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Anna Hedlund1,2, Maria Ahrén3, Håkan Gustafsson1,2, Natalia Abrikossova3, Marcel Warntjes2,4, Jan-Ingvar Jönsson5, Kajsa Uvdal3, Maria Engström1,21Division of Radiology, Department of Medical and Health Sciences, 2Center for Medical Image Science and Visualization, 3Division of Molecular Surface Physics and Nanoscience, Department of Physics, Chemistry, and Biology, 4Division of Clinical Physiology, Department of Medicine and Health Sciences, 5Department of Clinical and Experimental Medicine, Experimental Hematology Unit, Linköping University, Linköping, SwedenAbstract: As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s-1 mM-1 and 9.6–17.2 s-1 mM-1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.Keywords: gadolinium oxide, magnetic resonance imaging, contrast agent, cell labeling, Ba/F3 cells, THP-1 cells

Wide band gap materials such as SiC, AlN, GaN, ZnO, and diamond have excellent properties such as high operation temperature when used as field effect devices and a high resonating frequency of the substrate materials used in piezoelectric resonator devices. Integration of FET and resonating sensors on the same chip enables powerful miniaturized devices, which can deliver increased information about a gas mixture or complex liquid. Examples of sensor devices based on different wide band gap materials will be given. [ABSTRACT FROM AUTHOR]

Surface functionalization of wide band gap semiconductors, SiC, ZnO, and GaN, with organosilane is reported. Formation of self-assembled monolayers of mercaptopropyltrimethoxysilane is confirmed by x-ray photoelectron spectroscopy and atomic force microscopy. The molecules are adsorbed on the surfaces through the silane groups with the free thiol groups molecularly oriented away from the surface. Moreover, chemisorption via the thiolate is observed for the ZnO surface. Immobilization of a model biomolecule to the functionalized surface is demonstrated. An amino acid derivative, i.e., phosphotyrosine derived thiol, is linked on the functionalized ZnO and GaN surfaces via formation of disulfide bridges. [ABSTRACT FROM AUTHOR]

The aviation industry relies on lightweight carbon fiber-reinforced polymers (CFRP) for fuel efficiency, which necessitates lightning strike protection (LSP) and electromagnetic shielding due to their electrical insulating characteristics. Traditional metallic meshes used for LSP are heavy and corrosion-prone, prompting the exploration of alternatives. This research showcases CFRP nanocomposites with enhanced LSP properties through the incorporation of graphene nanoplatelets (GNPs) and carbon nanotubes (CNTs). While the enhanced conductivity in the nanofilled epoxy matrix did not impact the overall conductivity of CFRP panels, a significant damage reduction was observed after simulated lightning strike tests. Similar approaches in the literature have also noted this discrepancy, but no attempts to reconcile it have been made. This work provides a framework to explain the damage reduction mechanism while accounting for the modest conductivity improvements in the nanoreinforced CFRPs. Additionally, a simple, nondestructive method to assess surface resin degradation after a lightning strike test is proposed, based on the fluorescence of diphenyl ketones. The discussion is supported by electrical conductivity measurements, damage pattern evaluation using the proposed UV-illumination method, ATR-FTIR, and scanning electron microscopy analysis pre- and postlightning strike simulation., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Temperature homeostasis is critical for cells to perform their physiological functions. Among the diverse methods for temperature detection, fluorescent temperature probes stand out as a proven and effective tool, especially for monitoring temperature in cells and suborganelles, with a specific emphasis on mitochondria. The utilization of these probes provides a new opportunity to enhance our understanding of the mechanisms and interconnections underlying various physiological activities related to temperature homeostasis. However, the complexity and variability of cells and suborganelles necessitate fluorescent temperature probes with high resolution and sensitivity. To meet the demanding requirements for intracellular/subcellular temperature detection, several strategies have been developed, offering a range of options to address this challenge. This review examines four fundamental temperature-response strategies employed by small molecule and polymer probes, including intramolecular rotation, polarity sensitivity, Förster resonance energy transfer, and structural changes. The primary emphasis was placed on elucidating molecular design and biological applications specific to each type of probe. Furthermore, this review provides an insightful discussion on factors that may affect fluorescent thermometry, providing valuable perspectives for future development in the field. Finally, the review concludes by presenting cutting-edge response strategies and research insights for mitigating biases in temperature sensing.

