Abstract
Thanks to their usability and versatility, label free affinity based biosensors represent a promising tool for point of care diagnostics. However, their performance is strongly influenced by non-specific interactions occurring on the biochip surface (biofouling), which hinder data analysis and lead to loss of sensing performance. Therefore, the surface of a biochip is often modified with an anti fouling nanolayer coating, the state of the art of which are currently represented by zwitterionic polymer brush (PB) coatings. The development of these nanocoatings is partially held back by the fact that biofouling from complex biological samples (e.g. blood plasma) is not a fully understood process. There are currently no coatings that completely suppress biofouling; an elucidation of the relevant mechanisms of biomolecular fouling offers a path to create coatings that exceed the current state of the art.
In this work we aim to elucidate the process of biofouling of proteins from human plasma on PB-coated biochips by the means of mass spectrometry (MS), surface enhanced Raman spectroscopy (SERS), and molecular dynamics simulations (MDS). We investigate a series of copolymer brushes composed of different monomeric ratios of N-(2-hydroxypropyl) methacrylamide (HPMAA) and carboxybetaine methacrylamide (CBMAA). MS allows us to qualitatively and quantitatively characterize the proteins fouled from both real-world fluids (blood plasma) as well as model samples. Through comparison of SERS data obtained different surfaces we estimate the permeability of PB for different molecules, and the combination with MDS brings a novel approach in study of the interaction of biomolecules on PB surfaces.
Our results will help in the future design of nanocoatings for biochips used for a variety of applications.