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Fluorescence-guided surgery (FGS) is an emerging technique for tissue visualization during surgical procedures. Structures of interest are labeled with exogenous probes whose fluorescent emissions are acquired and viewed in real-time with optical imaging systems. This study investigated rare-earth-doped albumin-encapsulated nanocomposites (REANCs) as short-wave infrared emitting contrast agents for FGS. Experiments were conducted using an animal model of 4T1 breast cancer. The signal-to-background ratio (SBR) obtained with REANCs was compared to values obtained using indocyanine green (ICG), a near-infrared dye used in clinical practice. Prior to resection, the SBR for tumors following intratumoral administration of REANCs was significantly higher than for tumors injected with ICG. Following FGS, evaluation of fluorescence intensity levels in excised tumors and at the surgical bed demonstrated higher contrast between tissues at these sites with REANC contrast than ICG. REANCs also demonstrated excellent photostability over 2 hours of continuous illumination, as well as the ability to perform FGS under ambient lighting, establishing these nanocomposites as a promising contrast agent for FGS applications.

Excellent optically active photonic composites are indispensable for designing polymeric waveguide amplifiers which may spur the development of the next generation of high efficiency communication ...

Rare earth (RE) doped inorganic nanocrystals have been demonstrated as efficient contrast agents for deep tissue shortwave-infrared (SWIR) imaging with high sensitivities leading to potential early detection of tumors. However, a potential concern is the unknown long-term toxicity and incompatibility of inorganic nanocrystals. In this work, biodegradable rare earth nanocrystals of Nd doped SrFCl coated with polydopamine (SrFCl:Nd@PDA) were designed. Instead of traditional fluoride hosts, the chlorinated SrF2 (i.e. SrFCl) with low phonon energy which significantly improved the brightness of SrFCl:Nd in the SWIR region was used as the host. After coating with a NIR-absorptive PDA layer, the SrFCl:Nd nanoparticles serve as not only a contrast agent for photoacoustic imaging, but also a potential photothermal agent for cancer therapy. Moreover, these SrFCl:Nd@PDA nanoparticles can be rapidly and completely degraded in phosphate buffer solution within 1 h, which effectively addresses the concerns of the deleterious effects arising from potential long term accumulation. The increased accumulation and retention at tumor sites, and complete in vivo clearance ∼6 h after injection make these SrFCl:Nd@PDA nanoparticles a promising degradable phototheranostic agent.

To achieve the ambitious targets set out in the Paris Agreement, technological innovations that will advance direct air capture technology are needed. The grand challenge to increase total amount of CO2 capture directly from ambient air may be achieved by a direct air capture platform that can be implemented widely in urban spaces. In this work, we present a pioneering passive and distributed direct air capture (DAC) approach that leverages on the highly adaptable form factor of a carbon capture composite (C3) film. Through a synergy between a highly flexible form factor and surface texture engineering on the C3 film, effective passive CO2 capture has been demonstrated. The carbon capture performance (capacity, kinetics) of micro-textured C3 films were evaluated using an in-house controlled chamber as well as in a field study (e.g., bus-stop). Based on the findings from this study, it was observed that the micro-textured C3 films effectively improve direct air capture at a relatively low CO2 concentration. Additionally, field tests of the C3 films at a bus-stop shows a reduction in the number of CO2 surges associated with the arrival of buses. Together these findings demonstrated for the first time the potential to integrate the versatile and regenerable C3 films with existing infrastructure for distributed direct air capture in urban spaces.

Infrared (IR)-emitting RE doped materials have been extensively used to fabricate active components of integrated optical devices in various fields, such as fiber amplifiers, telecommunications, optoelectronics, and waveguides. Among various RE elements, trivalent erbium ions (Er 3+) are of great interest since their emissive behavior span the low loss telecommunication window of 1300–1650 nm. In this paper, we report two types of polymeric waveguide amplifiers. 8 cm long, lithographically patterned spiral waveguides provide 8 dB of gain using a 980 nm pump power of 95 mW. Gain is observed from 1530 to 1590 nm. We further report the first demonstration of polymeric waveguide amplifiers fabricated using 3D printing methods based on two-photon lithography, paving the way for rapid prototyping of active 3D printed devices and active photonic devices which may transcend planar limitations.

The growing demand of infrared sensors for emerging applications such as autonomous vehicles and remote control and sensing systems has driven the development of flexible, low-power, and sensitive infrared detectors for seamless product integration. Although semiconducting polymer (SCP)-based photodetectors are promising solutions, challenges in synthesis chemistry and high thermal dark currents associated with narrowing of band gaps have limited their progress. To address these challenges, we have designed a new class of composites comprising SCPs with moderate band gap and rare earth doped-nanoparticles (RENPs) that enable photon-to-electron conversion beyond the SCP's response range. Using this RENP-SCP (RE-SCP) composite, we demonstrated detection at multiple wavelengths (808, 975, and 1532 nm) for planar-type photodetectors. Notably, the RE-SCP composite-based device detected an eye-safe, shortwave infrared (SWIR) source at 1532 nm with high SWIR responsivity of 0.02 A/W and an SWIR external quantum efficiency of 2%. The key attribute governing the excellent SWIR responsivity and sensitivity was the distinctive SWIR upconversion characteristic of RENPs that extended and improved the SCP's detection range and performance, respectively. Additionally, the absence of significant performance degradation of the SWIR photodetector for bending curvatures from 0-0.67 cm

