Low Background Interference Research Articles

A red fluorogen: AIEE characteristic, photoluminescence mechanism and its application as chemosensor for ClO.

Red material is widely used in many fields because it has a lot of high performances such as strong penetrability, little trauma to cell and tissue, easy to prepare, and low background interference. However, a lot of organic materials were troubled with the aggregation caused emission quenching (ACQ) effect, which really limits their practical applications. In contrast, aggregation induced emission (AIE) and aggregation-induced enhanced emission (AIEE) effects provide an efficient method to break the obstacle of ACQ effect. Herein, a red light molecule was developed by integrating cyano and alkyl sulfide moieties. Its photoluminescence mechanism was further revealed by fluorescence spectrum, density functional theory (DFT) and X-ray single crystal diffraction, respectively. It is found that this compound has good planar construction and has no rotatory unit, it showed typical AIEE performance because of intramolecular D-π-A structure and the formation of J-aggregation. This molecular design principle may be able to offer an effective strategy to exploit red AIE/AIEE organic materials. Meanwhile, this fluorogen showed excellent response capability to ClO- including high selectivity and sensitivity, and cell imaging performance.

Development of a high-coverage matrix-assisted laser desorption/ionization mass spectrometry imaging method for visualizing the spatial dynamics of functional metabolites in Salvia miltiorrhiza Bge

Profiling the spatial distributions and dynamic changes of metabolites in plant tissue is critical to elucidate the complex metabolic regulation during plant growth, development, and responses to abiotic or biotic stresses. In this study, we developed a high-coverage MALDI-MS imaging method to visualize the spatial locations of a wide spectrum of metabolites in Salvia miltiorrhiza Bge. 1,5-Diaminonaphthalene (DAN) and 1,1′-binaphthyl-2,2′-diamine (BNDM) were optimized as MALDI matrices in positive and negative ion modes respectively, due to their low background interference and high sensitivity. Moreover, a simple organic washing protocol using acetone was shown to significantly improve the sensitivity of MALDI-MSI. Using this method, we successfully imaged the spatial locations of amino acids, phenolic acids, fatty acids, oligosaccharides, cholines, polyamines, tanshinones, and phospholipids in Salvia miltiorrhiza Bge. In addition, the distributions of some metabolites in Salvia miltiorrhiza Bge root and stem were found to exhibit good spatial match with plant tissue structure. Thus, our method provides a spatially-resolved way to map the plant metabolic networks and to understand the physiological roles of several plant metabolites.

Oxygen-Sensing Probes and Bandage for Optical Detection of Inflammation.

Small-molecular and macromolecular optical probes based on an iridium complex chromophore were designed for detecting hypoxic inflammation in this work. The optical probes had a large conjugated ligand that could extend its phosphorescence emission to the red-wavelength region, thus increasing the tissue penetration depth of the optical signal. Due to good water solubility, the macromolecular optical probe could image both monolayer cells and three-dimensional multicellular spheroids. Moreover, this macromolecular probe was able to effectively image inflammation and distinguish healthy and inflammatory regions in a mouse model of lipopolysaccharide (LPS)-induced inflammation with low background interference. Furthermore, we integrated the hydrophobic small-molecular probe into the polyurethane thin film, and the resulting film successfully monitored the inflammation of chronic wounds in a mouse model. This work demonstrated the great potential of the iridium complex in optical imaging hypoxia and hypoxia-associated inflammation and will have significant impact on the design of high-sensitivity sensors for the detection of hypoxia.

Spatial Heterodyne Raman Spectrometer (SHRS) for In Situ Chemical Sensing Using Sapphire and Silica Optical Fiber Raman Probes.

