Microfluidic device using metallic nanostructure arrays for the isolation, detection, and purification of exosomes

Abstract

Microfluidic devices are widely used in disease detection and specimen separation due to their low cost, rapid processing, and the ability to use even minuscule samples. This study reports on the embedding of metallic nanostructure arrays (MeNTAs) with tube-like features in microfluidic devices for the immunoaffinity-based detection and efficient isolation of exosomes. We assessed MeNTA candidates in terms of their ability to withstand the mechanical stress of microfluidic operations (indentation analysis) as well as X-ray diffraction, zeta potential, and electrostatic interactions involving antibody coatings. Note that Zr60Cu25Al10Ni5 thin film metallic glass (Zr-TFMG) features outstanding mechanical properties and a negative zeta potential exceeding those of other common materials (e.g., Cu, Bronze, Ag, 7075Al, Ti64, 718Ni, SS316, Cu-TFMG, W-TFMG, and Al-TFMG). The resulting microfluidic device featured Zr-based MeNTAs with an interdigital electrode embedded in a microchannel. When applied to MCF-7 derived exosomes using a liquid biopsy of only 500 μL, the proposed device (∼6.25 million nanostructures/cm2) achieved an exosome recovery rate of 95.3% within 1 h, while resisting nonspecific binding to HeLa-derived exosomes (recovery rate of<0.1%). The device enabled the isolation of 1 × 108 exosome particles per mL–1 for detection via electrochemical impedance spectroscopy. It also enabled the efficient release of captured exosomes via cyclic voltammetry (CV) operations over a potential range of –0.8 to +0.8 V. The proposed Zr-MeNTA microfluidic device has considerable potential for the isolation, detection, and purification of exosomes in liquid biopsy samples for cancer diagnosis.