Dirk H. Ortgies

1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window

Novel approaches for high contrast, deep tissue, in vivo fluorescence biomedical imaging are based on infrared-emitting nanoparticles working in the so-called second biological window (1,000–1,400 nm). This allows for the acquisition of high resolution, deep tissue images due to the partial transparency of tissues in this particular spectral range. In addition, the optical excitation with low energy (infrared) photons also leads to a drastic reduction in the contribution of autofluorescence to the in vivo image. Nevertheless, as is demonstrated here, working solely in this biological window does not ensure a complete removal of autofluorescence as the specimen’s diet shows a remarkable infrared fluorescence that extends up to 1,100 nm. In this work, we show how the 1,340 nm emission band of Nd3+ ions embedded in SrF2 nanoparticles can be used to produce autofluorescence free, high contrast in vivo fluorescence images. It is also demonstrated that the complete removal of the food-related infrared autofluorescence is imperative for the development of reliable biodistribution studies.

Hybrid Nanostructures for High‐Sensitivity Luminescence Nanothermometry in the Second Biological Window

Hybrid nanostructures containing neodymium-doped nanoparticles and infrared-emitting quantum dots constitute highly sensitive luminescent thermometers operating in the second biological window. They demonstrate that accurate subtissue fluorescence thermal sensing is possible.

Overcoming Autofluorescence: Long-Lifetime Infrared Nanoparticles for Time-Gated In Vivo Imaging.

The always present and undesired contribution of autofluorescence is here completely avoided by combining a simple time gating technology with long lifetime neodymium doped infrared-emitting nanoparticles.

In Vivo Deep Tissue Fluorescence and Magnetic Imaging Employing Hybrid Nanostructures

Breakthroughs in nanotechnology have made it possible to integrate different nanoparticles in one single hybrid nanostructure (HNS), constituting multifunctional nanosized sensors, carriers, and probes with great potential in the life sciences. In addition, such nanostructures could also offer therapeutic capabilities to achieve a wider variety of multifunctionalities. In this work, the encapsulation of both magnetic and infrared emitting nanoparticles into a polymeric matrix leads to a magnetic-fluorescent HNS with multimodal magnetic-fluorescent imaging abilities. The magnetic-fluorescent HNS are capable of simultaneous magnetic resonance imaging and deep tissue infrared fluorescence imaging, overcoming the tissue penetration limits of classical visible-light based optical imaging as reported here in living mice. Additionally, their applicability for magnetic heating in potential hyperthermia treatments is assessed.

Subtissue Imaging and Thermal Monitoring of Gold Nanorods through Joined Encapsulation with Nd-Doped Infrared-Emitting Nanoparticles.

Encapsulation of gold nanorods together with Nd-doped fluorescent nanoparticles in a biocompatible polymer creates multifunctional nanostructures, whose infrared fluorescence allows their subcutaneous localization in biological tissues while also adding the ability to measure the temperature from the emitted light in order to better monitor the light-to-heat conversion of the gold nanorods during photothermal therapy.

Enhancing Optical Forces on Fluorescent Up-Converting Nanoparticles by Surface Charge Tailoring

3D remote control of multifunctional fluorescent up-converting nanoparticles (UCNPs) using optical forces is being required for a great variety of applications including single-particle spectroscopy, single-particle intracellular sensing, controlled and selective light-activated drug delivery and light control at the nanoscale. Most of these potential applications find a serious limitation in the reduced value of optical forces (tens of fN) acting on these nanoparticles, due to their reduced dimensions (typically around 10 nm). In this work, this limitation is faced and it is demonstrated that the magnitude of optical forces acting on UCNPs can be enhanced by more than one order of magnitude by a controlled modification of the particle/medium interface. In particular, substitution of cationic species at the surface by other species with higher mobility could lead to UCNPs trapping with constants comparable to those of spherical metallic nanoparticles.

Gold nanoshells: Contrast agents for cell imaging by cardiovascular optical coherence tomography

Optical coherence tomography (OCT) has gained considerable attention in interventional cardiovascular medicine and is currently used in clinical settings to assess atherosclerotic lesions and to optimize stent placement. Artery imaging at the cellular level constitutes the first step towards cardiovascular molecular imaging, which represents a major advance in the development of personalized noninvasive therapies. In this work, we demonstrate that cardiovascular OCT can be used to detect individual cells suspended in biocompatible fluids. Importantly, the combination of this catheter-based clinical technique with gold nanoshells (GNSs) as intracellular contrast agents led to a substantial enhancement in the backscattered signal produced by individual cells. This cellular contrast enhancement was attributed to the large backscattering cross-section of GNSs at the OCT laser wavelength (1,300 nm). A simple intensity analysis of OCT cross-sectional images of suspended cells makes it possible to identify the sub-population of living cells that successfully incorporated GNSs. The generalizability of this method was demonstrated using two different cell lines (HeLa and Jurkat cells). This work provides novel insights into cardiovascular molecular imaging using specifically modified GNSs.

Lifetime-Encoded Infrared-Emitting Nanoparticles for in Vivo Multiplexed Imaging

Advanced diagnostic procedures are required to satisfy the continuously increasing demands of modern biomedicine while also addressing the need for cost reduction in public health systems. The development of infrared luminescence-based techniques for in vivo imaging as reliable alternatives to traditional imaging enables applications with simpler and more cost-effective apparatus. To further improve the information provided by in vivo luminescence images, the design and fabrication of enhanced infrared-luminescent contrast agents is required. In this work, we demonstrate how simple dopant engineering can lead to infrared-emitting rare-earth-doped nanoparticles with tunable (0.1-1.5 ms) and medium-independent luminescence lifetimes. The combination of these tunable nanostructures with time-gated infrared imaging and time domain analysis is employed to obtain multiplexed in vivo images that are used for complex biodistribution studies.

Rare-earth-doped fluoride nanoparticles with engineered long luminescence lifetime for time-gated in vivo optical imaging in the second biological window

Biomedicine is continuously demanding new luminescent materials to be used as optical probes for the acquisition of high resolution, high contrast and high penetration in vivo images. These materials, in combination with advanced techniques, could constitute the first step towards new diagnosis and therapy tools. In this work, we report on the synthesis of long lifetime rare-earth-doped fluoride nanoparticles by adopting different strategies: core/shell and dopant engineering. The here developed nanoparticles show intense infrared emission in the second biological window with a long luminescence lifetime close to 1 millisecond. These two properties make the here presented nanoparticles excellent candidates for time-gated infrared optical bioimaging. Indeed, their potential application as optical imaging contrast agents for autofluorescence-free in vivo small animal imaging has been demonstrated, allowing high contrast real-time tracking of gastrointestinal absorption of nanoparticles and transcranial imaging of intracerebrally injected nanoparticles in the murine brain.