Development of the next generation of SWIR emItting probes for bioimaging

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Current challenges and objectives for studying physio-pathological phenomena and disease-related processes in living organisms with non-invasive optical bioimaging are to realize a deep tissue penetration while maintaining a high detection sensitivity and a high spatial and temporal resolution. A promising spectral window for high contrast, high sensitivity, and high spatial resolution in small animal imaging is the shortwave infrared (SWIR) between ~900–2500 nm where scattering, absorption and autofluorescence of tissue are strongly reduced compared to the visible (400–700 nm) and NIR (~700–900 nm). Full exploitation of SWIR photoluminescence (PL) imaging (PLI) is currently hampered by i.) a lack of suitable contrast agents with a high PL quantum yield (PL QY) and a high brightness, that can be used safely in vivo and ii.) a lack of quantitative and reliable data on the optical properties of many SWIR emitters. This limits achievable contrast, spatial and temporal resolution and comparability of emitter performance, hampering the rational design of new SWIR contrast agents. Aiming at high spatial and temporal resolution (i.e., fast image acquisition) of the vascular network in PLI of animals, German and French experts in quantitative optical spectroscopy, photophysics, probe design, and optical imaging joined forces to develop new SWIR contrast agents and advanced image analysis methods. Therefore, we will rationally design bright SWIR reporters utilizing atomically precise gold nanoclusters (AuNCs) and heavy metal-free quantum dots (QDs) like Ag2S QDs with improved optical properties and spectroscopically characterize them in solution, artificial models mimicking tissues, and small animals. Strategies to improve detection sensitivity and resolution will be addressed i.) by comparing different spectral windows in the SWIR, thus considering wavelength-dependent absorption and scattering properties of tissue, and ii.) by preparing multimeric AuNCs to tune PL and brightness. In parallel, SWIR spectral multiplexing with these emitters will be studied. Best performing and “biologically safe” contrast agents will be evaluated in mice to determine their potential for SWIR PLI of organ vascularization. Spatial resolution and signal-to-noise ratios will be quantified, using different methods of image analysis, thereby enhancing PL data information content to resolve blood and lymphatic flows. The results i.) will provide bright and “safe” SWIR emitters and advanced methods of image analysis, enabling non-invasive real time deep imaging of vascular networks and 3D fluid flow mapping in live animals to better understand mechanisms of normal and pathological angiogenesis, ii.) yield quantitative and reliable data on the signal-relevant spectroscopic key features of different SWIR reporters in biologically relevant environments, iii.) allow to correlate these features and probe performance in SWIR PLI, and iv.) help to standardize SWIR PL measurements.