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Molecular design, synthesis, and characterization of conjugated polymers for interfacing electronic biomedical devices with living tissue

Published online by Cambridge University Press:  16 April 2015

David C. Martin*
Affiliation:
Materials Science and Engineering, Biomedical Engineering, The University of Delaware, 201 DuPont Hall, Newark, Delaware 19716, USA
*
Address all correspondence to David C. Martin atmilty@udel.edu
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Abstract

Conjugated polymers are being considered for use at the interface between hard inorganic metallic and semiconducting electrodes and soft biological tissues. These organic materials have properties that are intermediate to these two extremes, and their chemistry, structure, and performance can be precisely manipulated over a large range. Examples of current interest included copolymers of poly(3,4-ethylene dioxythiophene) and poly(3,4-propylene dioxythiophene). This paper will review past efforts, recent activities, and future possibilities in this rapidly expanding area of materials research and technology.

Type
Polymers/Soft Matter Prospective Articles
Copyright
Copyright © Materials Research Society 2015 

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References

1.Wilson, B.S. and Dorman, M.F.: Cochlear implants: a remarkable past and a brilliant future. Hearing Res. 242, 321 (2008).Google Scholar
2.Weiland, J.D., Cho, A.K., and Humayun, M.S.: Retinal prostheses: current clinical results and future needs. Ophthalmology 118, 22272237 (2011).CrossRefGoogle ScholarPubMed
3.Norlin, A., Pan, J., and Leygraf, C.: Electrochemical behavior of stimulation/sensing materials for pacemaker electrode applications. J. Electrochem. Soc. 152, J110J116 (2005).Google Scholar
4.Gimsa, J., Habel, B., Schreiber, U., van Rienen, U., Strauss, U., and Gimsa, U.: Choosing electrodes for deep brain stimulation experiments—electrochemical considerations. J. Neurosci. Methods 142, 251265 (2005).CrossRefGoogle ScholarPubMed
5.Drake, K.L., Wise, K.D., Farraye, J., Anderson, D.J., and BeMent, S.L.: Performance of planar multisite microprobes in recording extracellular single-unit intracortical activity. IEEE Trans. Biomed. Eng. 35, 719732 (1988).CrossRefGoogle ScholarPubMed
6.Kringelbach, M.L., Jenkinson, N., Owen, S.L.F., and Aziz, T.Z.: Translational principles of deep brain stimulation. Nat. Rev. Neurosci. 8, 623635 (2007).Google Scholar
7.Schlaepfer, T.E., Bewernick, B.H., Kayser, S., Hurlemann, R., and Coenen, V.A.: Deep brain stimulation of the human reward system for major depression—rationale, outcomes, and outlook. Neuropsychopmarmacology 39, 13031314 (2014).Google Scholar
8.Kung, T.A., Langhals, N.B., Martin, D.C., Cederna, P.S., and Urbanchek, M.G.: Regenerative peripheral nerve interface viability and signal transduction with an implanted electrode. Plastic Reconstruct. Surg. 133, 13801394 (2014).Google Scholar
9.Kuiken, T.A.: The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee. Prosthet. Orthot. Int. 28, 245 (2004).Google Scholar
10.Birmingham, K., Gardinaru, V., Anikeeva, P., Grill, W.M., Pikov, V., McLaughlin, B., Pasricha, P., Weber, D., Ludwig, K.A., and Famm, K.: Bioelectronic medicines: a research roadmap. Nat. Rev. Drug Discov. 13, 399400 (2014).Google Scholar
11.Merrill, D.R., Bikson, M., and Jefferys, J.G.R.: Electrical stimulation of excitable tissue: design of efficacious and safe protocols. J. Neurosci. Methods 141, 171198 (2005).Google Scholar
12.Chen, J.K., Wise, K.D., Hetke, J.F., and Bledsoe, S.C.: A multichannel neural probe for selective chemical delivery at the cellular level. IEEE Trans. Biomed. Eng. 44, 760769 (1997).Google Scholar
13.Meyers, M.A., Chen, P.-Y., Lin, A.Y.-M., and Seki, Y.: Biological materials: structure and mechanical properties. Prog. Mater. Sci. 53, 1206 (2008).Google Scholar
14.Subbaroyan, J., Martin, D.C., and Kipke, D.R.: A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex. J. Neural Eng. 2, 103113 (2005).Google Scholar
15.Lang, U., Naujoks, N., and Dual, J.: Mechanical characterization of PEDOT: PSS thin films. Synth. Met. 159, 473479 (2009).Google Scholar
16.Lang, U. and Dual, J.: Mechanical properties of the intrinsically conductive polymer poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT/PSS). Key Eng. Mater. 345–346, 11891192 (2007).Google Scholar
17.Yang, J. and Martin, D.C.: Impedance spectroscopy and nanoindentation of conducting pedot coatings on neural prosthetic devices. J. Mater. Res. 21, 11241132 (2006).Google Scholar
18.Aouada, F.A., Guilherme, M.R., Campese, G.M., Giroto, E.M., Rubira, A.F., and Muniz, E.C.: Electrochemical and mechanical properties of hydrogels based on conductive poly(3,4-ethylene dioxythiophene)/poly(styrenesulfonate) and PAAm. Polym. Test. 25, 158165 (2006).CrossRefGoogle Scholar
