Single-Molecule Acousto-Photonic Nanofluidics

Reading biomolecular signatures and understanding their role in health and disease is one of the greatest scientific challenges in genome and proteome biology. Yet, complete protein analysis at the single-molecule level remains an unmet milestone. This pursuit is fundamentally hindered by the huge dynamic range of protein expression in cells and the insufficient spatio-temporal resolution of current analysis methods. Next-generation single-molecule techniques that can precisely manipulate and sequence proteins in space and time are urgently needed to reach this goal. Among these, nanopore platforms are at the forefront, leading in terms of read length, throughput and sensitivity. However, the major challenges associated with translocation speed control and the precise-readout in solid-state nanopore devices, remain prohibitive. In SIMPHONICS, I will resolve these issues by developing the first integrated platform that combines nanopore transport measurements, spatially modulated acoustic wavefields and single-molecule fluorescence time traces to confine, scan and optically fingerprint proteins in a non-invasive and massively parallel manner. The feasibility of this method will be established by attaining three main objectives: 1) Confining and controllably manipulating individual molecules using acoustic nanotweezers; 2) On-demand engineering of 2D material optical emitters as ultrabright fluorescent probes for energy transfer based detection, and 3) Identifying proteins/peptides from their optical signatures in multi-color Frster resonance energy transfer (FRET) during acoustophoresis. With this powerful and unique platform, I will harness the vast potential of acousto-photonic interactions in monolithic nanopore devices. Successful achievement of the project objectives will result in a high-throughput and non-destructive protein fingerprinting platform and signify a considerable leap forward in our quest to unravel the human proteome.