Organic Electronics for Point-of-Care Metabolite Monitoring.

In this review we focus on demonstrating how organic electronic materials can solve key problems in biosensing thanks to their unique material properties and implementation in innovative device configurations. We highlight specific examples where these materials solve multiple issues related to complex sensing environments, and we benchmark these examples by comparing them to state-of-the-art commercially available sensing using alternative technologies. We have categorized our examples by sample type, focusing on sensing from body fluids in vitro and on wearable sensors, which have attracted significant interest owing to their integration with everyday life activities. We finish by describing a future trend for in vivo, implantable sensors, which aims to build on current progress from sensing in biological fluids ex vivo.

[1]  Alexander Kros,et al.  Poly(pyrrole) versus poly(3,4-ethylenedioxythiophene): implications for biosensor applications , 2005 .

[2]  Vamsi K Yadavalli,et al.  Conducting polymer-silk biocomposites for flexible and biodegradable electrochemical sensors. , 2016, Biosensors & bioelectronics.

[3]  Babak A. Parviz,et al.  Functional modular contact lens , 2009, NanoScience + Engineering.

[4]  Naresh Magan,et al.  Detection of Mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system. , 2004, Biosensors & bioelectronics.

[5]  Michael L Heien,et al.  Characterization of poly(3,4-ethylenedioxythiophene):tosylate conductive polymer microelectrodes for transmitter detection. , 2012, The Analyst.

[6]  Zhenan Bao,et al.  Hierarchical nanostructured conducting polymer hydrogel with high electrochemical activity , 2012, Proceedings of the National Academy of Sciences.

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

[8]  George G. Malliaras,et al.  The Rise of Organic Bioelectronics , 2014 .

[9]  Anthony P F Turner,et al.  Biosensors: sense and sensibility. , 2013, Chemical Society reviews.

[10]  Joseph Wang,et al.  A wearable chemical–electrophysiological hybrid biosensing system for real-time health and fitness monitoring , 2016, Nature Communications.

[11]  Feng Yan,et al.  Flexible Organic Electrochemical Transistors for Highly Selective Enzyme Biosensors and Used for Saliva Testing , 2015, Advanced materials.

[12]  Ingemar Lundström,et al.  Two‐Dimensional Gold‐Tungsten Disulphide Bio‐Interface for High‐Throughput Electrocatalytic Nano‐Bioreactors , 2014 .

[13]  Allen J. Bard,et al.  Electrochemical Methods: Fundamentals and Applications , 1980 .

[14]  Christophe Bernard,et al.  High-performance transistors for bioelectronics through tuning of channel thickness , 2015, Science Advances.

[15]  Stanley C. S. Lai,et al.  Electrochemistry of nanoparticles. , 2014, Angewandte Chemie.

[16]  Jitraporn Vongsvivut,et al.  Conducting polymer enzyme alloys: electromaterials exhibiting direct electron transfer. , 2010, Macromolecular rapid communications.

[17]  Aicheng Chen,et al.  Carbon Nanomaterials Based Electrochemical Sensors/Biosensors for the Sensitive Detection of Pharmaceutical and Biological Compounds , 2015, Sensors.

[18]  Anna-Maria Pappa,et al.  Lactate Detection in Tumor Cell Cultures Using Organic Transistor Circuits , 2017, Advanced materials.

[19]  A. Sher,et al.  Photovoltaic Retinal Prosthesis with High Pixel Density , 2012, Nature Photonics.

[20]  Mohammad Yusuf Mulla,et al.  Detection Beyond Debye's Length with an Electrolyte‐Gated Organic Field‐Effect Transistor , 2015, Advanced materials.

[21]  Rodrigo M. Iost,et al.  Glucose Biochip Based on Flexible Carbon Fiber Electrodes: In Vivo Diabetes Evaluation in Rats , 2015 .

[22]  George G. Malliaras,et al.  Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring , 2017, Microsystems & Nanoengineering.

[23]  Caizhi Liao,et al.  Highly sensitive glucose sensors based on enzyme-modified whole-graphene solution-gated transistors , 2015, Scientific Reports.

[24]  Fang Wei,et al.  Serum creatinine detection by a conducting-polymer-based electrochemical sensor to identify allograft dysfunction. , 2012, Analytical chemistry.

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

[26]  Youngsoo Kim,et al.  Smart Contact Lenses with Graphene Coating for Electromagnetic Interference Shielding and Dehydration Protection. , 2017, ACS nano.

[27]  Peng Zhai,et al.  Highly Sensitive Metabolite Biosensor Based on Organic Electrochemical Transistor Integrated with Microfluidic Channel and Poly(N‐vinyl‐2‐pyrrolidone)‐Capped Platinum Nanoparticles , 2016 .

[28]  G. Malliaras,et al.  Organic Transistor Arrays Integrated with Finger‐Powered Microfluidics for Multianalyte Saliva Testing , 2016, Advanced healthcare materials.