19.Naficy, S., Razal, J.M., Spinks, G.M., Wallace, G.G., and Whitten, P.G.: Electrically conductive, tough hydrogels with pH sensitivity. Chem. Mater. 24, 34253433 (2012).Google Scholar
20.Green, R.A., Hassarati, R.T., Goding, J.A., and Baek, S.: Conductive hydrogels: mechanically robust hybrids for use as biomaterials. Macromol. Biosci. 12, 494501 (2012).Google Scholar
21.Cho, W., Wu, J., Shim, B.S., Kuan, W.-F., Mastroianni, S.E., Young, W.-S., Kuo, C.-C., Epps III, T.H., and Martin, D.C.: Synthesis and characterization of bicontinuous cubic poly(3,4-ethylene dioxythiophene) gyroid (PEDOT GYR) gels. Phys. Chem. Chem. Phys. 17, 5115 (2015).Google Scholar
22.Skotheim, T.A., and Reynolds, J.R. (eds): Conjugated Polymers: Theory, Synthesis, Properties, and Characterization (CRC Press, Taylor & Francis Group, Boca Raton, FL, 2007).Google Scholar
23.Kirchmeyer, S. and Reuter, K.: Scientific importance, properties and growing applications of poly(3,4-ethylenedioxythiophene). J. Mater. Chem. 15, 20772088 (2005).Google Scholar
24.Asplund, M., von Holst, H., and Inganäs, O.: Composite biomolecule/PEDOT materials for neural electrodes. Biointerphases 3, 8393 (2008).CrossRefGoogle ScholarPubMed
25.Groenendall, L.B., Jonas, F., Freitag, D., Pielartzik, H., and Reynolds, J.R.: Poly(3,4-ethylenedioxythiophene) and its derivatives: past, present, and future. Adv. Mater. 12, 481494 (2000).Google Scholar
26.Groenendaal, L.B., Zotti, G., Aubert, P.-H., Waybright, S.M., and Reynolds, J.R.: Electrochemistry of poly(3,4-alkylenedioxythiophene) derivatives. Adv. Mater. 15, 855879 (2003).Google Scholar
27.Göpel, W. and Heiduschka, P.: Introduction to bioelectronics: interfacing biology with electronics. Biosens. Bioelectron. 9, iiixiii (1994).Google Scholar
28.Göpel, W.: Ultimate limits in the miniaturization of chemical sensors. Sens. Actuators A, Phys. 56, 83102 (1996).Google Scholar
29.Schmidt, C.E., Shastri, V.R., Vacanti, J.P., and Langer, R.: Stimulation of neurite outgrowth using an electrically conducting polymer. Proc. Natl. Acad. Sci. USA 94, 89488953 (1997).Google Scholar
30.Shastri, V.R., Schmidt, C.E., Langer, R.S., and Vacanti, J.P.: Neuronal stimulation using electrically conducting polymers. United States Patent No. 6,096,148, assigned to the Children's Medical Center Corporation, Massachusetts Institute of Technology, USA, 2000.Google Scholar
31.Winter, J.O. and Schmidt, C.E.: Biomimetic strategies and applications in the nervous system. In Biomimetic Design of Materials: Strategies for Interactive Biointerfacial Strategies, Tissue Engineering, and Targeted Drug Delivery, edited by Dillow, A., and Lowman, A. (Marcel-Dekker, New York, 2002), pp. 375415.Google Scholar
32.Cui, X., Hetke, J.F., Wiler, J.A., Anderson, D.J., and Martin, D.C.: Electrochemical deposition and characterization of conducting polymer polypyrrole/PSS on multichannel neural probes. Sens. Actuators A, Phys. 93, 818 (2001).Google Scholar
33.Cui, X., Lee, V.A., Raphael, Y., Wiler, J.A., Hetke, J.F., Anderson, D.J., and Martin, D.C.: Surface modification of neural recording electrodes with conducting polymer/biomolecule blends. J. Biomed. Mater. Res. 56, 261272 (2001).Google Scholar
34.Cui, X.: Surface modification of neural prosthetic devices by conducting polymers and biopolymers. Macromolecular Science and Engineering Ph.D. Dissertation, University of Michigan, Ann Arbor, MI, 197 (2002).Google Scholar
35.Cui, X. and Martin, D.C.: Electrochemical deposition and characterization of poly(3,4-ethylenedioxythiophene) on neural microelectrode arrays. Sens. Actuators B, Chem. 89, 92102 (2003).CrossRefGoogle Scholar
36.Corey, J.M., Lin, D.S., Martin, D.C., and Feldman, E.L.: Electrospun nanofibers confer directional contact guidance to regenerating neurons. Ann. Neurol. 58, S65 (2005).Google Scholar
37.Abidian, M.R., Kim, D.-H., and Martin, D.C.: Conducting polymer nanotubes for controlled drug release. Adv. Mater. 18, 405409 (2006).Google Scholar
38.Feng, Z.-Q., Wu, J., Cho, W., Leach, M.K., Franz, E.W., Naim, Y.I., Gu, Z.-Z., Corey, J.M., and Martin, D.C.: Highly aligned poly(3,4-ethylenedioxythiophene) (PEDOT) nano- and microscale fibers and tubes. Polymer 54, 702708 (2013).Google Scholar
39.Kim, D.-H., Richardson-Burns, S.M., Povlich, L.K., Abidian, M., Spanninga, S., Hendricks, J.L., and Martin, D.C.: ‘Soft, Fuzzy and Bioactive Conducting Polymer Coatings for Neural Prosthetic Devices’, Chapter 7 in Reichert, William, M. (ed.), Indwelling Neural Implants: Strategies for Contending with the In-Vivo Environment (Frontiers in Neuroengineering, Boca Raton, FL: Taylor and Francis, 2008), http://www.ncbi.nlm.nih.gov/books/NBK3940/Google Scholar
40.Rozlosnik, N.: New directions in medical biosensors employing poly(3,4-ethylenedioxy thiophene) derivative-based electrodes. Anal. Bioanal. Chem. 395, 637645 (2009).Google Scholar
41.Povlich, L.K., et al. : ‘Electroactive Polymeric Biomaterials’, in Ducheyne, P., Healy, K., Hutmacher, D.W., Grainger, D.W., and Kirkpatrick, C.J. (eds.), (Comprehensive Biomaterials, Elsevier, Amsterdam), 1st Edition, 1, pp. 547–561 (2011).Google Scholar
