Cryo-electron ptychography: Applications and potential in biological characterisation

Abstract

There is a clear need for developments in characterisation techniques that provide detailed information about structure-function relationships in biology. Using electron microscopy to achieve high resolution while maintaining a broad field of view remains a challenge, particularly for radiation-sensitive specimens where the signal-to-noise ratio required to maintain structural integrity is limited by low electron fluence. In this review, we explore the potential of cryogenic electron ptychography as an alternative method for characterising biological systems under low-fluence conditions. Using this method with increased information content from multiple sampled regions of interest potentially allows 3D reconstruction with far fewer particles than required in conventional cryo-electron microscopy. This is important for achieving higher resolution in systems where distributions of homogeneous single particles are difficult to obtain. We discuss the progress, limitations, and potential areas for future development of this approach for both single particle analysis and applications to heterogeneous large objects.