A new paradigm in sweat based wearable diagnostics biosensors using Room Temperature Ionic Liquids (RTILs)

Successful commercialization of wearable diagnostic sensors necessitates stability in detection of analytes over prolonged and continuous exposure to sweat. Challenges are primarily in ensuring target disease specific small analytes (i.e. metabolites, proteins, etc.) stability in complex sweat buffer with varying pH levels and composition over time. We present a facile approach to address these challenges using RTILs with antibody functionalized sensors on nanoporous, flexible polymer membranes. Temporal studies were performed using both infrared spectroscopic, dynamic light scattering, and impedimetric spectroscopy to demonstrate stability in detection of analytes, Interleukin-6 (IL-6) and Cortisol, from human sweat in RTILs. Temporal stability in sensor performance was performed as follows: (a) detection of target analytes after 0, 24, 48, 96, and 168 hours post-antibody sensor functionalization; and (b) continuous detection of target analytes post-antibody sensor functionalization. Limit of detection of IL-6 in human sweat was 0.2 pg/mL for 0–24 hours and 2 pg/mL for 24–48 hours post-antibody sensor functionalization. Continuous detection of IL-6 over 0.2–200 pg/mL in human sweat was demonstrated for a period of 10 hours post-antibody sensor functionalization. Furthermore, combinatorial detection of IL-6 and Cortisol in human sweat was established with minimal cross-talk for 0–48 hours post-antibody sensor functionalization.

[1]  David P. Norton,et al.  Functionalizing Zn- and O-terminated ZnO with thiols , 2007 .

[2]  A. C. Fernandes,et al.  TiCxOy thin films for decorative applications : tribocorrosion mechanisms and synergism , 2008 .

[3]  S. Humphries,et al.  Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? , 2000, Atherosclerosis.

[4]  J. Pernak,et al.  Anti-microbial activities of protic ionic liquids with lactate anion , 2004 .

[5]  S. Stolte,et al.  PAPER www.rsc.org/greenchem | Green Chemistry Effects , 2007 .

[6]  P. Ballone,et al.  Room temperature ionic liquids interacting with bio-molecules: an overview of experimental and computational studies , 2016 .

[7]  A. Ivaska,et al.  Applications of ionic liquids in electrochemical sensors. , 2008, Analytica chimica acta.

[8]  B. Aurian‐Blajeni,et al.  Molecularly “Wired” Cholesterol Oxidase for Biosensing , 2015, The Protein Journal.

[9]  Marc D. Porter,et al.  Succinimidyl Ester Surface Chemistry: Implications of the Competition between Aminolysis and Hydrolysis on Covalent Protein Immobilization , 2014, Langmuir : the ACS journal of surfaces and colloids.

[10]  Mohammad Hasanzadeh,et al.  Room-temperature ionic liquid-based electrochemical nanobiosensors , 2012 .

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

[12]  L. Ananthanarayan,et al.  Glucose oxidase--an overview. , 2009, Biotechnology advances.

[13]  D. Barreca,et al.  Analysis of Nanocrystalline ZnS Thin Films by XPS , 2002 .

[14]  E. Bixler,et al.  Impaired nighttime sleep in healthy old versus young adults is associated with elevated plasma interleukin-6 and cortisol levels: physiologic and therapeutic implications. , 2003, The Journal of clinical endocrinology and metabolism.

[15]  Roger A. Sheldon,et al.  Biocatalysis in ionic liquids. , 2002, Chemical reviews.

[16]  R. Sheldon,et al.  Biocatalysis in ionic liquids. , 2007, Chemical reviews.

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

[18]  W. Kunz.  Specific Ion Effects , 2009 .

[19]  S. Stolte,et al.  Effects of Different Head Groups and Functionalized Side Chains on the Cytotoxicity of Ionic Liquids. , 2007 .

[20]  Shalini Prasad,et al.  Flexible nanoporous tunable electrical double layer biosensors for sweat diagnostics , 2015, Scientific Reports.

[21]  Z. Alothman,et al.  Effect of ionic liquid on activity, stability, and structure of enzymes: a review. , 2012, International journal of biological macromolecules.

