Atomistic simulations of gold surface functionalization for nanoscale biosensors applications.

A wide class of biosensors can be built via functionalization of gold surface with proper bio conjugation element capable of interacting with the analyte in solution, and the detection can be performed either optically, mechanically or electrically. Any change in physico-chemical environment or any slight variation in mass localization near the surface of the sensor can cause differences in nature of the tranduction mechanism. The optimization of such sensors may require multiple experiments to determine suitable experimental conditions for the immobilization and detection of the analyte. Here, we employ molecular modeling techniques to assist the optimization of a gold-surface biosensor. The gold surface of a quartz-crystal-microbalance (QCM) sensor is functionalized using polymeric chains of poly(ethylene glycol) (PEG) of 2 KDa molecular weight, which is an inert long chain amphiphilic molecule, supporting biotin molecules (bPEG) as the ligand molecules for streptavidin analyte. The PEG linkers are immobilized onto the gold surface through sulphur chemistry. Four gold surfaces with different PEG linker density and different biotinylation ratio between bPEG and PEG, are modelled and investigated by means of state-of-the art atomistic simulations. Results suggest that the amount of biotin molecules accessible for the binding with the protein increases upon increasing the linkers density. At the high density a 1:1 ratio of bPEG/PEG can futher improve the accessibility of the biotin ligand due to a strong repulsion between linker chains and different degree of hydrophobicity between bPEG and PEG linkers. The study provides a computational protocol to model sensors at the level of single molecular interactions, and for optimizing the physical properties of surface conjugated ligand which is crucial to enhance output of the sensor.