한빛사논문
Byeonggeol Mun a,1, Hyein Jeong a,1, Ryunhyung Kim a, Boram Gu b, Jinyoung Kim a, Hye Young Son c, Hyun Wook Rho c, Eun-Kyung Lim d,e,f, Seungjoo Haam a
aDepartment of Chemical and Biomolecular Engineering, College of Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
bSchool of Chemical Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea
cDepartment of Radiology, College of Medicine, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
dBionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
eDepartment of Nanobiotechnology, KRIBB School of Biotechnology, University of Science and Technology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34113, Republic of Korea
fSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
1These authors contributed equally to this work.
Corresponding authors : Eun-Kyung Lim, Seungjoo Haam
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.
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