Isolation of circulating biomarkers for liquid biopsy using immunoaffinity-based stimuli-responsive hybrid hydrogel beads

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 (LBbeads) 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.

Researchers from the University of Michigan applied their 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. The researchers believe that this simple and versatile platform enables us to isolate prominent circulating biomarkers for clinical use in cancer diagnosis.

A fabrication and analytical procedure for liquid biopsy
using stimuli-responsive hybrid hydrogel beads


A) Fabrication of and modification of the liquid biopsy hydrogel to isolate circulating tumor cells (CTCs) and circulating exosomes; B) Reaction and procedure of circulating biomarkers isolation and subsequent recovery; C) The fabricated liquid biopsy hydrogel beads.

Kang YT, Kim YJ, Rupp B, Purcell E, Hadlock T, Ramnath N, Nagrath S. (2021) Isolation of Circulating Biomarkers for Liquid Biopsy using Immunoaffinity-Based Stimuli-Responsive Hybrid Hydrogel Beads. Analysis & Sensing [Epub ahead of print]. [article]

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