CryoEM samples are typically prepared by (i) depositing a 1-3 ul of sample solution onto  a TEM  grid, (ii) removing most of  the excess buffer by wicking it away into filter paper, (iii) rapidly plunging the TEM grid into a good cryogen (typically ethane or ethane/propane mix).  The thin layer of liquid sample is snapped from a liquid to a solid (vitreous) state in less than a millisecond preserving the native hydrated state of the sample. Sample substrate and dilution conditions are optimized as required and benefit from a highly successful proprietary workflow developed at NIS from the extensive know-how of our microscopy team. In addition to standard plunge-freezing methods, NIS also provides access to the SPTL chameleon instrument when samples are especially challenging with regard to available quantities or issues with air-water interface effects.

The grid is loaded on the microscope and images are generated using a focused electron beam and a series of electromagnetic lenses.   The images are collected using highly sensitive detectors and computationally analyzed. All microscopes at NIS are equipped for cryoEM data acquisition. For lower resolution studies supporting biologics and drug development, most work is carried out on the Tecnai T12 and or the TFS Glacios microscopes. High resolution studies of proteins and viruses for single particle analysis are performed using the TFS Glacios and Titan Krios microscopes. 

NIS provides project-specific analysis and reporting modes for cryoEM studies. The details of these reports vary depending on the research question posed and the completed study. Regardless of workflow, detailed reports with scientific interpretation by senior scientists are provided for all work performed, often complemented with follow-up conference calls to delve more deeply into the observations.  We also provide supplemental and potentially critical data for demonstrating procedures to ensure stability, batch-to-batch uniformity, and overall quality for IND and NDA submissions. We provide qualified evidence of established protocols and specifications for production process, as well as demonstration of bioequivalence, when manufacturing protocols are modified or improved.