NER: Chemical Probing of Biosensor Nano-environments using Dynamic AFM

Carnegie Mellon University, Pittsburgh PA

Investigators

Abstract

Biosensors are becoming increasingly important for genomic analysis, detection of warfare agents, and medical diagnostics. To optimize the performance of these devices, new tools must be developed to characterize the molecular-level phenomena that underlie their function. This exploratory nanotechnology proposal aims to develop a new method to measure nanoscopic properties of biosensor surfaces, utilizing the ultrafine resolution of atomic force microscopy (AFM) in dynamic mode. Biosensors must perform two functions at once. They must encourage the binding of specific analytes while discouraging the binding of adventitious material. Typically, these goals are achieved by building heterogeneous surfaces with antifouling polymers together with receptors specific for desired analytes. To maximize yield without sacrificing selectivity, an optimal density and thickness of polymer must be applied to the surface. In this work, the PI hopes to measure the nanoscopic energy landscape that a biomolecule traverses near the sensor surface in an attempt to guide the rational design of biosensors. For a realistic measurement, both polymer steric interactions and specific ligand-receptor interactions must be measured simultaneously. The dynamic AFM method involves oscillating the AFM cantilever and measuring the amplitude attenuation as the sample approaches the AFM tip. Amplitude attenuation is more sensitive to polymer steric forces than deflection, so the sharp tips required for specific ligand-receptor measurements can be used. Here, the PI will measure dynamic and conventional AFM force curves in a model biosensor system. Using a theoretical description of cantilever oscillation, we hope to demonstrate the sensitivity and accuracy of the dynamic method. If successful, the project will have an impact on many fronts. First, the technique will provide a unique nanoscopic probe of heterogeneous surfaces pertinent to biosensors. It will also be able to measure polymer steric forces with nanometer lateral resolution, with implications for lubrication and colloidal processing. Finally, since epithelial and bacterial cell surfaces also contain specific adhesion receptors together in a polymeric environment, the dynamic AFM force method may emerge as a powerful tool in the study of cell-cell and cell-surface adhesion.