Conjugated Polymers in Bioelectronics.

The emerging field of organic bioelectronics bridges the electronic world of organic-semiconductor-based devices with the soft, predominantly ionic world of biology. This crosstalk can occur in both directions. For example, a biochemical reaction may change the doping state of an organic material, generating an electronic readout. Conversely, an electronic signal from a device may stimulate a biological event. Cutting-edge research in this field results in the development of a broad variety of meaningful applications, from biosensors and drug delivery systems to health monitoring devices and brain-machine interfaces. Conjugated polymers share similarities in chemical "nature" with biological molecules and can be engineered on various forms, including hydrogels that have Young's moduli similar to those of soft tissues and are ionically conducting. The structure of organic materials can be tuned through synthetic chemistry, and their biological properties can be controlled using a variety of functionalization strategies. Finally, organic electronic materials can be integrated with a variety of mechanical supports, giving rise to devices with form factors that enable integration with biological systems. While these developments are innovative and promising, it is important to note that the field is still in its infancy, with many unknowns and immense scope for exploration and highly collaborative research. The first part of this Account details the unique properties that render conjugated polymers excellent biointerfacing materials. We then offer an overview of the most common conjugated polymers that have been used as active layers in various organic bioelectronics devices, highlighting the importance of developing new materials. These materials are the most popular ethylenedioxythiophene derivatives as well as conjugated polyelectrolytes and ion-free organic semiconductors functionalized for the biological interface. We then discuss several applications and operation principles of state-of-the-art bioelectronics devices. These devices include electrodes applied to sense/trigger electrophysiological activity of cells as well as electrolyte-gated field-effect and electrochemical transistors used for sensing of biochemical markers. Another prime application example of conjugated polymers is cell actuators. External modulation of the redox state of the underlying conjugated polymer films controls the adhesion behavior and viability of cells. These smart surfaces can be also designed in the form of three-dimensional architectures because of the processability of conjugated polymers. As such, cell-loaded scaffolds based on electroactive polymers enable integrated sensing or stimulation within the engineered tissue itself. A last application example is organic neuromorphic devices, an alternative computing architecture that takes inspiration from biology and, in particular, from the way the brain works. Leveraging ion redistribution inside a conjugated polymer upon application of an electrical field and its coupling with electronic charges, conjugated polymers can be engineered to act as artificial neurons or synapses with complex, history-dependent behavior. We conclude this Account by highlighting main factors that need to be considered for the design of a conjugated polymer for applications in bioelectronics-although there can be various figures of merit given the broad range of applications, as emphasized in this Account.

[1]  George G. Malliaras,et al.  Controlling the mode of operation of organic transistors through side-chain engineering , 2016, Proceedings of the National Academy of Sciences.

[2]  M. Berggren,et al.  1 Supporting Information for : Electronic Control of Cell Detachment Using a Self-Doped Conducting Polymer , 2011 .

[3]  Magnus Berggren,et al.  Electronic plants , 2015, Science Advances.

[4]  X. Cui,et al.  Poly (3,4-Ethylenedioxythiophene) for Chronic Neural Stimulation , 2007, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[5]  M. Marinella,et al.  A non-volatile organic electrochemical device as a low-voltage artificial synapse for neuromorphic computing. , 2017, Nature materials.

[6]  David Nilsson,et al.  Therapy using implanted organic bioelectronics , 2015, Science Advances.

[7]  Jonathan Rivnay,et al.  Benchmarking organic mixed conductors for transistors , 2017, Nature Communications.

[8]  George G. Malliaras,et al.  Neuromorphic device architectures with global connectivity through electrolyte gating , 2017, Nature Communications.

[9]  Elise M. Stewart,et al.  A Single Component Conducting Polymer Hydrogel as a Scaffold for Tissue Engineering , 2012 .

[10]  O. Inganäs From Metal to Semiconductor and Back: Thirty Years of Conjugated Polymer Electrochemistry , 2010 .

[11]  Edwin W H Jager,et al.  Electrochemical modulation of epithelia formation using conducting polymers. , 2009, Biomaterials.

[12]  Z. Yue,et al.  Influence of Biodopants on PEDOT Biomaterial Polymers: Using QCM‐D to Characterize Polymer Interactions with Proteins and Living Cells , 2014 .

[13]  D. Khodagholy,et al.  PEDOT:TOS with PEG: a biofunctional surface with improved electronic characteristics , 2012 .

