Once thought of as a means for cells to expel wastes, extracellular vesicles have been shown to contain important biological molecules including proteins, DNA, mRNA, and miRNA, and represent an important means for cells to communicate with neighboring or distant cells. Extracellular vesicles (EV) are heterogeneous both in size, molecular composition and biogenesis, hence the need for single vesicle analysis. Due to their small size, the stable trapping of nano-sized vesicles using optical tweezers (recently recognized with one-half of the 2018 Physics Nobel Prize) has been met with challenges due to the diffraction limit of light. Attempts to substantially increase the laser power to generate enough optical trapping potential for trapping such small biological objects, unfortunately, results in photo-toxicity and thermal stress, which damages the integrity of the biological specimens. An optical nanotweezer approach that can stably trap and analyze nano-sized vesicles without exposing them to high light intensity or heat which may physically alter or destroy detectable bioactivity is of paramount importance for fundamental EV biology research and translational biomedical applications. We are investigating novel optical nanotweezers capable of rapid integrated trapping and enhanced fluorescence analysis of single EVs. In this talk, I will discuss our newly developed large area array of integrated nano-traps that are capable of quickly (within seconds) trapping single nano-sized EVs as well as enhancing the immunofluorescence signal from single trapped EVs. These novel non-invasive optical nanotweezers with multifunctional capabilities are expected to open new horizons by enabling to address fundamental questions in EV biology and drive translational applications in EV liquid biopsy for non-invasive early detection.
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