Visible Fluorescence Research Articles

Reactivities of 4-amino salicylic acid and its ‘Green’ inhibition into nano sized β-cyclodextrin for Anti-Tuberculosis drug delivery

In the present work, 4-amino salicylic acid (PAS) which is an oral antibiotic against tuberculosis is being investigated for its potential “Green” effectivity in trapped conditions within nano sized good solubilizing drug receptor. The process is totally “green” as no toxic materials, chemicals and solvent other than water has been used throughout the encapsulation /complexation process. Cyclodextrin glycosyltransferase (3CGT) and its by-product beta (β)-cyclodextrin (β-CD) usually act as nano sized good solubilizing agents for many drugs. In aqueous medium both 3CGT and β-CD can create drug: receptor complex by encapsulating the drug into its nano sized cavity and can increase the aqueous solubility of probe drug depending on the ionic strength. PAS was initially screened by its drug likeness properties by ADMET analysis. Structural analysis and chemical reactivity of PAS have been checked by density functional theory with basis set B3LYP/6-311G++*(d,p) in aqueous environment. The electronic properties (atomic charges, electrostatic potential, and uv–visible absorption & fluorescence analysis) have been studied to check the possibility of 1:1 complex formation between PAS: β-CD. To understand the type and strength of interactions between PAS and receptor, molecular docking and molecular dynamics simulations have been performed between PAS and cyclodextrin glycosyltransferase (3GGT). PAS has shown strong interaction possibilities both as 1:1 inclusion complex (PAS: β-CD) and as PAS: 3CGT complex. Our in-silico and experimental outcomes have recommended 4-amino salicylic acid’s better efficacy as a promising inhibitor inside cyclodextrin nano-cavity for targeting tuberculosis.

DNA binding/cleavage study of mixed ligand complexes of di-/triorganotin 4-fluoroanthranilates with 1,10-phenanthroline/benzimidazole: Synthesis, characterization, X-ray structures of [Bu2Sn(FA)2.phen], [Me3Sn(FA).bz], and DFT calculations

The mixed ligand complexes of di-/tri-organotin 4-fluoroanthranilates with 1,10-phenanthroline (phen), viz. [R2Sn(FA)2.phen] {R=Bu (1), Oct (2), Me (3)} and benzimidazole (bz), viz. [R3Sn(FA).bz] {R=Me (4), Ph (5)} have been synthesized and satisfactorily characterized by analytical and spectroscopic techniques, especially FT-IR, NMR (1H, 13C, and 119Sn NMR) spectroscopy and ESI-MS spectrometry. Single crystal-Xray diffraction measurements (Sc-XRD) confirmed a distorted pentagonal-bipyramidal geometry for complex (1), where one carboxylate group is monodentate, and the second (–COO) group behaves as a bidentate, while complex (4) affirms trigonal–bipyramidal geometry around the tin centre. The bond angles, especially ∠C–Sn–C obtained by optimizing complexes’ gaseous phase geometry showed significant conformity with the data obtained from Sc-XRD and NMR. The Kb (binding constant) and Ksv (Stern-Volmer quenching constant) values, ranging from 103 to 107, have been obtained through UV–visible absorption and fluorescence titrations with CT-DNA. These results strongly indicate partial minor groove binding/electrostatic interactions between the complex and CT-DNA, which has also been evidenced by circular dichroism studies. The studied complexes cleaved efficiently pBR322 plasmid DNA in NC (nicked circular form), SC (supercoiled form), and linear form.

Synthesis, characterisation, and in vitro antiparasitic activity of new flavanoidal tetrazinan-6′-ones and their binding study with calf thymus DNA using molecular modelling and spectroscopic techniques

