Nanoplasmonic Approaches for Sensitive Detection and Molecular Characterization of Extracellular Vesicles

Abstract

All cells release a multitude of nanoscale extracellular vesicles (nEVs) into circulation, offering immense potential for new diagnostic strategies. Yet, clinical translation for nEVs remains a challenge due to their vast heterogeneity, our insufficient ability to isolate subpopulations, and the low frequency of disease-associated nEVs in biofluids. The growing field of nanoplasmonics is poised to address many of these challenges. Innovative materials engineering approaches based on exploiting nanoplasmonic phenomena, i.e., the unique interaction of light with nanoscale metallic materials, can achieve unrivaled sensitivity, offering real-time analysis and new modes of medical and biological imaging. We begin with an introduction into the basic structure and function of nEVs before critically reviewing recent studies utilizing nanoplasmonic platforms to detect and characterize nEVs. For the major techniques considered, surface plasmon resonance (SPR), localized SPR, and surface enhanced Raman spectroscopy (SERS), we introduce and summarize the background theory before reviewing the studies applied to nEVs. Along the way, we consider notable aspects, limitations, and considerations needed to apply plasmonic technologies to nEV detection and analysis.

Augmented COlorimetric NANoplasmonic (CONAN) Method for Grading Purity and Determine Concentration of EV Microliter Volume Solutions

“…In this paper, we present a step-by-step protocol to assign a purity grade and to subsequently titrate EV formulations by an augmented microplate version of the COlorimetric NANoplasmonic (CONAN) assay (Maiolo et al, 2015;Mallardi et al, 2018;Picciolini et al, 2018;Gualerzi et al, 2019;Rojalin et al, 2019) with an optimized balance between robustness and accessibility.…”

Membrane lipid binding molecules for the isolation of bona fide extracellular vesicle types and associated biomarkers in liquid biopsy

“…We propose that the use of membrane lipid binding ligands in EV isolation for liquid biopsy is a viable and robust strategy to circumvent the present technical limitations in isolating bona fide EVs from biological fluids for liquid biopsy. In addition, this isolation technique is versatile can be easily integrated into the current clinical analysis platforms using 96 well assay plates and even newer analytical platforms such as nano-plasmonics [44] which uses the interaction of light and electronic oscillations in metallic substrates in a nanometer-dimension to detect the presence of single EV.…”

Extracellular Vesicles in Diagnosis and Treatment of Pancreatic Cancer: Current State and Future Perspectives

“…The authors found that when SERS was coupled with PC-DFA, the technique had a sensitivity and specificity of 90.6% and 97.1%, respectively, and distinguished pancreatic cell lines from a healthy cell line [42]. The drawbacks associated with SERS include that it has weak signals when working with biological samples and the signals can be challenging to interpret [27,29,44]. Weak signals in biological samples can be overcome by using surface enhancement [29].…”

“…The drawbacks associated with SERS include that it has weak signals when working with biological samples and the signals can be challenging to interpret [27,29,44]. Weak signals in biological samples can be overcome by using surface enhancement [29]. SERS is an active area of current research, and new technologies are being created regularly, as evidenced by Tian et al In 2018 [5].…”