Simultaneous Measurement of Forces and Currents using an AFM-FET Hybrid Sensor for Studying Single Biomolecular Interactions

Abstract

The majority of biological functions are carried out at the molecular level by interactions between various biomolecules. Because these interactions are often the target of pharmaceutical agents, drug screening techniques must be capable of sensing the interactions. Field-effect transistors (FET) have been widely used as biosensors, but are generally used with a large number of molecules to obtain a sufficient signal. The measurements taken with the FET-based biosensors are mostly “on” or “off” measurements, which are determined by the presence or absence of a reaction. A specific type of FET, the p-type metal oxide semiconductor FET (pMOSFET) appears to be a promising biosensor device. The pMOSFET contains holes in the channel, also known as the inversion layer, opposite in carrier type to the substrate. An atomic force microscope (AFM) has shown the ability to measure molecular interactions down to the single molecular level and to control the distance between a ligand and a receptor protein up to subatomic resolution. The integration of AFM and FET technologies has the potential to provide not only valuable information about these biomolecular interactions that has not been accomplished by other methods, but also a much more rapid drug screening technique. The ability to control single molecules will allow for the comprehensive study of biomolecular interactions at the single-molecular level. This presentation will show how the AFM and FET were integrated into one functioning biosensor. The efficiency at detecting single molecular binding and unbinding events will be demonstrated by probing the interactions between avidin-biotin complexes.