Wireless Wearable Electrochemical Sensing Platform with Zero-Power Osmotic Sweat Extraction for Continuous Lactate Monitoring.

Wearable and wireless monitoring of biomarkers such as lactate in sweat can provide a deeper understanding of a subject's metabolic stressors, cardiovascular health, and physiological response to exercise. However, the state-of-the-art wearable and wireless electrochemical systems rely on active sweat released either via high-exertion exercise, electrical stimulation (such as iontophoresis requiring electrical power), or chemical stimulation (such as by delivering pilocarpine or carbachol inside skin), to extract sweat under low-perspiring conditions such as at rest. Here, we present a continuous sweat lactate monitoring platform combining a hydrogel for osmotic sweat extraction, with a paper microfluidic channel for facilitating sweat transport and management, a screen-printed electrochemical lactate sensor, and a custom-built wireless wearable potentiostat system. Osmosis enables zero-electrical power sweat extraction at rest, while continuous evaporation at the end of a paper channel allows long-term sensing from fresh sweat. The positioning of the lactate sensors provides near-instantaneous sensing at low sweat volume, and the custom-designed potentiostat supports continuous monitoring with ultra-low power consumption. For a proof of concept, the prototype system was evaluated for continuous measurement of sweat lactate across a range of physiological activities with changing lactate concentrations and sweat rates: for 2 h at the resting state, 1 h during medium-intensity exercise, and 30 min during high-intensity exercise. Overall, this wearable system holds the potential of providing comprehensive and long-term continuous analysis of sweat lactate trends in the human body during rest and under exercising conditions.

A Wearable Patch for Prolonged Sweat Lactate Harvesting and Sensing.

Operating at low sweat rates, such as those experienced by humans at rest, is still an unmet need for state-of-the-art wearable sweat harvesting and testing devices for lactate. Here, we report the on-skin performance of a non-invasive wearable sweat sampling patch that can harvest sweat at rest, during exercise, and post-exercise. The patch simultaneously uses osmosis and evaporation for long-term (several hours) sampling of sweat. Osmotic sweat withdrawal is achieved by skin-interfacing a hydrogel containing a concentrated solute. The gel interfaces with a paper strip that transports the fluid via wicking and evaporation. Proof of concept results show that the patch was able to sample sweat during resting and post-exercise conditions, where the lactate concentration was successfully quantified. The patch detected the increase in sweat lactate levels during medium level exercise. Blood lactate remained invariant with exercise as expected. We also developed a continuous sensing version of the patch by including enzymatic electrochemical sensors. Such a battery-free, passive, wearable sweat sampling patch can potentially provide useful information about the human metabolic activity.

Rational design of direct electron transfer type l-lactate dehydrogenase for the development of multiplexed biosensor.

The development of wearable multiplexed biosensors has been focused on systems to measure sweat l-lactate and other metabolites, where the employment of the direct electron transfer (DET) principle is expected. In this paper, a fusion enzyme between an engineered l-lactate oxidase derived from Aerococcus viridans, AvLOx A96L/N212K mutant, which is minimized its oxidase activity and b-type cytochrome protein was constructed to realize multiplexed DET-type lactate and glucose sensors. The sensor with a fusion enzyme showed DET to a gold electrode, with a limited operational range less than 0.5 mM. A mutation was introduced into the fusion enzyme to increase Km value and eliminate its substrate inhibition to construct "b2LOxS". Together with the employment of an outer membrane, the detection range of the sensor with b2LOxS was expanded up to 10 mM. A simultaneous lactate and glucose monitoring system was constructed using a flexible thin-film multiplexed electrodes with b2LOxS and a DET-type glucose dehydrogenase, and evaluated their performance in the artificial sweat. The sensors achieved simultaneous detection of lactate and glucose without cross-talking error, with the detected linear ranges of 0.5-20 mM for lactate and 0.1-5 mM for glucose, sensitivities of 4.1 nA/mM∙mm2 for lactate and 56 nA/mM∙mm2 for glucose, and limit of detections of 0.41 mM for lactate and 0.057 mM for glucose. The impact of the presence of electrochemical interferants (ascorbic acid, acetaminophen and uric acid), was revealed to be negligible. This is the first report of the DET-type enzyme based lactate and glucose dual sensing systems.