The nascent field of theranostics, which couples targeted therapy with diagnostics, has catalyzed efforts toward improved nanoprobe designs that facilitate both localized treatment and diagnostic imaging. Rare-earth-doped nanoparticles (RENPs) have emerged as a leading candidate for theranostics because of their versatile synthesis and modification chemistries, photostability, and relative safety. Furthermore, their bright, tunable fluorescence using near-infrared (NIR) excitation enables multispectral imaging with high signal-to-background ratios. In this work, we have synthesized double-shelled RENPs with tunable properties for optimal fluorescent imaging, photoacoustic imaging, and photothermal therapy. The properties of the double-shelled RENPs were tailored by controlling the density of rare-earth ions (i.e., activator or sensitizer) by using either a functional amorphous organic or a crystalline outermost shell. This study systematically analyzes the effects of the functional organic or inorganic outermost shell on the imaging and photothermal conversion properties of our RENPs. Despite the weaker infrared absorption enhancement, the functional organic outermost shell impregnated with a low density of rare-earth ions led to minimal reduction of fluorescence emissions. In contrast, the higher density of rare-earth ions in the inorganic shell led to higher infrared absorption and consequently significant reduction in emissions arising from the undesired optical attenuation. Inorganic shell thickness was therefore modified to reduce the deleterious attenuation, leading to brighter emissions that also enabled the in vitro SWIR detection of ∼2500 cells/cluster. Using the enhanced infrared properties that arise from this functional inorganic layer, which could be engineered to respond to either NIR or SWIR, we demonstrated that (1) bright SWIR emissions allowed detection of small cell clusters; (2) strong PA signals allowed clear visualization of particle distribution within tumors; and (3) strong photothermal effects resulted in localized elevated temperatures. Collectively, these results highlight the utility of these double-shelled RENPs as theranostic agents that are compatible with both photoacoustic or fluorescent imaging platforms.

Infrared-emitting rare-earth (ytterbium and erbium) doped nanoparticles (REDNPs) have recently emerged as an excellent probe for both deep tissue luminescence and photoacoustic (PA) imaging with high resolutions and contrast. Here we report on the first study of the size and surface effects of the infrared PA imaging of dual modal REDNPs. We show that the PA signal amplitude generated by REDNPs is increased by increasing the size and coating the inorganic shell (undoped NaYF4 or silica). We have also discovered that the choice of the coating material is critical as undoped NaYF4 shell was able to enhance PA signal amplitude (by up to ∼30%) and infrared emission (19 times) simultaneously. The simultaneous enhancement of PA signal amplitude and infrared emission was due to increased phonon modes and reduced surface effects. The in vivo PA images obtained demonstrated that in addition to being excellent luminescent probes, the REDNPs also performed as successful PA contrast agents to visualize rodent cortica...

Background The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900–1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers. Methods SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes. Results Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging. Conclusions The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.

Recent advancements in the infrared (IR) imaging system design as well as the co-development of compatible contrast agents have facilitated the potential application of fluorescence imaging systems for deep tissue diagnostics and real-time vasculature visualization for intraoperative surgical guidance. Compared to conventional imaging techniques that achieve superior tissue penetration depth through the use of high energy or ionizing radiation sources, complementary chemical compounds, also known as imaging probes or contrast agents, are required to enable enhancement of the imaging sensitivity required for improved image quality in the IR fluorescence imaging technique. Therefore, using a systems-level approach to plan research efforts where the requirements of the imaging setup are considered at the start of the contrast agent design to effectively improve detection sensitivity would reduce the technical entry barrier for the adoption of new technologies. In this paper, we highlight (1) the recent advancements and key operating differences in the reported IR imaging systems, and (2) the recent progress in creating biocompatible IR-emitting contrast agents as well as improving detection sensitivity using targeting agents. The ability to maximize the full benefits and performance of any IR imaging platform is highly reliant on the thorough understanding of the requirements of each imaging platform and the physical characteristics of the complementary contrast agents.

The widespread implementation and rapid development of autonomous systems pose stringent performance requirements on emerging sensory systems. In addition to the basic sensing requirements, leading sensory systems are required to process data and extract featured information from highly redundant data in real time. With the added edge‐computational capabilities, data shuttling is avoided, leading to significant reduction of computational burden and bandwidth pressure in the cloud. Among the different computing architectures, the neuromorphic sensory system stands out due to its high power efficiency, low latency, and excellent processing capability. Mimicking the biological neural network, the colocation of sensory, processor, and memory components of neuromorphic sensory systems enables the requirements for frequent data shuttles to be circumvented. In particular, artificial intelligent perceptions built on memristive neuromorphic systems exhibit outstanding characteristics of small footprint, low power consumption, 3D stacking ability, and high density. Herein, the two essential parts of the memristive artificial perceptron system are presented: 1) memristive systems for neuromorphic computing and 2) high‐performance sensors. Next, the current state of the art established on artificial perceptron systems covering visual, auditory, and tactile sensations is highlighted. To conclude, the current challenges and future direction in the area of advanced intelligent perceptions are presented.