With the developing resistance to traditional antiparasitic medications, the purpose of this study was to efficiently develop a series of six noble flavanoidal tetrazinane-6′-one derivatives by a one-pot reaction pathway. FT-IR, 1HNMR, 13CNMR, and Mass spectra were employed for the structural elucidation of the synthesized compounds (7–12). Clinostomum complanatum, a parasite infection model that has been well-established, demonstrated that all the synthesized compounds are potent antiparasitic agents. DNA is the main target for various medicinal compounds. As a result, thestudy of how small molecules attach to DNA has received a lot of attention. In the present study, we have performed various biophysical techniques to determine the mode of binding of synthesized compounds (7–12) with calf thymus DNA (ct-DNA). It was observed from the UV–visible absorbance and fluorescence spectra that all synthesized compounds (7–12) form complexes with the ct-DNA. The value of binding constant (Kb) was obtained to be in the range of 4.36–––24.50 × 103 M - 1 at 298 K. Competitive displacement assay with ethidium bromide (EB), CD spectral analysis, viscosity measurements, and in silico molecular docking confirmed that ligands (7–12) incorporate with ct-DNA through groove binding only. Molecular docking studies were performed for all synthesized compounds with the calf thymus DNA and it was found that all the newly synthesized compounds strongly bind with the chain B of DNA in the minor groove with the value of binding energy in the range of −8.54 to −9.04 kcal per mole and several hydrogen bonding interactions.

The Adoration of the Magi by Artemisia Gentileschi analyzed with multispectral imaging and XRF technique

The results of non-invasive diagnostic analyses of the painting Adoration of the Magi by Artemisia Gentileschi are presented. It was created in the 1630s to decorate the choir of the Cathedral of San Procolo in Pozzuoli (Naples, Italy).Multispectral imaging at different wavelengths (VIS, IR and UV) and X-ray fluorescence (XRF) were used. The data were integrated and compared with the art historical literature on Artemisia’s activity, especially in Naples after 1630. The research aims to identify the artist’s palette, the materials used, including in the restoration, and the possible influence on the use of color by artists working in Naples at the time. This will enrich the scientific details of the painting and the literature on the famous painter.The UVF (ultraviolet induced visible fluorescence) images show darker areas on the surface, such as retouching, while the IR image highlights dark outlines that could be traces of brushstrokes and painterly changes.The XRF technique, together with IRFC (infrared false color) imaging, suggested the pigments and materials used for the paint and preparatory layers. Calcium, strontium, lead and iron were identified as the main characteristic elements of the ground layer. Smalt was suggested for the various shades of blue due to the presence of cobalt in combination with pigments based on ultramarine blue, copper or lead white. Traces of mercury were detected in the red areas, suggesting the use of vermilion with other red pigments. Antimony was found in the yellow areas, indicating the use of Naples yellow, a pigment known to have been used by Artemisia only when she worked in Naples.Macro-XRF showed that the finger of one hand was made twice. In the first version, lead was detected, while in the second, this element is present together with mercury. Titanium and zinc indicate that the area investigated was restored.

A molecularly imprinted ratiometric fluorescent sensor for visual detection of 1-naphthol based on fluorescence-enhanced CdTeS QDs via APTES modification.

CdTeS quantum dots (CdTeS QDs) were synthesized using the hydrothermal method and subsequently modified with (3-aminopropyl)triethoxysilane (APTES). This modification resulted in a significant enhancement of the fluorescence intensity, which was observed to be five times stronger than that of unmodified CdTeS QDs at 597nm. Only after the fluorescence enhancement by APTES modification, the material showed a response to 1-naphthol (1-NP). Based on this, the molecularly imprinted polymers (MIPs) with ratiometric fluorescence were developed for the detection of 1-NP, that is, the synthetic raw material and the metabolite of the pesticide carbaryl. Under the excitation of 365nm UV, the bright orange-red fluorescence (597nm) of CdTeS QDs encapsulated in MIPs was quenched by 1-NP in the suspension, and 1-NP showed a gradually increasing blue emission (460nm) with the increase of its concentration. This sensor has a good linear relationship between fluorescence intensity ratio (F460/F597) and 1-NP concentration (C1-NP) in a large concentration range (6.0-140.0 µM, LOD=0.45 µM, RSD<4.41%). Itexhibits a visible fluorescence change from orange-red to blue-purple. Excellent recoveries in real samples were obtained by simulating carbaryl metabolism and demonstrated its potential in detection of 1-NP and carbaryl.