[29]  George G. Malliaras,et al.  Direct patterning of organic conductors on knitted textiles for long-term electrocardiography , 2015, Scientific Reports.

[30]  H R Mühlemann,et al.  Oral telemetry of fluoride ion activity. , 1969, Archives of oral biology.

[31]  R. Gifford,et al.  Continuous glucose monitoring: 40 years, what we've learned and what's next. , 2013, Chemphyschem : a European journal of chemical physics and physical chemistry.

[32]  Adam Heller,et al.  An electron-conducting cross-linked polyaniline-based redox hydrogel, formed in one step at pH 7.2, wires glucose oxidase. , 2007, Journal of the American Chemical Society.

[33]  Yi Shi,et al.  A nanostructured conductive hydrogels-based biosensor platform for human metabolite detection. , 2015, Nano letters.

[34]  Najm Nico Sommerdijk,et al.  Poly(3,4‐ethylenedioxythiophene)‐Based Glucose Biosensors , 2001 .

[35]  Itthipon Jeerapan,et al.  A Textile‐Based Stretchable Multi‐Ion Potentiometric Sensor , 2016, Advanced healthcare materials.

[36]  C. K. Chiang,et al.  Electrical Conductivity in Doped Polyacetylene. , 1977 .

[37]  Kuo-Chuan Ho,et al.  Synthesis of redox polymer nanobeads and nanocomposites for glucose biosensors. , 2013, ACS applied materials & interfaces.

[38]  George G. Malliaras,et al.  Polyelectrolyte Layer-by-Layer Assembly on Organic Electrochemical Transistors. , 2017, ACS applied materials & interfaces.

[39]  Vamsi K Yadavalli,et al.  Precise Patterning of Silk Microstructures Using Photolithography , 2013, Advanced materials.

[40]  Catalina Vallejo-Giraldo,et al.  Biofunctionalisation of electrically conducting polymers. , 2014, Drug discovery today.

[41]  Róisín M. Owens,et al.  The organic electrochemical transistor for biological applications , 2015 .

[42]  L. C. Clark,et al.  ELECTRODE SYSTEMS FOR CONTINUOUS MONITORING IN CARDIOVASCULAR SURGERY , 1962 .

[43]  Behzad Bavarian,et al.  Rapid Prototyping of a High Sensitivity Graphene Based Glucose Sensor Strip , 2015, PloS one.

[44]  Ashutosh Tiwari,et al.  Template-directed hierarchical self-assembly of graphene based hybrid structure for electrochemical biosensing. , 2013, Biosensors & bioelectronics.

[45]  John E. Anthony,et al.  High mobility transistors based on electrospray-printed small-molecule/polymer semiconducting blends , 2016 .

[46]  Santhisagar Vaddiraju,et al.  Emerging synergy between nanotechnology and implantable biosensors: a review. , 2010, Biosensors & bioelectronics.

[47]  Y. Yamasaki,et al.  WEARABLE ARTIFICIAL ENDOCRINE PANCREAS WITH NEEDLE-TYPE GLUCOSE SENSOR , 1982, The Lancet.

[48]  Anthony P F Turner,et al.  Bioelectrocatalytic systems for health applications. , 2016, Biotechnology advances.

[49]  G. S. Wilson,et al.  Biosensors for real-time in vivo measurements. , 2005, Biosensors & bioelectronics.

[50]  Filip Braet,et al.  Carbon nanomaterials in biosensors: should you use nanotubes or graphene? , 2010, Angewandte Chemie.

[51]  Dermot Diamond,et al.  Organic electrochemical transistor incorporating anionogel as solid state electrolyte for lactate sensing , 2012 .

[52]  G. Lanzani.  Materials for bioelectronics: organic electronics meets biology. , 2014, Nature materials.

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

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

[55]  Claire M. Lochner,et al.  Monitoring of Vital Signs with Flexible and Wearable Medical Devices , 2016, Advanced materials.

[56]  Z. Bao,et al.  Organic Thin‐Film Transistors Fabricated on Resorbable Biomaterial Substrates , 2010, Advanced materials.

[57]  Babak A. Parviz,et al.  A contact lens with an integrated lactate sensor , 2012 .

[58]  T. Itoh,et al.  Wearable Keyboard Using Conducting Polymer Electrodes on Textiles , 2016, Advanced materials.

[59]  Jonathan Rivnay,et al.  Catalytically enhanced organic transistors for in vitro toxicology monitoring through hydrogel entrapment of enzymes , 2017 .

[60]  Wolfgang Schuhmann,et al.  Amperometric enzyme biosensors based on optimised electron-transfer pathways and non-manual immobilisation procedures. , 2002, Journal of biotechnology.

[61]  Ashutosh Tiwari,et al.  Structuring Au nanoparticles on two-dimensional MoS2 nanosheets for electrochemical glucose biosensors. , 2017, Biosensors & bioelectronics.

