Quantitative and Multiplex Detection of Extracellular Vesicle-Derived MicroRNA via Rolling Circle Amplification within Encoded Hydrogel Microparticles

Dana Al Sulaiman; Nidhi Juthani; Patrick S. Doyle

doi:10.1002/adhm.202102332

Quantitative and Multiplex Detection of Extracellular Vesicle-Derived MicroRNA via Rolling Circle Amplification within Encoded Hydrogel Microparticles

Dana Al Sulaiman, Nidhi Juthani, Patrick S. Doyle^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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.

Original language	English (US)
Article number	2102332
Journal	Advanced healthcare materials
Volume	11
Issue number	10
DOIs	https://doi.org/10.1002/adhm.202102332
State	Published - May 18 2022

Bibliographical note

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.

Keywords

biomarkers
cancer
extracellular vesicles
hydrogels
liquid biopsies
microRNA

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering
Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/adhm.202102332

Cite this

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abstract = "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.",

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note = "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: {\textcopyright} 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.",

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Quantitative and Multiplex Detection of Extracellular Vesicle-Derived MicroRNA via Rolling Circle Amplification within Encoded Hydrogel Microparticles

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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