Single-molecule biosensing with MXene energy transfer
Lorena Manzanares a b
a Centrale Lille Institut, Cité Scientifique CS20048, Villeneuve d'Ascq Cedex, France
b Institut d'Electronique, de Microélectronique et de Nanotechnologie (IEMN) UMR CNRS 8520, Université de Lille - Faculté des Sciences et Technologies 50, avenue de Halley, 59658 Villeneuve d'Ascq, France
Proceedings of MATSUS Fall 2025 Conference (MATSUSFall25)
E9 Frontiers in MXene Research: From Fundamentals to Applications - #MXFrontiers
València, Spain, 2025 October 20th - 24th
Organizers: Sara GOBERNA FERRON and Ana Primo
Invited Speaker, Lorena Manzanares, presentation 184
Publication date: 21st July 2025

Förster Resonance Energy Transfer (FRET) is the gold-standard optical ruler for tracking nanometre-scale structural changes in biomolecules, sensitive to distance changes in the ~3-10 nm range. Yet every FRET experiment demands two covalently attached dyes whose photophysics, mutual orientation, and chemical stability can complicate data interpretation. Solid-state quenchers such as graphene or gold films remove the need for an acceptor dye and extend the working range far beyond 10 nm. Even though graphene has found elegant applications in single molecule fluorescence [1], their hydrophobicity, layer-dependent quenching and working distance range limit direct biological compatibility (beyond DNA), method robustness and certain applications (ultrathin assemblies), respectively.

Here we introduce titanium-carbide MXenes (Ti₃C₂Tₓ) as hydrophilic and robust surface-based quenchers that operate within an ultrashort distance window and possess superior biocompatibility.

We first characterised MXene-DNA interactions using ensemble fluorescence spectroscopy and molecular dynamic simulations [2]. DNA adsorption was found to occur through hydrated ion bridges, avoiding the strong hydrophobic and π–π stacking forces typical of graphene and thereby preserving nucleic-acid structure. In real-time surface hybridisation assays, a mere 0.3 nm increase in dye-MXene separation produced a clear fluorescence rise, demonstrating sub-nanometre axial sensitivity.

To map the distance law precisely, we employed dye-labeled DNA origami nanostructures that position fluorophores 1-8 nm above MXene-coated glass and determined the distance dependent energy transfer by single molecule fluorescence lifetime measurements [3]. We found that single-flake Ti₃C₂Tₓ extinguishes >95 % of donor emission at 1 nm and recovers to baseline by 8 nm, following a cubic distance dependence that is nearly insensitive to MXene thickness. With this calibration, we investigated 5-nm supported lipid bilayers, which are minimal cell-membrane mimics. MXenes enabled leaflet-specific, single-lipid read-out without the hydrophilic spacers required for graphene, underscoring both their compatibility with soft matter and their unique, steep sensitivity. 

Ti₃C₂Tₓ MXenes thus offer a powerful new tool for structural studies of ultrathin biological assemblies such as lipid membranes, protein monolayers, and DNA nanostructures, at the single molecule level.  

The author acknowledges support from the Alexander von Humboldt Foundation (Ref. 3.3 – ESP – 1218808 – HFST-P), and from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Actions Individual Fellowship (grant agreement no. 795347). The author also gratefully acknowledges all co-authors and collaborators involved in the above-mentioned studies.

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