Gadolinium chelates are employed worldwide today as clinical contrast agents for magnetic resonance imaging. Until now, the commonly used linear contrast agents based on the rare-earth element gadolinium have been considered safe and well-tolerated. Recently, concerns regarding this type of contrast agent have been reported, which is why there is an urgent need to develop the next generation of stable contrast agents with enhanced spin-lattice relaxation, as measured by improved T 1 relaxivity at lower doses. Here, we show that by the integration of gadolinium ions in cerium oxide nanoparticles, a stable crystalline 5 nm sized nanoparticulate system with a homogeneous gadolinium ion distribution is obtained. These cerium oxide nanoparticles with entrapped gadolinium deliver strong T 1 relaxivity per gadolinium ion ( T 1 relaxivity, r 1 = 12.0 mM -1 s -1 ) with the potential to act as scavengers of reactive oxygen species (ROS). The presence of Ce 3+ sites and oxygen vacancies at the surface plays a critical role in providing the antioxidant properties. The characterization of radial distribution of Ce 3+ and Ce 4+ oxidation states indicated a higher concentration of Ce 3+ at the nanoparticle surfaces. Additionally, we investigated the ROS-scavenging capabilities of pure gadolinium-containing cerium oxide nanoparticles by bioluminescent imaging in vivo, where inhibitory effects on ROS activity are shown., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Activatable fluorescent probes have been successfully used as molecular tools for biomedical research in the last decades. Fluorescent probes allow the detection of molecular events, providing an extraordinary platform for protein and cellular research. Nevertheless, most of the fluorescent probes reported are susceptible to interferences from endogenous fluorescence (background signal) and limited tissue penetration is expected. These drawbacks prevent the use of fluorescent tracers in the clinical setting. To overcome the limitation of fluorescent probes, we and others have developed activatable magnetic resonance probes. Herein, we report for the first time, an oligonucleotide-based probe with the capability to detect bacteria using magnetic resonance imaging (MRI). The activatable MRI probe consists of a specific oligonucleotide that targets micrococcal nuclease (MN), a nuclease derived from Staphylococcus aureus. The oligonucleotide is flanked by a superparamagnetic iron oxide nanoparticle (SPION) at one end, and by a dendron functionalized with several gadolinium complexes as enhancers, at the other end. Therefore, only upon recognition of the MRI probe by the specific bacteria is the probe activated and the MRI signal can be detected. This approach may be widely applied to detect bacterial infections or other human conditions with the potential to be translated into the clinic as an activatable contrast agent., (© 2021. The Author(s).)

Cerium oxide nanoparticles with integrated gadolinium have been proved to be useful as contrast agents in magnetic resonance imaging. Of question is their performance in dual-energy computed tomography. The aims of this work are to determine (1) the relation between the computed tomography number and the concentration of the I, Gd or Ce contrast agent and (2) under what conditions it is possible to resolve the type of contrast agent. Hounsfield values of iodoacetic acid, gadolinium acetate and cerium acetate dissolved in water at molar concentrations of 10, 50 and 100 mM were measured in a water phantom using the Siemens SOMATOM Definition Force scanner; gadolinium- and cerium acetate were used as substitutes for the gadolinium-integrated cerium oxide nanoparticles. The relation between the molar concentration of the I, Gd or Ce contrast agent and the Hounsfield value was linear. Concentrations had to be sufficiently high to resolve the contrast agents., (© The Author(s) 2021. Published by Oxford University Press.)

Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeO x nanocrystals with 5% or 14% Gd, Co 3 O 4 , and Fe 2 O 3 , were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico . Monocyte interaction with nanoparticle-protein complexes was assessed in vitro . Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co 3 O 4 -protein complexes can induce both 'danger signals', verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations.

Given the breadth of currently arising opportunities and concerns associated with nanoparticles for biomedical imaging, various types of nanoparticles have been widely exploited, especially for cellular/subcellular level probing. However, most currently reported nanoparticles either have inefficient delivery into cells or lack specificity for intracellular destinations. The absence of well-defined nanoplatforms remains a critical challenge hindering practical nano-based bio-imaging. Herein, the authors elaborate on a tailorable membrane-penetrating nanoplatform as a carrier with encapsulated actives and decorated surfaces to tackle the above-mentioned issues. The tunable contents in such a versatile nanoplatform offer huge flexibility to reach the expected properties and functions. Aggregation-induced emission luminogen (AIEgen) is applied to achieve sought-after photophysical properties, specific targeting moieties are installed to give high affinity towards different desired organelles, and critical grafting of cell-penetrating cyclic disulfides (CPCDs) to promote cellular uptake efficiency without sacrificing the specificity. Hereafter, to validate its practicability, the tailored nano products are successfully applied to track the dynamic correlation between mitochondria and lysosomes during autophagy. The authors believe that the strategy and described materials can facilitate the development of functional nanomaterials for various life science applications., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)

Amines are widely employed as additives for improving the performance of metal halide perovskite optoelectronic devices. However, amines are well-known for their high chemical reactivity, the impact of which has yet to receive enough attention from the perovskite light-emitting diode community. Here, by investigating an unusual positive aging effect of CH 3 NH 3 I/CsI/PbI 2 precursor solutions as an example, we reveal that amines gradually undergo N-formylation in perovskite precursors over time. This reaction is initialized by hydrolysis of dimethylformamide in the acidic chemical environment. Further investigations suggest that the reaction products collectively impact perovskite crystallization and eventually lead to significantly enhanced external quantum efficiency values, increasing from ∼2% for fresh solutions to ≳12% for aged ones. While this case study provides a positive aging effect, a negative aging effect is possible in other perovksite systems. Our findings pave the way for more reliable and reproducible device fabrication and call for further attention to underlying chemical reactions within the perovskite inks once amine additives are included.

Competing Interests: Conflict of interest Olle Inganäs has ownership in Epishine AB, developing printed organic photovoltaic devices. The other authors declared that they have no conflict of interest.

In this work, we report a novel protein-based nanoprobe (PNP) that can be employed for quantitative analysis of Cu 2+ in pure water medium and real samples. Structurally, the proposed nanoprobe comprises a biofriendly protein (hen egg-white lysozyme (HEWL)) and a Cu 2+ -specific chromogenic agent, where HEWL acts as a nanocarrier encapsulating a structurally tailored rhodamine B derivate. The resulting PNP exhibits a hydrodynamic diameter of ~ 106 nm and efficiently disperses in water, enabling the detection of Cu 2+ in pure aqueous systems without the aid of any organic co-solvents. The high sensitivity and selectivity of PNP allow the colorimetric detection of Cu 2+ in the presence of other metal interferents with a low detection limit of 160 nM. The satisfying recovery of trace level Cu 2+ in environmental samples demonstrate the great potential of employing PNP for the determination of Cu 2+ in actual applications. Most importantly, the simple co-grinding method employing proteins and chromogenic agents provides a novel strategy to generate sensing systems that are useful detection of pollutants in aqueous samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Photoemission electron microscopy and imaging X-ray photoelectron spectroscopy are today frequently used to obtain chemical and electronic states, chemical shifts, work function profiles within the fields of surface- and material sciences. Lately, because of recent technological advances, these tools have also been valuable within life sciences. In this study, we have investigated the power of photoemission electron microscopy and imaging X-ray photoelectron spectroscopy for visualization of human neutrophil granulocytes. These cells, commonly called neutrophils, are essential for our innate immune system. We hereby investigate the structure and morphology of neutrophils when adhered to gold and silicon surfaces. Energy-filtered imaging of single cells are acquired. The characteristic polymorphonuclear cellular nuclei divided into 2-5 lobes is visualized. Element-specific imaging is achieved based on O 1s, P 2p, C 1s, Si 2p, and N 1s core level spectra, delivering elemental distribution with submicrometer resolution, illustrating the strength of this type of cellular morphological studies.