42.Svennersten, K., Larsson, K.C., Berggren, M., and Richter-Dahlfors, A.: Organic bioelectronics in nanomedicine. Biochim. Biophys. Acta 1810, 276285 (2011).Google Scholar
43.Rivnay, J., Owens, R.M., and Malliaras, G.G.: The rise of organic bioelectronics. Chem. Mater. 26, 679685 (2014).Google Scholar
44.Wallace, G.G., Moulton, S., Higgins, M., and Kapsa, R.M.I.: Organic Bionics (Wiley-VCH, Weinheim, Germany, 2012).Google Scholar
45.Otero, T.F., Alfaro, M., Martinez, V., Perez, M.A., and Martinez, J.G.: Biomimetic structural electrochemistry from conducting polymers: processes, charges, and energies. coulovoltammetric results from films on metals revisited. Adv. Funct. Mater. 23, 39293940 (2013).Google Scholar
46.Fattahi, P., Yang, G., Kim, G., and Abidian, M.R.: A review of organic and inorganic biomaterials for neural interfaces. Adv. Mater. 26, 18461885 (2014).Google Scholar
47.Liao, C., Zhang, M., Yao, M.Y., Hua, T., Li, L., and Yan, F.: Flexible organic electronics in biology: materials and devices. Adv. Mater. (2014) doi: 10.1002/adma.201402625.Google Scholar
48.Balint, R., Cassidy, N.J., and Cartmell, S.H.: Conductive polymers: towards a smart biomaterial for tissue engineering. Acta Biomater. 10, 23412353 (2014).Google Scholar
49.Molino, P.J. and Wallace, G.G.: Next generation bioelectronics: advances in fabrication coupled with clever chemistries enable the effective integration of biomaterials and organic conductors. APL Mater. 3, 014913 (2015).Google Scholar
50.Isaakson, J., Kjäll, P., Nilsson, D., Robinson, N., Berggren, M., and Richter-Dahlfors, A.: Electronic control of Ca2+ signalling in neuronal cells using an organic electronic ion pump. Nat. Mater. 6, 673679 (2007).Google Scholar
51.Tybrandt, K., Forchheimer, R., and Berggren, M.: Logic gates based on ion transistors. Nat. Commun. 3, 871 (2012).Google Scholar
52.Leger, J., Berggren, M., and Carter, S. (eds): Iontronics: Ionic Carriers in Organic Electronic Materials and Devices (CRC Press, Taylor and Francis, ISBN 9781439806883, 2011).Google Scholar
53.Martin, D.C., Wu, J., Shaw, C.M., King, Z., Spanninga, S.A., Richardson-Burns, S.M., Hendricks, J., and Yang, J.: The morphology of poly(3,4-ethylenedioxythiophene). Polym. Rev. 50, 340384 (2010).Google Scholar
54.Salleo, A., Kline, R.J., DeLongchamp, D.M., and Chabinyc, M.L.: Microstructural characterization and charge transport in thin films of conjugated polymers. Adv. Mater. 22, 38123838 (2010).Google Scholar
55.Rivnay, J., Noriega, R., Northrup, J.E., Kline, R.J., Toney, M.F., and Salleo, A.: Structural origin of gap states in semicrystalline polymers and the implications for charge transport. Phys. Rev. B 83, 121306(R) (2011).Google Scholar
56.Rivnay, J., Mannsfeld, S.C.B., Miller, C.E., Salleo, A., and Toney, M.F.: Quantitative determination of organic semiconductor microstructure from the molecular to device scale. Chem. Rev. 112, 54885519 (2012).CrossRefGoogle ScholarPubMed
57.Noriega, R., Rivnay, J., Vandewal, K., Koch, F.P.V., Stingelin, N., Smith, P., Toney, M.F., and Salleo, A.: A general relationship between disorder, aggregation and charge transport in conjugated polymers. Nat. Mater. 12, 10381044 (2013).Google Scholar
58.Venkataraman, D., Nikolka, M., Sadhanala, A., Lemaur, V., Zelazny, M., Kepa, M., Hurhangee, M., Kronemeijer, A.J., Pecunia, V., Nasrallah, I., Romanov, I., Broch, K., McCulloch, I., Emin, D., Olivier, Y., Cornil, J., Beljonne, D., and Sirringhaus, H.: Approaching disorder-free transport in high-mobility conjugated polymers. Nature 515, 384388 (2014).Google Scholar
59.Yang, J., Lipkin, K., and Martin, D.C.: Electrochemical fabrication of conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) nanofibrils on microfabricated neural prosthetic devices. J. Biomater. Sci.—Polym. Ed. 18, 10751089 (2007).Google Scholar
60.Sharp, D.G. and Beard, J.W.: Size and density of polystyrene particles measured by ultracentrifugation. J. Biol. Chem. 185, 247253 (1950).Google Scholar
61.Yang, J. and Martin, D.C.: Microporous conducting polymers on neural prosthetic devices. II. Physical characterization. Sens. Actuators A, Phys. 113, 204211 (2004).Google Scholar
62.Yang, J. and Martin, D.C.: Microporous conducting polymers on neural prosthetic devices. I. electrochemical deposition. Sens. Actuators B, Chem. 101, 133142 (2004).Google Scholar
63.Euliss, L.E., DuPont, J.A., Gratton, S., and DeSimone, J.: Imparting size, shape, and composition control of materials for nanomedicine. Chem. Soc. Rev. 35, 10951104 (2006).Google Scholar
64.Rolland, J.P., Maynor, B.W., Euliss, L.E., Exner, A.E., Denison, G.M., and DeSimone, J.M.: Direct fabrication and harvesting of monodisperse, shape-specific nanobiomaterials. J. Am. Chem. Soc. 127, 1009610100 (2005).Google Scholar
