Search Results (23)

X-ray techniques provide powerful, non-destructive tools for structural characterization in semiconductor manufacturing and advanced packaging. Their strong penetration capability and sensitivity to multiple contrast mechanisms enable the investigation of lattice structure, strain, defects, interfaces, and elemental distribution across a wide range of length scales. As semiconductor devices evolve toward three-dimensional architectures and heterogeneous integration, there is an increasing demand for characterization approaches capable of probing complex, buried, and multi-scale structures in a consistent manner. In this review, we present a systematic overview of X-ray characterization techniques for advanced semiconductor systems, including diffraction-based methods, small-angle scattering, computed tomography, X-ray fluorescence, and spectroscopic approaches. These techniques are discussed in terms of the type of structural, morphological, and compositional information they provide, their applicable length scales, and their strengths and limitations in addressing key challenges such as thin films, high-aspect-ratio structures, buried interfaces, and full wafers. Particular attention is given to the complementary nature of different X-ray modalities and their roles in addressing practical metrology problems. The limitations associated with resolution, model dependence, and data interpretation are also outlined. Finally, emerging opportunities in laboratory X-ray sources, synchrotron-based methods, and integrated characterization strategies are briefly discussed. This review aims to provide a unified perspective for understanding and integrating X-ray techniques, offering insights into their roles in addressing the growing complexity of next-generation semiconductor devices. Full article

Most reported fluorescent Al³⁺ probes rely on fluorescence signal enhancement or quenching. Since the change in fluorescence intensity is the sole detection signal, various factors such as instrumental efficiency, environmental conditions, and probe concentration can interfere with the signal output. In contrast, ratiometric probes, which utilize two emission bands for self-calibration, provide significant advantages by minimizing or eliminating these uncertainties. In this study, a naphthalimide-rhodamine based the transition between the cyclic and open-ring forms of rhodamine as an Al³⁺-selective ratiometric probe, in which chitosan was identified as an ideal bridge and biocompatibility. The design concept was that when the target metal ion was present, the fluorescence intensity of naphthalimide remained largely unchanged, serving as an internal standard. In contrast, rhodamine B was employed to label the target molecules, with its fluorescence intensity varying in accordance with the target concentration. A series of experiments were carried out to investigate the fluorometric properties of the grafted polymer P. The results demonstrated that P exhibited selective interaction with Al³⁺ among the various metals tested. Using the fluorescence intensity ratio (I_{603 nm}/I_{538 nm}) of P, a good linear relationship was achieved for Al³⁺ concentrations ranging from 1.0 to 35.0 μM with a detection limit of 0.33 μM was obtained. Meanwhile, we employed the standard addition method for the quantitative analysis and detection of Al³⁺ in commercially available bottled water and tap water, achieving an ideal recovery rate. Full article

Background: Dry eye disease is a multifactorial ocular surface disorder characterized by tear film instability, inflammation, and neurosensory abnormalities that can lead to corneal pain and discomfort. In this study, we evaluated the effects of specific eye drops for dry eyes on neuronal pain receptors to gain insight into the mechanisms underlying corneal nerve pain in patients with dry eyes using a primary cell culture model of murine trigeminal ganglion cells. Methods: Trigeminal ganglia were obtained from wild-type postnatal day 7–10 mice. Primary cultures were prepared using the cell suspension method. After culturing for one week, the cells were stained with neuron-specific anti-neuronal nuclei, polymodal nociceptor, and transient receptor potential vanilloid 1 (TRPV1) antibodies. The calcium ion probe Fura2-AM^® was added to cultured cells after 2 weeks of incubation. The effects of capsaicin alone, in combination with the TRPV1 antagonist AMG9810, and in the presence of components of commercially available eye drops (cyclosporine, diquafosol tetrasodium, or rebamipide) were evaluated by monitoring calcium signals. Results: Neural excitation and capsaicin-induced increase in fluorescence intensity ratio were suppressed by AMG9810, cyclosporine, and diquafosol tetrasodium, but not by rebamipide. Conclusions: Inhibition of cellular excitation by cyclosporine and diquafosol tetrasodium may underlie their clinical pain suppressive effects. The primary culture model described here may serve as a useful tool for future studies on corneal perception. Full article

