An aptamer-functionalized chemomechanically modulated biomolecule catch-and-release system

Abstract

The efficient extraction of (bio)molecules from fluid mixtures is vital for applications ranging from target characterization in (bio)chemistry to environmental analysis and biomedical diagnostics. Inspired by biological processes that seamlessly synchronize the capture, transport and release of biomolecules, we designed a robust chemomechanical sorting system capable of the concerted catch and release of target biomolecules from a solution mixture. The hybrid system is composed of target-specific, reversible binding sites attached to microscopic fins embedded in a responsive hydrogel that moves the cargo between two chemically distinct environments. To demonstrate the utility of the system, we focus on the effective separation of thrombin by synchronizing the pH-dependent binding strength of a thrombin-specific aptamer with volume changes of the pH-responsive hydrogel in a biphasic microfluidic regime, and show a non-destructive separation that has a quantitative sorting efficiency, as well as the system's stability and amenability to multiple solution recycling.

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Figure 1: Design of the chemomechanically modulated biomolecule catch-and-release system.
Figure 2: Computer simulations of the selective binding and release.
Figure 3: Chemomechanically modulated sequential catch and release of thrombin in the microfluidic system.
Figure 4: System performance in multiple oscillation cycles with recycling of the ingoing solution.
Figure 5: Analysis of the components of the top and bottom solutions after cycling.

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Acknowledgements

This work was supported by the Department of Energy under Award No. DE-SC0005247. We thank M. Krogsgaard and C. Howell for their help with the XPS characterization of the aptamer functionalization of the microstructures.

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X.H., A.S., L.M.M., M.A., A.C.B. and J.A. designed the project. X.H., A.S., L.M.M., M.A., O.K., A.C.B. and J.A. wrote the manuscript. Y.L., A.B., Y.M., O.K. and A.C.B. performed the computational simulations and analysed the results. L.M.M. and V.H. performed the PAGE experiments and analysis, and participated in synthesizing the DNA aptamers. X.H. and A.S. conducted the catch-and-release experiments in the microfluidic system and performed the ELISA analysis. X.H., A.S., H.N., M.M. and V.H. conducted the ELONA experiments. A.S. performed the experiments to determine the pH-dependent behaviour of the aptamers. X.H. performed a confocal microscopy characterization of the system. Y.V., O.K. and M.A. contributed important discussions to the analysis of the results.

Corresponding authors

Correspondence to Joanna Aizenberg or Ximin He.

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The authors declare no competing financial interests.

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Shastri, A., McGregor, L., Liu, Y. et al. An aptamer-functionalized chemomechanically modulated biomolecule catch-and-release system. Nature Chem 7, 447–454 (2015). https://doi.org/10.1038/nchem.2203

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