65.Merkel, T.J., Herlihy, K.P., Nunes, J., Orgel, R.M., Rolland, J.P., and DeSimone, J.M.: Scalable, shape-specific, top-down fabrication methods for the synthesis of engineered colloidal particles. Langmuir 26, 1308613096 (2009).Google Scholar
66.Hulvat, J.F. and Stupp, S.I.: Anisotropic properties of conducting polymers prepared by liquid crystal templating. Adv. Mater. 16, 589592 (2004).Google Scholar
67.Hulvat, J.F. and Stupp, S.I.: Liquid crystal templating of conducting polymers. Angew. Chem., Int. Ed. 42, 778781 (2003).Google Scholar
68.Yang, J., Kim, D., Hendricks, J.L., Leach, M., Northey, R., and Martin, D.C.: Ordered surfactant-templated poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer on microfabricated neural probes. Acta Biomater. 1, 125136 (2005).Google Scholar
69.Kim, O., Kim, S.Y., Park, B., Hwang, W., and Park, M.J.: Factors affecting electromechanical properties of ionic polymer actuators based on ionic liquid-containing block copolymers. Macromolecules 47, 43574368 (2014).Google Scholar
70.Chen, B., Eddaoudi, M., Hyde, S. T., O'Keeffe, M., and Yaghi, O.M.: Interwoven metal-organic framework on a periodic minimal surface with extra-large pores. Science 291, 10211023 (2001).Google Scholar
71.Feng, X., Chen, L., Honsho, Y., Saengsawang, O., Liu, L., Wang, L., Saeki, A., Irle, S., Seki, S., Dong, Y., and Jiang, D.: An ambipolar conducting organic framework with self-sorted and periodic electron donor-acceptor ordering. Adv. Mater. 24, 30263031 (2012).Google Scholar
72.Ding, X., Feng, X., Saeki, A., Seki, S., Nagai, A., and Jiang, D.: Conducting metallophthalocyanine 2D covalent organic frameworks: the role of central metals in controlling pi-electronic functions. Chem. Commun. 48, 89528954 (2012).Google Scholar
73.Feng, X., Ding, X. and Jiang, D.: Covalent organic frameworks. Chem. Soc. Rev. 41, 60106022 (2012).CrossRefGoogle ScholarPubMed
74.Yang, P., Deng, T., Zhao, D., Feng, P., Pine, D., Chmelka, B.F., Whitesides, G.M., and Stuckey, G.D.: Hierarchically ordered oxides. Science 282, 22442246 (1998).Google Scholar
75.Yuan, D., Lasagni, A., Hendricks, J.L., Martin, D.C., and Das, S.: Patterning of periodic nano-cavities on PEDOT-PSS using nanosphere-assisted near-field optical enhancement and laser interference lithography. Nanotechnology 23, 015304 (2012).Google Scholar
76.Lasagni, A.F., Shao, P., Hendricks, J.L., Shaw, C.M., Martin, D.C., and Das, S.: Direct fabrication of periodic patterns with hierarchical sub-wavelength structures on poly(3,4-ethylene dioxythiophene)-poly(styrene sulfonate) thin films using femtosecond laser interference patterning. Appl. Surf. Sci. 256, 17081713 (2010).Google Scholar
77.Lasagni, A., Hendricks, J.L., Shaw, C.M., Yuan, D., Martin, D.C., and Das, S.: Direct laser interference patterning of poly(3,4-ethylene dioxythiophene)-poly(styrene sulfonate) (PEDOT-PSS) thin films. Appl. Surf. Sci. 255(22), 91869192 (2009).Google Scholar
78.Hong, J.-Y., Hwang, Y.-K., Kye, Y.M., Myung, H., Won, Y.S., and Huh, S.: Hierarchically structured functionalizable mesoporous PEDOT-derived conducting polymers. Mater. Lett. 96, 181184 (2013).Google Scholar
79.Peppas, N.A. and Langer, R.: New challenges in biomaterials. Science 263, 17151720 (1994).Google Scholar
80.Peppas, N.A., Bures, P., Leobandung, W., and Ichikawa, H.: Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 50, 2746 (2000).Google Scholar
81.Kim, D., Abidian, M., and Martin, D.C.: Conducting polymers grown in hydrogel scaffolds coated on neural prosthetic devices. J. Biomed. Mater. Res. 71A, 577585 (2004).Google Scholar
82.Abidian, M.R., and Martin, D.C.: ‘Multifunctional Nanobiomaterials for Neural Interfaces’, Advanced Functional Materials, 19(4), 573–85 (2009).Google Scholar
83.Poole-Warren, L., Lovell, N., Baek, S., and Green, R.: Development of bioactive conductive polymers for neural interfaces. Expert Rev. Med. Devices 7, 3549 (2010).Google Scholar
84.Green, R.A., Lim, K.S., Henderson, W.C., Hassarati, R.T., Martens, P.J., Lovell, N.H., and Poole-Warren, L.A.: Living electrodes: tissue engineering the neural interface. 35th Annual Int. Conf. of the IEEE EMBS, 2013, pp. 6957–6960.Google Scholar
85.Green, R.A., Matteucci, P.B., Hassarati, R.T., Giraud, B., Dodds, C.W.D., Chen, S., Byrnes-Preston, P.J., Suaning, G.J., Poole-Warren, L.A., and Lovell, N.H.: Performance of conducting polymer electrodes for stimulating neuroprosthetics. J. Neural Eng. 10, 016009 (2013).Google Scholar
86.Lu, Y., He, W., Cao, T., Guo, H., Zhang, Y., Li, Q., Shao, Z., Cui, Y., and Zhang, X.: Elastic, conductive, polymeric hydrogels and sponges. Sci. Rep. 4, 5792 (2014).Google Scholar
87.Nowak, A.P., Breedveld, V., Pakstis, L., Pine, D.J., Pochan, D.J., and Deming, T.J.: Rapid recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles. Nature 417, 424428 (2002).Google Scholar
88.Jia, X., Yeo, Y., Clifon, R.J., Jiao, T., Kohane, D.S., Kobler, J., Zeitels, S.M., and Langer, R.: Hyaluronic acid-based microgels and microgel networks for vocal fold regeneration. Biomacromolecules 7, 33363344 (2006).Google Scholar
