Pursuing “Zero” Protein Adsorption of Poly(carboxybetaine) from Undiluted Blood Serum and Plasma

Abstract

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 degrees C by a surface plasmon resonance (SPR) sensor. This was achieved with a film thickness of approximately 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.

Ultralow‐Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications

“…The ''graft-from'' method via surface-initiated ATRP is able to produce coatings with high packing densities while the ''graft-to'' method via DOPA linkage is convenient to be implemented for practical applications. These coated surfaces have been challenged with complex biological media such as protein, cells, [43,45] platelet, [71] blood, [46,47,72] and bacteria, [63,67,68] and in the in vivo environments. [73] While coated surfaces are often tested with protein adsorption and cell adhesion in the literature, protein adsorption from undiluted blood plasma and serum as well as bacterial adhesion and biofilm formation are far more challenging.…”

From Self-Assembled Monolayers to Coatings: Advances in the Synthesis and Nanobio Applications of Polymer Brushes

“…Low fouling zwitterionic materials are classified as either polybetaines, containing a positive and negative charge on the same monomer unit, or polyampholytes, which contain a mixture of negatively and positively charged monomers. Typically quartz crystal microbalance (QCM) [160,161] or surface plasmon resonance (SPR) [162][163][164][165] using single and multicomponent solution is used for the detection of adsorbed proteins. In pursuit to minimize protein adsorption, Surman and coworkers [166] recently compared polymer brushes of poly[oligo(ethylene glycol)methyl ether methacrylate], poly(2-hydroxyethyl methacrylate) (PHEMA)), poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) and poly(carboxybetaine acrylamide) and their resistance to fouling when exposed to blood plasma, showing PHPMA had the best hemocompatibility with good stability, preserved for two years [167].…”

Natural zwitterionic organosulfurs as surface ligands for antifouling and responsive properties

“…After optimization of the film thickness 35 and packing density, 36 surface-grafted zwitterionic polymer brushes enable to repel the protein adsorption, particularly in 100% serum and plasma, to levels below 5 ng cm…”

“…37 In previous study, Yang et al controlled the film thickness of the CB polymer by changing the mole ratio of catalysts and found that the lowest fouling level was achieved at the thickness of $21 nm. 35 For SAM systems, their antifouling properties are strongly limited by absence of chain flexibility (steric barrier) and complete coverage on "nonideal" flat surfaces. 3 However, the SAM coatings are still valuable due to their advantages of versatility, rapid, and facile preparation.…”