A spatial heterodyne Raman spectrometer (SHRS), constructed using a modular optical cage and lens tube system, is described for use with a commercial silica and a custom single-crystal (SC) sapphire fiber Raman probe. The utility of these fiber-coupled SHRS chemical sensors is demonstrated using 532 nm laser excitation for acquiring Raman measurements of solid (sulfur) and liquid (cyclohexane) Raman standards as well as real-world, plastic-bonded explosives (PBX) comprising 1,3,5- triamino- 2,4,6- trinitrobenzene (TATB) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) energetic materials. The SHRS is a fixed grating-based dispersive interferometer equipped with an array detector. Each Raman spectrum was extracted from its corresponding fringe image (i.e., interferogram) using a Fourier transform method. Raman measurements were acquired with the SHRS Littrow wavelength set at the laser excitation wavelength over a spectral range of ∼1750 cm-1 with a spectral resolution of ∼8 cm-1 for sapphire and ∼10 cm-1 for silica fiber probes. The large aperture of the SHRS allows much larger fiber diameters to be used without degrading spectral resolution as demonstrated with the larger sapphire collection fiber diameter (330 μm) compared to the silica fiber (100 μm). Unlike the dual silica fiber Raman probe, the dual sapphire fiber Raman probe did not include filtering at the fiber probe tip nearest the sample. Even so, SC sapphire fiber probe measurements produced less background than silica fibers allowing Raman measurements as close as ∼85 cm-1 to the excitation laser. Despite the short lengths of sapphire fiber used to construct the sapphire probe, well-defined, sharp sapphire Raman bands at 420, 580, and 750 cm-1 were observed in the SHRS spectra of cyclohexane and the highly fluorescent HMX-based PBX. SHRS measurements of the latter produced low background interference in the extracted Raman spectrum because the broad band fluorescence (i.e., a direct current, or DC, component) does not contribute to the interferogram intensity (i.e., the alternating current, or AC, component). SHRS spectral resolution, throughput, and signal-to-noise ratio are also discussed along with the merits of using sapphire Raman bands as internal performance references and as internal wavelength calibration standards in Raman measurements.

The Biological Applications of Two Aggregation‐Induced Emission Luminogens

Fluorescence imaging, as a commonly used scientific tool, is widely applied in various biomedical and material structures through visualization technology. Highly selective and sensitive luminescent biological probes, as well as those with good water solubility, are urgently needed for biomedical research. In contrast to the traditional aggregation-caused quenching of fluorescence, in the unique phenomenon of aggregation-induced emission (AIE), the individual luminogens have extremely weak or no emissivity because they each have free intramolecular motion; however, when they form aggregates, these components immediately "light up". Since the discovery of "turn-on" mechanism, researchers have been studying and applying AIE in a variety of fields to develop more sensitive, selective, and efficient strategies for the AIE dyes. There are numerous advantages to the use of AIE-based methods, including low background interference, strong contrast, high performance in intracellular imaging, and the ability for long-term monitoring in vivo. In this review, two typical examples of AIEgens, TPE-Cy and TPE-Ph-In, are described, including their structure properties and applications. Recent progress in the biological applications is mainly focused on. Undoubtedly, in the near future, an increasing number of encouraging and practical ideas will promote the development of more AIEgens for broad use in biomedical applications.

Rational design of stable near-infrared cyanine-based probe with remarkable large Stokes Shift for monitoring Carbon monoxide in living cells and in vivo

Carbon monoxide (CO) is an important kind of gasotransmitter associated closely with pathogenesis of inflammation and detection of CO in living systems is of great attraction in recent years. To data, accurate fluorescent detection of CO in vivo is still challenging. In this study, we reported for a new simple NIR fluorescent probe CO–B with stable allyl ether as the specific CO-reactive site. The detection mechanism of this probe has been proven through the rearrangement of conjugated π-electron system. CO–B featured large Stokes shift (135 nm), low toxicity, good sensitivity (detection limit of ∼110 nM) and selectivity for CO detection. CO–B successfully served as an indicator for imaging CO in Heme-stimulation inflammation model. Finally, CO–B was also employed for in vivo imaging CO in living mice with low background interference. All together, probe CO–B was potentially valuable as a promising tool for monitoring and tracking CO in preclinical applications.

In Vivo Assembly and Disassembly of Probes to Improve Near-Infrared Optical Bioimaging.

The near-infrared range (NIR, 700-1700 nm) has been used as a superior optical window for non-invasive bioimaging. Increasing signal-to-noise ratio (SNR) is the most fundamental method to improve NIR bioimaging. However, the low delivery efficiency of fluorescent contrast agents leads to weak signal at lesions. Moreover, non-specific accumulation and "always on" signals will cause "false positive" signals and high background noise, all of which result in low SNR and potential long-term biotoxicity. Thus, to reach precise detection of lesions, strong bioimaging signals and low background interference are the two important pre-requisites. This review provides an overview of in vivo assembly and disassembly strategies to improve tumor-specific accumulation, "turn-on" the silent signals, and reduce the background noise in NIR bioimaging windows. In vivo assembly and disassembly occurring spontaneously, responding to disease micro-environment or external stimuli, including pH, enzymes, reactive oxygen species, redox, light, and specific recognition is summarized, which may provide ideas and approaches to further enhance bioimaging and reduce long-term biotoxicity concerns.

