High Salt Stability and Protein Resistance of Poly(l-lysine)-g-poly(ethylene glycol) Copolymers Covalently Immobilized via Aldehyde Plasma Polymer Interlayers on Inorganic and Polymeric Substrates

Abstract

The electrostatic adsorption onto charged surfaces of comb copolymers comprising a polyelectrolyte backbone and pendent PEG side chains, such as poly(l-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), has in previous studies provided protein-repellent thin coatings, particularly on metal oxide surfaces. A drawback of this approach is, however, the instability of such adsorbed layers under extreme pH values or high ionic strength. We have overcome this limitation in the present study by covalently immobilizing PLL-g-PEG copolymers onto aldehyde plasma-modified substrates. Silicon wafers, optical waveguide chips, and perfluorinated ethylene-co-propylene (FEP) polymer substrates were first coated with a thin plasma polymer layer using a propionaldehyde plasma, followed by covalent immobilization of PLL-g-PEG via reductive amination between amine groups of the PLL backbone with aldehyde groups on the plasma-deposited interlayer. The stability in high salt media and the protein resistance of different molecular architectures of immobilized PLL-g-PEG layers were quantitatively investigated by XPS, an optical waveguide technique (OWLS), and ToF-SIMS. The adsorption of bovine serum albumin was found to be below the detection limit (<2 ng/cm(2)), as for electrostatically adsorbed PLL-g-PEG layers. However, after 24 h of exposure of covalently immobilized layers of PLL-g-PEG to high ionic strength buffer (2400 mM NaCl), no significant change in the protein resistance was observed, whereas under the same conditions electrostatically adsorbed PLL-g-PEG coatings lost their protein resistance. Moreover, covalent immobilization via an aldehyde plasma interlayer enabled the application of PLL-g-PEG layers onto substrates such as FEP onto which electrostatic binding is not possible. These findings create a generic platform for the covalent immobilization of PLL-g-PEG onto a wide variety of substrates.

Construction of a densely poly(ethylene glycol)-chain-tethered surface and its performance

“…The long-term stability of oligoamine-ended PEG on gold surfaces was confirmed by using gold colloid under physiological conditions. 28,39,40,53,54 Modified N6-PEG can be applied for other surfaces, especially for active-ester surfaces. 16,55,56 Because of the covalent conjugation of PEG on active-ester surfaces, mono-amine-ended PEG is commonly used.…”

“…This is especially true regarding the versatile techniques for surface coating using PEG that have been developed since the 1980s to improve blood and bio-compatibility. Figure 1 summarizes several methods for the immobilization of PEG on substrate surfaces: PEG gels, 19,20,36 the physical and chemical immobilization of PEG 13,21,37 (so-called grafting-to method), the adsorption of block [22][23][24][25][26][27]38 and graft 27,28,39,40 copolymers, polymerization from the surface 41 (the so-called grafting-from method), the immobilization of star-shape polymers and micelles, [42][43][44] and other methods.…”

Functionalizable low-fouling coatings for label-free biosensing in complex biological media: advances and applications

“…Surfaces with blood-plasma fouling levels of <100 pg mm −2 , of <50 pg mm −2 , and below the limit of detection (LOD) of the technique used are classified as "lowfouling", "ultra-low fouling", and "non-fouling", respectively. To preserve the biological activity of the immobilized biorecognition elements, hydrophilic low-fouling surfaces based on poly(ethylene glycol) (PEG) and its derivatives have been a popular choice [12]. Recent advances in polymer chemistry have led to the development of novel zwitterionic and non-ionic polymer brushes, which have been proved to provide excellent resistance to fouling even from the most complex biological fluids, including undiluted blood serum and plasma [6,8,11,13].…”

Interactions of Serum Derived Proteins with Sub‐Micrometer Structured Surfaces

“…The properties of the films can be controlled by tuning the plasma discharge parameters. [10] Many functional films can be produced by plasma polymerization with different functional groups, [11] e.g., carboxylic acid, [12] allylamine, [13] aldehyde, [14] epoxy, [15] and poly(ethylene oxide). [9,16] Besides, surfaces exhibiting chemical contrasts represent a platform of choice for optimizing the biomolecule-surface interactions.…”