the late stages of liver failure. Yet, neither breath nor skin analysis, as a noninvasive means of disease detection, are common practice among physicians to-date nor are they available to the general population. Ceramic sensor nanotechnology and nanomedicine are, however, capable of making breath-based diagnostics. VOCs in breath and skin are products of core metabolic processes, while inorganic molecules are related to other health conditions and can be indicators of a potential disease, recent exposure to a drug or an environmental pollutant. Therefore, an abnormally high or low measured concentration of certain breath or skin gases, so-called biomarkers, could potentially provide clues for diagnosing corresponding diseases. This work focuses on electronic olfaction systems which we have developed and used in breath-based testing of Volatile Organic Compound (VOC) biomarkers with great success. It also addresses the concept of skin-gas “smelling” of disease. These gas sensing nanotechnologies allow for the rapid and reliable output signals which indicate the host’s response to infection or metabolic changes. Using the library of specific prints/unique patterns for each of the targeted diseases, the following types of diseases could be potentially diagnosed: Metabolic diseases: diabetes, cholesterol-induced heart disease; Neurological diseases: Alzheimers, Parkinson’s; Chronic diseases: obesity, sleep apnea; Pulmonary diseases: CF, asthma, COPD; GI tract diseases: IBS, colitis; Cancers: breast, lung, pancreatic, colon, and Infectious diseases: flu, COVID-19; as well as diseases commonly found in ICU patients: Urinary tract infections, pneumonia, infections of the blood stream. Focusing on the most common gaseous biomarkers in breath and skin, that is Nitric Oxide and Carbon Monoxide and VOCs (acetone, isoprene, ammonia, alcohols, sulfides) effective discrimination between the diseases mentioned above is possible, by capturing the relative sensor output signals from the detection of each of these biomarkers and analyzing them to reveal the distinct breath print for each disease. We focus here on an electronic olfaction device based on resistive gas sensing utilizing a small number, just four at a time, of metal-oxide sensors that are specifically sensitive to the biomarkers of interest.A single-scan skin testing device comprises an array of gas sensors, each of which satisfies the following stringent conditions: high sensitivity to the target gas, high selectivity, stable response over extended periods of time and rapid response. The concentration of a target gas over a selective sensor is quantified by measurement of the sensor resistance. We also present a novel wearable device interfacing with a smart phone for disease detection and monitoring. This device utilizes conducting polymer actuators, since conductive polymers exhibit a low operating potential (typically <2V), and a high mechanical strength. Quantitative medical diagnostics require simultaneous monitoring of multiple gases because markers are affected differently in different diseases and this device allows for continuous measurement of acetone for diabetes monitoring.