A multitude of biological processes are enabled by complex interactions between lipid membranes and proteins. To understand such dynamic processes, it is crucial to differentiate the constituent biomolecular species and track their individual time evolution without invasive labels. Here, we present a label-free mid-infrared biosensor capable of distinguishing multiple analytes in heterogeneous biological samples with high sensitivity. Our technology leverages a multi-resonant metasurface to simultaneously enhance the different vibrational fingerprints of multiple biomolecules. By providing up to 1000-fold near-field intensity enhancement over both amide and methylene bands, our sensor resolves the interactions of lipid membranes with different polypeptides in real time. Significantly, we demonstrate that our label-free chemically specific sensor can analyze peptide-induced neurotransmitter cargo release from synaptic vesicle mimics. Our sensor opens up exciting possibilities for gaining new insights into biological processes such as signaling or transport in basic research as well as provides a valuable toolkit for bioanalytical and pharmaceutical applications.
Bibliographical noteFunding Information:
The research leading to these results has received funding from the European Research Council (ERC) under grant agreement no. 682167 VIBRANT-BIO, the European Union Horizon 2020 Framework Programme for Research and Innovation under grant agreements no. 665667 (call 2015), no. 777714 NOCTURNO and no. FETOPEN-737071 ULTRACHIRAL, and the European Union Seventh Framework Programme under grant agreement no. 625673 GRYPHON and no. 609416 ICFONest+. We also acknowledge École Polytechnique Fédérale de Lausanne, Center of MicroNano Technology (CMi) for nanofabrication, and Bioimaging and Optics Platform (BIOP) for fluorescence measurements. The views expressed are purely those of the authors and may not in any circumstances be regarded as stating an official position of the European Research Council Executive Agency.
© 2018 The Author(s).