Multivariate Surface Analysis of Plasma-Deposited Tetraglyme for Reduction of Protein Adsorption and Monocyte Adhesion

Abstract

Adsorbed proteins on implanted biomedical devices mediate platelet and leukocyte adhesion. Radio frequency plasma deposited tetraglyme (CH3O(CH2CH2O)4CH3), which forms a PEO-like coating, has been shown to resist protein adsorption and monocyte adhesion in vitro. By using different plasma deposition powers (5-80 W), we produced a series of plasma-deposited tetraglyme surfaces that varied in surface chemistry as measured by electron spectroscopy for chemical analysis (ESCA) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Both fibrinogen and IgG adsorption were increased on surfaces made at high plasma power. Monocyte adhesion correlated linearly with the amount of adsorbed protein. To identify the surface chemical features that contributed to the nonfouling properties of plasma-deposited tetraglyme, multivariate analysis using partial least squares (PLS) regression was applied. A PLS calibration model based on deposited tetraglyme samples placed downstream in the plasma reactor successfully predicted fibrinogen adsorption to deposited tetraglyme samples placed midstream in the reactor. The model identified how each surface spectral variable from ESCA and ToF-SIMS contributed to protein adsorption. The fraction of carbon in ether carbon linkages as measured by ESCA and ToF-SIMS peaks at m/z 59 and 103 was higher on surfaces that exhibited ultralow fibrinogen adsorption (<10 ng/cm 2 ). The fraction of hydrocarbon-like carbons as measured by ESCA and low-mass ToF-SIMS peaks such as m/z 29 and 31 was greater on surfaces exhibiting high fibrinogen adsorption (>200 ng/cm 2 ). This study elucidated the surface chemical features of deposited tetraglyme that most affect its resistance to protein and cell uptake and provided guidelines for engineering improved nonfouling biomaterial surfaces.

Stable low-fouling plasma polymer coatings on polydimethylsiloxane

“…From the literature, we can estimate that this level of nitrogen on the surface corresponds to <10 ng/cm 2 of protein. 47 These values are commensurate to results from a number of previous studies using ppTTg coatings 44,47,49 and match with the ELISA results discussed previously. Together this data suggest that coatings are able to retain significant functionality on PDMS even after extended periods of dry shelf storage.…”

“…This similarity between the precursor and deposited film composition is particularly important for the ethylene oxide-based protein resistant films used here, as the non-fouling properties have been directly linked to the ether carbon content of the film. Shen et al 47,49 and Johnston et al 58 have shown that the higher the content of ether carbon, the more functional the coatings become, and the less protein they adsorb.…”

“…The results suggest that the level of silicon migration, if not induced by the exposure to UHV, is insufficient to disturb the contact angle measurements. By comparison, data collected from the single layer ppTTg coatings illustrated rapid changes in contact angle from 49 to 60 over the first few days of storage, with the contact angle increasing gradually and stabilizing at 64 . …”

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

“…This adsorption layer can lead to complications such as leukocyte adhesion or blood coagulation, which may impair the function of the device and limit its therapeutic effects [157]. Its noteworthy that as little as 10 ng/cm 2 of fibronectin can induce substantial platelet adhesion [158]. Polymer brush type, density and length are variables that can be manipulated to produce a stable, low fouling surface.…”

Reduced adhesion of human blood platelets to polyethylene tubing by microplasma surface modification

“…To date, most studies of plasma-modified biomaterials make use of a large-volume plasma reactors to modify the surface of a small disk or film substrate. [3][4][5][6] However, such reactors are not very practical for surface modification of small diameter tubing 1 and many small-scale biomedical devices. 9 This is because the plasma tends to quench itself near the ends of the tubing, 7,8 when placed in a large-volume reactor, and thus only small portions near the ends of the tube are treated.…”