89.Jha, A.K., Hule, R.A., Jiao, T., Teller, S.S., Clifton, R.J., Duncan, R.L., Pochan, D.J., and Jia, X.: Structural analysis and mechanical characterization of hyaluronic acid-based doubly crosslinked networks. Macromolecules 42, 537546 (2009).CrossRefGoogle Scholar
90.Zhang, H., Dicker, K.T., Xu, X., Jia, X., and Fox, J.M.: Interfacial bioorthogonal crosslinking. ACS Macro Lett. 3, 727731 (2014).CrossRefGoogle Scholar
91.Rothberg, L., Paquette, S., Rhinehart, J., McCamant, D., Kas, O., Charati, M., Galvin, M., and Kiick, K.L.: Photophysical consequences of interactions between conjugated chromophores. Laser Sci. LMA1 (2010). http://dx.doi.org/10.1364/LS.2010.LMA1.Google Scholar
92.Xiao, Y., Cui, X., and Martin, D.C.: Electrochemical polymerization and properties of PEDOT/S-PEDOT on neural microelectrode arrays. J. Electroanal. Chem. 573, 4348 (2004).Google Scholar
93.Xiao, Y., Martin, D.C., Cui, X., and Shenai, M.: Surface modification of neural probes with conducting polymer poly(hydroxymethylated-3,4-ethylenedioxythiophene) and its biocompatibility. Appl. Biochem. Biotechnol. 128, 117129 (2006).Google Scholar
94.Luo, S.-C., Ali, E.M., Tansil, N.C., Yu, H.-h., Gao, S., Kantchev, E.A.B., and Ying, J.Y.: Poly(3,4-ethylenedioxythiophene) (PEDOT) nanobiointerfaces: thin, ultrasmooth, and functionalized PEDOT films with in vitro and in vivo biocompatibility. Langmuir 24, 80718077 (2008).Google Scholar
95.Zhang, L., Wen, Y., Yao, Y., Xu, J., Duan, X., and Zhang, G.: Synthesis and characterization of PEDOT derivative with carboxyl group and its chemo/bio sensing application as nanocomposite, immobilized biological and enhanced optical materials. Electrochim. Acta 116, 343354 (2014).Google Scholar
96.Povlich, L.K., Cho, J.C., Spanninga, S., Martin, D.C., and Kim, J.: Carboxylic acid-modified EDOT for bio-functionalization of neural probe electrodes. Polym. Preprints 48, 78 (2007).Google Scholar
97.Bhagwat, N., Kiick, K.L., and Martin, D.C.: Electrochemical deposition and characterization of carboxylic-acid functionalized PEDOT copolymers. J. Mater. Res. 29, 28352844 (2014).Google Scholar
98.Povlich, L.K., Cho, J.C., Leach, M.K., Kim, J., Corey, J.M., and Martin, D.C.: Synthesis, copolymerization, and peptide-modification of carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) for neural electrode interfaces. Biochim. Biophys. Acta 1830, 42884293 (2012).CrossRefGoogle Scholar
99.Feldman, K. and Martin, D.C.: Functional conducting polymers via thiol-ene chemistry. Biosens. Bioelectron. 2, 305317 (2012).Google Scholar
100.Wei, B., Ouyang, L., Liu, J., and Martin, D.C.: Post-polymerization functionalization of poly(3,4-propylenedioxythiophene) (PProDOT) via thiol-ene “click” chemistry. J. Mater. Chem. B (2015). doi: 10.1039/C4TB02033B.Google Scholar
101.Ouyang, L.: Crosslinking, electrografting, and in vivo polymerization of poly(3,4-ethylene dioxythiophene) (PEDOT) and derivatives as reliable neural interfacing materials. Materials Science and Engineering Ph.D. dissertation, University of Delaware (2014).Google Scholar
102.Richardson-Burns, S.M., Hendricks, J.L., Povlich, L.K., Foster, B., Kim, D.-H., and Martin, D.C.: Polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) around living neural cells. Biomaterials 28, 15391552 (2007).Google Scholar
103.Richardson-Burns, S.M., Hendricks, J.L., and Martin, D.C.: Electrochemical polymerization of conducting polymers in living neural tissue. J. Neural Eng. 4, L6L13 (2007).Google Scholar
104.Ouyang, L., Feldman, K.E., Green, R., and Martin, D.C.: Direct local polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in rat cortex. Prog. Brain Res. 194, 263271 (2011).Google Scholar
105.Wilks, S.J., Wooley, A.J., Ouyang, L., Martin, D.C., and Otto, K.J.: In vivo polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in rodent cerebral cortex. Conf. of the IEEE EMBS 2011, 5412–5415 (2011).Google Scholar
106.Biran, R., Martin, D.C., and Tresco, P.A.: Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp. Neurol. 195, 115126 (2005).Google Scholar
107.Ouyang, L., Shaw, C., Liu, J., Griffin, A.L., and Martin, D.C.: In vivo polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in living rat hippocampus does not cause a significant loss of performance in a delayed alternation (DA) task. J. Neural Eng. 11, 026005 (2014).Google Scholar
108.Lu, W., Fadeev, A.G., Qi, B., Smela, E., Mattes, B.R., Ding, J., Spinks, G.M., Mazurkiewicz, J., Zhou, D., Wallace, G.G., MacFarlane, D.R., Forsyth, S.A., and Forsyth, M.: Use of ionic liquids for pi-conjugated polymer electrochemical devices. Science 297, 983987 (2002).Google Scholar
109.Luo, X. and Cui, X.T.: Electrochemical deposition of conducting polymer coatings on magnesium surfaces in ionic liquid. Acta Biomater. 7, 441446 (2011).Google Scholar
