Nanoplasmonic pillars engineered for single exosome detection

Raghu, Deepa; Christodoulides, Joseph A.; Christophersen, M.; Liu, Jinny L.; Anderson, George P.; Robitaille, Michael; Byers, Jeff M.; Raphael, Marc P.

doi:10.1371/journal.pone.0202773

Cited by 67 publications

(68 citation statements)

References 32 publications

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“…23,24 Examples of advanced exosomal analytical approaches include interferometry, 25 electrochemistry, 26,27 and optical sensors utilizing nanoplasmonics. 28,29 Recently, Rupert et al successfully demonstrated surface plasmon resonance (SPR) based sensing of CD63-positive exosomes through surface based immunocapture. 30 Collectively, the above-mentioned techniques provide a sensitive, label-free, and real-time assessment of exosomes.…”

Section: ■ Introductionmentioning

confidence: 99%

Acoustic Immunosensing of Exosomes Using a Quartz Crystal Microbalance with Dissipation Monitoring

Suthar¹,

Parsons²,

Hoogenboom³

et al. 2019

Preprint

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Exosomes are endocytic lipid-membrane bound bodies with potential to be used as biomarkers in cancer and neurodegenerative disease. The limitations and scarcity of current exosome characterisation approaches has led to a growing demand for translational techniques, capable of determining their molecular composition and physical properties in physiological fluids. Here, we investigate label-free immunosensing, using a quartz crystal microbalance with dissipation (QCM-D), to detect exosomes by exploiting their surface protein profile. Exosomes expressing the transmembrane protein CD63 were isolated by size-exclusion chromatography from cell culture media. QCM-D sensors functionalised with anti-CD63 antibodies formed a direct immunoassay towards CD63-positive exosomes, exhibiting a limit-of-detection of 1.7x10^8 and 1.1x10^8 exosome sized particles (ESPs) ml^-1 for frequency and dissipation response respectively, i.e., clinically relevant concentrations. Our proof-of-concept findings support the adoption of dual-mode acoustic analysis of exosomes, leveraging both frequency and dissipation monitoring for use in diagnostic assays.

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Section: ■ Introductionmentioning

confidence: 99%

Acoustic Immunosensing of Exosomes Using a Quartz Crystal Microbalance with Dissipation Monitoring

Suthar¹,

Parsons²,

Hoogenboom³

et al. 2019

Preprint

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“…Therefore, target exosomes could be detected at concentrations as low as 5 × 10 3 /mL by dual amplification between Au plate-Au nanoparticle and Au-Au nanoparticle. Raghu et al discussed Au nanoplasmonic pillar arrays developed using nano-and micro-fabrication techniques for single exosome detection by an LSPR imaging analytical method [90] (Figure 8a). By sizing the individual nanopillar to approximately 100 nm, similar to the size of an exosome, it is possible to observe in situ single-exosome binding events in sub-femtomolar concentrations of exosomes via LSPR imaging signal.…”

Section: Analytical Methods For Extracellular Vesicles (Evs)mentioning

confidence: 99%

Noble Metal-Assisted Surface Plasmon Resonance Immunosensors

Choi

Lee

Son

et al. 2020

Sensors

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For the early diagnosis of several diseases, various biomarkers have been discovered and utilized through the measurement of concentrations in body fluids such as blood, urine, and saliva. The most representative analytical method for biomarker detection is an immunosensor, which exploits the specific antigen-antibody immunoreaction. Among diverse analytical methods, surface plasmon resonance (SPR)-based immunosensors are emerging as a potential detection platform due to high sensitivity, selectivity, and intuitive features. Particularly, SPR-based immunosensors could detect biomarkers without labeling of a specific detection probe, as typical immunosensors such as enzyme-linked immunosorbent assay (ELISA) use enzymes like horseradish peroxidase (HRP). In this review, SPR-based immunosensors utilizing noble metals such as Au and Ag as SPR-inducing factors for the measurement of different types of protein biomarkers, including viruses, microbes, and extracellular vesicles (EV), are briefly introduced.

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“…Flow cytometric techniques are beginning to elucidate single-EV biology (Marcoux et al, 2016 ; Stoner et al, 2016 ; Saugstad et al, 2017 ; Mastoridis et al, 2018 ; Tian et al, 2018 ; Kanada et al, 2019 ; Padda et al, 2019 ; Ricklefs et al, 2019 ; Zaborowski et al, 2019 ) and we expect to see significant growth in this area. There have also been a number of notable studies implementing nanoplasmonic technologies for single-EV detection and characterization (Im et al, 2014 ; Raghu et al, 2018 ; Rojalin et al, 2019 ).…”

Section: Experimental Approachesmentioning

confidence: 99%

Characterizing Extracellular Vesicles and Their Diverse RNA Contents

2020

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Cells release nanometer-scale, lipid bilayer-enclosed biomolecular packages (extracellular vesicles; EVs) into their surrounding environment. EVs are hypothesized to be intercellular communication agents that regulate physiological states by transporting biomolecules between near and distant cells. The research community has consistently advocated for the importance of RNA contents in EVs by demonstrating that: (1) EV-related RNA contents can be detected in a liquid biopsy, (2) disease states significantly alter EV-related RNA contents, and (3) sensitive and specific liquid biopsies can be implemented in precision medicine settings by measuring EV-derived RNA contents. Furthermore, EVs have medical potential beyond diagnostics. Both natural and engineered EVs are being investigated for therapeutic applications such as regenerative medicine and as drug delivery agents. This review focuses specifically on EV characterization, analysis of their RNA content, and their functional implications. The NIH extracellular RNA communication (ERC) program has catapulted human EV research from an RNA profiling standpoint by standardizing the pipeline for working with EV transcriptomics data, and creating a centralized database for the scientific community. There are currently thousands of RNA-sequencing profiles hosted on the Extracellular RNA Atlas alone (Murillo et al., 2019 ), encompassing a variety of human biofluid types and health conditions. While a number of significant discoveries have been made through these studies individually, integrative analyses of these data have thus far been limited. A primary focus of the ERC program over the next five years is to bring higher resolution tools to the EV research community so that investigators can isolate and analyze EV sub-populations, and ultimately single EVs sourced from discrete cell types, tissues, and complex biofluids. Higher resolution techniques will be essential for evaluating the roles of circulating EVs at a level which impacts clinical decision making. We expect that advances in microfluidic technologies will drive near-term innovation and discoveries about the diverse RNA contents of EVs. Long-term translation of EV-based RNA profiling into a mainstay medical diagnostic tool will depend upon identifying robust patterns of circulating genetic material that correlate with a change in health status.

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Nanoplasmonic pillars engineered for single exosome detection

Cited by 67 publications

References 32 publications

Acoustic Immunosensing of Exosomes Using a Quartz Crystal Microbalance with Dissipation Monitoring

Acoustic Immunosensing of Exosomes Using a Quartz Crystal Microbalance with Dissipation Monitoring

Noble Metal-Assisted Surface Plasmon Resonance Immunosensors

Characterizing Extracellular Vesicles and Their Diverse RNA Contents

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