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Atomic force microscopy (AFM) is a part of the scanning probe microscopy family. It provides a platform for high-resolution topographical imaging, surface analysis as well as nanomechanical property mapping for stiff and soft samples (live cells, proteins, and other biomolecules). AFM is also crucial for measuring single-molecule interaction forces and important parameters of binding dynamics for receptor-ligand interactions or protein-protein interactions on live cells. However, performing AFM measurements and the associated data analytics are tedious, laborious experimental procedures requiring specific skill sets and continuous user supervision. Significant progress has been made recently in artificial intelligence (AI) and deep learning (DL), extending into microscopy. In this review, we summarize how researchers have implemented machine learning approaches so far to improve the performance of atomic force microscopy (AFM), make AFM data analytics faster, and make data measurement procedures high-throughput. We also shed some light on the different application areas of AFM that have significantly benefited from applications of machine learning frameworks and discuss the scope and future possibilities of these crucial approaches. 

Atomic force microscopy (AFM) provides a platform for high-resolution topographical imaging and the mechanical characterization of a wide range of samples, including live cells, proteins, and other biomolecules. AFM is also instrumental for measuring interaction forces and binding kinetics for protein–protein or receptor–ligand interactions on live cells at a single-molecule level. However, performing force measurements and high-resolution imaging with AFM and data analytics are time-consuming and require special skill sets and continuous human supervision. Recently, researchers have explored the applications of artificial intelligence (AI) and deep learning (DL) in the bioimaging field. However, the applications of AI to AFM operations for live-cell characterization are little-known. In this work, we implemented a DL framework to perform automatic sample selection based on the cell shape for AFM probe navigation during AFM biomechanical mapping. We also established a closed-loop scanner trajectory control for measuring multiple cell samples at high speed for automated navigation. With this, we achieved a 60× speed-up in AFM navigation and reduced the time involved in searching for the particular cell shape in a large sample. Our innovation directly applies to many bio-AFM applications with AI-guided intelligent automation through image data analysis together with smart navigation.