The global growth of consumption and disposal of information and communication technology (ICT) appears to be one of the main factors that fuels the increased level of ICT-waste. With ICT-waste causing environmental degradation, there is urgency in the public interest to achieve more sustainable development. This study develops a conceptual framework for reduce behavior at workplace premised on the classic theory of planned behavior (TPB). The theoretical contribution of this study is primarily upon expanding existing knowledge on factors influencing pro-environmental behaviors, by firstly conceptualizing reduce behavior and secondly emphasizing the mediating effect of corporate environmental responsibility (CER) on the relationships between attitude, subjective norms and perceived benefits, and reduce behavior. In short, a well-communicated environmental policy within organizations is urgently required, being a strong signal that encourages employees to engage in pro-environmental actions.Keywords: reduce, corporate environmental responsibility, ICT-waste, theory of planned behaviorJEL Classification: P28

In this work, we reported NaLuF4:Yb3+/Er3+ optical-magnetic bifunctional material by a facile hydrothermal method. The modulation of luminescent and magnetic properties by introducing the secondary phase NaMnF3 was investigated in detail. It was found that the multi-color emissions of the proposed material can be easily controlled due to the energy level match between the Mn and the lanthanide ions. In addition, these microcrystals presented paramagnetic and ferromagnetic property, and the relative intensity showed an opposite variation to the content of NaMnF3 phase. Finally, we briefly discussed the dye detection based on this bifunctional material as fluorescent probe, and the integral intensity ratio of red to green emission was found being sensitive to the concentration of the basic fuchsin (BF), and a detection limit of 0.0015 μg/ml was achieved. These findings can be helpful to understand NaMnF3 induced optical-magnetic property modulation and provide some applications in the biosensing and bioimaging area.

Gene therapy is emerging as the next generation of therapeutic modality with United States Food and Drug Administration approved gene-engineered therapy for cancer and a rare eye-related disorder, but the challenge of real-time monitoring of on-target therapy response remains. In this study, we have designed a theranostic nanoparticle composed of shortwave-infrared-emitting rare-earth-doped nanoparticles (RENPs) capable of delivering genetic cargo and of real-time response monitoring. We showed that the cationic coating of RENPs with branched polyethylenimine (PEI) does not have a significant impact on cellular toxicity, which can be further reduced by selectively modifying the surface characteristics of the PEI coating using counter-ions and expanding their potential applications in photothermal therapy. We showed the tolerability and clearance of a bolus dose of RENPs@PEI in mice up to 7 days after particle injection in addition to the RENPs@PEI ability to distinctively discern lung tumor lesions in a breast cancer mouse model with an excellent signal-to-noise ratio. We also showed the availability of amine functional groups in the collapsed PEI chain conformation on RENPs, which facilitates the loading of genetic cargo that hybridizes with target gene in an in vitro cancer model. The real-time monitoring and delivery of gene therapy at on-target sites will enable the success of an increased number of gene- and cell-therapy products in clinical trials.

Direct write (DW) technologies offer a potential avenue towards reducing existing long lead times required for fabrication of prototypes and evaluation of new materials and integrated circuit designs. Nanostructured metallic DW inks are widely utilized due to their excellent electrical conductivity which dictates the performance of printed sensors and circuits. Besides controlling the surface chemistry and rheology of these inks to control the print resolution, the essential joining of these conductive nanomaterials to create functional sensors and devices remains a challenge. Low-temperature interconnecting techniques are required to minimize the deleterious heat effects on the shape of printed conductive networks and electronic components. Therefore, the reduced melting temperatures characteristic of metallic nanomaterials offer opportunities to bridge this technological gap. Amongst the reported low-temperature sintering approaches, the chemically-induced sintering method emerges as a readily scalable approach with relatively low energy input. By uncovering the underlying relationship between particle size effects and the role of the ionic salts used to induce sintering under ambient conditions, we aim to elucidate the compatible chemistries (i.e., size and salt) to achieve optimal chemically-induced sintering. The sintering of polyacrylic acid-modified Ag nanoparticle-based DW inks of different size distributions (bimodal vs. monodispersed distribution) and average sizes (e.g., 5 nm and 17 nm) was systematically investigated to elucidate the role of a commonly used salt, NaCl, in the chemically-induced sintering process. An observed enhancement in our ink conductivities by about 4 orders of magnitude for the monodispersed 17 nm and bimodally distributed 9 and 170 nm particles resulted mainly from the sintering between neighboring Ag nanoparticles. In the case of monodispersed 5 nm nanoparticles, a low electrical resistivity was observed despite an increase in grain size which indicated successful sintering. The low measured electrical resistivity was mainly due to significant AgCl formation that had a lower electrical conductivity. Our results show that the chloride ions played an active role in triggering first the oxidative decomposition of Ag to Ag+ resulting in AgCl formation which subsequently led to the sintering between neighboring Ag nanoparticles. The difference in the results for the 5 nm and 17 nm monodispersed Ag nanoparticles was attributed to the differences in the size-dependent surface reactivities and relative amounts (i.e., packing density, thickness) of the polymeric PAA coating.

