3D-Nanostructured microfluidic device arranged in a herringbone pattern for the highly effective capture of HER2-Positive cancer-derived exosomes in urine

Abstract

Exosomes in body fluids are important in liquid biopsy as they reflect the information of their originating cells. Thus, exosome analysis can provide valuable insights into diseases such as cancer. However, the low concentration of exosomes in body fluids is accompanied by background noise, making exosome analysis challenging. Here, a microfluidic chip in which three-dimensional nanostructures were arranged in a herringbone pattern (nanochip) that could efficiently capture specific exosomes was developed. Nanostructures were prepared by stacking silica nanoparticles to enhance the contact and interaction between the exosomes and structures, which were then arranged in a herringbone pattern to improve mass transfer through micromixing. To analyze exosomes derived from human epidermal growth factor receptor 2 (HER2, an important marker for cancer progression and patient survival)-positive cancer, anti-HER2 antibody was introduced into the nanostructures in the nanochip and approximately 97.7% of exosome capture efficiency was confirmed. The nanochip performed better than chips with a solid herringbone structure or without a structure (solid and flat chips). The feasibility of capturing multiple exosomes was demonstrated using both in vitro and in vivo samples by employing a dual nanochip configuration in which nanochips with different antibodies were interconnected in a series. This nanochip can effectively capture HER2-positive exosomes and has potential for multiple exosome isolations. Additionally, this chip can capture and detect various disease-related exosomes because various antibodies can be applied; this nanochip will be useful for exosome-based disease diagnosis and monitoring in liquid biopsies.