This article establishes the feasibility of time-resolved microcrystal electron diffraction by using a microfluidic mixing device to deposit microcrystals onto electron microscopy grids during plunge-freezing. The resulting vitrified crystals were of sufficient quality to solve a model protein structure.

This review describes how an integrated structural biology platform at Merck Sharp & Dohme LLC, Rahway, New Jersey, USA, combining X-ray crystallography, cryo-EM, MicroED and cryo-ET, enables seamless three-dimensional insights from molecular to cellular length scales. By uniting ex situ and in situ approaches with AI/ML-enabled data integration, the platform directly informs target selection, structure-based drug design, formulation strategies and mechanism-of-action studies across multiple therapeutic areas. These advances illustrate a scalable and impactful framework for accelerating mechanism-based, next-generation therapeutic discovery and development.