Deep tissue imaging in the second near-infrared (NIR-II) window holds great promise for physiological studies and biomedical applications. However, inhomogeneous signal attenuation in biological matter hampers the application of multiple-wavelength NIR-II probes to multiplexed imaging. Here, we present lanthanide-doped NIR-II nanoparticles with engineered luminescence lifetimes for in vivo quantitative imaging using time-domain multiplexing. To achieve this, we have devised a systematic approach based on controlled energy relay that creates a tunable lifetime range spanning three orders of magnitude with a single emission band. We consistently resolve selected lifetimes from the NIR-II nanoparticle probes at depths of up to 8 mm in biological tissues, where the signal-to-noise ratio derived from intensity measurements drops below 1.5. We demonstrate that robust lifetime coding is independent of tissue penetration depth, and we apply in vivo multiplexing to identify tumour subtypes in living mice. Our results correlate well with standard ex vivo immunohistochemistry assays, suggesting that luminescence lifetime imaging could be used as a minimally invasive approach for disease diagnosis.

The contrast and sensitivity of in vivo fluorescence imaging has been revolutionized by molecular fluorophores operating in the second near-infrared window (NIR-II; 1000-1700 nm), but an ongoing challenge is the solvatochromism-caused quenching in aqueous solution for the long-wavelength absorbing fluorophores. Herein, we develop a series of anti-quenching pentamethine cyanine fluorophores that significantly overcome the severe solvatochromism, thus affording stable absorption/emission beyond 1000 nm with up to ~ 44-fold enhanced brightness and superior photostability in aqueous solution. These advantages allow for deep optical penetration (8 mm) as well as high-contrast and highly-stable lymphatic imaging superior to clinical-approved indocyanine green. Additionally, these fluorophores exhibit pH-responsive fluorescence, allowing for noninvasive ratiometric fluorescence imaging and quantification of gastric pH in vivo. The results demonstrate reliable accuracy in tissue as deep as 4 mm, comparable to standard pH electrode method. This work unlocks the potential of anti-quenching pentamethine cyanines for NIR-II biological applications.

Multifunctional composite microspheres with spinel Fe(3)O(4) cores and anatase TiO(2) shells (Fe(3)O(4)@TiO(2)) are synthesized by combining a solvothermal reaction and calcination process. The size, morphology, microstructure, phase purity, and magnetic properties are characterized by scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, selected-area electron diffraction, electron energy loss spectroscopy, powder X-ray diffraction, and superconducting quantum interference device magnetometry. The results show that the as-synthesized microspheres have a unique morphology, uniform size, good crystallinity, favorable superparamagnetism, and high magnetization. By varying the experimental conditions such as Fe(3)O(4) size and concentration, microspheres with different core sizes and shell thickneses can be readily synthesized. Furthermore, the microwave absorption properties of these microspheres are investigated in terms of complex permittivity and permeability. By integration of the chemical composition and unique structure, the Fe(3)O(4)@TiO(2) microspheres possess lower reflection loss and a wider absorption frequency range than pure Fe(3)O(4). Moreover, the electromagnetic data demonstrate that Fe(3)O(4@TiO(2) microspheres with thicker TiO(2) shells exhibit significantly enhanced microwave absorption properties compared to those with thinner TiO(2) shells, which may result from effective complementarities between dielectric loss and magnetic loss. All the results indicate that these Fe(3)O(4)@TiO(2) microspheres may be attractive candidate materials for microwave absorption applications.

Over the past decade, high-quality lanthanide doped upconverting nanoparticles (UCNPs) have been successfully synthesized with the rapid development of nanotechnology. Due to the unique electron configuration of lanthanide ions, there are rich energy level structures in the near-infrared, visible and ultraviolet spectral range. However, for UCNPs, only a limited number of efficient upconversion excitation and emission have been generated due to the limited number of sensitizer (Yb(3+)) and activator (Tm(3+), Er(3+), and Ho(3+)) ions, and the application is mainly focused on the bio-imaging by using the upconversion luminescence of UCNPs. Recently, more and more researchers have started to focus on tuning of upconversion optical properties and developing of multi-functional UCNPs by using the combination of sub-lattice mediated energy migration, core@shell structural engineering and UCNPs based nanocomposites which greatly expands the range of applications for lanthanide-doped UCNPs. Therefore, a "nanolab" can be created on UCNPs, where the property modulation can be realized via the designed host-dopants combinations, core@shell nanostructure, energy exchange with "alien species" (organic dyes, quantum dots, etc.), and so on. In this paper, we provide a comprehensive survey of the latest advances made in developing lanthanide-doped UCNPs, which include excitation and emission energy levels guided designing of the UCNP nanostructure, the synthesis techniques to fabricate the nanostructure with optimum energy level structure and optical properties, the fabrication of UCNPs-based nanocomposites to extend the applications by introducing the additional functional components, or integrating the functional moiety into one nanocomposite.

Figure 2. Schematic illustration of structural engineeringfor longer wavelength fluorophores. A) Some NIR-I fluorophores can be used for NIR-II bioimaging by virtue of their tail emissions (in blue). Representative strategies for achieving longer wavelength fluorophores (key modifications are marked in red): B) elongating the conjugated chain, C) donor modificationb yincreasing the electron density,D )acceptor modification by decreasing the electron density,E)exchange of heteroatoms, F) formation of J-aggregates.( F) is reproduced with permission from ref. [29].