Smartphones equipped with highly integrated sensors are increasingly being recognized as powerful tools for rapid on-site testing. Here, we propose a low-cost, portable, and highly multiplexed smartphone-based spectrometer capable of collecting three types of spectra—transmission, reflection, and fluorescence—by simply replacing the optical fiber attached to the housing. Spectral analysis is performed directly on the smartphone using a custom-developed app. Furthermore, we introduce a high signal-to-noise ratio (SNR) caffeine detection scheme that leverages aspirin and salicylic acid as fluorescent probes, allowing for the rapid and straightforward detection of caffeine in various samples. The fluorescence quenching of the probes was found to be linearly related to the caffeine concentration (0–200 μM), and the recoveries of the commercially available caffeine-containing samples were in the range of 98.0333–105.6000%, with a limit of detection (LOD) of 2.58 μM. The reliability and stability of the on-site assay using the smartphone spectrometer were verified. More importantly, this spectrometer demonstrates great potential as a versatile device for use outside of laboratory settings by enabling different operating modes tailored to various scenarios. Full article

With the recent surge in the development of highly selective probes, fluorescence microscopy has become one of the most widely used approaches to studying cellular properties and signaling in living cells and tissues. Traditionally, microscopy image analysis heavily relies on manufacturer-supplied software, which often demands extensive training and lacks automation capabilities for handling diverse datasets. A critical challenge arises if the fluorophores employed exhibit low brightness and a low signal-to-noise ratio (SNR). Consequently, manual intervention may become a necessity, introducing variability in the analysis outcomes even for identical samples when analyzed by different users. This leads to the incorporation of blinded analysis, which ensures that the outcome is free from user bias to a certain extent but is extremely time-consuming. To overcome these issues, we developed a tool called DL-SCAN that automatically segments and analyzes fluorophore-stained regions of interest such as cell bodies in fluorescence microscopy images using deep learning. We demonstrate the program’s ability to automate cell identification and study cellular ion dynamics using synthetic image stacks with varying SNR. This is followed by its application to experimental Na⁺ and Ca²⁺ imaging data from neurons and astrocytes in mouse brain tissue slices exposed to transient chemical ischemia. The results from DL-SCAN are consistent, reproducible, and free from user bias, allowing efficient and rapid analysis of experimental data in an objective manner. The open-source nature of the tool also provides room for modification and extension to analyze other forms of microscopy images specific to the dynamics of different ions in other cell types. Full article

The efficacy of glioblastoma treatment is closely associated with complete tumor resection. However, conventional surgical techniques often result in incomplete removal, leading to poor prognosis. A major challenge is the accurate delineation of tumor margins from healthy tissues. Imaging-guided surgery, particularly using fluorescent probes, is a promising solution for intraoperative guidance. The recently developed ‘always-on’ types of targeted fluorescence probes generate signals irrespective of their presence in tumor cells or in blood circulation, hampering their effectiveness. Here, we propose a novel activatable fluorescence imaging probe, Q-cRGD, that targets glioma cells via the specific binding of the cyclic Arg-Gly Asp-containing pentapeptide (cRGD) to integrins. The Q-cRGD probe was synthesized by conjugating a near-infrared (NIR) dye to a tryptophan quencher via a disulfide linkage, including a cRGD-targeting ligand. This activatable probe remained inactive until the redox-responsive cleavage of the disulfide linkage occurred within the target cell. The zwitterionic nature of NIR dyes minimizes nonspecific interactions with serum proteins, thereby enhancing the tumor-to-background signal ratio (TBR). An in vivo fluorescence imaging study demonstrated a TBR value of 2.65 within 3 h of the intravenous injection of Q-cRGD, confirming its potential utility in imaging-guided brain cancer surgery. Full article

Organic fluorescent probes have attracted attention for bioimaging due to their advantages, including high sensitivity, biocompatibility, and multi-functionality. However, some limitations related to low signal-to-background ratio and false positive and negative signals make them difficult for in situ target detection. Recently, organelle targeting self-assembled fluorescent probes have been studied to meet this demand. Most of the dye molecules suffer from a quenching effect, but, specifically, some dyes like Pyrene, Near-Infrared (NIR), Nitrobenzoxadiazole (NBD), Fluorescein isothiocyanate (FITC), Naphthalenediimides (NDI), and Aggregation induced emission (AIE) show unique characteristics when they undergo self-assembly or aggregation. Therefore, in this review, we classified the molecules according to the dye type and provided an overview of the organelle-targeting strategy with an emphasis on the construction of fluorescent nanostructures within complex cellular environments. Results demonstrated that fluorescent probes effectively target and localized inside the organelles (mitochondria, lysosome, and golgi body) and undergo self-assembly to form various nanostructures that possess bio-functionality with long retention time, organelles membrane disruption/ROS generation/enzyme activity suppression ability, and enhanced photodynamic properties for anticancer treatment. Furthermore, we systematically discussed the challenges that remain to be resolved for the high performance of these probes and mentioned some of the future directions for the design of molecules. Full article