The identification and molecular profiling of early metastases remains a major challenge in cancer diagnostics and therapy. Most in vivo imaging methods fail to detect small cancerous lesions, a problem that is compounded by the distinct physical and biological barriers associated with different metastatic niches. Here, we show that intravenously injected rare-earth-doped albumin-encapsulated nanoparticles emitting short-wave infrared light (SWIR) can detect targeted metastatic lesions in vivo, allowing for the longitudinal tracking of multi-organ metastases. In a murine model of basal human breast cancer, the nanoprobes enabled whole-body SWIR detection of adrenal gland microlesions and bone lesions that were undetectable via contrast-enhanced magnetic resonance imaging (CE-MRI) as early as, respectively, three weeks and five weeks post-inoculation. Whole-body SWIR imaging of nanoprobes functionalized to differentially target distinct metastatic sites and administered to a biomimetic murine model of human breast cancer resolved multi-organ metastases that showed varied molecular profiles at the lungs, adrenal glands and bones. Real-time surveillance of lesions in multiple organs should facilitate pre-therapy and post-therapy monitoring in preclinical settings.

Checkpoint immunotherapy, through the reversal of tumor-mediated inactivation of the immune system, has shown promise in the treatment of several types of cancer. This has culminated in the approval of seven immune checkpoint inhibitors (ICIs). However, only a small population of patients respond to these drugs. Because of the physical and economic burden of ICIs on the patient, there is a critical need to identify biomarkers that can inform on the potential response to ICIs. The presence of tumor infiltrating lymphocytes (TILs) has demonstrated good prognostic value in determining if a patient should receive ICIs. Current clinical methods to assess TILs involve invasive biopsies and immunohistochemistry, which suffer from intratumoral heterogeneity, observer variability, and a lack of real-time feedback. Here, we report on near infrared light excitable rare earth metal-based nanoparticles, termed rare earth albumin nanocomposites (ReANCs), that emit shortwave infrared (SWIR) light, allowing for deep tissue imaging and high signal-to-noise ratios compared to visible or near infrared fluorescence probes. Tumor-targeted ReANCs have been previously employed to monitor tumor progression and response to chemotherapy in mouse models of breast cancer metastasis. In this study, to target CD3+ T cells, ReANCs were conjugated using the zero-length cross-linker 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) to a peptide derived from the sequence of the CD3-ϵ receptor sub-unit. Target specific binding was validated by flow cytometry as a measure of increased uptake of peptide-conjugated ReANCs by Jurkat cells. To specifically target cytotoxic T lymphocytes, we employed the fragment antigen binding (Fab) derived from enzymatic digestion of a CD8 antibody (clone 53-6.7) with papain. The Fab fragments were conjugated to ReANCs with sulfo-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC). Conjugation was confirmed by non-reducing gel electrophoresis and high performance liquid chromatography (HPLC). A loading efficiency of approximately 60% was achieved. Target specific binding was validated by flow cytometry as a measure of increased uptake of Fab-conjugated ReANCs by T cells isolated from splenocytes. We generated a metric for measuring immune burden around tumor spheroids by pre-labeling T cells with ReANCs and co-culturing them with tumor cell spheroids in vitro. Imaging of T cells with CD3 and CD8-targeted ReANCs provides a basis for future in vivo small animal imaging studies where we will investigate the potential of this technology to track immune cells in relation to a tumor in real time. Metrics of immune cell imaging will then inform on the potential of immunotherapy and monitor response to treatment in a longitudinal study. Citation Format: Jay V. Shah, Jake N. Siebert, Amber Gonda, Rahul Pemmaraju, Shashank Kosuri, Carolina Bobadilla Mendez, Xinyu Zhao, Shuqing He, Richard E. Riman, Mei Chee Tan, Mark C. Pierce, Edmund C. Lattime, Prabhas V. Moghe, Vidya Ganapathy. Rare earth albumin nanoparticles engineered to target cytotoxic T cells to evaluate response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2802.

Silver nanostructures have expansive applications in catalysis, photonic and electronic devices. In this work, nanostructured silver micro-colloids (MCs) with uniform in size and shape (size distribution

In this work, we report a detailed study of the synthesis of sub-micron sized Gd2O2S spheres using a two-step process: (1) amorphous precursor synthesis using the solvothermal method where a surfactant was used to control particle morphology, followed by (2) crystallization to form Gd2O2S polycrystalline spheres in a sulfur-rich environment. The crystallization and sulfurization processes are investigated by monitoring the crystal growth at different temperatures and under different environments using mainly X-ray diffraction and analysis of the precursor's thermal decomposition profile. The optical emissions of the Er and Yb-Er doped Gd2O2S upon excitation at 975 nm were investigated to identify the optimal dopant concentrations, optimal heat treatment temperature as well as to further elucidate any fine structure changes. Our results also show that the maximum emission intensities were obtained for a heat treatment temperature of 800 °C, where increased dopant diffusion coupled with non-uniform surface segregation at much higher temperatures led to non-uniform dopant distribution and reduced emission intensities. Our findings from these studies would be useful towards the synthesis of brightly-emitting Gd2O2S based luminescent materials as well as for the controlled gas-aided sulfurization of other metal oxysulfides.

