Large-Range HS-AFM Imaging of DNA Self-Assembly through In Situ Data-Driven Control

Understanding hierarchical self-assembly of biological structures requires real-time measurement of the self-assembly process over a broad range of length- and timescales. The success of high-speed atomic force microscopy (HS-AFM) in imaging small-scale molecular interactions has fueled attempts to introduce this method as a routine technique for studying biological and artificial self-assembly processes. Current state-of-the-art HS-AFM scanners achieve their high imaging speed by trading achievable field of view for bandwidth. This limits their suitability when studying larger biological structures. In ambient conditions, large-range scanners with lower resonance frequencies offer a solution when combined with first principle model-based schemes. For imaging molecular self-assembly processes in fluid, however, such traditional control techniques are less suited. In liquid, the time-varying changes in the behavior of the complex system necessitate frequent update of the compensating controller. Recent developments in data-driven control theory offer a model-free, automatable approach to compensate the complex system behavior and its changes. Here, a data-driven control design method is presented to extend the imaging speed of a conventional AFM tube scanner by one order of magnitude. This enables the recording of the self-assembly process of DNA tripods into a hexagonal lattice at multiple length scales.