Exosomes trapping, manipulation and size-based separation using opto-thermo-electrohydrodynamic tweezers

Owing to the heterogeneity of exosomes in size and biomolecular composition, there is a need for new approaches for trapping, manipulating, and sorting of single exosomes in solution. Due to their small size ranging from 30 nm to 150 nm and their relatively low refractive index, their stable trapping using optical tweezers has been met with challenges. Trapping exosomes in an optical trap requires nearly 100 mW of input power, which predisposes them to photo-induced damage and membrane rupture at the laser focus. Here, we report a high stability opto-thermo-electrohydrodynamic tweezer for the stable stand-off trapping of single exosomes based on a concentric nanohole array (CNA) using laser illumination and an a.c. field. The CNA system generates two regions of electrohydrodynamic potentials several microns away from the laser focus where single exosomes are trapped. We demonstrate the rapid trapping within seconds, and selective dynamic manipulation of exosomes based on size using only 4.2 mW of input laser power. The proposed platform opens up a promising approach for stabilizing single exosomes in solution and controlling their distribution based on size without the risk of photo-induced damage.