The recent emergence of wearable electronics has driven the advancements of flexible and elastic conductive metal–polymer composites as electrodes and sensors. Surface modification of the conductive metal fillers are required to achieve a good dispersion within the matrix to obtain suitable conductivity and sensing properties. Additionally, it would be critical to ensure that the inclusion of these fillers does not affect the curing of the pre-polymers so as to ensure sufficient filler loading to form functional composites. In this work, a one-step approach is used to modify Ag–PAA nanoparticles via hydrogen bonds to form PAA–PVP complex modified Ag nanoparticles. The interfacial characteristics and thermal stability of these surface-modified Ag nanoparticles were studied to elucidate the underlying chemistries that governed the surface modification process. After surface modification, we successfully improved the dispersion of Ag nanoparticles and enabled curing of PDMS to higher Ag loadings of ∼25 vol%, leading to much lower electrical resistivity of ∼6 Ω cm. Our studies also showed that Ag nanoparticles modified at a PAA/PVP molar ratio of 1 : 10 resulted in a minimal particle aggregation. In a preliminary testing of our conductive composites as electrodes, clear electrocardiography signals were obtained. The facile surface modification method introduced here can be adapted for other systems to modify the particle interfacial behavior and improve the filler dispersion and loading without adversely affecting the polymer curing chemistry.

Near-infrared photoacoustic (PA) imaging is an emerging diagnostic technology that utilizes the tissue transparent window to achieve improved contrast and spatial resolution for deep tissue imaging. In this study, we investigated the enhancement effect of the SiO2 shell on the PA property of our core/shell rare-earth nanoparticles (REs) consisting of an active rare-earth doped core of NaYF4:Yb,Er (REDNPs) and an undoped NaYF4 shell. We observed that the PA signal amplitude increased with SiO2 shell thickness. Although the SiO2 shell caused an observed decrease in the integrated fluorescence intensity due to the dilution effect, fluorescence quenching of the rare earth emitting ions within the REDNPs cores was successfully prevented by the undoped NaYF4 shell. Therefore, our multilayer structure consisting of an active core with successive functional layers was demonstrated to be an effective design for dual-modal fluorescence and PA imaging probes with improved PA property. The result from this work addresses a critical need for the development of dual-modal contrast agent that advances deep tissue imaging with high resolution and signal-to-noise ratio.

CuInSe2 quantum dots (QDs) are one of the most important Cd-free fluorescent probes; they usually exhibited low fluorescence intensity, suggesting that a considerable amount of absorbed photon energy was lost as heat. In this study we aimed to improve the fluorescence intensity of CuInSe2 QDs and investigate their photoacoustic (PA) signal resulting from the heat dissipation, which was previously rarely reported. Cu–In–Zn–Se/ZnSe QDs were synthesized by adopting two strategies of Zn doping and ZnSe shell growth. It was found that there was an upper limit for Zn concentration beyond which the fluorescence intensity began to decrease. In addition, a blue shift of the emission peak of Cu–In–Zn–Se/ZnSe QDs was observed at high concentrations of ZnSe precursor due to the diffusion of excessive Zn. To prepare the dual-modal fluorescence and PA imaging probe, poly(maleic anhydride-alt-1-octadecene) (PMAO) modified with polyethylene glycol (PEG) was coated on the QDs, which led to a slight reduction in fluorescence. Cellular labeling on HeLa cells was performed to demonstrate the utility of these probes for fluorescence imaging. We further studied the in vitro PA imaging capabilities of the Cu–In–Zn–Se/ZnSe/PMAO-g-PEG nanoparticles, which showed a distinct PA signal beyond 1.0 mg ml−1. The current work demonstrated that a moderate amount of Zn doping is necessary for enhancing fluorescence and there is a limit beyond which the fluorescence will be diminished. We also demonstrated the proof of concept that Cu–In–Zn–Se/ZnSe QDs are able to serve as a potential PA imaging contrast agent.

