Imaging
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Optical imaging methods have driven much of the extraordinary progress in biology over the last 50 years, and innovations are only accelerating with time. We are contributing to this area with projects on:
(1) Fluorophore Photostabilisation: We are retrofitting known fluorophores to create high-brightness, long-lived, photoresistant and biologically innocent fluorescent imaging agents. These may have particular applications in single-molecule imaging, smFRET, and membrane-localised fluorescent probes for live cells; they may also unlock ultra-high-framerate imaging with organic fluorophores.
[Boehringer Ingelheim Stiftung Exploration Grant #2, Superfluorophores]
• 51* Stabilised Fluorophores, compositions, methods of preparation, conjugates thereof, and methods of use; US Patent Application 2024, 18/737,536 (OTS*, V Glembockyte, B Baumgartner, A Wiegand)
(2) Photoacoustics: Molecular switches and rotors are highly photostable chromophores, but they have rarely been used for modern bioimaging since they are almost entirely nonfluorescent, and they tend to absorb in the UV/blue region rather than the NIR/SWIR biotransparency window. We are now harnessing the light-fast photochemistry of these photomotile motifs into NIR/SWIR photoacoustic imaging, towards high-performance multispectral optoacoustic tomographic (MSOT) molecular imaging.
[Boehringer Ingelheim Stiftung Exploration Grant #1, High-Resolution Enzyme Imaging]
• 52* Molecular rotors are loud, highly photostable, NIR/SWIR- active molecular optoacoustic contrast agents; ChemRxiv 2024 (M Müller*, et al., OTS*)
• 49* Merged molecular switches excel as optoacoustic dyes: azobenzene-cyanines are loud and photostable NIR imaging agents; Angewandte 2024 (VIP) (M Müller, et al., OTS*)
(3) Functional Probes: we develop probes to detect transitions of biochemical heterogeneity (ferroptosis, changes of membrane integrity, etc). While biochemical probes for molecular imaging aim to quantify individual molecular actors (cf. our oxidoreductase imaging projects), these heterogeneous processes can be initiated or driven by many, molecularly diverse actors: therefore, sensing overall downstream outcomes rather than any particular upstream actor may give useful information.
• 60* Logic-gating the HaloTag system with Conditional-Halo-ligator 'CHalo' reagents; BioRxiv 2025 (P Mauker, et al., OTS*)
• 59* Compound, composition, kit and their use for HaloTag protein labelling; Patent Application 2025, LU602798 (OTS*, P Mauker)
• 58* Cellularly-Retained Fluorogenic Probes for Sensitive Cell-Resolved Bioactivity Imaging; Chem Sci 2025 (P Mauker, et al., O Thorn-Seshold*)
• 44* Fluorogenic chemical probes for wash-free imaging of cell membrane damage in ferroptosis, necrosis, and axon injury; J Am Chem Soc 2024 (P Mauker, D Beckmann, et al., O Thorn-Seshold*)
And just next door: the world-leading TU Dresden Dye Collection for inspiration!