pubs.acs.org/Langmuir © 2009 American Chemical Society
Pursuing “Zero” Protein Adsorption of Poly(carboxybetaine) from Undiluted Blood Serum and Plasma Wei Yang,†,‡ Hong Xue,† Wei Li,‡ Jinli Zhang,‡ and Shaoyi Jiang*,† †
Department of Chemical Engineering, University of Washington, Box 351750, Seattle, Washington 98195, and ‡ School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China Received May 3, 2009. Revised Manuscript Received June 14, 2009
Human blood serum and plasma pose significant challenges to blood-contacting devices and implanted materials because of their high nonspecific adsorption onto surfaces. In this work, we investigated nonspecific protein adsorption from single protein solutions and complex media such as undiluted human blood serum and plasma onto poly (carboxybetaine acrylamide) (polyCBAA)-grafted surfaces at different temperatures. The polyCBAA grafting was done via atom-transfer radical polymerization (ATRP) with varying film thicknesses. The objective is to create a surface that experiences “zero” protein adsorption from complex undiluted human blood serum and plasma. Results show that protein adsorption from undiluted human blood serum, plasma, and aged serum on the polyCBAA-grafted surface is undetectable at both 25 and 37 °C by a surface plasmon resonance (SPR) sensor. This was achieved with a film thickness of ∼21 nm. Furthermore, it is demonstrated that the polyCBAA surfaces after antibody immobilization maintain undetectable protein adsorption from undiluted human blood serum. This is the first time that an effective nonfouling material suitable for applications in complex blood media has been demonstrated.
1. Introduction Nonspecific protein adsorption has been a crucial issue for many biomedical applications, such as medical implants,1 drug delivery vehicles,2 and biosensors.3 At present, there are a very limited number of effective nonfouling biomaterials available to meet the challenges of practical applications.1-3 Poly(ethylene glycol) (PEG) or oligo(ethylene glycol) (OEG) has been widely used to resist nonspecific protein adsorption.4-6 However, PEG or OEG can decompose in the presence of oxygen and transitionmetal ions.6-8 Previous in vivo studies showed that PEG was subject to oxidation by superoxide anions and H2O2 during the respiratory burst.9 It was also shown that surfaces covered with or without PEG polymers produced a similar degree of fouling after 28 days of implantation.10 Phosphorylcholine (PC)-based materials are another class of nonfouling materials, but their monomers are generally difficult to synthesize.11,12 Recently, zwitterionic materials such as sulfobetaine methacrylate (SBMA),13 carboxybetaine methacrylate (CBMA),14 and mixed charge materials15 *Corresponding author. E-mail:
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Langmuir 2009, 25(19), 11911–11916
have been shown to exhibit ultralow protein adsorption16 (fibrinogen adsorption