Cryo-Electron Microscopy (cryo-EM) is used to obtain high-resolution structural images of macromolecular structures. Samples must be purified and loaded onto cryo-EM grids before imaging. The ideal cryo-EM grid consists of particles that are evenly and richly distributed in a broad distribution of orientations throughout the holes of the support film. Current techniques to prepare cryo-EM grids are performed manually and require trial and error, resulting in a bottleneck in cryo-EM workflows.

Researchers from NIEHS developed a device and method for time-resolved preparation of liquid samples for cryo-EM experiments. In particular, the mixing and dispensation of liquid samples is achieved by electrical signals that are transduced into specific acoustic frequencies to mix the liquid samples (low frequency) and then dispense the mixture (high frequency) in small, nanoliter volumes onto a cryo-EM grid. This novel apparatus and method provides more precise control over liquid sample mixing and dispensing, and improved dispensation of the mixture onto the EM grid. Also, the improved quality of captured images of homogeneous macromolecular structures is achieved due to a uniformly mixed and dispensed sample on the EM grid. This allows electrons to be transmitted through the very thin liquid film in the holes of the cryo-EM grid to form an image.