The ArrayGrid: A methodology for applying multiple samples to a single TEM specimen grid

Abstract

High throughput transmission electron microscopy (TEM) is limited by the time that it takes to prepare each specimen and insert it on the microscope. It is further impeded by the deteriorating vacuum of the microscope upon frequent specimen cycling. Nevertheless, in most cases only a small fraction of the specimen is examined and sufficient to provide hundreds of images. Here we demonstrate that microarray technology can be used to accurately position picoliter quantities of different samples in a single TEM grid, with negligible cross-contamination. Key features are a contact-mode deposition on a robust formvar-carbon support. The TEM grid containing a microarray of different samples, the ArrayGrid, can also be negatively stained. The ArrayGrid increases the efficiency of TEM grid preparation and examination by at least by one order of magnitude, and is very suitable for screening and data collection especially in experiments that generate a multiplicity of samples.