[14]  Keld West,et al.  Vapor-Phase Polymerization of 3,4-Ethylenedioxythiophene: A Route to Highly Conducting Polymer Surface Layers , 2004 .

[15]  Johannes C. Brendel,et al.  A High Transconductance Accumulation Mode Electrochemical Transistor , 2014, Advanced materials.

[16]  G. Malliaras,et al.  Electrical Control of Protein Conformation , 2012, Advanced materials.

[17]  P. Leleux,et al.  In vivo recordings of brain activity using organic transistors , 2013, Nature Communications.

[18]  Julie Oziat,et al.  Conducting Polymer Scaffolds for Hosting and Monitoring 3D Cell Culture , 2017 .

[19]  Jonathan Rivnay,et al.  Combined Optical and Electronic Sensing of Epithelial Cells Using Planar Organic Transistors , 2014, Advanced materials.

[20]  George G. Malliaras,et al.  Synaptic plasticity functions in an organic electrochemical transistor , 2015 .

[21]  D E Ingber,et al.  Electrically conducting polymers can noninvasively control the shape and growth of mammalian cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  W. Lövenich,et al.  PEDOT: Principles and Applications of an Intrinsically Conductive Polymer , 2010 .

[23]  T. Berzina,et al.  Hybrid electronic device based on polyaniline-polyethyleneoxide junction , 2005 .

[24]  N. Brosy,et al.  PEDOT , 2020, Catalysis from A to Z.

[25]  M. Takafuji,et al.  Helical superstructure of conductive polymers as created by electrochemical polymerization by using synthetic lipid assemblies as a template. , 2004, Angewandte Chemie.

[26]  Christopher J. Tassone,et al.  Structural control of mixed ionic and electronic transport in conducting polymers , 2016, Nature Communications.

[27]  Aram Amassian,et al.  N-type organic electrochemical transistors with stability in water , 2016, Nature Communications.

[28]  Elise M. Stewart,et al.  Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth of Primary Prefrontal Cortical Neurons from NRG1-KO and DISC1-LI Mice , 2017, Scientific Reports.

[29]  O. Inganäs,et al.  Electronic polymers in lipid membranes , 2015, Scientific Reports.

[30]  Michelle K. Leach,et al.  Synthesis, copolymerization and peptide-modification of carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) for neural electrode interfaces. , 2013, Biochimica et biophysica acta.

[31]  G. Malliaras,et al.  Neuromorphic Functions in PEDOT:PSS Organic Electrochemical Transistors , 2015, Advanced materials.

[32]  L. Poole-Warren,et al.  Effects of dopants on the biomechanical properties of conducting polymer films on platinum electrodes. , 2014, Journal of biomedical materials research. Part A.

[33]  George G. Malliaras,et al.  A Microfluidic Ion Pump for In Vivo Drug Delivery , 2017, Advanced materials.

[34]  Michael D Joseph,et al.  Poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings facilitate smaller neural recording electrodes , 2011, Journal of neural engineering.

[35]  Kyriaki Manoli,et al.  Organic field-effect transistor sensors: a tutorial review. , 2013, Chemical Society reviews.

[36]  G. Buzsáki,et al.  NeuroGrid: recording action potentials from the surface of the brain , 2014, Nature Neuroscience.

[37]  G. Malliaras,et al.  Electroconductive Hydrogel Based on Functional Poly(Ethylenedioxy Thiophene) , 2016, Chemistry of materials : a publication of the American Chemical Society.

[38]  Alberto Salleo,et al.  Organic Electronics for Point-of-Care Metabolite Monitoring. , 2018, Trends in biotechnology.

[39]  M. Los,et al.  Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering , 2016, Advanced healthcare materials.

[40]  Victor Erokhin,et al.  First steps towards the realization of a double layer perceptron based on organic memristive devices , 2016 .

[41]  David C. Martin,et al.  Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devices , 2008 .

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

[43]  Gordon G Wallace,et al.  Conducting polymers, dual neurotrophins and pulsed electrical stimulation--dramatic effects on neurite outgrowth. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[44]  Feng Yan,et al.  Organic Thin‐Film Transistors for Chemical and Biological Sensing , 2012, Advanced materials.

[45]  Aram Amassian,et al.  Molecular Design of Semiconducting Polymers for High-Performance Organic Electrochemical Transistors , 2016, Journal of the American Chemical Society.

[46]  David C. Martin,et al.  Polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) around living neural cells. , 2007, Biomaterials.