A rhodamine B-based sensor (RS) was designed and synthesized by a combination of the spirolacton rhodamine B (fluorophore) and multidentate chelates (ionophore) with high affinity towards Hg 2+ . In the presence of Hg 2+ , the resulting red-orange fluorescence (under UV light) and naked eye red color of RS are supposed to be used for quantitative and qualitative measurement of Hg 2+ . Further fluorescent titration and analysis demonstrate that RS can selectively detect Hg 2+ within 1 s with a low limit of detection (LOD) of 16 nM in acetonitrile media, meanwhile, the association constant (K a ) was calculated to be 0.32 × 10 5  M -1 . More importantly, the resultant complex (RSHg) of RS and Hg 2+ has also been successfully applied to detect limited water content in acetonitrile solution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Transition-metal oxides (TMOs) are potential candidates for anode materials of lithium-ion batteries (LIBs) due to their high theoretical capacity (∼1000 mA h/g) and enhanced safety from suppressing the formation of lithium dendrites. However, the poor electron conductivity and the large volume expansion during lithiation/delithiation processes are still the main hurdles for the practical usage of TMOs as anode materials. In this work, the CoSnO 3 @NC@MnO@NC hierarchical nanobox (CNMN) is then proposed and fabricated to solve those issues. The as-prepared nanobox contains hollow cubic CoSnO 3 as a core and dual N-doped carbon-"sandwiched" MnO particles as a shell. As anode materials of LIBs, the hollow and carbon interlayer structures effectively accommodate the volume expansion while dual active TMOs of CoSnO 3 and MnO efficiently increase the specific capacity. Notably, the dual-layer structure of N-doped carbons plays a critical functional role in the incorporated composites, where the inner layer serves as a reaction substrate and a spatial barrier and the outer layer offers electron conductivity, enabling more effective involvement of active anode materials in lithium storage, as well as maintaining their high activity during lithium cycling. Subsequently, the as-prepared CNMN exhibits a high specific capacity of 1195 mA h/g after the 200th cycle at 0.1C and an excellent stable reversible capacity of about 876 mA h/g after the 300th cycle at 0.5C with only 0.07 mA h/g fade per cycle after 300 cycles. Even after a 250 times fast charging/discharging cycle both at 5C, it still retains a reversible capacity of 422.6 mA h/g. We ascribe the enhanced lithium storage performances to the novel hierarchical architectures achieved from the rational design.

Intracellular lipid metabolism occurs in lipid droplets (LDs), which is critical to the survival of cells. Imaging LDs is an intuitive way to understand their physiology in live cells. However, this is limited by the availability of specific probes that can properly visualize LDs in vivo. Here, an LDs-specific red-emitting probe is proposed to address this need, which is not merely with an ultrahigh signal-to-noise (S/N) ratio and a large Stokes shift (up to 214 nm) but also with superior resistance to photobleaching. The probe has been successfully applied to real-time tracking of intracellular LDs behaviors, including fusion, migration, and lipophagy processes. We deem that the proposed probe here offers a new possibility for deeper understanding of LDs-associated behaviors, elucidation of their roles and mechanisms in cellular metabolism, and determination of the transition between adaptive lipid storage and lipotoxicity as well.

