Nanorobot enabled in situ sensing molecular interactions for drug discovery

Nanorobot has the potential to automate the manipulation and observation processes at molecular scale. Current drug discovery process is labor and cost intensive. Thus, a strong demand exists to automate this process. Here, we developed an Atomic Force Microscopy (AFM) based nanorobot for in situ sensing molecular interactions for drug discovery. The AFM tip and sample substrate are functionalized by the molecules of interest. Via measuring the interactive binding forces between these two molecules using the AFM based nanorobot, we are able to test the effectiveness of drug candidates on attenuating or enhancing the molecular interactions involved in cell signaling pathways. To measure the single molecular interactions precisely, we developed a new substrate coating method. The new method functionalizes the substrate much more evenly compared with the previous method. We further optimized settings during measuring the interactive binding force, such as coating with bovine serum albumin (BSA) and the level of indentation of AFM tip onto the substrate. With these progresses, this nanorobot measures single molecular interactions automated. We further used this nanorobot to test a small peptide, which was designed to attenuate the interactive binding force between focal adhesion kinase (FAK) and protein kinase B (AKT), two molecules involved in cell adhesion.