110.Döbbelin, M., Pozo-Gonzalo, C., Marcilla, R., Blanco, R., Segura, J.L., Pomposo, J.A., and Mecerreyes, D.: Electrochemical synthesis of PEDOT derivatives bearing imidazolium-ionic liquid moieties. J. Polym. Sci. A, Polym. Chem. 47, 30103021 (2009).Google Scholar
111.Cui, X.T., and Zhou, D.D.: Poly(3,4-Ethylenedioxythiophene) for chronic neural stimulation. IEEE Trans. Neural Syst. Rehab. Eng. 15, 502508 (2007).Google Scholar
112.Abidian, M.R., Corey, J.M., Kipke, D.R., and Martin, D.C.: Conducting polymer nanotubes improve electrical properties, mechanical adhesion, neural attachment, and neurite outgrowth of neural electrodes. Small 6, 421429 (2010).Google Scholar
113.Khodagholy, D., Doublet, T., Gurfinkel, M., Quilichini, P., Ismailova, E., Leleux, P., Herve, T., Sanaur, S., Bernard, C., and Malliaras, G.G.: Highly conformable conducting polymer electrodes for in vivo recordings. Adv. Mater. 23, H268H272 (2011).Google Scholar
114.Stavrinidou, E., Leleux, P., Rajaona, H., Khodagholy, D., Rivnay, J., Lindau, M., Sanaur, S., and Malliaras, G.G.: Direct measurement of ion mobility in a conducting polymer. Adv. Mater. 25, 44884493 (2013).Google Scholar
115.Pires, F., Ferreira, Q., Rodrigues, C.A.V., Morgado, J., and Ferreira, F.C.: Neural stem cell differentiation by electrical stimulation using a cross-linked PEDOT substrate: expanding the use of biocompatible conjugated conductive polymers for neural tissue engineering. Biochem. Biophys. Acta 1850, 11581168 (2015).Google Scholar
116.Riess, I.: Mixed ionic-electronic conductors—material properties and applications. Solid State Ion. 157, 117 (2003).Google Scholar
117.Litzelman, S.J. and Tuller, H.L.: Measurement of mixed conductivity in thin films with microstructured Hebb-Wagner blocking electrodes. Solid State Ion. 180, 11901197 (2009).Google Scholar
118.Tuller, H.L.: Solid state electrochemical systems—opportunities for nanofabricated or nanostructured materials. J. Electroceram. 1, 211218 (1997).Google Scholar
119.Barsoukov, E. and Macdonald, J.R.: Impedance Spectroscopy: Theory, Experiment, and Applications (John Wiley & Sons, New York, NY, 2005).Google Scholar
120.Abidian, M. and Martin, D.C.: Experimental and theoretical characterization of implantable neural microelectrodes modified with conducting polymer nanotubes. Biomaterials 29, 12731283 (2008).Google Scholar
121.Ren, X. and Pickup, P.G.: Impedance measurements of ionic conductivity as a probe of structure in electrochemically deposited polypyrrole films. J. Electroanal. Chemistry 396, 359364 (1995).Google Scholar
122.Ren, X. and Pickup, P.G.: An impedance study of electron transport and electron transfer in composite polypyrrole + polystyrenesulphonate films. J. Electroanal. Chem. 420, 251257 (1997).Google Scholar
123.Lefebvre, M., Qi, Z., Rana, D., and Pickup, P.G.: Chemical synthesis, characterization, and electrochemical studies of poly(3,4-ethylenedioxythiophene)/poly(styrene-4-sulfonate) composites. Chem. Mater. 11, 262268 (1999).Google Scholar
124.Li, G. and Pickup, P.G.: Ion transport in poly(3,4-ethylendioxythiophene)-poly(styrene-4-sulfonate) composites. Phys. Chem. Chem. Phys. 2, 12551260 (2000).Google Scholar
125.Sotzing, G.A., Reynolds, J.R., and Steel, P.J.: Electrochromic conducting polymers via electrochemical polymerization of bis(2-(3,4-ethylenedioxy)thienyl) monomers. Chem. Mater. 8, 882889 (1996).Google Scholar
126.Pei, Q., Zuccarello, G., Ahlskog, M., and Inganäs, O.: Electrochromic and highly stable poly(3,4-ethylenedioxythiophene) switches between opaque blue-black and transparent sky blue. Polymer 35, 13471351 (1994).Google Scholar
127.Wang, X., Shapiro, B., and Smela, E.: Visualizing ion currents in conjugated polymers. Adv. Mater. 16, 16051609 (2004).Google Scholar
128.Stavrinidou, E., Leleux, P., Rajaona, H., Fiochhi, M., Sanaur, S., and Malliaras, G.G.: A simple model for ion injection and transport in conducting polymers. J. Appl. Phys. 113, 244501 (2013).Google Scholar
129.Cogan, S.F.: Neural stimulation and recording electrodes. Annu. Rev. Biomed. Eng. 10, 275309 (2008).Google Scholar
130.Li, D., Cao, C., Zhang, J., Zhan, S., Chen, S., and Sun, B.: Subthalamic nucleus deep brain stimulation for Parkinson's disease: 8 years of follow up. Transl. Neurodegener. 2, 11 (2013).Google Scholar
131.Blanksby, S.J. and Ellison, G.B.: Bond dissociation energies of organic molecules. Acc. Chem. Res. 36, 255263 (2003).Google Scholar
132.Wu, J., Shaw, C.M., and Martin, D.C.: ‘Electron Microscopy of Organic Materials: An Overview and Review of Recent Developments’, in Hashimoto, H., and Thomas, E.L. (eds.), Volume 2: Polymer Characterization (Comprehensive Polymer Science, Elsevier), 509525 (2012).Google Scholar
133.Chung, K. and Deisseroth, K.: CLARITY for mapping the nervous system. Nat. Methods 10, 508513 (2013).Google Scholar
134.Tomer, R., Ye, L., Hsueh, B., and Deisseroth, K.: Advanced CLARITY for rapid and high-resolution imaging of intact tissues. Nat. Protoc. 9, 16821697 (2014).Google Scholar
135.Chen, F., Tillberg, P.W., and Boyden, E.S.: Expansion microscopy. Science 347, 543548 (2015).Google Scholar