Fluorophores and probes are invaluable for the visualization of the location and dynamics of gene expression, protein expression, and molecular interactions in complex living systems. Rhodamine dyes are often used as scaffolds in biological labeling and turn-on fluorescence imaging. To date, their absorption and emission spectra have been expanded to cover the entire near-infrared region (650-950 nm), which provides a more suitable optical window for monitoring biomolecular production, trafficking, and localization in real time. This review summarizes the development of rhodamine fluorophores since their discovery and provides strategies for modulating their absorption and emission spectra to generate specific bathochromic-shifts. We also explain how larger Stokes shifts and dual-emissions can be obtained from hybrid rhodamine dyes. These hybrid fluorophores can be classified into various categories based on structural features including the alkylation of amidogens, the substitution of the O atom of xanthene, and hybridization with other fluorophores., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hypochlorous acid (HClO) is one of the most important ROS (reactive oxygen species) and common pollutant in tap-water. However, the determination of HClO with fast response and high sensitivity/selectivity is still an urgent demanding. Here we fabricated a ratiometric fluorescent probe RC based on TBET (through-bond energy transfer) on the platform of coumarin and rhodamine with the thiosemicarbazide group as the linker. This probe could display the characteristic fluorescence emission of coumarin. Upon addition of HClO, the linker was reacted into an oxadiazole, resulting in the opening of spiro-ring of rhodamine. The resultant then gives ratiometric fluorogenic changes. The probe exhibits fast response and high selectivity and sensitivity towards HClO with a low limit of detection (~140 nM). Eventually, RC is successfully applicated for determining spiked HClO in water samples and imaging endogenous HClO in living cells., (Copyright © 2019. Published by Elsevier B.V.)

Gases, such as nitrogen dioxide, formaldehyde and benzene, are toxic even at very low concentrations. However, so far there are no low-cost sensors available with sufficiently low detection limits and desired response times, which are able to detect them in the ranges relevant for air quality control. In this work, we address both, detection of small gas amounts and fast response times, using epitaxially grown graphene decorated with iron oxide nanoparticles. This hybrid surface is used as a sensing layer to detect formaldehyde and benzene at concentrations of relevance (low parts per billion). The performance enhancement was additionally validated using density functional theory calculations to see the effect of decoration on binding energies between the gas molecules and the sensor surface. Moreover, the time constants can be drastically reduced using a derivative sensor signal readout, allowing the sensor to work at detection limits and sampling rates desired for air quality monitoring applications.

A complementary metal-oxide-semiconductor (CMOS) chip biosensor was developed for cell viability monitoring based on an array of capacitance sensors utilizing a ring oscillator. The chip was packaged in a low temperature co-fired ceramic (LTCC) module with a flip chip bonding technique. A microcontroller operates the chip, while the whole measurement system was controlled by PC. The developed biosensor was applied for measurement of the proliferation stage of adherent cells where the sensor response depends on the ratio between healthy, viable and multiplying cells, which adhere onto the chip surface, and necrotic or apoptotic cells, which detach from the chip surface. This change in cellular adhesion caused a change in the effective permittivity in the vicinity of the sensor element, which was sensed as a change in oscillation frequency of the ring oscillator. The sensor was tested with human lung epithelial cells (BEAS-2B) during cell addition, proliferation and migration, and finally detachment induced by trypsin protease treatment. The difference in sensor response with and without cells was measured as a frequency shift in the scale of 1.1 MHz from the base frequency of 57.2 MHz. Moreover, the number of cells in the sensor vicinity was directly proportional to the frequency shift.

A novel donor-π-acceptor-π-donor type (D-π-A-π-D') Schiff base derivative (L) has been designed and synthesized. The structure of L is confirmed by single-crystal X-ray diffraction analysis as well. The photophysical properties of compound L were comprehensively investigated by using both experimental and theoretical methods. The results indicate that L exhibits large Stokes shift and moderate two-photon action (2PA) cross-section in the near infrared (NIR) region. Furthermore, the confocal microscopy imaging study demonstrates that compound L could penetrate into cells and target the cellular mitochondria compartment. Due to its low cytotoxicity, compound L provides a promising tool for directly lighting up the mitochondria compartment in living HepG2 cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue- and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce 3+ and Ce 4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3-5 nm in size, have r 1 -relaxivities between 7-13 mM -1  s -1 and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.

