Nanoplasmonic Sensor Approaches for Sensitive Detection of Disease-Associated Exosomes

Exosomes are abundantly secreted by most cells that carry membrane and cytosolic factors that can reflect the physiologic state of their source cells and thus have strong potential to serve as biomarkers for early diagnosis, disease staging, and treatment monitoring. However, traditional diagnostic or prognostic applications that might use exosomes are hindered by the lack of rapid and sensitive assays that can exploit their biological information. An array of assay approaches have been developed to address this deficit, including those that integrate immunoassays with nanoplasmonic sensors to measure changes in optical refractive indexes in response to the binding of low concentrations of their targeted molecules. These sensors take advantage of enhanced and tunable interactions between the electron clouds of nanoplasmonic particles and structures and incident electromagnetic radiation to enable isolation-free and ultrasensitive quantification of disease-associated exosome biomarkers present in complex biological samples. These unique advantages make nanoplasmonic sensing one of the most competitive approaches available for clinical applications and point-of-care tests that evaluate exosome-based biomarkers. Researchers from Tulane University summarize the origin and clinical utility of exosomes and the limitations of current isolation and analysis approaches before discussing the specific advantages and limitations of nanoplasmonic sensing devices and indicating what additional developments are necessary to allow the translation of these approaches into clinical applications.

Nanoplasmon-enhanced scattering assays for exosome analysis

(a) Near-field nanoplasmon-enhanced scattering (nPES) assay approach for specific EV detection where exosomes captured by a general exosome marker (e.g., anti-CD81 antibody) are incubated with morphologically distinct gold nanoparticles conjugated with antibody probes to general exosome (e.g., CD9 and CD63) and disease-specific surface markers. (b) Far-field nPES assay approach four automated dark-field imaging of plasmon-enhanced light scattering from gold nanoparticles conjugated to a general exosome marker (e.g., CD9) that are bound to target EVs captured by a disease-associated exosome surface marker (e.g., EpCAM). (c) Biomimetic coating approach allows selective capture of cancer cell-derived exosomes and reduces signal artifacts when plasmonic signal from captured nanoprobes is detected by dark field microscope image analysis. (d) Noise reduction approach to resolve nPES signal from nanoparticle probes from scattering artifacts.