Integrated sudomotor axon reflex sweat stimulation for continuous sweat analyte analysis with individuals at rest.

Eccrine sweat has rapidly emerged as a non-invasive, ergonomic, and rich source of chemical analytes with numerous technological demonstrations now showing the ability for continuous electrochemical sensing. However, beyond active perspirers (athletes, workers, etc.), continuous sweat access in individuals at rest has hindered the advancement of both sweat sensing science and technology. Reported here is integration of sudomotor axon reflex sweat stimulation for continuous wearable sweat analyte analysis, including the ability for side-by-side integration of chemical stimulants & sensors without cross-contamination. This integration approach is uniquely compatible with sensors which consume the analyte (enzymatic) or sensors which equilibrate with analyte concentrations. In vivo validation is performed using iontophoretic delivery of carbachol with ion-selective and impedance sensors for sweat analysis. Carbachol has shown prolonged sweat stimulation in directly stimulated regions for five hours or longer. This work represents a significant leap forward in sweat sensing technology, and may be of broader interest to those interested in on-skin sensing integrated with drug-delivery.

[1]  William Montagna,et al.  Atlas of Normal Human Skin , 1992, Springer New York.

[2]  Wenzhao Jia,et al.  Wearable temporary tattoo sensor for real-time trace metal monitoring in human sweat , 2015 .

[3]  D. Fayuk,et al.  Regulation of Nicotinic Acetylcholine Receptor Channel Function by Acetylcholinesterase Inhibitors in Rat Hippocampal CA1 Interneurons , 2004, Molecular Pharmacology.

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

[5]  N. Taylor,et al.  Regional variations in transepidermal water loss, eccrine sweat gland density, sweat secretion rates and electrolyte composition in resting and exercising humans , 2013, Extreme Physiology & Medicine.

[6]  Xian Huang,et al.  Stretchable, wireless sensors and functional substrates for epidermal characterization of sweat. , 2014, Small.

[7]  Isao Karube,et al.  Analysis of metabolites in sweat as a measure of physical condition , 1994 .

[8]  Y. Kalia,et al.  Optimizing Iontophoretic Drug Delivery: Identification and Distribution of the Charge-Carrying Species , 2001, Pharmaceutical Research.

[9]  M. Meyerhoff,et al.  Ionophore-based membrane electrodes: New analytical concepts and non-classical response mechanisms , 2000 .

[10]  Joseph Wang,et al.  Noninvasive Alcohol Monitoring Using a Wearable Tattoo-Based Iontophoretic-Biosensing System , 2016 .

[11]  P. Hauser,et al.  Effect of pressure on the potentiometric response of ion-selective electrodes and reference electrodes , 1996 .

[12]  G TASHIRO,et al.  A bromphenol blue method for visualizing sweat at the openings of the sweat ducts. , 1961, The Journal of investigative dermatology.

[13]  Hiroyuki Kudo,et al.  Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment. , 2011, Talanta.

[14]  F. Bǎnicǎ,et al.  Chemical sensors and biosensors : fundamentals and applications , 2012 .

[15]  R. Naik,et al.  Label free nano-aptasensor for interleukin-6 in protein-dilute bio fluids such as sweat , 2016 .

[16]  D. Claus,et al.  Stimulation of sudomotor axon reflex mechanism by carbachol in healthy subjects and patients suffering from diabetic polyneuropathy , 1995, Acta neurologica Scandinavica.

[17]  Jason Heikenfeld,et al.  Bioanalytical devices: Technological leap for sweat sensing , 2016, Nature.

[18]  Jason Heikenfeld,et al.  Non‐invasive Analyte Access and Sensing through Eccrine Sweat: Challenges and Outlook circa 2016 , 2016 .

[19]  P. Low,et al.  In vivo studies on receptor pharmacology of the human eccrine sweat gland , 1992, Clinical Autonomic Research.

[20]  Aviad Hai,et al.  Acetylcholinesterase-ISFET based system for the detection of acetylcholine and acetylcholinesterase inhibitors. , 2006, Biosensors & bioelectronics.

[21]  I. Doull,et al.  The evaluation of a novel conductometric device for the diagnosis of cystic fibrosis , 2006, Annals of clinical biochemistry.

