Thiol-ene=acrylate substrates for softening intracortical electrodes Taylor Ware, 1 Dustin Simon, 1 Clive Liu, 2 Tabassum Musa, 3 Srikanth Vasudevan, 4 Andrew Sloan, 5 Edward W. Keefer, 3 Robert L. Rennaker II, 5 and Walter Voit 1,2 1 The University of Texas at Dallas, Department of Materials Science and Engineering, Richardson, Texas 2 The University of Texas at Dallas, Department of Mechanical Engineering, Richardson, Texas 3 Plexon Inc., Dallas, Texas 4 The University of Texas at Arlington, Department of Bioengineering, Arlington, Texas 5 The University of Texas at Dallas, School of Behavioral and Brain Sciences, Richardson, Texas Received 29 October 2012; revised 20 February 2013; accepted 06 March 2013 Published online 13 May 2013 in Wiley Online Library (wileyonlinelibrary.com). 10.1002/jbm.b.32946 Abstract: Neural interfaces have traditionally been fabricated on rigid and planar substrates, including silicon and engineer- ing thermoplastics. However, the neural tissue with which these devices interact is both 3D and highly compliant. The mechanical mismatch at the biotic–abiotic interface is expected to contribute to the tissue response that limits chronic signal recording and stimulation. In this work, novel ternary thiol-ene=acrylate polymer networks are used to create softening substrates for neural recording electrodes. Thermo- mechanical properties of the substrates are studied through differential scanning calorimetry and dynamic mechanical analysis both before and after exposure physiological condi- tions. This substrate system softens from more than 1 GPa to 18 MPa on exposure to physiological conditions: reaching body temperature and taking up less than 3% fluid. The im- pedance of 177 mm 2 gold electrodes electroplated with plati- num black fabricated on these substrates is measured to be 206 kX at 1 kHz. Specifically, intracortical electrodes are fabri- cated, implanted, and used to record driven neural activity. This work describes the first substrate system that can use the full capabilities of photolithography, respond to physiological conditions by softening markedly after insertion, and record driven neural activity for 4 weeks. V C 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1–11, 2014. Key Words: thiol-ene, intracortical electrode, smart polymer, neural interface, plasticization How to cite this article: Ware T, Simon D, Liu C, Musa T, Vasudevan S, Sloan A, Keefer EW, Rennaker RL, Voit W. 2014. Thiol- ene=acrylate substrates for softening intracortical electrodes. J Biomed Mater Res Part B 2014:102B:1–11. INTRODUCTION Silicon-based neural interfaces have been shown to have poor stability during chronic implantation. 1–3 This general failure of devices, usually within a year of implantation, has been in part attributed to the extreme mechanical mismatch between the silicon substrate and neural tissue. 4,5 To address this problem, advances in the field of flexible elec- tronics, using polymers as substrates, have been incorpo- rated in the design of neural interfaces. 6 Neural interfaces designed to be inserted in the tissue, such as intracortical or intrafascicular electrodes, have generally used various polyimides or Parylene-C (modulus 3 GPa) as flexible replacements for silicon (modulus 140 GPa). Devices have been fabricated from these materials in forms that maintain sufficient stiffness to allow implantation into tissue. 7,8 These and other similar materials have also been used in flexible electronics research to successfully demonstrate a host of passive and active electronic devices. 9,10 Silicone-based elas- tomeric neural interfaces (modulus 2 MPa) have also shown promise in the literature. 11,12 These silicone-based materials are an obvious choice for substrates for in vivo electronics because of their low modulus and widely recog- nized biocompatibility. 13,14 However, these materials lack the requisite stiffness to penetrate even soft tissue. 15 Stiff secondary insertion aids for soft elastomeric devices have been proposed, but necessitate larger insertion footprints that increase trauma at the implant site. The benefits of smart polymers, rigid during insertion and elastomeric dur- ing use, present a property space of interest in neural inter- faces for polymers capable of softening from glassy to rubbery in response to a stimulus. Previous devices demon- strated in this space were limited by unnecessarily large fluid uptake and strict temperature and processing limits during photolithography. 16 A schematic listing the moduli of Additional Supporting Information may be found in the online version of this article. Correspondence to: W. Voit (e-mail: walter.voit@utdallas.edu) Contract grant sponsor: National Institutes of Neurological Disorders and Stroke; contract grand number: 5R01DC008982 Contract grant sponsor: National Science Foundation Partnerships for Innovation and Graduate Research Fellowship; contract grand number: 1147385 Contract grant sponsor: FUSION support from the State of Texas V C 2013 WILEY PERIODICALS, INC. 1