Article pubs.acs.org/Langmuir
Nonfouling Property of Zwitterionic Cysteine Surface Peter Lin,† Ling Ding,‡ Chii-Wann Lin,‡ and Frank Gu*,† †
Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada ‡ Graduate Institute of Biomedical Engineering, Department of Electrical Engineering, National Taiwan University, Taipei 106, Taiwan S Supporting Information *
ABSTRACT: Applications of implantable bioelectronics for analytical and curative purposes are currently limited by their poor long-term biofunctionality in physiological media and nonspecific interactions with biomolecules. In an attempt to prolong in vivo functionality, recent advances in surface modifications have demonstrated that zwitterionic coatings can rival the performance of conventional poly(ethylene glycol) polymers in reducing nonspecific protein fouling. Herein, we report the fabrication of a very thin layer of nonfouling zwitterionic cysteine surface capable of protecting implantable bioelectronics from nonspecific adsorption of plasma proteins. This work is the first of its kind to fabricate, through solution chemistry, a cysteine surface exhibiting zwitterionic state as high as 88% and to demonstrate antibiofouling under the exposure of bovine serum albumin (BSA) and human serum. The fabricated surface utilized a minimal amount of gold substrate, approximately 10 nm, and an extremely thin antifouling layer at 1.14 nm verified by ellipsometry. X-ray photoelectron spectroscopy assessment of the nitrogen (N1s) and carbon (C1s) spectra conclude that 87.8% of the fabricated cysteine surface is zwitterionic, 2.5% is positively charged, and 9.6% is noncharged. Antibiofouling performance of the cysteine surface is quantitatively determined by bicinchoninic acid (BCA) protein assay as well as qualitatively confirmed using scanning electron spectroscopy. Cysteine surfaces demonstrated a BSA fouling of 3.9 ± 4.84% μg/cm2, which is 93.6% and 98.5% lower than stainless steel and gold surfaces, respectively. Surface plasmon resonance imaging analysis returned similar results and suggest that a thinner cysteine coating will enhance performance. Scanning electron microscopy confirmed the results of BCA assay and suggested that the cysteine surface demonstrated a 69% reduction to serum fouling. The results reported in this paper demonstrate that it is possible to achieve a highly zwitterionic surface through solution chemistry on a macroscopic level that is capable of improving biocompatibility of long-term implantable bioelectronics.
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INTRODUCTION Recent advances in microfabrication techniques have opened numerous new avenues for implantable bioelectronics such as implantable biosensor,1 neuron stimulators,2 and electrodebased pain-control treatments.3 For nearly all biomedical applications, the interface between the implanted device and the biological environment is of great significance and often dictates the performance of the device in vivo. Biofouling, in the form of nonspecific protein adsorption, is one of the major contributions to device failure for implantable bioelectronics, especially for surface-based diagnostic devices.4−6 For example, there are currently six minimally invasive implantable glucose sensors approved by the FDA that provide periodic readings;6 © 2014 American Chemical Society
however, due to biofouling, the optimal performance in vivo is limited to 7 days.6 Biofouling has similar adverse effects on neuro-stimulating electrodes, in which case, the effective electric signal decays proportionally with the thickness of the adhered biomass as governed by Coulomb’s law. Zwitterionic molecules have demonstrated promising characteristics as antifouling coating materials7,8 and are capable of achieving ultralow protein adsorption in the range of