136.Tang, H.X., Foran, B., and Martin, D.C.: Quantitative measurement of adhesion between polypropylene blends and paints by tensile mechanical testing. Polym. Eng. Sci. 41, 440448 (2001).Google Scholar
137.Martin, D.C. and Thomas, E.L.: Experimental high-resolution electron microscopy of polymers. Polymer 36, 17431759 (1995).Google Scholar
138.Martin, D.C., Chen, J., Yang, J., Drummy, L.F., and Kübel, C.: High resolution electron microscopy of ordered polymers and organic molecular crystals: recent developments and future possibilities. J. Polym. Sci., Phys. 43, 17491778 (2005).Google Scholar
139.de Jonge, N. and Ross, F.M.: Electron microscopy of specimens in liquid. Nat. Nanotechnol. 6, 695704 (2011).Google Scholar
140.Schneider, N.M., Norton, M.M., Mendel, B.J., Grogan, J.M., Ross, F.M., and Bau, H.H.: Electron-water interactions and implications for liquid cell electron microscopy. J. Phys. Chem. C 118, 2237322382 (2014).Google Scholar
141.Shibuta, Y., Okajima, Y., and Suzuki, T.: Phase-field modeling for electrodeposition process. Sci. Technol. Adv. Mater. 8, 511518 (2007).Google Scholar
142.Shibuta, Y., Okajima, Y., and Suzuki, T.: A phase-field simulation of bridge formation in a nanometer-scale switch. Scr. Mater. 55, 10951098 (2006).Google Scholar
143.Yu, H.-C. and Thornton, K.: The rough idea of modeling electro-polymerization. The University of Michigan, 2008.Google Scholar
144.Thornton, K., Agren, J., and Voorhees, P.W.: Modelling the evolution of phase boundaries in solids at the meso- and nano-scales. Acta Mater. 51, 56755710 (2003).Google Scholar
145.ISO 10993: Biological Evaluation and Biocompatibility Testing of Medical Devices (International Organization for Standardization, Geneva, Switzerland, 1995).Google Scholar
146.Kim, Y.J., Wu, W., Chun, S.E., Whitacre, J., and Bettinger, C.J.: Biologically derived melanin electrodes in aqueous sodium-ion energy storage devices. Proc. Natl. Acad. Sci. USA 110, 2091220917 (2013).Google Scholar
147.Bettinger, C.J., Bruggeman, J.P., Misra, A., Borenstein, J.T., and Langer, R.: Biocompatibility of biodegradable semiconducting melanin films for nerve tissue engineering. Biomaterials 30, 30503057 (2009).Google Scholar
148.Bettinger, C.J., Misra, A.C., Langer, R., and Borenstein, J.T.: Microcontact printing of melanin thin films for neuronal tissue engineering applications. Symp. MM: Biomolecular and Biologically Inspired Interfaces and Assemblies; Materials Research Society, MM 6.22. Boston, MA, Fall (2007) http://www.mrs.org/f07-abstract-mm/.Google Scholar
149.Povlich, L.K., Le, J., Kim, J., and Martin, D.C.: Poly(5,6-dimethoxyindole-2-carboxylic acid) (PDMICA): a melanin-like polymer with unique electrochromic and structural properties. Macromolecules 43, 37703774 (2010).Google Scholar
150.Irimia-Vladu, M., Sariciftci, N.S., and Bauer, S.: Exotic materials for bio-organic electronics. J. Mater. Chem. 21, 13501361 (2011).Google Scholar
151.Irimia-Vladu, M., Glowacki, E.D., Troshin, P.A., Schwabegger, G., Leonat, L., Susarova, D.K., Krystal, O., Ullah, M., Kanbur, Y., Bodea, M.A., Razumov, V.F., Sitter, H., Bauer, S., and Sariciftci, N.S.: Indigo—a natural pigment for high performance ambipolar organic field effect transistors and circuits. Adv. Mater. 24, 375380 (2012).Google Scholar
152.Pirbadian, S., Barchinger, S.E., Leung, K.M., Byun, H.S., Jangir, Y., Bouhenni, R.A., Reed, S.B., Romine, M.F., Saffarini, D.A., Shi, L., Gorby, Y.A., Golbeck, J.H., and El-Naggar, M.Y.: Shewanella oneidensis MR-1 nanowires are outer membrane and periplasmic extensions of the extracellular electron transport components. Proc. Natl. Acad. Sci. USA 111, 1288312888 (2014).Google Scholar
153.Pfeffer, C., Larsen, S., Song, J., Dong, M., Besenbacher, F., Meyer, R.L., Kjeldsen, K.U., Schreiber, L., Gorby, Y.A., El-Naggar, M.Y., Leung, K.M., Schramm, A., Risgaard-Petersen, N., and Nielsen, L.P.: Filamentous bacteria transport electrons over centimetre distances. Nature 491, 218221 (2012).Google Scholar
154.El-Naggar, M.Y., Wanger, G., Leung, K.M., Yuzvinsky, T.D., Southam, G., Yang, J., Lau, W.M., Nealson, K.H., and Gorby, Y.A.: Electrical transport along bacterial nanowires from Shewanella oneidensis MR-1. Proc. Natl. Acad. Sci. USA 107, 1812718131 (2007).Google Scholar
155.Seymour, J. and Kipke, D.R.: Neural probe design for reduced tissue encapsulation. Biomaterials 28, 35943607 (2007).Google Scholar
156.Seymour, J. and Kipke, D.R.: Open-architecture neural probes reduce cellular encapsulation. Mater. Res. Soc. CC2.4 (2006). http://dx.doi.org/10.1557/PROC-0926-CC02-04.Google Scholar
157.Skousen, J.L., Bridge, M.J., and Tresco, P.A.: A strategy to reduce neuroinflammation surrounding devices implanted chronically in brain tissue by manipulating device surface permeability. Biomaterials 36, 3334 (2015).Google Scholar