[22]  M D Luque de Castro,et al.  Sweat: a sample with limited present applications and promising future in metabolomics. , 2014, Journal of pharmaceutical and biomedical analysis.

[23]  P. Dyck,et al.  Quantitative sudomotor axon reflex test in normal and neuropathic subjects , 1983, Annals of neurology.

[24]  F. Erbguth,et al.  Dose thresholds and duration of the local anhidrotic effect of botulinum toxin injections: measured by sudometry , 2001, The British journal of dermatology.

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

[26]  K. Sato,et al.  Biology of sweat glands and their disorders. I. Normal sweat gland function. , 1989, Journal of the American Academy of Dermatology.

[27]  C. Crandall,et al.  Effect of local acetylcholinesterase inhibition on sweat rate in humans. , 2001, Journal of applied physiology.

[28]  P. Low,et al.  Evaluation of sudomotor function , 2004, Clinical Neurophysiology.

[29]  P. Atanassov,et al.  Wearable Sensor System Powered by a Biofuel Cell for Detection of Lactate Levels in Sweat. , 2016, ECS journal of solid state science and technology : JSS.

[30]  K. Soltani,et al.  Iontophoresis in dermatology. A review. , 1986, Journal of the American Academy of Dermatology.

[31]  F. Birklein,et al.  Autonomic failure after stroke – is it indicative for pathophysiology of complex regional pain syndrome? , 2001, Acta neurologica Scandinavica.

[32]  Jean-Charles Sanchez,et al.  Human sweat metabolomics for lung cancer screening , 2015, Analytical and Bioanalytical Chemistry.

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

[34]  S. Grimnes,et al.  Improved Estimation of Sweating Based on Electrical Properties of Skin , 2013, Annals of Biomedical Engineering.

[35]  Phillip Won,et al.  A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat , 2016, Science Translational Medicine.

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

[37]  Ashley N. Johnson,et al.  Dual-task motor performance with a tongue-operated assistive technology compared with hand operations , 2012, Journal of NeuroEngineering and Rehabilitation.

[38]  M. Uematsu,et al.  Static Dielectric Constant of Water and Steam , 1980 .

[39]  S. Grimnes,et al.  Electrodermal activity by DC potential and AC conductance measured simultaneously at the same skin site , 2011, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[40]  R. Johnson,et al.  Ionophore-based ion-selective potentiometric and optical sensors , 2003, Analytical and bioanalytical chemistry.

[41]  R. Sittl,et al.  Sudomotor function in sympathetic reflex dystrophy , 1997, Pain.

[42]  J Heikenfeld,et al.  A new oil/membrane approach for integrated sweat sampling and sensing: sample volumes reduced from μL's to nL's and reduction of analyte contamination from skin. , 2016, Lab on a chip.

[43]  N De Giovanni,et al.  The current status of sweat testing for drugs of abuse: a review. , 2013, Current medicinal chemistry.

[44]  M. Brys,et al.  Assessing function and pathology in familial dysautonomia: assessment of temperature perception, sweating and cutaneous innervation. , 2004, Brain : a journal of neurology.

[45]  B. Kayser,et al.  Control and sensation of breathing during cycling exercise in hypoxia under naloxone: a randomised controlled crossover trial , 2013, Extreme Physiology & Medicine.

[46]  F. Priego-Capote,et al.  Optimization study for metabolomics analysis of human sweat by liquid chromatography-tandem mass spectrometry in high resolution mode. , 2014, Journal of chromatography. A.

[47]  J. Windmiller,et al.  A potentiometric tattoo sensor for monitoring ammonium in sweat. , 2013, The Analyst.

[48]  D. Cunningham Transdermal Microfluidic Continuous Monitoring Systems , 2009 .

[49]  P. Low,et al.  Comparison of directly stimulated with axon‐reflex–mediated sudomotor responses in human subjects and in patients with diabetes , 1993, Muscle & nerve.

[50]  Yie W. Chien,et al.  Iontophoretic delivery of drugs: Fundamentals, developments and biomedical applications , 1988 .

[51]  H P Rang,et al.  Rang and Dale's pharmacology , 2012 .

[52]  B. Neundörfer,et al.  Spatial extension of sudomotor axon reflex sweating in human skin. , 1998, Journal of the autonomic nervous system.

[53]  Sam Emaminejad,et al.  Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis , 2016, Nature.

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