Improving Deterministic Lateral Displacement Toward Nanofractionation of Exosomes

Abstract

Over the past two decades, extracellular vesicles have emerged as intercellular messengers in a broad range of eukaryotic biological processes. These vesicles, the smallest of which are exosomes 50-100 nm in diameter, carry proteins and genetic information with putative functional roles in tumorigenesis, virology, neurophysiology, and immunology. Significantly, exosomes appear to function in tumor-stroma interactions influencing cancer metastasis, and can cross the blood-brain barrier for potential new methods to deliver drugs to the brain. However, research and therapeutic applications of exosomes are hampered by lack of efficient and scalable tools for isolating exosomes. The deterministic lateral displacement array, a microfluidic technology capable of sorting particles based on size, promises a new method for isolating exosomes with high efficiency and robust yield. A revised design of the deterministic lateral displacement array, the cascade array, was developed to expand the dynamic range of the separation process with reduced clogging. Nanometer-scale DLD cascade arrays were then fabricated and tested to separate nanoparticles. Preliminary results from tests of the cascade device leave open the possibility that it may be able to fractionate micro- and nanoparticles such as exosomes, and have laid the groundwork for future investigations into the cascade array performance.