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After sample is purified it is important to assess whether a sample purification quality is suitable for further EM analysis. The biochemical methods are not really sufficient as even intact complexes can be a mixture of compositionally different sub-complexes, and even compositionally homogeneous complexes can potentially adopt many different conformations.
An easy and straightforward method to assess the quality of purified biological specimens at the microscopic scale is negative-stain electron microscopy. The objective of this screening is to qualitatively assess particle compositional and conformational homogeneity. This assessment can only be done at the microscopic scale.
Often this assessment of biochemical quality is done on a simple side-entry microscope (e.g. Thermo Scientific Talos™ L120C or Thermo Scientific Talos F200C), since screening is usually done one grid at a time, and the actual time spend on the microscope is short.
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