A two-photon active probe for physiological copper (Cu2+) detection is expected to play an important role in monitoring biological metabolism. Herein, a novel Schiff base derivative (E)-2,2'-((4-((4-(diethylamino)-2-hydroxybenzylidene)amino)phenyl)azanediyl)bis(ethan-1-ol) (L) with remarkable two-photon activity was developed and synthetically investigated. L presents high selectivity and sensitivity for Cu2+ sensing in ethanol/HEPES buffer (v/v, 1 : 1), which is accompanied by the fluorescence switching "off" and subsequently "on" with the addition of EDTA. The mechanism for the detection of Cu2+ is further analyzed using 1H NMR titration, mass spectra and theoretical calculations. Furthermore, since the probe L possesses good photophysical properties, excellent biocompatibility and low cytotoxicity, it is successfully applied to track Cu2+ in the cellular endoplasmic reticulum by two-photon fluorescence imaging, showing its potential value for practical applications in biological systems.

Combined photoemission electron microscopy (PEEM) and imaging x-ray photoelectron spectroscopy (XPS), i.e., electron spectroscopy for chemical analysis in the nanoregion, has been used for surface characterization of bio-relevant and biological samples. In the first example, the authors prepared a gold patterned silicon substrate, stepwise surface modified by self-assembled monolayers followed by quantum dot (QDot) specific linking and investigated by means of work function mapping and elemental imaging in the submicrometer range. Spatially resolved core level images of C1s, V2p, and Y3d are obtained, which verify the selective thiol adsorption on the gold squares and specific binding of europium doped yttrium vanadate QDots on the self-assembled monolayer. The second example is platelet adhesion to Immunoglobulin G modified silicon surfaces, investigated by means of laterally resolved PEEM. Images of platelets clearly show activated cells with a morphology change including an enlarged surface area and elongated pseudopodia, with a lateral resolution of 140 nm. In the last example, neutrophils were allowed to attach to plain silicon surfaces and investigated by means of PEEM and imaging XPS. Here, the cells show a round shaped morphology, as expected. Threshold imaging with work function contrast is used to localize the area of interest, followed by elemental specific mapping on cells in the submicrometer region. Chemical shifts of C1s in photoemission are used to distinguish vital parts of the cell structure. The strong C1s (C-C) signal is achieved from the region of the cell membrane, i.e., high density of phospholipids, while C1s (C-N) and C1s (C-O) signals are obtained from the core of the cell, in good agreement with the presence of cytoplasm and deoxyribonucleic acid containing cell nucleus. The combination of PEEM and imaging XPS is shown here as a tool to deliver new insight into biological samples, i.e., a rapid sample overview is obtained based on low energy secondary electrons with work function contrast, followed by detailed studies in the narrow mode for elemental compositions based on photoemission. This study illustrates the strength of combined PEEM and XPS in the imaging mode on cell studies.

Small, biocompatible and water-soluble molecules with high two-photon absorption (2PA) cross-section values ( δ ) are in high demand for specific bioimaging applications. Here, two novel terpyridine derivative ligands with donor-acceptor (D-A) ( L1 ) and donor-π-acceptor (D-π-A) ( L2 ) models, and their corresponding Zn(ii) complexes are designed and characterized. It was found that the two-photon absorption cross section values ( δ ) in the near-infrared region (NIR, about 800 nm) are significantly enhanced for complexes 1 and 2 compared to their free D-A type ligand L1 , while those of complexes 3 and 4 were greatly decreased relative to their free ligand L2 , thus confirming that the smaller ligand (D-A type) displays a suitable Turn-ON fluorescence pair for two-photon fluorescence microscopy (2PFM). Firstly, the potential of simultaneously labeling a live cell plasma membrane and nucleus using complex 1 is demonstrated. In addition, live larval and adult zebrafish incubated with an optimal concentration of 1 demonstrated clear brain uptake. Lastly and importantly, using such a probe to visualize the blood-brain-barrier (BBB) capillary endothelial cells and penetrate the BBB into the central nervous system (CNS) intravenously in a mouse model is also explored.

