Real time and label free profiling of clinically relevant exosomes

Sina, Abu Ali Ibn; Vaidyanathan, Ramanathan; Dey, Shuvashis; Carrascosa, Laura G.; Shiddiky, Muhammad J. A.; Trau, Matt

doi:10.1038/srep30460

Cited by 132 publications

(133 citation statements)

References 37 publications

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“…74 Lastly, surface plasmon resonance (SPR)-based sensing platforms rely on functionalization of gold surfaces for exosome capture, and therefore also fall into this category. 44,75 …”

Section: Microfluidic-based Exosome Isolationmentioning

confidence: 99%

“…as part of a two-step isolation and detection process. 75 Custom-made SPR chips were employed for analysis of exosomes from breast cancer patient samples, where characteristics of the resulting spectral shifts enabled identification and quantification of exosome populations from serum samples. Electrokinetic methods have also been employed for analysis of exosomal materials, as demonstrated by Akagi et al .…”

Section: Microfluidic-based Exosome Detection and Analysismentioning

confidence: 99%

“…used a custom-built SPR-based platform for analysis of exosome subpopulations, although isolation and detection of relevant exosomes occurred sequentially and without multiplexing. 75 Exosomes were first isolated on a gold surface using ubiquitous markers (CD9 or CD63), followed by label-free immunoaffinity detection of cancer-specific exosomes expressing HER2. Both processes produced characteristic spectral shifts that could be monitored in real-time.…”

Section: Integrated Microfluidic Platforms For Exosome Analysismentioning

confidence: 99%

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Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

2017

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Exosomes, the smallest sized extracellular vesicles (30 ~ 150 nm) packaged with lipids, proteins, functional messenger RNAs and microRNAs, and double-stranded DNA from their cells of origin, have emerged as key players in intercellular communication. Their presence in bodily fluids, where they protect their cargo from degradation, makes them attractive candidates for clinical application as innovative diagnostic and therapeutic tools. But routine isolation and analysis of high purity exosomes in clinical settings is challenging, with conventional methods facing a number of drawbacks including low yield and/or purity, long processing times, high cost, and difficulties in standardization. Here we review a promising solution, microfluidic-based technologies that have incorporated a host of separation and sensing capabilities for exosome isolation, detection, and analysis, with emphasis on point of care and clinical applications. These new capabilities promise to advance fundamental research while paving the way toward routine exosome-based liquid biopsy for personalized medicine.

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“…74 Lastly, surface plasmon resonance (SPR)-based sensing platforms rely on functionalization of gold surfaces for exosome capture, and therefore also fall into this category. 44,75 …”

Section: Microfluidic-based Exosome Isolationmentioning

confidence: 99%

Section: Microfluidic-based Exosome Detection and Analysismentioning

confidence: 99%

Section: Integrated Microfluidic Platforms For Exosome Analysismentioning

confidence: 99%

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Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

2017

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“…Furthermore, Sina et al integrated SPR detection into their two-step isolation and detection strategy [105]. …”

Section: Efforts and Progress Towards Integrated On-a-chip Systems Fomentioning

confidence: 99%

Microfluidics‐based on‐a‐chip systems for isolating and analysing extracellular vesicles

Guo

Tao

Dawn

2018

J of Extracellular Vesicle

141

111

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Extracellular vesicles (EVs), which can be found in almost all body fluids, consist of a lipid bilayer enclosing proteins and nucleic acids from their cells of origin. EVs can transport their cargo to target cells and have therefore emerged as key players in intercellular communication. Their potential as either diagnostic and prognostic biomarkers or therapeutic drug delivery systems (DDSs) has generated considerable interest in recent years. However, conventional methods used to study EVs still have significant limitations including the time-consuming and low throughput techniques required, while at the same time the demand for better research tools is getting stronger and stronger. In the past few years, microfluidics-based technologies have gradually emerged and have come to play an essential role in the isolation, detection and analysis of EVs. Such technologies have several advantages, including low cost, low sample volumes, high throughput and precision. This review summarizes recent advances in microfluidics-based technologies, compares conventional and microfluidics-based technologies, and includes a brief survey of recent progress towards integrated “on-a-chip” systems. In addition, this review also discusses the potential clinical applications of “on-a-chip” systems, including both “liquid biopsies” for personalized medicine and DDS devices for precision medicine, and then anticipates the possible future participation of cloud-based portable disease diagnosis and monitoring systems, possibly with the participation of artificial intelligence (AI).

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“…[18] Others have been reported to be enriched in certain tumor-associated exosomes, like EGFR and HER2. [19,20] Given that several recent studies have demonstrated enrichment of particular integrins in exosomes derived from a variety of tumor cells, they are interesting potential targets. [21–26] …”

Section: Introductionmentioning

confidence: 99%

Targeting Tumor‐Associated Exosomes with Integrin‐Binding Peptides

et al. 2017

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All cells expel a variety of nano-sized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells’ biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application. Yet, it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here we demonstrate peptide binding to tumor-associated EVs via overexpressed membrane protein. We find that SKOV-3 ovarian tumor cells and their released EVs express α3β1 integrin, which can be targeted by our in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enabled us to differentiate cancer-associated exosomes from non-cancer exosomes. Furthermore, we introduce the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30. LXY30 not only exhibits high specificity and affinity to α3β1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.

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Real time and label free profiling of clinically relevant exosomes

Cited by 132 publications

References 37 publications

Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine

Microfluidics‐based on‐a‐chip systems for isolating and analysing extracellular vesicles

Targeting Tumor‐Associated Exosomes with Integrin‐Binding Peptides

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