Wearable multiplexed biosensor system toward continuous monitoring of metabolites.

Comprehensive metabolic panels are the most reliable and common methods for monitoring general physiology in clinical healthcare. Translation of this clinical practice to personal health and wellness tracking requires reliable, non-invasive, miniaturized, ambulatory, and inexpensive systems for continuous measurement of biochemical analytes. We report the design and characterization of a wearable system with a flexible sensor array for non-invasive and continuous monitoring of human biochemistry. The system includes signal conditioning, processing, and transmission parts for continuous measurement of glucose, lactate, pH, and temperature. The system can operate three discrete electrochemical cells. The system draws 15 mA under continuous operation when powered by a 3.7 V 150 mAh battery. The analog front-end of the electrochemical cells has four potentiostats and three multiplexers for multiplexed and parallel readout from twelve working electrodes. Utilization of redundant working electrodes improves the measurement accuracy of sensors by averaging chronoamperometric responses across the array. The operation of the system is demonstrated in vitro by simultaneous measurement of glucose and lactate, pH, and skin temperature. In benchtop measurements, the sensors are shown to have sensitivities of 26.31 µA mM-1·cm-2 for glucose, 1.49 µA mM-1·cm-2 for lactate, 54 mV·pH-1 for pH, and 0.002 °C-1 for temperature. With the custom wearable system, these values were 0.84 ± 0.03 mV µM-1·cm-2 or glucose, 31.87 ± 9.03 mV mM-1·cm-2 for lactate, 57.18 ± 1.43 mV·pH-1 for pH, and 63.4 µV·°C-1 for temperature. This miniaturized wearable system enables future evaluation of temporal changes of the sweat biomarkers.

Measuring and regulating oxygen levels in microphysiological systems: design, material, and sensor considerations.

As microfabrication techniques and tissue engineering methods improve, microphysiological systems (MPS) are being engineered that recapitulate complex physiological and pathophysiological states to supplement and challenge traditional animal models. Although MPS provide unique microenvironments that transcend common 2D cell culture, without proper regulation of oxygen content, MPS often fail to provide the biomimetic environment necessary to activate and investigate fundamental pathways of cellular metabolism and sub-cellular level. Oxygen exists in the human body in various concentrations and partial pressures; moreover, it fluctuates dramatically depending on fasting, exercise, and sleep patterns. Regulating oxygen content inside MPS necessitates a sensitive biological sensor to quantify oxygen content in real-time. Measuring oxygen in a microdevice is a non-trivial requirement for studies focused on understanding how oxygen impacts cellular processes, including angiogenesis and tumorigenesis. Quantifying oxygen inside a microdevice can be achieved via an array of technologies, with each method having benefits and limitations in terms of sensitivity, limits of detection, and invasiveness that must be considered and optimized. This article will review oxygen physiology in organ systems and offer comparisons of organ-specific MPS that do and do not consider oxygen microenvironments. Materials used in microphysiological models will also be analyzed in terms of their ability to control oxygen. Finally, oxygen sensor technologies are critically compared and evaluated for use in MPS.

Fabric-Based Wearable Dry Electrodes for Body Surface Biopotential Recording.

A flexible and conformable dry electrode design on nonwoven fabrics is examined as a sensing platform for biopotential measurements. Due to limitations of commercial wet electrodes (e.g., shelf life, skin irritation), dry electrodes are investigated as the potential candidates for long-term monitoring of ECG signals. Multilayered dry electrodes are fabricated by screen printing of Ag/AgCl conductive inks on flexible nonwoven fabrics. This study focuses on the investigation of skin-electrode interface, form factor design, electrode body placement of printed dry electrodes for a wearable sensing platform. ECG signals obtained with dry and wet electrodes are comparatively studied as a function of body posture and movement. Experimental results show that skin-electrode impedance is influenced by printed electrode area, skin-electrode interface material, and applied pressure. The printed electrode yields comparable ECG signals to wet electrodes, and the QRS peak amplitude of ECG signal is dependent on printed electrode area and electrode on body spacing. Overall, fabric-based printed dry electrodes present an inexpensive health monitoring platform solution for mobile wearable electronics applications by fulfilling user comfort and wearability.