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A hydrogel-based mechanical metamaterial for the interferometric profiling of extracellular vesicles in patient samples

Nature Biomedical Engineering volume 7, pages 135–148 (2023)Cite this article

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Abstract

The utility of mechanical metamaterials for biomedical applications has seldom been explored. Here we show that a metamaterial that is mechanically responsive to antibody-mediated biorecognition can serve as an optical interferometric mask to molecularly profile extracellular vesicles in ascites fluid from patients with cancer. The metamaterial consists of a hydrogel responsive to temperature and redox activity functionalized with antibodies to surface biomarkers on extracellular vesicles, and is patterned into micrometric squares on a gold-coated glass substrate. Through plasmonic heating, the metamaterial is maintained in a transition state between a relaxed form and a buckled state. Binding of extracellular vesicles from the patient samples to the antibodies on the hydrogel causes it to undergo crosslinking, induced by free radicals generated via the activity of horseradish peroxidase conjugated to the antibodies. Hydrogel crosslinking causes the metamaterial to undergo fast chiral re-organization, inducing amplified changes in its mechanical deformation and diffraction patterns, which are detectable by a smartphone camera. The mechanical metamaterial may find broad utility in the sensitive optical immunodetection of biomolecules.

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Fig. 1: Critically locked mechanical metamaterial for amplified molecular profiling.
Fig. 2: Critical point in pattern transformation.
Fig. 3: Plasmonic locking of the critical point.
Fig. 4: Interferometric projection of metamaterial deformation.
Fig. 5: MORPH for the profiling of exosomes in patient samples.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analyzed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding author on reasonable request.

Code availability

The custom code used for the statistical analyses is available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank X. Qiu, J.W.S. Tan, C.Y.J. Chee and S.C. Teo for assistance with clinical-sample collection. This work was supported in part by funding from the National University of Singapore (NUS), the NUS Research Scholarship, the Ministry of Education, the National Medical Research Council and the Institute for Health Innovation & Technology, and by an IMCB Independent Fellowship and a NUS Early Career Research Award.

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Author notes

  1. These authors contributed equally: Haitao Zhao, Sijun Pan.

Authors and Affiliations

  1. Institute for Health Innovation & Technology, National University of Singapore, Singapore, Singapore

    Haitao Zhao, Sijun Pan, Auginia Natalia, Xingjie Wu & Huilin Shao

  2. Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore

    Auginia Natalia & Huilin Shao

  3. Division of Surgical Oncology, National Cancer Centre, Singapore, Singapore

    Chin-Ann J. Ong & Melissa C. C. Teo

  4. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Jimmy B. Y. So & Huilin Shao

  5. Division of Surgical Oncology, National University Cancer Institute, Singapore, Singapore

    Jimmy B. Y. So

  6. Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore

    Huilin Shao

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Contributions

H.Z., S.P. and H.S. designed the study. C.-A.J.O., M.C.C.T. and J.B.Y.S. provided de-identified clinical samples and health information. H.Z., S.P., X.W. and A.N. performed the research. H.Z., S.P., A.N. and H.S. analyzed the data and wrote the manuscript. All authors contributed to revising the manuscript.

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Correspondence to Huilin Shao.

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Nature Biomedical Engineering thanks Giuseppe Strangi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Zhao, H., Pan, S., Natalia, A. et al. A hydrogel-based mechanical metamaterial for the interferometric profiling of extracellular vesicles in patient samples. Nat. Biomed. Eng 7, 135–148 (2023). https://doi.org/10.1038/s41551-022-00954-7

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