Stanford Advisors


All Publications


  • A wearable patch for continuous analysis of thermoregulatory sweat at rest. Nature communications Nyein, H. Y., Bariya, M. n., Tran, B. n., Ahn, C. H., Brown, B. J., Ji, W. n., Davis, N. n., Javey, A. n. 2021; 12 (1): 1823

    Abstract

    The body naturally and continuously secretes sweat for thermoregulation during sedentary and routine activities at rates that can reflect underlying health conditions, including nerve damage, autonomic and metabolic disorders, and chronic stress. However, low secretion rates and evaporation pose challenges for collecting resting thermoregulatory sweat for non-invasive analysis of body physiology. Here we present wearable patches for continuous sweat monitoring at rest, using microfluidics to combat evaporation and enable selective monitoring of secretion rate. We integrate hydrophilic fillers for rapid sweat uptake into the sensing channel, reducing required sweat accumulation time towards real-time measurement. Along with sweat rate sensors, we integrate electrochemical sensors for pH, Cl-, and levodopa monitoring. We demonstrate patch functionality for dynamic sweat analysis related to routine activities, stress events, hypoglycemia-induced sweating, and Parkinson's disease. By enabling sweat analysis compatible with sedentary, routine, and daily activities, these patches enable continuous, autonomous monitoring of body physiology at rest.

    View details for DOI 10.1038/s41467-021-22109-z

    View details for PubMedID 33758197

    View details for PubMedCentralID PMC7987967

  • A Wearable Nutrition Tracker ADVANCED MATERIALS Zhao, J., Nyein, H., Hou, L., Lin, Y., Bariya, M., Ahn, C., Ji, W., Fan, Z., Javey, A. 2021; 33 (1): e2006444

    Abstract

    Nutrients are essential for the healthy development and proper maintenance of body functions in humans. For adequate nourishment, it is important to keep track of nutrients level in the body, apart from consuming sufficient nutrition that is in line with dietary guidelines. Sweat, which contains rich chemical information, is an attractive biofluid for routine non-invasive assessment of nutrient levels. Herein, a wearable sensor that can selectively measure vitamin C concentration in biofluids, including sweat, urine, and blood is developed. Detection through an electrochemical sensor modified with Au nanostructures, LiClO4 -doped conductive polymer, and an enzymes-immobilized membrane is utilized to achieve wide detection linearity, high selectivity, and long-term stability. The sensor allows monitoring of temporal changes in vitamin C levels. The effect of vitamin C intake on the sweat and urine profile is explored by monitoring concentration changes upon consuming different amounts of vitamin C. A longitudinal study of sweat's and urine's vitamin C correlation with blood is performed on two individuals. The results suggest that sweat and urine analysis can be a promising method to routinely monitor nutrition through the sweat sensor and that this sensor can facilitate applications such as nutritional screening and dietary intervention.

    View details for DOI 10.1002/adma.202006444

    View details for Web of Science ID 000591310100001

    View details for PubMedID 33225539

  • Flexible Electrochemical Bioelectronics: The Rise of In Situ Bioanalysis ADVANCED MATERIALS Yu, Y., Nyein, H., Gao, W., Javey, A. 2020; 32 (15): e1902083

    Abstract

    The amalgamation of flexible electronics in biological systems has shaped the way health and medicine are administered. The growing field of flexible electrochemical bioelectronics enables the in situ quantification of a variety of chemical constituents present in the human body and holds great promise for personalized health monitoring owing to its unique advantages such as inherent wearability, high sensitivity, high selectivity, and low cost. It represents a promising alternative to probe biomarkers in the human body in a simpler method compared to conventional instrumental analytical techniques. Various bioanalytical technologies are employed in flexible electrochemical bioelectronics, including ion-selective potentiometry, enzymatic amperometry, potential sweep voltammetry, field-effect transistors, affinity-based biosensing, as well as biofuel cells. Recent key innovations in flexible electrochemical bioelectronics from electrochemical sensing modalities, materials, systems, fabrication, to applications are summarized and highlighted. The challenges and opportunities in this field moving forward toward future preventive and personalized medicine devices are also discussed.