Development of a novel sensory material for rapid detection of mercury ions in various water sources: Solution and solid-state analysis

A xanthene propane nitrile-based sensor material was successfully prepared, and an attempt towards the preparation of polymer bead form was made for the sensitive or selective detection of mercury ions (Hg2+) in water. The sensor material in solution as well as in polymeric form showed amazing selectivity over other added metal ions with a naked eye color change, UV visible spectral and fluorescence spectral change, and a rapid and excellent color change from colorless to purple. The 1H NMR study exposed the probable binding site of the probe with the added mercury ion. In this study, the imine nitrogen and the C = O interact with the mercury ion, resulting in the ring opening of lactam with a vivid color change. The EDTA test was done to verify the reversible behavior of the probe and confirmed its reversibility by UV–visible and fluorescence spectral studies. The polymer bead made using this probe can be used as a tool for monitoring mercury ions in real time in different sources of water samples. The sensor molecule itself senses the mercury ion in its solid state by simple grinding and changes its color from pale yellow to deep purple. The sensor color change response is very rapid towards mercury detection, which is confirmed by the prepared test strip.

Condensed DNA incorporating mercaptoundecahydro-closo-dodecaborate (BSH) coated gold nanoparticles as a model system for boron neutron capture therapy (BNCT)

The experimental radiation therapy involving thermal neutron capture by boron (boron neutron capture therapy, BNCT) offers the advantage of high-LET ions with ranges on the order of a cell nucleus. Efforts to implement it have encountered serious difficulties. A practical model system would be able to address the underlying mechanisms of DNA damage and also calibrate Monte Carlo simulations. We describe the characterization of a plasmid-based model in which DNA condensed with a tetra-arginine peptide is co-aggregated with mercapto-closo-dodecaborate (BSH) coated gold nanoparticles (AuNPs). Condensed DNA is an excellent model for cellular chromatin, and the AuNPs are able to function as boron carriers and neutron dosimeters. Data from light scattering, UV–visible spectroscopy, fluorescence spectroscopy, sedimentation behavior, gel electrophoresis, and atomic force microscopy all indicate that the basic peptide acts to co-aggregate the two polyanionic species DNA and BSH-coated AuNPs. This aggregation is easily reversed by an increase in ionic strength to free the plasmid for subsequent assay. We argue that this three-component system is simpler, more convenient, and more flexible than other models requiring covalent attachments between DNA, boron, and/or gold.

Femtosecond laser activation of the photochemistry of bismuth and associated three-dimensional sub-micron fluorescence patterning

Localized sub-micrometer-scale visible and near-IR fluorescence structures have been achieved in three-dimension (3D) thanks to femtosecond laser-activated photochemistry of Bismuth in a Bismuth-doped phosphate glass. These structures exhibit high fluorescence contrast with good spatial resolution with spectral emission in the red and near-IR ranges. These fluorescence properties arise from femtosecond laser-induced multi-photon absorption and the creation of free electrons, which activates local redox reactions of Bi3+ that allow for the dose-dependent formation of low valence Bismuth ions such as Bi2+ and Bi+. These new species promote not only new selective fluorescence emission properties in the VIS and near-IR spectral range but also co-localized positive refractive index changes. The thermal treatment of 3D patterns evidences the possibility of Bismuth cluster formation with good thermal stability up to the glass temperature transition. These observations open the way for laser-inscribed photonic integrated circuits for potential laser amplification devices in the second telecommunication windows around 1.3 μm.

A biologically inspired fluorescent probe with enhanced sensing performance for detection of Al3+ based on metal replacement strategy

Salicylaldehyde acyl-hydrazone derivatives have been widely applied to design fluorescent probe for Al3+ detection, but they are always restricted to detect Al3+ in water and actual samples by their poor solubility, low sensitivity, and long response time. Biologically inspired, four salicylaldehyde acyl-hydrazone compounds were designed and synthesized and H4L1 as one of them was selected for in-situ assembly of the ytterbium complex (FP-Al), which has been developed to be a new fluorescent probe for Al3+ detection by the central mental displacement process. The in-situ structure transformation from FP-Al to Al-L was fully characterized by X-ray crystal structure analysis, 1H NMR, FT-IR, and spectral analysis. The intrinsic driving force was explained and elaborated by theoretical calculation. FP-Al showed a significant visible fluorescence enhancement and near-infrared luminescence decreased upon the addition of Al3+. Compared with the ligand H4L1, FP-Al showed enhanced sensing performance during Al3+ detection, especially in improving water solubility and selectivity to Al3+, promoting response speed, reducing background fluorescence and increase cell-membrane permeability. The application of spontaneous metal replacement reaction might be able to provide a new strategy to develop high-performance optical chemo-sensors.

