TY - JOUR
T1 - Quantitative and Multiplex Detection of Extracellular Vesicle-Derived MicroRNA via Rolling Circle Amplification within Encoded Hydrogel Microparticles
AU - Al Sulaiman, Dana
AU - Juthani, Nidhi
AU - Doyle, Patrick S.
N1 - Funding Information:
The authors gratefully acknowledge funding from the National Institutes of Health (NIH) R01 grant (No. 1R01CA235740‐01A1) and the Natural Sciences & Engineering Research Council (NSERC) of Canada. This work was supported in part by the Koch Institute Support (core) Grant No. P30‐CA14051 from the National Cancer Institute. They thank the Koch Institute's Robert A. Swanson (1969) Biotechnology Center for technical support, specifically the nanotechnology materials core.
Funding Information:
The authors gratefully acknowledge funding from the National Institutes of Health (NIH) R01 grant (No. 1R01CA235740-01A1) and the Natural Sciences & Engineering Research Council (NSERC) of Canada. This work was supported in part by the Koch Institute Support (core) Grant No. P30-CA14051 from the National Cancer Institute. They thank the Koch Institute's Robert A. Swanson (1969) Biotechnology Center for technical support, specifically the nanotechnology materials core.
Publisher Copyright:
© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2022/5/18
Y1 - 2022/5/18
N2 - Extracellular vesicle-derived microRNA (EV-miRNA) represent a promising cancer biomarker for disease diagnosis and monitoring. However, existing techniques to detect EV-miRNA rely on complex, bias-prone strategies, and preprocessing steps, making absolute quantification highly challenging. This work demonstrates the development and application of a method for quantitative and multiplex detection of EV-miRNA, via rolling circle amplification within encoded hydrogel particles. By a one-pot extracellular vesicle lysis and microRNA capture step, the bias and losses associated with standard RNA extraction techniques is avoided. The system offers a large dynamic range (3 orders of magnitude), ease of multiplexing, and a limit of detection down to 2.3 zmol (46 × 10−18 m), demonstrating its utility in clinical applications based on liquid biopsy tests. Furthermore, orthogonal measurements of EV concentrations coupled with the direct, absolute quantification of miRNA in biological samples results in quantitative measurements of miRNA copy numbers per volume sample, and per extracellular vesicle.
AB - Extracellular vesicle-derived microRNA (EV-miRNA) represent a promising cancer biomarker for disease diagnosis and monitoring. However, existing techniques to detect EV-miRNA rely on complex, bias-prone strategies, and preprocessing steps, making absolute quantification highly challenging. This work demonstrates the development and application of a method for quantitative and multiplex detection of EV-miRNA, via rolling circle amplification within encoded hydrogel particles. By a one-pot extracellular vesicle lysis and microRNA capture step, the bias and losses associated with standard RNA extraction techniques is avoided. The system offers a large dynamic range (3 orders of magnitude), ease of multiplexing, and a limit of detection down to 2.3 zmol (46 × 10−18 m), demonstrating its utility in clinical applications based on liquid biopsy tests. Furthermore, orthogonal measurements of EV concentrations coupled with the direct, absolute quantification of miRNA in biological samples results in quantitative measurements of miRNA copy numbers per volume sample, and per extracellular vesicle.
KW - biomarkers
KW - cancer
KW - extracellular vesicles
KW - hydrogels
KW - liquid biopsies
KW - microRNA
UR - http://www.scopus.com/inward/record.url?scp=85123496194&partnerID=8YFLogxK
U2 - 10.1002/adhm.202102332
DO - 10.1002/adhm.202102332
M3 - Article
C2 - 35029040
AN - SCOPUS:85123496194
SN - 2192-2640
VL - 11
JO - Advanced healthcare materials
JF - Advanced healthcare materials
IS - 10
M1 - 2102332
ER -