158.Skousen, J.L., Merriam, Sr.M.E., Srivannavit, O., Perlin, G., Wise, K.D., and Tresco, P.A.: Chapter 12—reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays. Prog. Brain Res. 194, 167180 (2011).Google Scholar
159.Kim, D.-H., Viventi, J., Amsden, J., Xiao, J., Vigeland, L., Kim, Y.-S., Blanco, J.A., Panilaitis, B., Frechette, E.S., Contreras, D., Kaplan, D.L., Omenetto, F.G., Huang, Y., Hwang, K.-C., Zakin, M.R., Litt, B., and Rogers, J.A.: Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. Nat. Mater. 9, 511517 (2010).Google Scholar
160.Xu, S., Yan, Z., Jang, K.-I., Huang, W., Fu, H., Kim, J., Wei, Z., Flavin, M., McCracken, J., Wang, R., Badea, A., Liu, Y., Xiao, D., Zhou, G., Lee, J., Chung, H.U., Cheng, H., Ren, W., Banks, A., Li, X., Paik, U., Nuzzo, R.G., Huang, Y., Zhang, Y., and Rogers, J.A.: Assembly of micro/nanomaterials into complex, three-dimensional architectures by compressive buckling. Science 347, 154159 (2015).Google Scholar
161.Smela, E.: Conjugated polymer actuators for biomedical applications. Adv. Mater. 15, 481494 (2003).Google Scholar
162.Jager, E.W.H., Smela, E., and Inganas, O.: Microfabricating conjugated polymer actuators. Science 290, 15401545 (2000).Google Scholar
163.Jager, E.W.H., Smela, E., and Inganäs, O.: Polypyrrole microactuators. Synth. Met. 102, 13091310 (1999).Google Scholar
164.Smela, E., Inganäs, O., and Lundström, I.: Controlled folding of micrometer-size structures. Science 268, 17351738 (1995).Google Scholar
165.Kozai, T.D.Y., Jaquins-Gerstl, A.S., Vazquez, A.L., Michael, A.C., and Cui, X.T.: Brain tissue responses to neural implants impact signal sensitivity and interventional strategies. ACS Chem. Neurosci. 6, 4867 (2015).Google Scholar
166.Kozai, T.D.Y., Alba, N.A., Zhang, H., Kotov, N.A., Gaunt, R.A., and Cui, X.T.: ‘Chapter 5: Nanostructured Coatings for Improved Charge Delivery to Neurons’, in De Vittorio, M., Martiradonna, L., and Assad, J. (eds.), Nanotechnology and Neuroscience: Nano-electronic, Photonic, and Mechanical Neuronal Interfacing (New York, NY: Springer), 293 (2014). http://link.springer.com/chapter/10.1007%2F978-1-4899-8038-0_4#page-1Google Scholar
167.Kozai, T.D.Y., Catt, K., Gugel, Z.V., Olafsson, V.T., Vazquez, A.L., and Cui, X.T.: Mechanical failure modes of chronically implanted planer silicon-based neural probes for laminar recording. Biomaterials 37, 2539 (2014).Google Scholar
168.Canales, A., Jia, X., Froriep, U.P., Koppes, R.A., Tringides, C.M., Selvidge, J., Lu, C., Hou, C., Wei, L., Fink, Y., and Anikeeva, P.: Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo. Nat. Biotechnol. 33, 277284 (2015).Google Scholar
169.Minev, I.R., Musienko, P., Hirsch, A., Barraud, Q., Wenger, M., Moraud, E.M., Gandar, J., Capogrosso, M., Milekovic, T., Asboth, L., Torres, R.F., Vachicouras, N., Liu, Q., Pavlova, N., Duis, S., Larmagnac, A., Vörös, J., Micera, S., Suo, Z., Courtine, G., and Lacour, S.P.: Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159 (2015).Google Scholar
170.Nguyen, J.K., Park, D.J., Skousen, J.L., Hess-Dunning, A.E., Tyler, D.J., Rowan, S.J., Weder, C., and Capadona, J.R.: Mechanically-compliant intracortical implants reduce the neuroinflammatory response. J. Neural Eng. 11, 056014 (2014).Google Scholar
171.Jorfi, M., Skousen, J.L., Weder, C., and Capadona, J.R.: Progress towards biocompatible intracortical microelectrodes for neural interfacing applications. J. Neural Eng. 12, 01101 (2015).Google Scholar
172.Hu, H., Ni, Y., Montana, V., Haddon, R.C., and Parpura, V.: Chemically functionalized carbon nanotubes as substrates for neuronal growth. Nano Lett. 4, 507511 (2004).Google Scholar
173.Keefer, E.W., Botterman, B.R., Romero, M.I., Rossi, A.F., and Gross, G.W.: Carbon nanotube coating improves neuronal recordings. Nat. Nanotechnol. 3, 434438 (2008).Google Scholar
174.Luo, X., Weaver, C.L., Tan, S., and Cui, X.T.: Pure graphene oxide doped conducting polymer nanocomposite for bio-interfacing. J. Mater. Chem. B 1, 13401348 (2013).Google Scholar
175.Xiao, X., Wang, J., Carlisle, J.A., Mech, B., Greenberg, R., Freda, R., Humayun, M., Weiland, J., and Auciello, O.: In vitro and in vivo evaluation of ultrananocrystalline diamond for coating of implantable retinal microchips. J. Biomed. Mater. 77B, 273281 (2006).Google Scholar
176.Luo, X., Weaver, C.L., Zhou, D.D., Greenberg, R., and Cui, X.T.: Highly stable carbon nanotube doped poly(3,4-ethylenedioxythiophene) for chronic neural stimulation. Biomaterials 32, 55515557 (2011).Google Scholar
177.Mousavi, Z., Bobacka, J., Lewenstam, A., and Ivaska, A.: Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with carbon nanotubes as ion-to-electron transducer in polymer membraned-based potassium ion-selective electrodes. J. Electroanal. Chem. 633, 246252 (2009).Google Scholar
Supplementary material: Link

David C. Martin supplementary video

Conjugated polymers for interfacing electronic biomedical devices with living tissue

https://www.youtube.com/watch?v=550V_9nu82Q
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