Bis-butoxyphenyl dipyridine cation with high affinity for PF6−: Enhancement of solid fluorescence and inhibits Escherichia coli and Staphylococcus aureus activity through anion-π+ interactions

The contamination of anions and the overuse of antibiotics pose significant hazards to human health. Excess anions can cause serious damage to organisms and the natural environment, while the misuse of antibiotics has led to the emergence of multi-drug resistant bacteria. Therefore, it is important to develop multifunctional fluorescent sensing devices that integrate the rapid and sensitive detection of specific anions and that exhibit excellent antimicrobial activity against multi-resistant bacteria. This study describes the synthesis of three water-soluble cationic fluorescent molecules, DPPT-R (R = 5C, 6C, 7C). Their structures were characterized using 1H NMR spectroscopy, HRMS, and single crystal X-ray diffraction. Spectroscopic properties of the probes were recorded using UV–visible absorption and fluorescence spectroscopy. The recognition mode and mechanism of the fluorescent probes towards PF6− were investigated. Under aqueous solution conditions involves the PF6− induced aggregation of the probe via strong electrostatic interactions, leading to fluorescence quenching. Adjusting the alkyl chain length of the probe can enhance the sensitivity for the detection of the target anions. The detection limits are 0.892 μM, 0.786 μM and 0.444 μM for R = 5C, 6C, 7C, respectively. In addition, DPPT-R and DPPT-R@PF6 exhibit good inhibitory activity and fluorescence imaging capability against methicillin-resistant Staphylococcus aureus and multidrug-resistant Escherichia coli. Among them, the side chain of DPPT-R@PF6 with an almost 90° bend may be more advantageous for membrane insertion, thus enhancing its antimicrobial activity. In particular, after DPPT-R and PF6− form the DPPT-R@PF6 complex, the complex enhances its solid-state fluorescence, intensity of bacterial fluorescence imaging, and antibacterial activity through anion-π+ interactions. Therefore, this study can provide a new strategy and theoretical basis for the design and application of multifunctional fluorescent sensing materials and antibacterial molecules based on electrostatic interactions and anion-π+ interactions.

Lab on the Microneedles: A Wearable Metal-organic Frameworks-Based Sensor for Visual Monitoring of Stress Hormone.

Abnormal secretion and dysrhythmias of cortisol (CORT) are associated with various diseases such as sleep disorders, depression, and chronic fatigue. Wearable devices are a cutting-edge technology for point-of-care detection and dynamic monitoring of CORT with inspiring convenience. Herein, we developed a minimally invasive skin-worn device with the advanced integration of both interstitial fluid (ISF) sampling and target molecule sensing for simultaneous detection of CORT via a microneedle-based sensor with high sensitivity, excellent efficiency, and outstanding reproducibility. In the microneedle patch, swellable hydrogel was employed as the adsorption matrix for ISF extraction. Meanwhile, europium metal-organic frameworks (Eu-MOF) wrapped in the matrix played a vital role in CORT recognition and quantitative analysis. The wearable and label-free Eu-MOF-loaded microneedle patch exhibited high sensitivity in CORT detection with the detection limit reaching 10-9 M and excellent selectivity. Molecular dynamics simulation-driven mechanism exploration revealed that the strong interface interaction promoted fluorescence quenching of Eu-MOF. Moreover, in vitro and in vivo investigation confirmed the feasibility and reliability of the sensing method, and excellent biocompatibility was validated. Overall, a sensitive approach based on the wearable Eu-MOF microneedle (MN) patch was established for the simultaneous detection of CORT via visible fluorescence quenching with exciting clinical-translational ability.

