Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis

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.

[1]  J. Windmiller,et al.  Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration. , 2013, Analytical chemistry.

[2]  Andrew G. Gillies,et al.  Nanowire active-matrix circuitry for low-voltage macroscale artificial skin. , 2010, Nature materials.

[3]  Benjamin C. K. Tee,et al.  Skin-like pressure and strain sensors based on transparent elastic films of carbon nanotubes. , 2011, Nature nanotechnology.

[4]  E. Nadel,et al.  Importance of skin temperature in the regulation of sweating. , 1971, Journal of applied physiology.

[5]  Michael C. McAlpine,et al.  Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors. , 2007, Nature materials.

[6]  Zhibin Yu,et al.  User-interactive electronic skin for instantaneous pressure visualization. , 2013, Nature materials.

[7]  Nancy Kelley-Loughnane,et al.  Adhesive RFID Sensor Patch for Monitoring of Sweat Electrolytes , 2015, IEEE Transactions on Biomedical Engineering.

[8]  S. Galloway,et al.  Variations in Regional Sweat Composition in Normal Human Males , 2000, Experimental physiology.

[9]  Wenzhao Jia,et al.  Tattoo-based noninvasive glucose monitoring: a proof-of-concept study. , 2015, Analytical chemistry.

[10]  P Wach,et al.  Thin-film microbiosensors for glucose-lactate monitoring. , 1996, Analytical chemistry.

[11]  Andrea Ridolfi,et al.  BIOTEX—Biosensing Textiles for Personalised Healthcare Management , 2010, IEEE Transactions on Information Technology in Biomedicine.

[12]  Raeed H. Chowdhury,et al.  Epidermal Electronics , 2011, Science.

[13]  J. Vörös,et al.  Electrochemical Biosensors - Sensor Principles and Architectures , 2008 .

[14]  Joseph Wang,et al.  Epidermal tattoo potentiometric sodium sensors with wireless signal transduction for continuous non-invasive sweat monitoring. , 2014, Biosensors & bioelectronics.

[15]  J. Bobacka,et al.  Potential Stability of All-Solid-State Ion-Selective Electrodes Using Conducting Polymers as Ion-to-Electron Transducers. , 1999, Analytical chemistry.

[16]  G. Cage,et al.  Effects of water intake on composition of thermal sweat in normal human volunteers. , 1970, Journal of applied physiology.

[17]  Frank Davis,et al.  Lactate in human sweat: a critical review of research to the present day , 2012, Journal of Physiological Sciences.

[18]  Zhong Lin Wang,et al.  Piezoelectricity of single-atomic-layer MoS2 for energy conversion and piezotronics , 2014, Nature.

[19]  Shyamal Patel,et al.  A review of wearable sensors and systems with application in rehabilitation , 2012, Journal of NeuroEngineering and Rehabilitation.

[20]  Hiroyuki Kudo,et al.  A flexible and wearable glucose sensor based on functional polymers with soft-MEMS techniques. , 2006, Biosensors & bioelectronics.

[21]  Dae-Hyeong Kim,et al.  Flexible and stretchable electronics for biointegrated devices. , 2012, Annual review of biomedical engineering.

[22]  Amay J Bandodkar,et al.  Non-invasive wearable electrochemical sensors: a review. , 2014, Trends in biotechnology.

[23]  Sanat S Bhole,et al.  Soft Microfluidic Assemblies of Sensors, Circuits, and Radios for the Skin , 2014, Science.

[24]  M. Kaltenbrunner,et al.  An ultra-lightweight design for imperceptible plastic electronics , 2013, Nature.

[25]  Chi-An W. Emhoff,et al.  Lactate kinetics at the lactate threshold in trained and untrained men. , 2013, Journal of applied physiology.

[26]  S. Barr,et al.  Effects of dehydration on exercise performance. , 1999, Canadian journal of applied physiology = Revue canadienne de physiologie appliquee.

[27]  J. Vörös,et al.  Electrochemical Biosensors - Sensor Principles and Architectures , 2008, Sensors.

[28]  K. Sato,et al.  A modified anaerobic method of sweat collection. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[29]  M. Nimmo,et al.  Acute effects of dehydration on sweat composition in men during prolonged exercise in the heat. , 2004, Acta physiologica Scandinavica.

[30]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[31]  F. Amorim,et al.  Comparison of sweat rate during graded exercise and the local rate induced by pilocarpine. , 2005, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[32]  Yonggang Huang,et al.  Ultrathin conformal devices for precise and continuous thermal characterization of human skin. , 2013, Nature materials.

[33]  Dermot Diamond,et al.  A wearable electrochemical sensor for the real-time measurement of sweat sodium concentration , 2010 .

[34]  Michael J. Buono,et al.  The relationship between exercise intensity and the sweat lactate excretion rate , 2010, The Journal of Physiological Sciences.

[35]  J Heikenfeld,et al.  The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. , 2015, Biomicrofluidics.

[36]  S Sprigle,et al.  Clinical skin temperature measurement to predict incipient pressure ulcers. , 2001, Advances in skin & wound care.

[37]  Zhibin Yu,et al.  Elastomeric polymer light-emitting devices and displays , 2013, Nature Photonics.

[38]  Mark S. Talary,et al.  In vivo life sign application of dielectric spectroscopy and non-invasive glucose monitoring , 2007 .

[39]  F. Rius,et al.  A reference electrode based on polyvinyl butyral (PVB) polymer for decentralized chemical measurements. , 2014, Analytica chimica acta.

[40]  T D Noakes,et al.  Exercise-associated hyponatremia: a review. , 2001, Emergency medicine.

[41]  Yu Qin,et al.  Preparation of all solid-state potentiometric ion sensors with polymer-CNT composites , 2009 .