A Single Molecular AFM-FET Biosensor Using Nanomanipulation
The atomic force microscope (AFM) and field effect transistor (FET) were integrated into one functioning biosensor to probe single molecular interactions between biomolecules, such as a protein, and a ligand. The AFM-FET biosensor has advantages over current drug screening methods based on microfluidics, because it is faster and records single interactions more accurately. In this study, the interactions between avidin-biotin complexes were studied using the AFM-FET biosensor. Biotin molecules were attached to the AFM cantilever via flexible PEG cross-linkers, and avidin molecules were bound to the palladium gate surface of the FET via the cross-linker molecules of cystamine and glutaraldehyde. The force of the AFM and the FET current between the drain and source were measured as a function of distance when the biotin molecules approached and retracted from the avidin molecules. The measurement data showed that the FET current changed abruptly when binding and unbinding events occurred between the two molecules. The change in current was converted into the corresponding electric potential, which was related to the magnitude of rupture force during the binding and unbinding events. The relationship suggests that the AFM-FET sensor can provide additional information on molecular interactions at the single molecular level, and could potentially be used as a quantitative and efficient method for detecting single molecular interactions.