    View details for DOI 10.1002/adma.201902083

    View details for Web of Science ID 000482303900001

    View details for PubMedID 31432573

  • Regional and correlative sweat analysis using high-throughput microfluidic sensing patches toward decoding sweat SCIENCE ADVANCES Nyein, H., Bariya, M., Kivimaki, L., Uusitalo, S., Liaw, T., Jansson, E., Ahn, C., Hangasky, J. A., Zhao, J., Lin, Y., Happonen, T., Chao, M., Liedert, C., Zhao, Y., Tai, L., Hiltunen, J., Javey, A. 2019; 5 (8): eaaw9906

    Abstract

    Recent technological advancements in wearable sensors have made it easier to detect sweat components, but our limited understanding of sweat restricts its application. A critical bottleneck for temporal and regional sweat analysis is achieving uniform, high-throughput fabrication of sweat sensor components, including microfluidic chip and sensing electrodes. To overcome this challenge, we introduce microfluidic sensing patches mass fabricated via roll-to-roll (R2R) processes. The patch allows sweat capture within a spiral microfluidic for real-time measurement of sweat parameters including [Na+], [K+], [glucose], and sweat rate in exercise and chemically induced sweat. The patch is demonstrated for investigating regional sweat composition, predicting whole-body fluid/electrolyte loss during exercise, uncovering relationships between sweat metrics, and tracking glucose dynamics to explore sweat-to-blood correlations in healthy and diabetic individuals. By enabling a comprehensive sweat analysis, the presented device is a crucial tool for advancing sweat testing beyond the research stage for point-of-care medical and athletic applications.

    View details for DOI 10.1126/sciadv.aaw9906

    View details for Web of Science ID 000481798400045

    View details for PubMedID 31453333

    View details for PubMedCentralID PMC6697435

  • A Wearable Microfluidic Sensing Patch for Dynamic Sweat Secretion Analysis ACS SENSORS Nyein, H., Tai, L., Quynh Phuong Ngo, Chao, M., Zhang, G. B., Gao, W., Bariya, M., Bullock, J., Kim, H., Fahad, H. M., Javey, A. 2018; 3 (5): 944–52

    Abstract

    Wearable sweat sensing is a rapidly rising research area driven by its promising potential in health, fitness, and diagnostic applications. Despite the growth in the field, major challenges in relation to sweat metrics remain to be addressed. These challenges include sweat rate monitoring for its complex relation with sweat compositions and sweat sampling for sweat dynamics studies. In this work, we present a flexible microfluidic sweat sensing patch that enhances real-time electrochemical sensing and sweat rate analysis via sweat sampling. The device contains a spiral-patterned microfluidic component that is embedded with ion-selective sensors and an electrical impedance-based sweat rate sensor on a flexible plastic substrate. The patch is enabled to autonomously perform sweat analysis by interfacing the sensing component with a printed circuit board that is capable of on-site signal conditioning, analysis, and transmission. Progressive sweat flow in the microfluidic device, governed by the pressure induced by the secreted sweat, enhances sweat sampling and electrochemical detection via a defined sweat collection chamber and a directed sweat route. The characteristic of the sweat rate sensor is validated through a theoretical simulation, and the precision and accuracy of the flow rate is verified with a commercial syringe pump and a Macroduct sweat collector. On-body simultaneous monitoring of ion (H+, Na+, K+, Cl-) concentration and sweat rate is also demonstrated for sensor functionality. This sweat sensing patch provides an integrated platform for a comprehensive sweat secretion analysis and facilitates physiological and clinical investigations by closely monitoring interrelated sweat parameters.

    View details for DOI 10.1021/acssensors.7b00961

    View details for Web of Science ID 000433635300007

    View details for PubMedID 29741360

  • Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Emaminejad, S., Gao, W., Wu, E., Davies, Z. A., Nyein, H. Y., Challa, S., Ryan, S. P., Fahad, H. M., Chen, K., Shahpar, Z., Talebi, S., Milla, C., Javey, A., Davis, R. W. 2017; 114 (18): 4625-4630

