Romantic surfaces : Zwitterionic polymer brushes for biomedical applications

Abstract

In order to enhance the sensitivity and selectivity of surface-based (bio)sensors, it is of crucial importance to diminish background signals that arise from the non-specific binding of biomolecules, so-called biofouling. Zwitterionic polymer brushes have been shown to be excellent antifouling materials. However, for sensing purposes, antifouling does no suffice, but needs to be combined with the possibility to efficiently modify the brush with recognition units. So far this has only been achieved at the expense of either antifouling properties or binding capacity. Herein we present a conceptually new approach by integrating both characteristics into a single, tailor-made monomer: a novel sulfobetainebased zwitterionic monomer equipped with a clickable azide moiety. Copolymerization of this monomer with a well-established standard sulfobetaine monomer results in highly antifouling surface coatings with a high, yet tunable amount of clickable groups present throughout the entire brush. Subsequent functionalization of the azido-brushes, via e.g. widely used strain-promoted alkyne azide click reactions yields fully zwitterionic 3D-functionalized coatings with a recognition unit of choice that can be tailored for any specific application. Here we show a proof of principle with biotin-functionalized brushes on Si 3 N 4 that combine excellent antifouling properties with specific avidin binding from a protein mixture. The signal-to-noise ratio is significantly improved over traditional chain end modification of sulfobetaine polymer brushes, even if the azide content is lowered to 1%. This therefore offers a viable approach for the development of biosensors with greatly enhanced performance. Non-specific adsorption of biomolecules to solid surfaces, a process called biofouling, is a major concern in many biomedical applications. Great effort has been made in the development of antifouling polymer coatings that are capable of repelling the non-specific adsorption of proteins, cells and microorganisms. In this respect, we herein contribute to the understanding of which polymer brush results in the best antifouling coating. To this end, we compared five different monomers: two sulfobetaines, a carboxybetaine, a phosphocholine and a hydroxyl acrylamide. The antifouling coatings were analyzed using the in chapter 3 described bead-based method with flow cytometry as read-out system. This method allows for the quick and automated analysis of thousands of beads per second, enabling fast analysis and good statistics. We report the first direct comparison made between a sulfobetaine with opposite charges separated by two and three methylene groups and a carboxybetaine bearing two separating methylene groups. It was concluded that both the distance between opposite charges and the nature of the anionic groups have a distinct effect on the antifouling performance. Phosphocholines and simple hydroxyl acrylamides are not often compared with the betaines. However, here we found that they perform equally well or even better, with as ove...

Temperature and pH responsive behavior of antifouling zwitterionic mesoporous silica nanoparticles

“…Nanotechnology is undoubtedly one of the most powerful tools in present-day in a variety of fields such as electronics, environment, health and medicine. Nanocarriers are being considered as compelling platforms for all sorts of applications, including biosensors, microfluidics, biomolecule detection and cell sorting, tissue engineering, imaging, drug delivery and nanobiotechnology 1,2 . As drug delivery systems, nanocarriers should resolve critical issues of conventional drug treatments, such as rapid clearance, uncontrollable release and low bioavailabity 3 .…”

“…Zwitterionic polymers have been also used for surface modification of microparticles of different nature. On the one hand, polystyrene (PS) microbeads (2.8 μm diameter) have been functionalized with a sulfobetaine polymer to be used in mass spectrometry-based proteomics 2 , and also in synthesized sulfobetainefunctionalized PS colloidal spheres (367 ± 18 nm) for tunable and responsive photonic crystals arrays 24 . On the other hand, colloidal SNP (1-1000 nm) have been used for diagnosis and biosensing devices, including pCMB-SNP colloidal crystals (280 nm diameter) 25 , pSBMA-SNP carriers (50 nm diameter) 26 , lysine-SNP (80 nm) as additives for ultrafiltration membrane improvement 27 , and amino acid-based SNP (30 nm diameter) for biomolecule immobilization or biofunctional surface preparation 11 .…”