HSA and DNA binding analysis of antiviral drug cidofovir: Spectroscopic and molecular docking techniques

This article discusses the interaction of antiviral drug cidofovir (CDV) with biomolecules (HSA and DNA) under simulated physiological conditions (pH 7.4). The binding propensity of CDV with DNA was assessed through UV–visible absorption spectroscopy, fluorescence spectroscopy, and molecular docking. The results of fluorescence spectroscopy indicated that the binding of CDV to DNA induced fluorescence quenching through a static quenching mechanism, with a binding constant of 1.03 × 103 M−1 at 293 K. The groove mode of CDV binding to calf thymus DNA (ct-DNA) was validated using dye displacement assays. The results from molecular docking confirmed the binding mode and supported the findings obtained through spectroscopic techniques. Furthermore, the binding propensity of CDV with HSA was assessed through fluorescence spectroscopy, UV–visible absorption spectroscopy, and docking simulation. The fluorescence data indicated that CDV quenches the intrinsic fluorescence of the protein through a static quenching process, with a binding constant of 5.60 × 103 M−1 at 293 K. Meanwhile, the results of docking simulation confirmed our spectroscopic findings.

Investigation of antimicrobial potential of nanocomposites based on functionalization of graphene oxide with zinc porphyrin complexes

Herein, zinc porphyrin complexes were synthesised by passing through the formation of free base porphyrin ligands and metalation of free base porphyrins with zinc metal ions. The synthesised zinc porphyrin complexes were functionalised with graphene oxide leading to the formation of zinc porphyrin anchored graphene oxide hybrid nanocomposites. The zinc porphyrins complexes were anchored with graphene oxide through the particular functional group present at the periphery of zinc porphyrins (hydroxyl and carboxyl functional groups in Pr1 and Pr2 respectively). 1H NMR and UV–visible spectroscopic techniques have monitored the successful formation of free base porphyrins and their matching zinc-integrated metalloporphyrin complexes. Various spectroscopic techniques like, photophysical properties (UV–Visible spectroscopy and Fluorescence spectroscopy), Fourier transform infrared (FT-IR), powdered X-ray diffraction (P-XRD) patterns, FE-SEM and EDAX analysis were used to examine the intrinsic characteristics of the prepared nanocomposites. The in-vitro antimicrobial activity of the synthesized complexes and nanocomposites was tested against Staphylococcus aureus gram-positive strain, Klebsiella pneumonia, and Escherichia coli. By working on the antimicrobial behaviour, it has been observed that the compound containing –COOH substitute has shown enhanced antimicrobial activity. The in silico molecular docking studies of the synthesized compounds with the S. aureus nucleoside diphosphate kinase receptor showed strong interactions via hydrogen bonding, π − π interactions and hydrophobic interactions. Molecular dynamics (MDs) simulations were used to study the dynamic behaviour of the complexes as well as nanocomposites which revealed the stability of docked structures with S. aureus nucleoside diphosphate kinase receptor. The in-silico pharmacokinetics studies showed the drug-likeness, non-toxic nature and safe oral administration of the synthesized compounds.

Construction of Polysiloxane Induced Multilevel Bowl-shaped Janus Particles for Fabrication of Photoluminescent, Enhanced, Heat-insulative Poly(styrene-co-butyl acrylate) Latex Coating

Silica-based nanoparticles (SNPs) are highly regarded as advantageous nanofillers for composite coating, owing to their high surface area, robust mechanical properties, chemical stability, and adaptability for surface modification. Recent studies have unveiled the potential photoluminescence of SNPs induced by intrinsic defect sites, eliminating the need for additional fluorescein molecules. However, the inadequate quantum yield and complex preparation processes for generating defect sites within SNPs have constrained their broader applications. Herein, we propose a facile method to prepare Janus silicon-based nanoparticles with a hierarchical bowl-shaped structure (JHSNPs) through the emulsification of methyltriethoxysilane hydrolysis and condensation products, coupled with the capillary force during nanoparticle formation. The distinctive structure enhances the formation of dioxasilyrane (=Si(O2)) and silylene (=Si:) defects, thereby exhibiting strong blue photoluminescence. The JHSNPs then serve as nanofillers for commonly used poly(styrene-co-butyl acrylate) (SA) waterborne coatings, significantly enhancing their mechanical properties, abrasion resistance, and UV radiation resistance compared to the original SA coatings. Moreover, with just a 1% addition of JHSNPs, the composite coating exhibits visible fluorescence intensity, conferring the self-detecting monitoring properties for external scratches. Due to the hierarchical air-entrapping void structure, JHSNPs composite coatings demonstrate excellent thermal isolation performance, with a 22% reduction in thermal conductivity. The design of JHSNPs opens new avenues to expand the versatility of silica-based nanoparticles in composite coatings, especially in the optical, safety, and energy-saving fields.

