Acoustic Enrichment of Extracellular Vesicles from Biological Fluids

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Acoustic Enrichment of Extracellular Vesicles from Biological Fluids. / Ku, Anson; Lim, Hooi Ching; Evander, Mikael; Lilja, Hans; Laurell, Thomas; Scheding, Stefan; Ceder, Yvonne.

In: Analytical Chemistry, Vol. 90, No. 13, 2018, p. 8011-8019.

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TY - JOUR

T1 - Acoustic Enrichment of Extracellular Vesicles from Biological Fluids

AU - Ku, Anson

AU - Lim, Hooi Ching

AU - Evander, Mikael

AU - Lilja, Hans

AU - Laurell, Thomas

AU - Scheding, Stefan

AU - Ceder, Yvonne

PY - 2018

Y1 - 2018

N2 - Extracellular vesicles (EVs) have emerged as a rich source of biomarkers providing diagnostic and prognostic information in diseases such as cancer. Large-scale investigations into the contents of EVs in clinical cohorts are warranted, but a major obstacle is the lack of a rapid, reproducible, efficient, and low-cost methodology to enrich EVs. Here, we demonstrate the applicability of an automated acoustic-based technique to enrich EVs, termed acoustic trapping. Using this technology, we have successfully enriched EVs from cell culture conditioned media and urine and blood plasma from healthy volunteers. The acoustically trapped samples contained EVs ranging from exosomes to microvesicles in size and contained detectable levels of intravesicular microRNAs. Importantly, this method showed high reproducibility and yielded sufficient quantities of vesicles for downstream analysis. The enrichment could be obtained from a sample volume of 300 μL or less, an equivalent to 30 min of enrichment time, depending on the sensitivity of downstream analysis. Taken together, acoustic trapping provides a rapid, automated, low-volume compatible, and robust method to enrich EVs from biofluids. Thus, it may serve as a novel tool for EV enrichment from large number of samples in a clinical setting with minimum sample preparation.

AB - Extracellular vesicles (EVs) have emerged as a rich source of biomarkers providing diagnostic and prognostic information in diseases such as cancer. Large-scale investigations into the contents of EVs in clinical cohorts are warranted, but a major obstacle is the lack of a rapid, reproducible, efficient, and low-cost methodology to enrich EVs. Here, we demonstrate the applicability of an automated acoustic-based technique to enrich EVs, termed acoustic trapping. Using this technology, we have successfully enriched EVs from cell culture conditioned media and urine and blood plasma from healthy volunteers. The acoustically trapped samples contained EVs ranging from exosomes to microvesicles in size and contained detectable levels of intravesicular microRNAs. Importantly, this method showed high reproducibility and yielded sufficient quantities of vesicles for downstream analysis. The enrichment could be obtained from a sample volume of 300 μL or less, an equivalent to 30 min of enrichment time, depending on the sensitivity of downstream analysis. Taken together, acoustic trapping provides a rapid, automated, low-volume compatible, and robust method to enrich EVs from biofluids. Thus, it may serve as a novel tool for EV enrichment from large number of samples in a clinical setting with minimum sample preparation.

KW - Acoustics

KW - Cell Fractionation/instrumentation

KW - Cell Line, Tumor

KW - Exosomes/metabolism

KW - Extracellular Vesicles/metabolism

KW - Humans

KW - MicroRNAs/genetics

KW - Plasma/cytology

KW - Urine/cytology

U2 - 10.1021/acs.analchem.8b00914

DO - 10.1021/acs.analchem.8b00914

M3 - Article

C2 - 29806448

VL - 90

SP - 8011

EP - 8019

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 1520-6882

IS - 13

ER -