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Isolation of Circulating Biomarkers for Liquid Biopsy using Immunoaffinity‐Based Stimuli‐Responsive Hybrid Hydrogel Beads
Author(s) -
Kang YoonTae,
Kim Young Jun,
Rupp Brittany,
Purcell Emma,
Hadlock Thomas,
Ramnath Nithya,
Nagrath Sunitha
Publication year - 2021
Publication title -
analysis and sensing
Language(s) - English
Resource type - Journals
ISSN - 2629-2742
DOI - 10.1002/anse.202100016
Subject(s) - circulating tumor cell , microvesicles , self healing hydrogels , liquid biopsy , exosome , chemistry , materials science , biophysics , cancer , biochemistry , medicine , biology , microrna , polymer chemistry , gene , metastasis
This work presents chemically stable and biodegradable hydrogel beads for the isolation of circulating tumor cells (CTCs) and circulating exosomes in liquid biopsy. The liquid biopsy hydrogel beads ( LB beads) consisting of alginate and poly(vinyl alcohol) hydrogels show both chemical stability and stimuli‐degradable characteristics. Unlike single‐component hydrogels, this hybrid form is not easily degraded by buffers or cell culture media while its degradable characteristic remains; thus, it is useful in bio‐applications requiring multi‐step processes with various reagents and lengthy incubation periods. We applied our platform to clinical samples for isolating two promising circulating biomarkers for a liquid biopsy, CTCs and exosomes, by conjugating the hydrogel surface with anti‐EpCAM and anti‐CD63 antibodies, respectively, thus achieving 37.4 CTCs and comparable amount of exosome recovery per 1 milliliter of blood. The results show easy device‐free isolation and retrieval of CTCs and exosomes, with recovered circulating biomarkers successfully analyzed by western blot analysis and fluorescence microscopy. We believe that this simple and versatile platform enables us to isolate prominent circulating biomarkers for clinical use in cancer diagnosis.