[62]  F. Collins,et al.  The path to personalized medicine. , 2010, The New England journal of medicine.

[63]  Takao Someya,et al.  The rise of plastic bioelectronics , 2016, Nature.

[64]  Antonio Guerrieri,et al.  Interference-free glucose sensor based on glucose-oxidase immobilized in an overoxidized non-conducting polypyrrole film , 1992 .

[65]  H R Mühlemann,et al.  Telemetry of plaque pH from interdental area. , 1966, Helvetica odontologica acta.

[66]  Peter Andersson,et al.  The Origin of the High Conductivity of Poly(3,4-ethylenedioxythiophene)−Poly(styrenesulfonate) (PEDOT−PSS) Plastic Electrodes , 2006 .

[67]  P. N. Bartlett.  Measurement of low glucose concentrations using a microelectrochemical enzyme transistor , 1998 .

[68]  Changcheng Zhu,et al.  A simple poly(3,4-ethylene dioxythiophene)/poly(styrene sulfonic acid) transistor for glucose sensing at neutral pH. , 2004, Chemical communications.

[69]  Larry A. Nagahara,et al.  A Conducting Polymer Nanojunction Sensor for Glucose Detection , 2004 .

[70]  A. Afanasiev,et al.  A dual microscale glucose sensor on a contact lens, tested in conditions mimicking the eye , 2011, 2011 IEEE 24th International Conference on Micro Electro Mechanical Systems.

[71]  George G. Malliaras,et al.  Organic Electronics at the Interface with Biology , 2010 .

[72]  Mohammad Reza Abidian,et al.  High Performance Conducting Polymer Nanofiber Biosensors for Detection of Biomolecules , 2014, Advanced materials.

[73]  George G. Malliaras,et al.  A Disposable paper breathalyzer with an alcohol sensing organic electrochemical transistor , 2016, Scientific Reports.

[74]  D. Cliffel,et al.  Electrochemical sensors and biosensors. , 2012, Analytical chemistry.

[75]  W. Schuhmann,et al.  Electron-transfer pathways between redox enzymes and electrode surfaces: reagentless biosensors based on thiol-monolayer-bound and polypyrrole-entrapped enzymes. , 2000, Faraday discussions.

[76]  Joseph Wang,et al.  Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. , 2015, Biosensors & bioelectronics.

[77]  A. Pud,et al.  Stability and degradation of conducting polymers in electrochemical systems , 1994 .

[78]  J. Brédas,et al.  Polarons, bipolarons, and solitons in conducting polymers , 1985 .

[79]  B. Fraboni,et al.  Textile Organic Electrochemical Transistors as a Platform for Wearable Biosensors , 2016, Scientific Reports.

[80]  Christopher K. Ober,et al.  Advances in polymers for anti-biofouling surfaces , 2008 .

[81]  Yongfang Li,et al.  Polyaniline-polyisoprene composite film based glucose biosensor with high permselectivity , 2001 .

[82]  A. Turner,et al.  Home blood glucose biosensors: a commercial perspective. , 2005, Biosensors & bioelectronics.

[83]  Se Hyun Kim,et al.  Electrolyte‐Gated Transistors for Organic and Printed Electronics , 2013, Advanced materials.

[84]  Meng Zhang,et al.  Highly-sensitive epinephrine sensors based on organic electrochemical transistors with carbon nanomaterial modified gate electrodes , 2015 .

[85]  David Bloor,et al.  The role of polypyrrole as charge transfer mediator and immobilization matrix for d-fructose dehydrogenase in a fructose sensor , 1997 .

[86]  Michael Schivo,et al.  Chemically Polymerized Polypyrrole for On-Chip Concentration of Volatile Breath Metabolites. , 2010, Sensors and actuators. B, Chemical.

[87]  Romain Coppard,et al.  Screen-printed organic electrochemical transistors for metabolite sensing , 2015 .

[88]  Ashutosh Tiwari,et al.  Self-Reporting Micellar Polymer Nanostructures for Optical Urea Biosensing , 2014 .

[89]  George G. Malliaras,et al.  Fully Printed Electrodes on Stretchable Textiles for Long‐Term Electrophysiology , 2017 .

[90]  Anthony Turner,et al.  Unsubstituted phenothiazine as a superior water-insoluble mediator for oxidases. , 2014, Biosensors & bioelectronics.

[91]  Subhas C. Kundu,et al.  Silk Protein Lithography as a Route to Fabricate Sericin Microarchitectures , 2014, Advanced materials.

[92]  B.A. Parviz.  For your eye only , 2009, IEEE Spectrum.

[93]  Bansi D Malhotra,et al.  Prospects of conducting polymers in biosensors. , 2006, Analytica chimica acta.

[94]  Ashutosh Tiwari,et al.  Acetylene-sourced CVD-synthesised catalytically active graphene for electrochemical biosensing. , 2017, Biosensors & bioelectronics.