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RAP opportunity at National Institute of Standards and Technology     NIST

Analytical Metrology for Production and Characterization of Extracellular Vesicles (EVs) as a Drug Delivery System


Material Measurement Laboratory, Biosystems and Biomaterials Division

opportunity location
50.64.41.C0414 Gaithersburg, MD

NIST only participates in the February and August reviews.


name email phone
Bryant C. Nelson 301.975.2517
Lili Wang 301.975.2447


Extracellular vesicles (EVs) have the potential to better ensure the safety and efficacy as well as the efficient delivery of gene therapies to patients [1]. Due to their natural low immunogenicity and capacity to target specific cell types with minimal off-target effects, EVs are currently being investigated for their broad use as drug/gene delivery vehicles and as therapeutic agents in numerous disease types [2]. Robust and reproducible purification and analytical characterization of EV isolates is required due to EV population heterogeneity (e.g., size, cargo, biogenesis) and/or potential sample contamination by cellular debris, non-EV vesicles, protein aggregates, viruses, etc., before the isolated EVs can be manufactured into high quality drug delivery vehicles and/or therapeutic agents. The most common method for isolating EVs from biological samples (cell cultures and/or biofluids) is based on differential ultracentrifugation, although other methods such as magnetic or immunoaffinity separation, size exclusion chromatography, hydrophobic precipitation and tangential flow filtration, etc. are also utilized [3]. Current approaches for characterizing the particle size distribution and/or particle number concentration of EVs typically involve the application of either ensemble or single particle counting methods such as nanoparticle tracking analysis, nanoflow cytometry, tunable resistive pulse sensing, etc. The lack of fit for purpose high-quality reference materials that can be used to help normalize and benchmark data from the various EV isolation and characterization methods is a key bottle-neck inhibiting the comparability of data generated by the different methods and limits the overall advancement of EV therapeutics [3]. Standardized methods for isolating and characterizing EVs from biological samples do not exist and this is a critical research gap that has been recognized by the International Society for Extracellular Vesicles. Recently, it has been recognized that non-traditional EV heterogeneity (e.g., in vivo spatial and/or temporal EV heterogeneity) is a critical area of concern for EV measurement assurance. EV characterization methods that are able to discriminate localized EVs in organs and organ models (organoids) are slowly being developed. This postdoctoral solicitation features an opportunity to comprehensively examine and expand upon current methods or to develop completely new, reproducible methods for isolating, purifying and characterizing EVs from biological matrices that can be developed into gene delivery or gene-based therapeutics. Emerging characterization methods can potentially focus on incorporating novel, high-throughput forms of single particle EV detection schemes involving nano-flow cytometry, microfluidics, plasmonic or fluorescence imaging using nanoparticles, droplet digital PCR and/or aptamer conformation changes. Method development efforts should focus on the incorporation of a robust and optimized experimental design aimed at assessing the sources of variability, repeatability, and reproducibility for isolating and purifying EVs from a representative biological model. Measurements should incorporate the use of process controls, rigorous statistical analysis techniques and method robustness evaluations appropriate for high-quality protocol development.

For more information, please contact Bryant C. Nelson, ( and/or Lili Wang, (


1. Cecchin, R., et al., Extracellular vesicles: The next generation in gene therapy delivery. Mol Ther, 2023. 31(5): p. 1225-1230.

2. Wiklander, O.P.B., et al., Advances in therapeutic applications of extracellular vesicles. Science Translational Medicine, 2019. 11(492).

3. Nelson, B.C., et al., Measurement and standardization challenges for extracellular vesicle therapeutic delivery vectors. Nanomedicine (Lond), 2020. 15(22): p. 2149-2170.

key words
production; characterization; drug delivery; exosomes; extracellular vesicles; gene delivery; purification; measurement assurance; method development; reference materials; therapeutics


Citizenship:  Open to U.S. citizens
Level:  Open to Postdoctoral applicants


Base Stipend Travel Allotment Supplementation
$82,764.00 $3,000.00
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