Quantifying DNA and protein structure and their interactions for improved therapeutic targeting

Atomic Force Microscopy (AFM) is a powerful technique to determine the morphology of complex nanoscale assemblies, such as mRNA therapeutics used in the fight against COVID-19. It therefore has huge potential to transform materials characterization across sectors from medicine to manufacturing, providing rapid feedback into the efficiency of their manufacturing processes. AFM is limited, however, by its analysis tools, with the majority still carried out by hand, relying on highly trained and experienced researchers. The lack of automated analysis tools for the field is the rate limiting step for the use of AFM in translational settings including in the development of novel therapeutics. We have developed a transformative, rapid AFM analysis pipeline, combining the state-of-the-art AFM, carried out in the Henry Royce Nanocharacterization Laboratory and our open-source analytical AFM tool TopoStats, which automates identification and characterisation of molecules such as mRNAs within AFM images (www.github.com/AFM-SPM/TopoStats). This project will determine the shape, morphology and homogeneity of DNA, proteins and novel therapeutics in solution and correlate these with measurements of living cells.