4,4’-(Thiophene-2,5-diylbis(ethyne-2,1-diyl))bis(1-methyl-1-pyridinium) Iodide

In the vast field of organic functional materials, viologens are widely recognized as an extremely versatile family of substances, due in part to the possibility of extending conjugation between the terminal pyridinium rings, for instance through the insertion of additional aromatic moieties. In this work, a new, extended viologen with a thiophene core and two acetylene bonds is presented. It was synthesized through a straightforward route, using well-established Sonogashira coupling reactions, and its optical properties were investigated by UV–visible absorption and fluorescence spectroscopy, revealing a very interesting material for diverse fluorescence-related applications.

A novel “Turn-Off-On” fluorescent probe for specific sequential detection of Cu2+ and glyphosate and its application in biological imaging

As common pollutants, Cu2+ and glyphosate pose a serious threat to human health and the ecosystem. Herein, a fluorescent probe (E)-7-(diethylamino)-N'(4-(diethylamino)-2-hydroxybenzyl)-2-oxo-2H chromophore-3-carbazide (DDHC) was designed and synthesised for the sequential recognition of Cu2+ and glyphosate. DDHC has the advantages of a short synthesis path, easy-to-obtain raw materials, good anti-interference ability, and strong stability. The interaction of the DDHC-Cu2+ complexes with glyphosate allows the amino and carboxyl groups in glyphosate molecules to coordinate with Cu2+ strongly, competing for the Cu2+ in the DDHC-Cu2+ complexes and releasing the DDHC, leading to the recovery of fluorescence. The recognition was further validated through Job’s plot, HRMS, and DFT calculations. In addition, the successful recovery of Cu2+ and glyphosate in different environmental water samples fully demonstrates the practical application potential of DDHC. Especially, DDHC has low cytotoxicity and can enter zebrafish and HeLa cells, rapidly reacting with Cu2+ and glyphosate in the body, generating visible fluorescence quenching and recovery phenomena, achieving real-time visual monitoring of exogenous Cu2+ and glyphosate in zebrafish and HeLa cells. The targeting and dual selectivity of DDHC greatly enhance its potential application value in the field of detection, providing important theoretical support for studying the fate of multiple pollutants in the environment.

Synthesis, Characterization and Photophysical Properties of 2-Quinolone-Based Compounds

2-Quinolone (1,2-dihydroquinoline) and 1-aza coumarin derivatives are quinoline class pharmacophore structures known for their versatile bioactive and stable photophysical properties. In the present study, N-amino (2) and N-acetamido (3) derivatives of 2-quinolone-based 1-aza Coumarin-3-carboxylic acid were synthesized. Structure characterizations of the synthesized compounds were performed using 1H NMR, IR, 13C NMR spectral techniques. The synthesized compounds are thought to be precursor structures for the development of new bioactive agents because of their structural similarity. The photophysical sensitivities of compounds (2 and 3), which have the 1-Aza coumarin skeleton, in different solvents were examined by ultraviolet−visible (UV−Vis) absorption spectroscopy and fluorescence spectroscopy methods. In addition, the compounds synthesized in this study could serve as fluorophores, fluorescently active and bioactive new Schiff base sensors in different fluorescence studies.

In vivo assessment of bladder cancer with diffuse reflectance and fluorescence spectroscopy: A comparative study.