    Abstract

    Perspiration-based wearable biosensors facilitate continuous monitoring of individuals' health states with real-time and molecular-level insight. The inherent inaccessibility of sweat in sedentary individuals in large volume (≥10 µL) for on-demand and in situ analysis has limited our ability to capitalize on this noninvasive and rich source of information. A wearable and miniaturized iontophoresis interface is an excellent solution to overcome this barrier. The iontophoresis process involves delivery of stimulating agonists to the sweat glands with the aid of an electrical current. The challenge remains in devising an iontophoresis interface that can extract sufficient amount of sweat for robust sensing, without electrode corrosion and burning/causing discomfort in subjects. Here, we overcame this challenge through realizing an electrochemically enhanced iontophoresis interface, integrated in a wearable sweat analysis platform. This interface can be programmed to induce sweat with various secretion profiles for real-time analysis, a capability which can be exploited to advance our knowledge of the sweat gland physiology and the secretion process. To demonstrate the clinical value of our platform, human subject studies were performed in the context of the cystic fibrosis diagnosis and preliminary investigation of the blood/sweat glucose correlation. With our platform, we detected the elevated sweat electrolyte content of cystic fibrosis patients compared with that of healthy control subjects. Furthermore, our results indicate that oral glucose consumption in the fasting state is followed by increased glucose levels in both sweat and blood. Our solution opens the possibility for a broad range of noninvasive diagnostic and general population health monitoring applications.

    View details for DOI 10.1073/pnas.1701740114

    View details for PubMedID 28416667

  • A Wearable Electrochemical Platform for Noninvasive Simultaneous Monitoring of Ca(2+) and pH. ACS nano Nyein, H. Y., Gao, W., Shahpar, Z., Emaminejad, S., Challa, S., Chen, K., Fahad, H. M., Tai, L., Ota, H., Davis, R. W., Javey, A. 2016; 10 (7): 7216-7224

    Abstract

    Homeostasis of ionized calcium in biofluids is critical for human biological functions and organ systems. Measurement of ionized calcium for clinical applications is not easily accessible due to its strict procedures and dependence on pH. pH balance in body fluids greatly affects metabolic reactions and biological transport systems. Here, we demonstrate a wearable electrochemical device for continuous monitoring of ionized calcium and pH of body fluids using a disposable and flexible array of Ca(2+) and pH sensors that interfaces with a flexible printed circuit board. This platform enables real-time quantitative analysis of these sensing elements in body fluids such as sweat, urine, and tears. Accuracy of Ca(2+) concentration and pH measured by the wearable sensors is validated through inductively coupled plasma-mass spectrometry technique and a commercial pH meter, respectively. Our results show that the wearable sensors have high repeatability and selectivity to the target ions. Real-time on-body assessment of sweat is also performed, and our results indicate that calcium concentration increases with decreasing pH. This platform can be used in noninvasive continuous analysis of ionized calcium and pH in body fluids for disease diagnosis such as primary hyperparathyroidism and kidney stones.

    View details for DOI 10.1021/acsnano.6b04005

    View details for PubMedID 27380446

  • Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis NATURE Gao, W., Emaminejad, S., Nyein, H. Y., Challa, S., Chen, K., Peck, A., Fahad, H. M., Ota, H., Shiraki, H., Kiriya, D., Lien, D., Brooks, G. A., Davis, R. W., Javey, A. 2016; 529 (7587): 509-?

    Abstract

    Wearable sensor technologies are essential to the realization of personalized medicine through continuously monitoring an individual's state of health. Sampling human sweat, which is rich in physiological information, could enable non-invasive monitoring. Previously reported sweat-based and other non-invasive biosensors either can only monitor a single analyte at a time or lack on-site signal processing circuitry and sensor calibration mechanisms for accurate analysis of the physiological state. Given the complexity of sweat secretion, simultaneous and multiplexed screening of target biomarkers is critical and requires full system integration to ensure the accuracy of measurements. Here we present a mechanically flexible and fully integrated (that is, no external analysis is needed) sensor array for multiplexed in situ perspiration analysis, which simultaneously and selectively measures sweat metabolites (such as glucose and lactate) and electrolytes (such as sodium and potassium ions), as well as the skin temperature (to calibrate the response of the sensors). Our work bridges the technological gap between signal transduction, conditioning (amplification and filtering), processing and wireless transmission in wearable biosensors by merging plastic-based sensors that interface with the skin with silicon integrated circuits consolidated on a flexible circuit board for complex signal processing. This application could not have been realized using either of these technologies alone owing to their respective inherent limitations. The wearable system is used to measure the detailed sweat profile of human subjects engaged in prolonged indoor and outdoor physical activities, and to make a real-time assessment of the physiological state of the subjects. This platform enables a wide range of personalized diagnostic and physiological monitoring applications.

    View details for DOI 10.1038/nature16521

    View details for Web of Science ID 000368673800033

    View details for PubMedCentralID PMC4996079