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Is there an isolation protocol that tends to yield the most reproducible results?

There’s no single, validated standard for consistently purifying exosomes, and identifying one might be impossible because effective protocols may vary based on the cell line being studied.
This is not to say researchers can’t take steps to enhance reproducibility of the protocol they use. For example, one challenge faced by exosome researchers is setting up density gradients manually.1 Not only is this step tedious and time-consuming but it’s also subject to user, lab and method variability. To avoid this, an automated liquid handling workstation, already found in many labs, can overcome the potential for human error and provide a more consistent, reproducible, high-throughput method for gradient setup.
[1] Jeppesen DK, Hvam, M, et al. Comparative analysis of discrete exosome fractions obtained by differential centrifugation. J Extracell Vesicles. 3; 25011: (2014). doi: org/10.3402/jev.v3.25011.