The aim of this work is to assess the performance of multimodal spectroscopic approach combined with single core optical fiber for detection of bladder cancer during surgery in vivo. Multimodal approach combines diffuse reflectance spectroscopy (DRS), fluorescence spectroscopy in the visible (405 nm excitation) and near-infrared (NIR) (690 nm excitation) ranges, and high-wavenumber Raman spectroscopy. All four spectroscopic methods were combined in a single setup. For 21 patients with suspected bladder cancer or during control cystoscopy optical spectra of bladder cancer, healthy bladder wall tissue and/or scars were measured. Classification of cancerous and healthy bladder tissue was performed using machine learning methods. Statistically significant differences in relative total haemoglobin content, oxygenation, scattering, and visible fluorescence intensity were found between tumor and normal tissues. The combination of DRS and visible fluorescence spectroscopy allowed detecting cancerous tissue with sensitivity and specificity of 78% and 91%, respectively. The addition of features extracted from NIR fluorescence and Raman spectra did not improve the quality of classification. This study demonstrates that multimodal spectroscopic approach allows increasing sensitivity and specificity of bladder cancer detection in vivo. The developed approach does not require special probes and can be used with single-core optical fibers applied for laser surgery.

On-chip wavelength division multiplexing by angled multimode interferometer fabricated on erbium-doped thin film lithium niobate on insulator

Abstract Photonic-integrated circuits based on erbium-doped thin film lithium niobate on insulator has attracted broad interests with insofar various waveguide amplifiers and microlasers demonstrated. Wideband operation facilitated by the broadband absorption and emission of erbium ions necessitates the functional integration of wavelength filter and multiplexer on the same chip. Here, a low-loss wavelength division multiplexer at the resonant pumping and emission wavelengths (∼1480 nm and 1530–1560 nm) of erbium ions based on angled multimode interferometer is realized in the erbium-doped thin film lithium niobate on insulator fabricated by the photolithography assisted chemomechanical etching technique. The minimum on-chip insertion losses of the fabricated device are &lt;0.7 dB for both wavelength ranges, and a 3-dB bandwidth of &gt;20 nm is measured at the telecom C-band. Besides, direct visualization of the multimode interference pattern by the visible upconversion fluorescence of erbium ions compares well with the simulated light propagation in the multimode interferometer. Spectral tuning of the wavelength division multiplexer by structural design is also demonstrated and discussed.

Single-cell analysis of 5-aminolevulinic acid intraoperative labeling specificity for glioblastoma.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor, and resection is a key part of the standard of care. In fluorescence-guided surgery (FGS), fluorophores differentiate tumor tissue from surrounding normal brain. The heme synthesis pathway converts 5-aminolevulinic acid (5-ALA), a fluorogenic substrate used for FGS, to fluorescent protoporphyrin IX (PpIX). The resulting fluorescence is believed to be specific to neoplastic glioma cells, but this specificity has not been examined at a single-cell level. The objective of this study was to determine the specificity with which 5-ALA labels the diversity of cell types in GBM. The authors performed single-cell optical phenotyping and expression sequencing-version 2 (SCOPE-seq2), a paired single-cell imaging and RNA sequencing method, of individual cells on human GBM surgical specimens with macroscopically visible PpIX fluorescence from patients who received 5-ALA prior to surgery. SCOPE-seq2 allowed the authors to simultaneously image PpIX fluorescence and unambiguously identify neoplastic cells from single-cell RNA sequencing. Experiments were also conducted in cell culture and co-culture models of glioma and in acute slice cultures from a mouse glioma model to investigate cell- and tissue-specific uptake and secretion of 5-ALA and PpIX. SCOPE-seq2 analysis of human GBM surgical specimens revealed that 5-ALA treatment resulted in labeling that was not specific to neoplastic glioma cells. The cell culture further demonstrated that nonneoplastic cells could be labeled by 5-ALA directly or by PpIX secreted from surrounding neoplastic cells. Acute slice cultures from mouse glioma models showed that 5-ALA preferentially labeled GBM tumor tissue over nonneoplastic brain tissue with significant labeling in the tumor margins, and that this contrast was not due to blood-brain barrier disruption. Together, these findings support the use of 5-ALA as an indicator of GBM tissue but question the main advantage of 5-ALA for specific intracellular labeling of neoplastic glioma cells in FGS. Further studies are needed to systematically compare the performance of 5-ALA to that of potential alternatives for FGS.