Self-Testing of Ketone Bodies, along with Glucose, Using Touch-Based Sweat Analysis

Abstract

β-Hydroxybutyrate (HB) is one of the main physiological ketone bodies that play key roles in human health and wellness. Besides their important role in diabetes ketoacidosis, ketone bodies are currently receiving tremendous attention for personal nutrition in connection to the growing popularity of oral ketone supplements. Accordingly, there are urgent needs for developing a rapid, simple, and low-cost device for frequent onsite measurements of β-hydroxybutyrate (HB), one of the main physiological ketone bodies. However, real-time profiling of dynamically changing HB concentrations is challenging and still limited to laboratory settings or to painful and invasive measurements (e.g., a commercial blood ketone meter). Herein, we address the critical need for pain-free frequent HB measurements in decentralized settings and report on a reliable noninvasive, simple, and rapid touch-based sweat HB testing and on its ability to track dynamic HB changes in secreted fingertip sweat, following the intake of commercial ketone supplements. The new touch-based HB detection method relies on an instantaneous collection of the fingertip sweat at rest on a porous poly(vinyl alcohol) (PVA) hydrogel that transports the sweat to a biocatalytic layer, composed of the β-hydroxybutyrate dehydrogenase (HBD) enzyme and its nicotinamide adenine dinucleotide (NAD+) cofactor, covering the modified screen-printed carbon working electrode. As a result, the sweat HB can be measured rapidly by the mediated oxidation reaction of the nicotinamide adenine dinucleotide (NADH) product. A personalized HB dose-response relationship is demonstrated within a group of healthy human subjects taking commercial ketone supplements, along with a correlation between the sweat and capillary blood HB levels. Furthermore, a dual disposable biosensing device, consisting of neighboring ketone and glucose enzyme electrodes on a single-strip substrate, has been developed toward the simultaneous touch-based detection of dynamically changing sweat HB and glucose levels, following the intake of ketone and glucose drinks.