The unique atomic-like absorption and emission spectra of rare earth (RE) doped materials have shaped a unique niche of applications, especially those that benefit from a better utilization of the infrared (IR) electromagnetic range. These materials in the bulk form have mostly been utilized in their earliest development for illuminators, lasers and displays. In the past decade, new frontiers, especially in the field of biomedical imaging and theranostics, have emerged as a result of the advancements in chemical methods to synthesize nano-sized RE doped materials. The distinctive characteristics of RE doped nanoparticles (RENPs) to absorb IR photons and emit at any specific desired wavelength spanning from the ultraviolet (UV) to the IR region have unlocked an avenue to a myriad of applications. This review article covers briefly some aspects on the fundamental principles that govern the luminescence characteristics of these RE doped materials, such as the mechanisms for electronic transitions, dopants and host chemistries. Next, we will present an overview on the state-of-the-art methods to synthesize RENPs with controlled size, morphology, core–shell heterostructure and surface chemistry. The underlying relationships of the physical characteristics of RENPs, such as particle size and structure, with the optical emission properties will also be discussed so as to offer some material guidelines for designing brightly IR-emitting RENPs. The applications of RENPs are next broadly grouped according to the material form where they are required for some applications: (1) single particle systems, and (2) monolithic nanostructured optically active polymeric composites. This review will provide some guidelines for the engineering design of RENPs and their composites to meet the optical material performance requirements of various selected applications.

Erbium (Er) doped CaF2 nanophosphors with enhanced short-wavelength infrared light (SWIR) emission synthesized in this work have promising potential for biomedical applications in diagnostics and deep tissue imaging due to their low vibrational energy, large optical transparency and superior biocompatibility. For deep tissue imaging application, it is critical to achieve highly emissive SWIR emitting CaF2 nanophosphors to enhance detection resolution and depth using the “tissue-transparent window”. In this work, we demonstrate substantial enhancement in the IR emission of CaF2 nanocrystals using a tri-doping scheme of ytterbium (Yb), erbium (Er) and cerium (Ce). The effects of Er, Ce and Yb dopant concentration on the IR emission intensity was systematically studied and the optimum Er, Ce and Yb dopant concentration was estimated to be ∼2, ∼10 and ∼20 mol%, respectively. At Yb 20 mol%, the IR emission intensity was increased ∼12 fold by optimizing the Ce dopant concentration.

We demonstrate the ability of multi-spectral confocal microscopy to distinguish the visible upconversion emissions from erbium- and thulium-doped nanoparticles under 980 nm illumination in breast cancer cell lines.

In this work, we report a detailed study of the synthesis of sub-micron sized Gd2O2S spheres using a two-step process: (1) amorphous precursor synthesis using the solvothermal method where a surfactant was used to control particle morphology, followed by (2) crystallization to form Gd2O2S polycrystalline spheres in a sulfur-rich environment. The crystallization and sulfurization processes are investigated by monitoring the crystal growth at different temperatures and under different environments using mainly x-ray diffraction and analysis of the precursor’s thermal decomposition profile. The optical emissions of the Er and Yb-Er doped Gd2O2S upon excitation at 975 nm were investigated to identify the optimal dopant concentrations, optimal heat treatment temperature as well as to further elucidate any fine structure changes. Our results also show that the maximum emission intensities were obtained for a heat treatment temperature of 800 °C, where increased dopant diffusion coupled with non-uniform surface segregation at much higher temperatures led to non-uniform dopant distribution and reduced emission intensities. Our findings from these studies would be useful towards the synthesis of brightly-emitting Gd2O2S based luminescent materials as well as for the controlled gas-aided sulfurization of other metal oxysulfides.

Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking of cancerous growths in order to maximize treatment options and improve patient outcomes. However, this goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect diseased lesions, due to their small size and sub-organ localization. With proper probes, optical imaging techniques can overcome this limitation by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, we propose the first use of nanophotonic short wave infrared technology to molecularly phenotype small sub-surface lesions for more sensitive detection and improved patient outcomes. To this end, we designed human serum albumin encapsulated rare-earth (RE) nanoparticles (ReANCs)[1, 2] with ligands for targeted lesion imaging. AMD3100, an antagonist to CXCR4 (a chemokine receptor involved in cell motility and a classic marker of cancer metastasis) was adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). Functionalized nanoparticles were able to discriminate and preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. Additionally, fReANCs, administered intravenously, were able to target sub-tissue tumor micro-lesions, at a maximum depth of 10.5 mm, in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs were 2.25 times smaller than those detected with unfunctionalized ReANCs (p < .01) with the smallest tumor being 18.9 mm3. Thus, we present an integrated nanoprobe detection platform that allows target-specific identification of sub-tissue cancerous lesions.

Seasonal and spatial variations of the light absorption coefficient, a(λ), were investigated in the New York/New Jersey Harbor Estuary (i.e., Jamaica Bay, Hudson/Raritan Bay, and Inner Harbor) from August 2008 through June 2009 to characterize the bio-optical characteristics of the estuary. The nonalgal particles (NAP) made a constant light absorption contribution of 18 ± 6% (mean ± standard deviation) (440 nm) over the entire estuary. Covariation among chlorophyll a, total suspended solid, and colored dissolved organic matter (CDOM) was not observed, indicating optical complexity of the estuary. Two optical domains were observed: a phytoplankton-dominated regime (Jamaica Bay) and a CDOM dominated regime (Inner Harbor and Hudson/Raritan Bay). Specific absorption coefficient a ph * (λ) decreased with increasing chlorophyll a; this was due to the large cell sizes of diatoms based on package effect analysis. The sources of CDOM and NAP were terrestrial and of in situ origins, respectively. The slopes of CDOM (S CDOM) and NAP (S NAP) of the estuary were reported for the first time. Overall, this study provided the most complete characterization of light absorption for the New York/New Jersey Harbor Estuary, which will provide critical parameters and insights to build/refine remote sensing models for monitoring water quality in the estuary.