We strategize to utilize the precursors of (imino)coumarin fluorophores to deliver novel reactive Cu(+) probes, where tris[(2-pyridyl)-methyl] amine (TPA) works as a reactive receptor towards Cu(+). To verify this strategy, CP1, a representative probe and relevant sensing behaviors towards Cu(+) are presented here. CP1 features good solubility and fast response for monitoring labile copper in aqueous solution and live cells. The sensing mechanism of CP1 is determined by HPLC titration and mass spectrometric analysis. The probe CP1 exhibits a 60-fold fluorescence enhancement and a detection limitation of 10.8 nM upon the detection of Cu(+). CP1 is further applied for imaging labile copper in live cells. This work provides a starting point for future development of Cu(+) probes, based on in situ formation of (imino)coumarin scaffolds, as well as their further investigations of copper signaling and biological events., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A new colorimetric and fluorogenic probe (RN3) based on rhodamine-B has been successfully designed and synthesized. It displays a selective response to Hg(2+) in the aqueous buffer solution over the other competing metals. Upon addition of Hg(2+), the solution of RN3 exhibits a 'naked eye' observable color change from colorless to red and an intensive fluorescence with about 105-fold enhancement. The changes in the color and fluorescence are ascribed to the ring-opening of spirolactam in rhodamine fluorophore, which is induced by a binding of the constructed receptor to Hg(2+) with the association and dissociation constants of 0.22 × 10(5) M(-1) and 25.2 μM, respectively. The Job's plot experiment determines a 1:1 binding stoichiometry between RN3 and Hg(2+). The resultant "turn-on" fluorescence in buffer solution, allows the application of a method to determine Hg(2+) levels in the range of 4.0-15.0 μM, with the limit of detection (LOD) calculated at 60.7 nM (3σ/slope). In addition, the fluorescence 'turn-off' and color 'fading-out' happen to the mixture of RN3-Hg(2+) by further addition of I(-) or S(2-). The reversible switching cycles of fluorescence intensity upon alternate additions of Hg(2+) and S(2-) demonstrate that RN3 can perform as an INHIBIT logic gate. Furthermore, the potential of RN3 as a fluorescent probe has been demonstrated for cellular imaging., (Copyright © 2016 Elsevier B.V. All rights reserved.)

It is still a challenge to obtain two-photon excited fluorescent bioimaging probes with intense emission, high photo-stability and low cytotoxicity. In the present work, four Zn(ii)-coordinated complexes (1-4) constructed from two novel D-A and D-π-A ligands (L 1 and L 2 ) are investigated both experimentally and theoretically, aiming to explore efficient two-photon probes for bioimaging. Molecular geometry optimization used for theoretical calculations is achieved using the crystallographic data. Notably, the results indicate that complexes 1 and 2 display enhanced two-photon absorption (2PA) cross sections compared to their corresponding D-A ligand (L 1 ). Furthermore, it was found that complex 1 has the advantages of moderate 2PA cross section in the near-infrared region, longer fluorescence lifetime, higher quantum yield, good biocompatibility and enhanced two-photon excited fluorescence. Therefore, complex 1 is evaluated as a bioimaging probe for in vitro imaging of HepG2 cells, in which it is observed under a two-photon scanning microscope that complex 1 exhibits effective co-staining with endoplasmic reticulum (ER) and nuclear membrane; as well as for in vivo imaging of zebrafish larva, in which it is observed that complex 1 exhibits specificity in the intestinal system.