Fast response near-infrared fluorescent probe for hydrogen sulfide in natural waters

Rapid and sensitive detection of hydrogen sulfide (H2S) is of great importance for the environmental monitoring. Near-infrared fluorescent probes are recently developed for the sensitive H2S detection thanks to their low background interference, while often hampered by relatively long response time (around 30 min). In this work, we reported a fast response (within 5 min), highly sensitive near-infrared (NIR) fluorescent probe (DCM-OCN) for H2S. The rapid nucleophilic reaction between cyanate moiety and H2S endowed fast response of the NIR probe. The influence of experimental parameters (including CTAB concentration, reaction time, pH value etc.), interference study, and possible mechanism were investigated in detail. The fluorescence increment was linear with H2S concentration in 1–10 μM with a detection limit of 0.28 μM (3σ). The probe was successfully applied to environmental water samples including river water, tap water, lake water, mineral water and artificial wastewater.

ICT-based near infrared fluorescent switch-on probe for nitric oxide bioimaging in vivo

A cyanine dye (Cy7) based turn-on fluorescence probe has been successfully synthesized for the detection of nitric oxide through the attachment of a methyl amino group at the meso position of Cy7 dye. The probe exhibits weak fluorescent emission at 800 nm due to intramolecular charge transfer process, while it quickly turns into highly NIR fluorescent state upon the treatment with NO. The detection limit is as low as 11.3 nM. In addition, the selectivity of the probe toward NO over reactive oxygen species, reactive nitrogen species, and metal ions was also demonstrated. Importantly, the fluorescence response of this probe to NO occurs in the physiologically favorable NIR region, enabling its further use to image endogenous NO in an inflamed mouse model with low background interference and deep penetration depth.

Aggregation-Induced Emission: Lighting Up hERG Potassium Channel.

Based on the scaffold of astemizole and E-4031, four AIE light-up probes (L1–L4) for Human Ether-a-go-go-Related Gene (hERG) potassium channel were developed herein using AIE fluorogen(TPE). These probes showing advantages such as low background interference, superior photostability, acceptable cell toxicity, and potent inhibitory activity, which could be used to image hERG channels at the nanomolar level. These AIE light-up probes hoped to provide guidelines for the design of more advanced AIE sensing and imaging hERG channels to a broad range of applications.

Nanocarrier-Based Biological Fluorescent Probes for Simultaneous Detection of Ketamine and Amphetamine in Latent Fingermarks

Nanocarrier-based biological fluorescent probes for ketamine and amphetamine have been prepared by conjugating red and green fluorescent nanoparticles (150-nm-sized) with anti-ketamine and anti-amphetamine antibodies, respectively, with the assistance of carbodiimide/[Formula: see text]-hydroxysuccinimide. Biological fluorescent probes for ketamine and amphetamine could simultaneously detect these two drugs within a single fingermark by one-step test. Nanoparticles as carrier played dual-functional roles for not only fingermark visualization but also drug recognition. Latent fingermarks were visualized by the fluorescence signal generated from nanoparticles. The developed fingermarks clearly revealed ridge pattern and sufficient minutiae for individual identification. Ketamine and amphetamine were recognized by simply observing the colors of fluorescent images when the fingermark was checked in red and green channels. Detection limit of ketamine or amphetamine was 50[Formula: see text]ng in fingermark. This work therefore provides a novel nanocarrier-based strategy of drug detection as well as personal identification with high selectivity, low background interference and fast testing, which can be further broadened to other drugs and molecules.

Recent Progress in Fluorescent Vesicles with Aggregation-induced Emission

Fluorescent vesicles have recently attracted increasing attention because of their potential applications in bioimaging, diagnostics, and theranostics, for example, in vivo study of the delivery and the distribution of active substances. However, fluorescent vesicles containing conventional organic dyes often suffer from the problem of aggregation-caused quenching (ACQ) of fluorescence. Fluorescent vesicles working with aggregation-induced emission (AIE) offer an extraordinary tool to tackle the ACQ issue, showing advantages such as high emission efficiency, superior photophysical stability, low background interference, and high sensitivity. AIE fluorescent vesicles represent a new type of fluorescent and functional nanomaterials. In this review, we summarize the recent advances in the development of AIE fluorescent vesicles. The review is organized according to the chemical structures and architectures of the amphiphilic molecules that constitute the AIE vesicles, i.e., small-molecule amphiphiles, amphiphilic polymers, and amphiphilic supramolecules and supramacromolecules. The studies on the applications of these AIE vesicles as stimuli-responsive vesicles, fluorescence-guided drug release carriers, cell imaging tools, and fluorescent materials based on fluorescence resonance energy transfer (FRET) are also discussed.