Featuring subtle lithological alterations in the host rocks and containing colossal gemstone crystals, the scheelite deposit at Xuebaoding in the Pingwu region of Sichuan Province exhibits characteristics typical of a vein-like hydrothermal-type deposit. The scheelite from the Xuebaoding region is renowned for its high saturation of color, perfect crystal shape, and pure color. In this study, its crystal structure and mineralogical, geochemical, and in situ Sr-Nd isotope characteristics are all systematically characterized. Our objective is to determine the source of ore-forming materials, the timing of the mineralization, and the chemical composition of scheelite, including major elements, trace elements, and rare earths elements (REE). The scheelite samples were analyzed with a variety of methods such as polarizing microscopy, X-ray powder diffraction (XRD), X-ray fluorescence spectrometry (XRF), electron probing, and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In addition, conventional gemological tests were performed using instruments including gemstone microscopes, GI-UVB ultraviolet fluorescent lamps, grating spectroscopy, etc. The results demonstrate that scheelite exhibits a high refractive index, excellent crystallinity, and a granular structure. Clear color bands and ring structures are observed within the minerals, accompanied by interference colors of light blue, blue, and yellow. Additionally, the mineral components are relatively concentrated, with muscovite and illite serving as accessory minerals. Furthermore, the chemical composition of scheelite reveals a WO₃/CaO mass ratio that approaches or exceeds the ideal value. Moreover, it exhibits a wide range of variations in total rare earth element (∑REE) content, which is characterized by an enrichment of light rare earths (LREE), significant negative Eu anomalies, and insignificant Ce anomalies. In addition, the metallogenic formation of scheelite can be estimated to have occurred during the Toarcian stage in the Lower Jurassic Epoch period, approximately 183 Ma. The study further revealed that A-type granite serves as the genesis type of scheelite, with most of the ore-forming materials originating from the upper crust and a few derived from younger crustal sources. Full article

Smoking and diabetes mellitus have been recognized as significant modifying factors of the evolution of periodontitis, being considered at the moment as descriptive factors in the periodontitis grading system. The purpose of this study was to assess the consequence of smoking, type 2 diabetes, and the combination of these two factors on clinical periodontal parameters, on the levels of gingival crevicular fluid (GCF), and also on ratios of pro-inflammatory and anti-inflammatory cytokines by using a commercially available kit-based multiplex fluorescent immunoassay. The study was carried out on 124 volunteers (control (C) group = 29, diabetes mellitus (DM) group = 32, smoking (S) group = 31, and S + DM group = 32). Total mean bleeding on probing was significantly lower in the S and S + DM groups, compared to that of the other groups (p < 0.05). Total amounts of TGF-β, MIP-1α, IL-6, IL-2, and IL-17 were significantly increased in the periodontally healthy sites of diabetes patients (p < 0.05), compared to those of the controls. Systemically healthy smoking patients had higher values of GM-CSF, TGF-β, IL-4, TNF-α, IL-5, and IL-7, while diabetic smoking patients showed higher values of IL-4, TGF-β, and MIP-1α. In smoking and systemically healthy patients, IL-23, IL-7, and IL-12 showed increased concentrations, while concentrations of TGF-β, MIP-1α, IL-2, IL-7, IL-12, IL-17, IL-21, and IL-23 were higher in smoking DM patients. In conclusion, in our study, diabetes mellitus induced a general pro-inflammatory state, while smoking mainly stimulated immunosuppression in the periodontal tissues of periodontitis subjects. Full article

