Abstract
AbstractThe effective isolation of rare target cells, such as circulating tumor cells, from whole blood is still challenging due to the lack of a capturing surface with strong target-binding affinity and non-target-cell resistance. Here we present a solution leveraging the flexibility of bacterial virus (phage) nanofibers with their sidewalls displaying target circulating tumor cell-specific aptamers and their ends tethered to magnetic beads. Such flexible phages, with low stiffness and Young’s modulus, can twist and adapt to recognize the cell receptors, energetically enhancing target cell capturing and entropically discouraging non-target cells (white blood cells) adsorption. The magnetic beads with flexible phages can isolate and count target cells with significant increase in cell affinity and reduction in non-target cell absorption compared to magnetic beads having rigid phages. This differentiates breast cancer patients and healthy donors, with impressive area under the curve (0.991) at the optimal detection threshold (>4 target cells mL−1). Immunostaining of captured circulating tumor cells precisely determines breast cancer subtypes with a diagnostic accuracy of 91.07%. Our study reveals the power of viral mechanical attributes in designing surfaces with superior target binding and non-target anti-fouling.
Funder
General Research Fund of Hong Kong
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Reference61 articles.
1. Wu, L. et al. Fluidic multivalent membrane nanointerface enables synergetic enrichment of circulating tumor cells with high efficiency and viability. J. Am. Chem. Soc. 142, 4800–4806 (2020).
2. Jeong, W. J. et al. Hierarchically multivalent peptide-nanoparticle architectures: a systematic approach to engineer surface adhesion. Adv. Sci. 9, 2103098 (2022).
3. Guo, L. et al. Directing multivalent aptamer-receptor binding on the cell surface with programmable atom-like nanoparticles. Angew. Chem. Int. Ed. 61, e202117168 (2022).
4. Sabaté del Río, J., Henry, O. Y. F., Jolly, P. & Ingber, D. E. An antifouling coating that enables affinity-based electrochemical biosensing in complex biological fluids. Nat. Nanotechnol. 14, 1143–1149 (2019).
5. Banerjee, I., Pangule, R. C. & Kane, R. S. Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine Organisms. Adv. Mater. 23, 690–718 (2011).