Bright Chromenylium Polymethine Dyes Enable Fast, Four-Color In Vivo Imaging with Shortwave Infrared Detection
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Engineering topics
Publications and source records attributed to Bruns, Oliver T..
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Significance Imaging in the shortwave IR (SWIR) spectral window allows the observation of processes deep within living animals. Recent studies have shown that SWIR imaging enables unprecedented imaging opportunities, including contact-free monitoring of vital signs, generation of microvasculature blood flow maps, real-time metabolic imaging, and molecularly targeted imaging. Yet, whereas bright SWIR fluorophores have been developed for preclinical research settings, applications in the clinic have been held back by the conventional belief that no clinically approved fluorophore is available. Here, we show that indocyanine green, a clinically approved near-IR dye, exhibits a remarkable amount of SWIR emission, which enables state-of-the-art SWIR imaging with direct translation potential into clinical settings, and even outperforms other commercially available SWIR emitters.
Abstract Bright fluorophores in the near‐infrared and shortwave infrared (SWIR) regions of the electromagnetic spectrum are essential for optical imaging in vivo. In this work, we utilized a 7‐dimethylamino flavylium heterocycle to construct a panel of novel red‐shifted polymethine dyes, with emission wavelengths from 680 to 1045 nm. Photophysical characterization revealed that the 1‐ and 3‐methine dyes display enhanced photostability and the 5‐ and 7‐methine dyes exhibit exceptional brightness for their respective spectral regions. A micelle formulation of the 7‐methine facilitated SWIR imaging in mice. This report presents the first polymethine dye designed and synthesized for SWIR in vivo imaging.
For in vivo imaging, the short-wavelength infrared region (SWIR; 1,000–2,000 nm) provides several advantages over the visible and near-infrared regions: general lack of autofluorescence, low light absorption by blood and tissue, and reduced scattering. However, the lack of versatile and functional SWIR emitters has prevented the general adoption of SWIR imaging by the biomedical research community. In this work, we introduce a class of high-quality SWIR-emissive indium-arsenide-based quantum dots that are readily modifiable for various functional imaging applications, and that exhibit narrow and size-tunable emission and a dramatically higher emission quantum yield than previously described SWIR probes. To demonstrate the unprecedented combination of deep penetration, high spatial resolution, multicolour imaging and fast acquisition speed afforded by the SWIR quantum dots, we quantified, in mice, the metabolic turnover rates of lipoproteins in several organs simultaneously and in real time as well as heartbeat and breathing rates in awake and unrestrained animals, and generated detailed three-dimensional quantitative flow maps of the mouse brain vasculature.
With the emergence of applications based on short-wavelength infrared light, indium arsenide quantum dots are promising candidates to address existing shortcomings of other infrared-emissive nanomaterials. However, III–V quantum dots have historically struggled to match the high-quality optical properties of II–VI quantum dots. Here we present an extensive investigation of the kinetics that govern indium arsenide nanocrystal growth. Based on these insights, we design a synthesis of large indium arsenide quantum dots with narrow emission linewidths. We further synthesize indium arsenide-based core-shell-shell nanocrystals with quantum yields up to 82% and improved photo- and long-term storage stability. We then demonstrate non-invasive through-skull fluorescence imaging of the brain vasculature of murine models, and show that our probes exhibit 2–3 orders of magnitude higher quantum yields than commonly employed infrared emitters across the entire infrared camera sensitivity range. Finally, we anticipate that these probes will not only enable new biomedical imaging applications, but also improved infrared nanocrystal-LEDs and photon-upconversion technology.
Magneto-fluorescent particles have been recognized as an emerging class of materials that exhibit great potential in advanced applications. However, synthesizing such magneto-fluorescent nanomaterials that simultaneously exhibit uniform and tunable sizes, high magnetic content loading, maximized fluorophore coverage at the surface and a versatile surface functionality has proven challenging. Here we report a simple approach for co-assembling magnetic nanoparticles with fluorescent quantum dots to form colloidal magneto-fluorescent supernanoparticles. Importantly, these supernanoparticles exhibit a superstructure consisting of a close-packed magnetic nanoparticle ‘core’, which is fully surrounded by a ‘shell’ of fluorescent quantum dots. A thin layer of silica coating provides high colloidal stability and biocompatibility, and a versatile surface functionality. Here, we demonstrate that after surface pegylation, these silica-coated magneto-fluorescent supernanoparticles can be magnetically manipulated inside living cells while being optically tracked. Moreover, our silica-coated magneto-fluorescent supernanoparticles can also serve as an in vivo multi-photon and magnetic resonance dual-modal imaging probe.