[22]  Hongtao Yuan,et al.  Hydrogenation-induced surface polarity recognition and proton memory behavior at protic-ionic-liquid/oxide electric-double-layer interfaces. , 2010, Journal of the American Chemical Society.

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

[24]  Kenta Kimura,et al.  An increase in salivary interleukin-6 level following acute psychosocial stress and its biological correlates in healthy young adults , 2013, Biological Psychology.

[25]  Yingchun Fu,et al.  Recent advances in electrochemical glucose biosensors: a review , 2013 .

[26]  Abbul Bashar Khan,et al.  Recent Advances in the Applications of Ionic Liquids in Protein Stability and Activity: A Review , 2014, Applied Biochemistry and Biotechnology.

[27]  유한나,et al.  Power Study 사례연구 , 2011 .

[28]  Sandy Shuo Zhao,et al.  Imidazolium-based ionic liquid surfaces for biosensing. , 2013, Analytical chemistry.

[29]  Esther M. Sternberg,et al.  Elevated Neuroimmune Biomarkers in Sweat Patches and Plasma of Premenopausal Women with Major Depressive Disorder in Remission: The POWER Study , 2008, Biological Psychiatry.

[30]  Yi Wang,et al.  Label-free electronic detection of interleukin-6 using horizontally aligned carbon nanotubes , 2016 .

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

[32]  S. Poole,et al.  The international standard for interleukin-6. Evaluation in an international collaborative study. , 1993, Journal of immunological methods.

[33]  Anilesh Kumar,et al.  Activity and stability of α-chymotrypsin in biocompatible ionic liquids: enzyme refolding by triethyl ammonium acetate. , 2011, Physical chemistry chemical physics : PCCP.

[34]  D. Armbruster,et al.  Limit of blank, limit of detection and limit of quantitation. , 2008, The Clinical biochemist. Reviews.

[35]  Hua Zhao.  Protein Stabilization and Enzyme Activation in Ionic Liquids: Specific Ion Effects. , 2016, Journal of chemical technology and biotechnology.

[36]  A. Kornyshev,et al.  Ionic liquids at electrified interfaces. , 2014, Chemical reviews.

[37]  R. E. Del Sesto,et al.  Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization , 2014, Proceedings of the National Academy of Sciences.

[38]  Kemin Wang,et al.  Programmable Self-Assembly of DNA-Protein Hybrid Hydrogel for Enzyme Encapsulation with Enhanced Biological Stability. , 2016, Biomacromolecules.

[39]  D. Pang,et al.  Interaction between room temperature ionic liquid [bmim]BF4 and DNA investigated by electrochemical micromethod. , 2008, The journal of physical chemistry. B.

[40]  S. Pandey.  Analytical applications of room-temperature ionic liquids: a review of recent efforts. , 2006, Analytica chimica acta.

[41]  J. Pernak,et al.  Anti-microbial activities of ionic liquids , 2003 .

[42]  Vitaly V. Chaban,et al.  Enhanced stability of the model mini‐protein in amino acid ionic liquids and their aqueous solutions , 2015, J. Comput. Chem..

[43]  Masashi Kawasaki,et al.  Electrostatic and electrochemical nature of liquid-gated electric-double-layer transistors based on oxide semiconductors. , 2010, Journal of the American Chemical Society.

[44]  C. Herrmann,et al.  How ionic liquids can help to stabilize native proteins. , 2012, Physical chemistry chemical physics : PCCP.

[45]  T. Tsuda,et al.  Human perspiration measurement. , 1998, Physiological measurement.

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

[47]  Shalini Prasad,et al.  Lancet-free and label-free diagnostics of glucose in sweat using Zinc Oxide based flexible bioelectronics , 2017 .

[48]  E. Suzuki,et al.  Identification of the interface of a large protein-protein complex using H/D exchange and Fourier transform ion cyclotron resonance mass spectrometry. , 2002, Rapid communications in mass spectrometry : RCM.

[49]  J. Kaar,et al.  Stabilization of enzymes in ionic liquids via modification of enzyme charge , 2013, Biotechnology and bioengineering.