In our experience exosome isolation from plasma appears reduced and rare exosomes can be observed by TEM.
Can anyone suggest the best way to improve both recovery and purity of plasma exosomes?
try Total exosome isolation (from plasma) reagent. There are two protocol options- with proteinase K and without, depending on your downstream assays. Plasma is probably the most challenging sample type for isolation of exosomes/EVs- as its viscous and contain plenty of "contaminants" - misc proteins, aggregates, etc
I would like to point out that isolation efficiency doesn't necessarily correlate with the number of exosomes you can visualize under TEM. You actually should let the exosomes to settle down on the grid for about 10-20 minutes. You can find our detail protocol for TEM at our recent publication: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004424
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