Infrared (IR)-emitting rare-earth (RE) doped materials have been extensively studied for many years due to their diverse application in various fields. It is critically important to demonstrate that the significant enhancement of IR emission in nanophosphors can be achieved, not only for better understanding of the physical mechanism but also for expanding the IR-related applications of these nanophosphors, which include optical amplifiers, waveguides, laser materials and infrared imaging probes. In this work, we report the control of particle morphology and IR emission enhancement of hexagonal-phase NaYF4 particles using a tri-dopant scheme of ytterbium (Yb), erbium (Er) and cerium (Ce). By optimizing the Ce dopant concentrations, IR emission was enhanced by 73.1% and 109.6% for NaYF4 microparticles (N-MPs) and nanoparticles (N-NPs), respectively. The effects of Ce dopant concentrations on the nucleation and growth mechanism as well as the optical behavior of N-MPs and N-NPs were studied systematically.

Rare-earth-doped nanocomposites have appealing optical properties for use as biomedical contrast agents, but few systems exist for imaging these materials. We describe the design and characterization of (i) a preclinical system for whole animal in vivo imaging and (ii) an integrated optical coherence tomography/confocal microscopy system for high-resolution imaging of ex vivo tissues. We demonstrate these systems by administering erbium-doped nanocomposites to a murine model of metastatic breast cancer. Short-wave infrared emissions were detected in vivo and in whole organ imaging ex vivo. Visible upconversion emissions and tissue autofluorescence were imaged in biopsy specimens, alongside optical coherence tomography imaging of tissue microstructure. We anticipate that this work will provide guidance for researchers seeking to image these nanomaterials across a wide range of biological models.

Ring resonators on silicon rich nitride for potential use as rare-earth doped amplifiers pumped at 1310 nm with amplification at telecommunications-band are designed and characterized. The ring resonators are fabricated on 300 nm and 400 nm silicon rich nitride films and characterized at both 1310 nm and 1550 nm. We demonstrate ring resonators exhibiting similar quality factors exceeding 10,000 simultaneously at 1310 nm and 1550 nm. A Dysprosium-Erbium material system exhibiting photoluminescence at 1510 nm when pumped at 1310 nm is experimentally demonstrated. When used together with Dy-Er co-doped particles, these resonators with similar quality factors at 1310 nm and 1550 nm may be used for O-band pumped amplifiers for the telecommunications-band.

Imaging techniques have been instrumental in the visualization of fundamental biological processes, identification and diagnosis of diseased states and the development of structure-function relationships at the cellular, tissue and anatomical levels. Together with the advancements made in imaging techniques, complementary chemical compounds, also known as imaging probes or contrast agents, are developed to improve the visibility of the image by enhancing sensitivity, and for the identification and quantitation of specific molecular species or structures. Extensive studies have been conducted to explore the use of inorganic nanoparticles which exhibit magnetic and optical properties unique to the nano regime so as to enhance the signals sensitivity for magnetic resonance and fluorescent imaging. These physical properties are tailored by controlling the size, shape and surface properties of nanoparticles. In addition, surface modification of nanoparticles is often required to improve its stability, compatibility and functionality. Surfactants, surface-active agents, have been used to engineer the surface characteristics of nanoparticles to improved particle stability and functionality. Surfactants enhance nanoparticle stability through the reduction of surface energy, and by acting as a barrier to agglomeration through either steric hindrance or repulsive electrostatic forces. Coupling of nanoparticles with biomolecules such as antibodies or tumor targeting peptides are enabled by the presence of functional groups (e.g., carboxyl or amine groups) on surfactants. This paper provides an overview of the chemistry underlying the synthesis and surface modification of nanomaterials together with a discussion on how the physical properties (e.g., magnetic, absorption and luminescent) can be controlled. The applications of these nanoparticles for magnetic resonance, fluorescent and photoacoustic imaging techniques that do not rely on ionizing radiation are also covered in this review.

Contrast agents designed to visualize the molecular mechanisms underlying cancer pathogenesis and progression have deepened our understanding of disease complexity and accelerated the development of enhanced drug strategies targeted to specific biochemical pathways. For the next generation probes and imaging systems to be viable, they must exhibit enhanced sensitivity and robust quantitation of morphologic and contrast features, while offering the ability to resolve the disease-specific molecular signatures that may be critical to reconstitute a more comprehensive portrait of pathobiology. This feature article provides an overview on the design and advancements of emerging biomedical optical probes in general and evaluates the promise of rare earth nanoprobes, in particular, for molecular imaging and theranostics. Combined with new breakthroughs in nanoscale probe configurations, and improved dopant compositions, and multimodal infrared optical imaging, rare-earth nanoprobes can be used to address a wide variety of biomedical challenges, including deep tissue imaging, real-time drug delivery tracking and multispectral molecular profiling.