Near-infrared turn-on fluorescent probe for discriminative detection of Cys and application in in vivo imaging.

Near-infrared (NIR) fluorescent probes are widely employed in biological detection because of their lower damage to biological samples, low background interference, and high signal-to-noise ratio. Herein, a highly water-soluble NIR probe (NIRHA) based on a hemicyanine skeleton and bearing an acrylate moiety was synthesized. The probe showed high selectivity toward cysteine (Cys) over homocysteine (Hcy) and glutathione (GSH). The probe also had low cytotoxicity and was successfully applied in HeLa cells and mouse experiments. Results of bioimaging experiments indicated that the probe was effective for visualizing endogenous Cys in vitro and in vivo.

Magnetic metal-organic framework nanocomposites for enrichment and direct detection of environmental pollutants by negative-ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Nowadays, the detection and removal of environmental pollutants are particularly important, owing to their harmful influence on human beings’ health. Specifically, metal-organic frameworks (MOFs) as the hot materials with great potential have been widely employed as adsorbents for pollutants removal, as well as matrixes for mass spectrometry detection. In this work, magnetic Zr-based MOF (denoted as Fe3O4@PDA@ZrMOF) with outstanding properties, such as low background interference, high desorption/ionization efficiency, excellent signal reproducibility, ultrahigh surface area and strong magnetic responsiveness, was synthesized by a modified thermal annealing method. The Fe3O4@PDA@ZrMOF not only can be utilized as adsorbent towards small molecules by π-π stacking interaction between nitrophenols and ZrMOF, but also can serve as a matrix for detection of small molecules under the negative ion mode of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). As a result, with the use of Fe3O4@PDA@ZrMOF, the detection limits of 4-nitrocatechol and 4-nitroguaiacol were estimated to be about 68 μg/ml and 25 μg/ml, respectively. In addition, enrichment of nitrophenols from PM2.5 was investigated. The detected mass concentrations of 4-nitrocatechol and 4-nitroguaiacol in collected PM2.5 samples were 0.11 ng/m3 and 0.15 ng/m3, respectively, indicating the highly efficient enrichment performance of Fe3O4@PDA@ZrMOF for low-abundance nitrophenol compounds in the environment.

Recent Progress in 808 nm Excited Upconversion Nanomaterials as Multifunctional Nanoprobes for Visualized Theranostics in Cancers.

Near-infrared (NIR) light responsive nanomaterials have attracted considerable attention due to their location in the biological window. Especially, lanthanide-doped nanomaterials exhibit unique upconversion luminescence (UCL) properties with low background interference and long luminescence lifetime, which makes them promising in imaging diagnosis of cancers. Compared with traditional upconversion nanomaterials excited by 980 nm laser, 808 nm excitation can overcome the disadvantages of high heating effect and weak penetration depth induced by excitation source. Therefore, developing 808 nm excited upconversion nanoprobes will be important for the in vivo bio-imaging and visualized theranostics of tumors in deep-tissue. In the review paper, we systematically summarized the synthesis strategy and luminescence modulation of Nd3+-sensitized upconversion nanomaterials under 808 nm excitation, discussed the influence of excitation source on heating effect and penetration depth, and particularly focused on their applications in UCL imaging, multi-modal imaging and imaging-guided therapy of cancers.

Real-time monitoring of γ-Glutamyltranspeptidase in living cells and in vivo by near-infrared fluorescent probe with large Stokes shift

γ-Glutamyltranspeptidase (GGT) is a cell surface-bound enzyme that is closely implicated in various physiological disorders such as tumor. Thus, an efficient method for monitoring GGT is extremely important for biological studies and disease diagnosis. Herein, a near-infrared fluorescent probe (TMN-Glu) has been developed for turn-on trapping of GGT activity in vitro and in vivo based on conjugating a dicyanoisophorone derivative fluorophore with a GGT activatable γ-glutamyl amide moiety. Advantages of the probe include near-infrared emission (658 nm), with large Stokes shift (213 nm), high specificity, high sensitivity (LOD = 0.024 U/L), low cytotoxicity and high imaging resolution, allowing for the real-time imaging endogenous GGT in living cells. Probe TMN-Glu was highly feasible to report on the GGT levels in different types of cells. Notably, we also demonstrated its applicability in real-time visualizing endogenous GGT in tumor-bearing nude mice with low background interference. These results indicated that the probe held great promise for real-time sensing and tracking GGT in complex biological systems, which would be useful for basic researches and clinical diagnosis of GGT-related diseases.

