Wednesday, July 26, 2017
A wearable chemical–electrophysiological hybrid biosensing system for real-time health and fitness monitoring Somayeh Imani , Amay J. Bandodkar , A. M. Vinu Mohan , Rajan Kumar , Shengfei Yu , Joseph Wang & Patrick P. Mercie Abstract Flexible, wearable sensing devices can yield important information about the underlying physiology of a human subject for applications in real-time health and fitness monitoring. Despite significant progress in the fabrication of flexible biosensors that naturally comply with the epidermis, most designs measure only a small number of physical or electrophysiological parameters, and neglect the rich chemical information available from biomarkers. Here, we introduce a skin-worn wearable hybrid sensing system that offers simultaneous real-time monitoring of a biochemical (lactate) and an electrophysiological signal (electrocardiogram), for more comprehensive fitness monitoring than from physical or electrophysiological sensors alone. The two sensing modalities, comprising a three-electrode amperometric lactate biosensor and a bipolar electrocardiogram sensor, are co-fabricated on a flexible substrate and mounted on the skin. Human experiments reveal that physiochemistry and electrophysiology can be measured simultaneously with negligible cross-talk, enabling a new class of hybrid sensing devices. Introduction Wearable sensors present an exciting opportunity to measure human physiology in a continuous, real-time and non-invasive manner1,2. Recent advances in hybrid fabrication techniques have enabled the design of wearable sensing devices in thin, conformal form factors that naturally comply with the smooth curvilinear geometry of human skin, thereby enabling intimate contact necessary for robust physiological measurements1,3,4. Development of such epidermal electronic sensors has enabled devices that can monitor respiration rate5,6,7, heart rate8,9, electrocardiograms4,10,11,12, blood oxygenation13, skin temperature14,15, bodily motion16,17,18,19,20, brain activity21,22,23 and blood pressure24,25. To date, most systems have targeted only a single measurement at a time, and most such sensors measure only physical and electrophysiological parameters, significantly limiting monitoring and diagnostic opportunities. For example, the human body undergoes complex physiological changes during physical activities such as exercise26,27, and monitoring the physiologic effect of physical activity can be important for a wide variety of subjects ranging from athletes to the elderly28,29,30. However, current wearable devices that only measure heart rate, motion and electrocardiogram provide an incomplete picture of the complex physiological changes taking place. As a result, further progress in the area of wearable sensors must include new, relevant sensing modalities, and must integrate these different modalities into a single platform for continuous, simultaneous sensing of multiple parameters relevant to a wide range of conditions, diseases, health and performance states. Inclusion of chemical measurements can provide extremely useful insights not available from physical or electrophysiological sensors31. Chemical information can be conventionally acquired via clinical labs or point-of-care devices32,33,34; unfortunately, such approaches do not support continuous, real-time measurements, therefore limiting their utility to applications where stationary, infrequent tests are sufficient. While recent work, including our own, has demonstrated that chemicals such as electrolytes and metabolites can be measured continuously using epidermal electronics on the skin35,36,37,38, or through non-invasive monitoring of other body fluids38,39,40, these devices measure only a single parameter at once, and are not integrated with other sensing modalities. Recently, Gao et al.41 demonstrated a wearable patch that can simultaneously track levels of metabolites and electrolytes in human sweat. However, electrophysiology sensors were not included, and such multimodal sensor fusion is crucial to obtain a more comprehensive knowledge about a wearer’s well-being. Here, we introduce a wearable device that can simultaneously measure chemical and electrophysiological parameters in the form factor of a single epidermal patch. The hybrid wearable, termed here as a Chem–Phys patch, comprises a screen-printed three-electrode amperometric lactate biosensor and two electrocardiogram electrodes, enabling concurrent real-time measurements of lactate and electrocardiogram. When used in physical-exertion monitoring, electrocardiogram measurements can help monitor heart health and function, while sweat lactate can be used to track an individual’s performance and exertion level, and is also an important biomarker for tissue oxygenation and pressure ischaemia42,43,44,45,46,47. Although prior work has demonstrated separate wearable electrocardiogram and lactate sensors, these devices were fabricated on separate platforms and thus mandate applying multiple patches on the human body, which is inconvenient and can deter long-term use. By combining a lactate biosensor and an electrocardiogram sensor, the new Chem–Phys hybrid wearable patch represents a powerful platform capable of simultaneously tracking both physicochemical and electrophysiological attributes, thus providing a more comprehensive view of a person’s health status than current wearable fitness monitors. The Chem–Phys hybrid patch was fabricated by leveraging screen-printing technology on a thin, highly flexible polyester sheet that conforms well with the complex three-dimensional (3D) morphology of human skin to provide a low-noise signal. The working electrode of the lactate biosensor was functionalized and coated with a biocompatible biocatalytic layer (lactate oxidase (LOx)-modified prussian blue). The three amperometric electrodes were separated from the Ag/AgCl electrocardiogram electrodes via a printed hydrophobic layer to maximize sensor stability and signal-to-noise ratio even in the presence of significant perspiration. The dimensions of the electrodes and the inter-electrode distances have been optimized based on the human trials to acquire a clean electrocardiogram signal and lactate response with minimal interference between the two sensors. The two sensors were interfaced to a custom-printed circuit board (PCB) featuring a potentiostat, an electrocardiogram analogue front-end (AFE), and a bluetooth low-energy (BLE) radio for wireless telemetry of the results to a mobile platform, such as a smartphone or laptop. The hybrid sensing system was tested on three human subjects during exercise on a stationary bicycle, showing that lactate and electrocardiogram can be measured simultaneously with negligible co-interference. Electrocardiogram data was found to be similar to the data collected from standard electrode types, and extracted heart rate correlated well to commercial heart rate detectors. A control experiment, where an enzyme-free amperometric sensor was applied to a perspiring human subject, corroborated the lactate sensor’s sensitivity and selectivity towards on-body detection of physiologic lactate levels. The promising data obtained in this work thus supports the possibility of developing more advanced hybrid wearable sensors that involve complex integration of several physical and chemical sensors on the same platform for monitoring many relevant modalities.