Biological applications of silver nanoparticles (AgNPs) depend on the covalently attached or adsorbed proteins. A series of biological effects of AgNPs within cells are determined by the size, shape, aspect ratio, surface charge, and modifiers. Herein, the morphology dependent interaction between AgNPs and protein was investigated. AgNPs with three different morphologies, such as silver nanospheres, silver nanorods, and silver nanotriangles, were employed to investigate the morphological effect on the interaction with a model protein: bovine serum albumin (BSA). The adsorptive interactions between BSA and the AgNPs were probed by UV-Vis spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), Fourier transform infrared spectrometry (FTIR), transmission electron microscopy (TEM), and circular dichroism (CD) techniques. The results revealed that the particle size, shape, and dispersion of the three types of AgNPs markedly influence the interaction with BSA. Silver nanospheres and nanorods were capsulated by protein coronas, which led to slightly enlarged outer size. The silver nanotriangles evolved gradually into nanodisks in the presence of BSA. Fluorescence spectroscopy confirmed the static quenching the fluorescence emission of BSA by the three AgNPs. The FTIR and CD results suggested that the AgNPs with different morphologies had different effects on the secondary structure of BSA. The silver nanospheres and silver nanorods induced more pronounced structural changes than silver nanotriangles. These results suggest that the formation of a protein corona and the aggregation behaviors of AgNPs are markedly determined by their inherent morphologies. Full article

Purpose: With the increasing detection rate of early prostate cancer (PCa), the proportion of surgical treatment is increasing. Surgery is the most effective treatment for PCa. Precise targeting of tumors during surgery can reduce the incidence of positive surgical margins (PSMs) and preserve the neurovascular bundles (NVBs) as much as possible. The objective of this study was to synthesize a PSMA fluorescent probe (PSMA-Cy5) and verify the targeting specificity of the probe for prostate cancer, thereby providing a theoretical basis for the development of PSMA fluorescent probes for clinical application in the future. Methods: In this study, a novel water-soluble 3H-indocyanine-type bioluminescent dye-Cy5-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-Cy5) was synthesized by liquid phase synthesis. The PSMA ligand was developed based on the glutamine-urea-lysine (Glu-urea-Lys) structure. The new fluorescent probe was evaluated in vitro and in vivo, and its safety was evaluated. Confocal microscopy was used to observe the binding uptake of PSMA-Cy5 with PSMA (+) LNCaP cells, PSMA (-) PC3 cells and blocked LNCaP cells. In in vivo optical imaging studies, the targeting specificity of PSMA (+) 22Rv1 tumors to probe binding was validated by tail vein injection of PSMA-Cy5. The safety of the PSMA-Cy5 probe was evaluated by histopathological analysis of mouse organs by a single high-dose tail vein injection of PSMA-Cy5. Results: In vitro fluorescence cell uptake experiments showed that the binding of PSMA-Cy5 to LNCaP cells has targeting specificity. PC3 cells and blocked LNCaP cells showed almost no uptake. The results of in vivo optical imaging studies showed that the tumor-to-background ratio in the 22Rv1 group was 3.39 ± 0.47; in the 22Rv1 blocking group it was 0.78 ± 0.15, and in the PC3 group it was 0.94 ± 0.09, consistent with the in vitro results. After a high-dose injection of PSMA-Cy5, there were no abnormalities in the tissues or organs of the mice. The probe showed good safety. Conclusions: PSMA-Cy5 is a probe with good targeting specificity and low toxicity that can accurately visualize tumors in vivo. This study has an important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to precise tumor imaging during radical prostatectomy to reduce the incidence of postoperative PSM. Full article

Rare-earth labeling in biological apatite could provide critical information for the pathologic transition (osteoclastic) and physiologic regeneration (osteogenesis) of bone and teeth because of their characteristic site-sensitive fluorescence in different coordinative conditions of various tissues in many biological processes. However, the rare-earth labeling method for biological apatites, i.e., carbonated-hydroxyapatite, has been rarely found in the literature. In this paper, we report a Pourbaix-diagram guided mineralizing strategy to controllable carbonation and doping of rare-earth ions in the hydroxyapatite (HA) lattice. The carbonation process of hydroxyapatite was achieved by controllable mineralization in hydrothermal condition with K₂CO₃ as the carbonate source, which results into the pure B-type carbonated hydroxyapatite (CHA) with tunable carbonate substitution degree. All of the as-synthesized materials crystalized into P63/m (No. 176) space group with the lattice parameter of a decreases and c increases with the increasing of carbonate content in the reactants. Structural refinement results revealed that the substitution of planar CO₃²⁻ is superimposed on one of the faces of PO₄³⁻ tetrahedral sub-units with a rotation angle of 30° in reference to c-axis. All of the hydrothermally synthesized CHA nanocrystals show hexagonal rod-like morphology with the length of 70–110 nm and diameter of 21–35 nm, and the decreasing length/diameter ratio from 3.61 to 2.96 from low to high carbonated level of the samples. Five rare-earth cations, of Pr³⁺, Sm³⁺, Eu³⁺, Tb³⁺, and Ho³⁺, were used as possible probe ions that can be doped into either HA or CHA lattice. The site-preference of Tb³⁺ doping is the same in the crystallographic site of HA and CHA according to characteristic emission peaks of ⁵D₄–⁷F_j (j = 3–6) transitions in their photoluminescent spectroscopy. Our work provides a controllable carbonation method for rare-earth labeling hydroxyapatite nanomaterials with potential biologically active implant powders for bone repair and tissue regeneration. Full article