Exploration of Fungal Metabolic Interactions Using Imaging Mass Spectrometry on Nanostructured Silicon.

Application of matrix-assisted laser desorption/ionization imaging mass spectrometry to microbiology and natural product research has opened the door to the exploration of microbial interactions and the consequent discovery of new natural products and their functions in the interactions. However, several drawbacks of matrix-assisted laser desorption/ionization imaging mass spectrometry have limited its application especially to complicated and uneven microbial samples. Here, we applied nanostructured silicon as a substrate for surface-assisted laser desorption/ionization mass spectrometry for microbial imaging mass spectrometry to explore fungal metabolic interactions. We chose Phellinus noxius and Aspergillus strains to evaluate the potential of microbial imaging mass spectrometry on nanostructured silicon because both fungi produce a dense mass of aerial mycelia, which is known to complicate the collection of high-quality imaging mass spectrometry data. Our simple and straightforward sample imprinting method and low background interference resulted in an efficient analysis of small metabolites from the complex microbial interaction samples.

Ultrasensitive Silicon Nanoparticle Ratiometric Fluorescence Determination of Mercury(II)

ABSTRACTA novel ratiometric fluorescence sensing system for the ultrasensitive detection of Hg2+ was developed. It used aminofunctionalized silicon nanoparticles and rhodamine B, which exhibit two distinct fluorescence emission peaks at 449 and 581 nm, respectively, under a single excitation wavelength (350 nm). The fluorescence of the amino-functionalized silicon nanoparticles was selectively quenched by Hg2+, while that of rhodamine B was insensitive to Hg2+. The ratio of fluorescence intensities at 449–581 nm linearly decreased with increasing concentrations of Hg2+ from 0.005–0.1 and 0.1–7 µM within 0.5 min, and a detection limit as low as 3.3 nM was achieved. Moreover, the ratiometric fluorescence sensing system exhibited good selectivity toward Hg2+ over other metal ions with relatively low background interference, even in a complex matrix such as lake water. Most importantly, the practical use of this sensing system for Hg2+ detection in real water samples was also demonstrated.

A novel BODIPY-based fluorescent probe for selective detection of hydrogen sulfide in living cells and tissues

Hydrogen sulfide (H2S) is a critical biological messenger in numerous physiological and pathophysiological processes. Small-molecule fluorescent probes combined with fluorescent microscopy have been developed for the sensitive detection of H2S. Here, we designed and synthesized a long-wavelength BODIPY-based probe (TMSDNPOB) based on the thiolysis of dinitrophenyl ether according to photo-induced electron transfer theory and the results of computational calculation. 4,4-Difluoro-8-phenyl-1,5,7-trimethyl-3-(4-(2,4-dinitrophenoxy)styryl- 4-bora-3a,4a-diaza-s-indacene (TMSDNPOB) is nearly non-fluorescent, but the reaction product (TMSHOB) emits strong red fluorescence at 592nm when excited at 574nm. The long wavelengths of the designed probe indicate low background interference from biological matrix and little photo damage on fluorescence imaging of H2S. With the advantages of the turn-on probe for H2S including high sensitivity, high selectivity, good biocompatibility and low toxicity, the probe has been used for imaging H2S in living cells and liver tissues.

N-Phenyl-2-naphthylamine as a Novel MALDI Matrix for Analysis and in Situ Imaging of Small Molecules.

Due to its strong ultraviolet absorption, low background interference in the small molecular range, and salt tolerance capacity, N-phenyl-2-naphthylamine (PNA) was developed as a novel matrix in the present study for analysis and imaging of small molecules by matrix-assisted laser desorption/ionization mass spectrometry time-of-fight (MALDI-TOF MS). The newly developed matrix displayed good performance in analysis of a wide range of small-molecule metabolites including free fatty acids, amino acids, peptides, antioxidants, and phospholipids. In addition, PNA-assisted LDI MS imaging of small molecules in brain tissue of rats subjected to middle cerebral artery occlusion (MCAO) revealed unique distributions and changes of 89 small-molecule metabolites including amino acids, antioxidants, free fatty acids, phospholipids, and sphingolipids in brain tissue 24 h postsurgery. Fifty-nine of the altered metabolites were identified, and all the changed metabolites were subject to relative quantitation and statistical analysis. The newly developed matrix has great potential application in the field of biomedical research.