Maximum sensitivity and minimum use of sample resources are achieved in ESI-MS by spraying samples in the nanospray mode, which is inefficient in the manual mode but with recent technological advances can be fully automated [38-42]. Using the Advion automated nanospray system, the ultimate in sample sensitivity can be achieved for directly analyzing GPC spin column eluates with a reduced effect on signal suppression due to the presence of buffer ions. This technique should give strong response to molecules of low abundance, viz. weak non-covalent binders, and thereby conserve the amount of protein used in the GPC spin column assay. The down side of the nanospray technique is the longer data acquisition times needed to acquire spectra of high signal-to-noise ratio.
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