Among heavy metals silver ions (Ag⁺) severely impact water, the environment and have serious side effects on human health. This article proposes a facile and ultrasensitive fluorescent probe for the detection of Ag⁺ ions using SYBR Green I (SGI) and cytosine-rich (C-rich) silver-specific oligonucleotide (SSO). Maximum fluorescent intensities with the highest sensitivity were obtained using a 0.61 dye/SSO base ratio (DBR). The established sensing principle using the optimized parameters for bath temperature, SSO concentration, DBR, ionic strength, pH, reaction time, incubation duration and temperature effect achieved a sensitive limit of detection of 59.9 nM for silver ions (calculated through 3σ, n = 11) with a linear working range of 100–1000 nM and 0.997 R². The total time for one assay is below 10 min; The relative standard derivation for ten repeated measurements is 8.6%. No blatant interferences were observed in the selectivity test when fluorescent probe is evaluated by investigating the effects of 11 common interference factors in the aqueous matrix. In extreme cases, three false-negative factors were observed, including calcium hardness, magnesium hardness, and hypochlorite. The recovery ratios were within the range of 79~110% for three types of diluted water. Full article

Reactive sulfane sulfur, including persulfide and polysulfide, is a type of regular cellular component, playing an antioxidant role. Its function may be organelle-dependent; however, the shortage of probes for detecting organellar reactive sulfane sulfur has hindered further investigation. Herein, we reported a red fluorescent protein (mCherry)-based probe for specifically detecting intracellular reactive sulfane sulfur. By mutating two amino acid residues of mCherry (A150 and S151) to cysteine residues, we constructed a mCherry mutant, which reacted with reactive sulfane sulfur to form an intramolecular –S_n– bond (n ≥ 3). The bond largely decreased the intensity of 610 nm emission (excitation at 587 nm) and slightly increased the intensity of 466 nm emission (excitation at 406 nm). The 466/610 nm emission ratio was used to indicate the relative abundance of reactive sulfane sulfur. We then expressed this mutant in the cytoplasm and mitochondria of Saccharomyces cerevisiae. The 466/610 nm emission ratio revealed that mitochondria had a higher level of reactive sulfane sulfur than cytoplasm. Thus, the mCherry mutant can be used as a specific probe for detecting reactive sulfane sulfur in vivo. Full article

In this study, new types of amphiphilic calix[4]arene derivatives bearing N-alkyl/aryl imidazolium/benzimidazolium fragments were designed and synthesized by two step transformation: Regioselective Blanc chloromethylation of distal-di-O-butyl calix[4]arene and subsequent interaction with N-Substituted imidazole/benzimidazole. Critical aggregation concentration (CAC) values were estimated using pyrene fluorescent probe. Obtained macrocycles were found to form submicron particles with electrokinetic potential +44–+57 mV in aqueous solution. For the first time it was found that amphiphilic calixarene causes the fast transformation of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) multilamellar vesicles into unilamellar ones and leads to the ordering of the lipid in membranes at the molar calixarene/DPPC ratio more than 0.07. In situ complexes of calixarene aggregates with Pd(OAc)₂ were found to be active in Suzuki–Miyaura coupling of 1-bromo-4-nitrobenzene with phenylboronic acid in water. It was shown that bulky N-substituents of heterocycle decrease the catalytic activity of the aggregates. These result can be assigned to the inhibition effect of Pd(II) complex in situ formation by bulky substituents located on the aggregate surface. Embedding of the most active palladium N-heterocyclic carbene (NHC) complex with methylimidazolium headgroups into DPPC vesicles enhances its catalytic activity in Suzuki–Miyaura coupling. Full article