Nanoparticles exhibiting bright near-infrared (NIR) fluorescence, T 1 - and T 2 -weighted MR were synthesized for specific tumor imaging. Clinically used Fe 3 O 4 nanoparticles exhibit an intrinsic dark signal (T 2 -weighted MRI), which sometimes misleads clinical diagnosis. Here, for the first time we integrated ultrasmall Fe 3 O 4 nanoparticles (2-3 nm) with an NIR emitting semiconducting polymer for both T 1 - and T 2 -weighted MRI as well as fluorescence imaging of tumors. Bio-functionalized multi-modality fluorescent magnetic nanoparticles (FMNPs) functionalized with folic acid exhibit bright fluorescence and high relaxation (r 1 = 7.008 mM -1 s -1 , r 2 = 26.788 mM -1 s -1 , r 2 /r 1 = 3.8). These FMNPs have a small average dynamic size of about 20 nm with low aggregation and long circulation time. In vitro studies revealed that FMNPs can serve as an effective fluorescent probe to achieve targeting images of human A549 lung cancer cells without obvious cytotoxicity. In vivo experimental results show that the FMNPs are able to preferentially accumulate in tumor tissues for specific fluorescence imaging, T 1 - and T 2 -weighted MRI.

A facile one-step Cu(i)-catalyzed "click" reaction, between a dansyl-azide and a propargyl-substituted rhodamine B hydrazide, is employed to fabricate a novel FRET ratiometric "off-on" fluorescent probe. The sensitive emission of the donor, a dansyl group, overlaps perfectly with the absorption of the acceptor, xanthene in the open-ring rhodamine. The proposed probe shows high selectivity towards Cu 2+ . The ratio of emission intensities at 568 and 540 nm (I 568 /I 540 ) exhibits a drastic 28-fold enhancement upon addition of Cu 2+ . The probe shows an excellent linear relationship between emission ratios and the concentrations of Cu 2+ from 10 to 50 μM, with a detection limit (S/N = 3) of 0.12 μM. The preliminary cellular studies demonstrated that the probe is cell membrane permeable and could be applied for ratiometric fluorescence imaging of intracellular Cu 2+ with almost no cytotoxicity. The ingenuity of the probe design is to construct a FRET donor-acceptor interconnector and a selective receptor simultaneously by "click" reaction. The strategy was verified to have great potential for developing novel FRET probes for Cu 2+ .

Uniform, highly water-dispersible and ultra-small Fe3O4 nanoparticles were synthesized via a modified one-step coprecipitation approach. The prepared Fe3O4 nanoparticles not only show good magnetic properties, long-term stability in a biological environment, but also exhibit good biocompatibility in cell viability and hemolysis assay. Due to the ultra-small sized and highly water-dispersibility, they exhibit excellent relaxivity properties, the 1.7 nm sized Fe3O4 nanoparticles reveal a low r2/r1 ratio of 2.03 (r1 = 8.20 mM(-1) s(-1), r2 = 16.67 mM(-1) s(-1)); and the 2.2 nm sized Fe3O4 nanoparticles also appear to have a low r2/r1 ratio of 4.65 (r1 = 6.15 mM(-1) s(-1), r2 = 28.62 mM(-1) s(-1)). This demonstrates that the proposed ultra-small Fe3O4 nanoparticles have great potential as a new type of T1 magnetic resonance imaging contrast agents. Especially, the 2.2 nm sized Fe3O4 nanoparticles, have a competitive r1 value and r2 value compared to commercial contrasting agents such as Gd-DTPA (r1 = 4.8 mM(-1) s (-1)), and SHU-555C (r2 = 69 mM(-1) s(-1)). In vitro and in vivo imaging experiments, show that the 2.2 nm sized Fe3O4 nanoparticles exhibit great contrast enhancement, long-term circulation, and low toxicity, which enable these ultra-small sized Fe3O4 nanoparticles to be promising as T1 and T2 dual contrast agents in clinical settings.

Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained EuIII-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4 nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13 nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r1=6.4 and 6.3 s−1 mM−1 with r2/r1 ratios close to unity at 1.4 T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.