Monodisperse β-NaYF4:Yb,Er nanocrystals with mean sizes of 11, 40, and 110 nm were synthesized by a thermal decomposition solvothermal process to better understand the relationship between particle size and optical properties. A systematic study of luminescence intensity versus size revealed that both visible upconversion and infrared downconversion emission intensities decrease with decreasing nanocrystal size. The intrinsic quantum efficiency of the infrared 4I13/2 → 4I15/2 downconversion transition was studied in great detail since this specific transition allows us to quantify the contribution of nonradiative losses more easily than the observed upconversion transitions. The intrinsic quantum efficiency of the 4I13/2→4I15/2 transition decreased from 50% (110 nm) to 15% (11 nm). Multiphonon relaxation and −OH quenching was studied in these materials by measuring the vibrational characteristics of β-NaYF4:Yb,Er nanospheres. While multiphonon relaxation exhibited increased contribution to nonradiative de...

We describe the development and testing of a line-scanning confocal microscope and integrated confocal / optical coherence tomography system for imaging biological cells and tissues labeled with molecularly-targeted rare-earth-doped nanocomposites.

Infrared-to-visible rare earth doped upconversion phosphors that convert multiple photons of lower energy to higher energy photons offer a wide range of technological applications. The brightness (i.e., emission intensities) and energy efficiency of phosphors are important performance characteristics that determine which applications are appropriate. Optical efficiency can be used as a measure of the upconversion emission performance of these rare earth doped phosphors. In this work, hexagonal-phase NaYF(4):Yb-Er was synthesized using the hydrothermal method in the presence of surfactants like trioctylphosphine, polyethylene glycol monooleate, and polyvinylpyrrolidone. The upconversion emission optical efficiencies of NaYF(4):Yb-Er were measured to quantify and evaluate the effects of surface coatings and accurately reflect the brightness and energy efficiency of these phosphors. Polyvinylpyrrolidone-modified NaYF(4):Yb-Er particles were found to be ~5 times more efficient and brighter than the unmodified particles. The difference in efficiency was attributed to reduced reflectance losses at the particle-air interface via refractive index mismatch reduction between the core NaYF(4):Yb-Er particles and air using polyvinylpyrrolidone as a surfactant.

Several methods and corresponding parameters have been used to measure the emission intensities and efficiencies of luminescent materials (e.g., organic dyes, quantum dots, rare-earth-doped materials). The important performance parameters characterizing the emission intensities or brightness are overall quantum yield, intrinsic quantum efficiency, and radiant efficiency. Currently, the measurement parameter used to evaluate the brightness varies with the type of material (e.g., organic dyes vs rare-earth-doped phosphors) that is studied. Since different performance parameters are used, the relative performance among the different material classes cannot be compared easily. This work demonstrates that optical efficiency can be use as a single performance parameter to measure the short wave infrared (SWIR) emission performance of rare-earth-doped materials with different emission mechanisms and branching. NaYF4:Yb–Er (with visible upconversion emissions), CeF3:Yb–Er (no upconversion), ErGdVO4 (quantum cutti...

Ln(SePh)(3) (Ln = Ce, Pr, Nd) reacts with elemental Se in the presence of Na ions to give (py)(16)Ln(17)NaSe(18)(SePh)(16), a spherical cluster with a 1 nm diameter. All three rare-earth metals form isostructural products. The molecular structure contains a central Ln ion surrounded by eight five-coordinate Se(2-) that are then surrounded by a group of 16 Ln that define the cluster surface, with additional μ(3) and μ(5) Se(2-), μ(3) and μ(4) SePh(-), and pyridine donors saturating the vacant coordination sites of the surface Ln, and a Na ion coordinating to selenolates, a selenido, and pyridine ligands. NIR emission studies of the Nd compound reveal that this material has a 35% quantum efficiency, with four transitions from the excited state (4)F(3/2) ion to (4)I(9/2), (4)I(11/2), (4)I(13/2), and (4)I(15/2) states clearly evident. The presence of Na(+) is key to the formation of these larger clusters, where reactions using identical concentrations of Nd(SePh)(3) and Se with either Li or K led only to the isolation of (py)(8)Nd(8)Se(6)(SePh)(12).

The room temperature Ca(C2H3O2)2−K3PO4−H2O equilibrium system was examined for the preparation of hydroxyapatite nanopowder with sizes less than 10 nm. The reaction products were characterized with X-ray diffraction, transmission electron microscopy (TEM), nitrogen-adsorption surface area, helium pycnometry, thermogravimetric analysis, and Karl Fisher titration methods. TEM revealed that ∼5 nm nanopowders could be successfully prepared with this synthesis approach. However, the vast instability of these powders brought upon by the method of sample separation or the characterization method itself made it impossible to use other conventional methods of characterization to validate TEM data. This study has identified key processing steps that control the order and disorder of these nanomaterials, as well as the conditions that lead to surface area reduction. The most unique phenomenon from this work is the observed crystalline to amorphous phase transformation when washed or unwashed nanopowders are aged for...