Magnetic separation of heavy metal ions and evaluation based on surface‐enhanced Raman spectroscopy: Copper(II) ions as a case study

A new approach was developed for the magnetic separation of copper(II) ions with easy operation and high efficiency. p‐Mercaptobenzoic acid served as the modified tag of Fe₂O₃@Au nanoparticles both for the chelation ligand and Raman reporter. Through the chelation between the copper(II) ions and carboxyl groups on the gold shell, the Fe₂O₃@Au nanoparticles aggregated to form networks that were enriched and separated from the solution by a magnet. A significant decrease in the concentration of copper(II) ions in the supernatant solution was observed. An extremely sensitive method based on surface‐enhanced Raman spectroscopy was employed to detect free copper(II) ions that remained after the magnetic separation, and thus to evaluate the separation efficiency. The results indicated the intensities of the surface‐enhanced Raman spectroscopy bands from p‐mercaptobenzoic acid were dependent on the concentration of copper(II) ions, and the concentration was decreased by several orders of magnitude after the magnetic separation. The present protocol effectively decreased the total amount of heavy metal ions in the solution. This approach opens a potential application in the magnetic separation and highly sensitive detection of heavy metal ions.     

Hippocampal metabolomics using ultrahigh-resolution mass spectrometry reveals neuroinflammation from Alzheimer’s disease in CRND8 mice

In the wake of genomics, metabolomics characterizes the small molecular metabolites revealing the phenotypes induced by gene mutants. To address the metabolic signatures in the hippocampus of the amyloid-beta (Aβ) peptides produced in transgenic (Tg) CRND8 mice, high-field ion cyclotron resonance–Fourier transform mass spectrometry supported by LC-LTQ-Orbitrap was introduced to profile the extracted metabolites. More than 10,000 ions were detected in the mass profile for each sample. Subsequently, peak alignment and the 80 % rule followed by feature selection based on T score computation were performed. The putative identification was also conducted using the highly accurate masses with isotopic distribution by interfacing the MassTRIX database as well as MS/MS fragmentation generated in the LTQ-Orbitrap after chromatographic separation. Consequently, 58 differentiating masses were tentatively identified while up to 44 differentiating elemental compositions could not be biologically annotated in the databases. Nonetheless, of the putatively annotated masses, eicosanoids in arachidonic acid metabolism, fatty acid beta-oxidation disorders as well as disturbed glucose metabolism were highlighted as metabolic traits of Aβ toxicity in Tg CRND8 mice. Furthermore, a web-based bioinformatic tool was used for simulation of the metabolic pathways. As a result of the obtained metabolic signatures, the arachidonic acid metabolism dominates the metabolic perturbation in hippocampal tissues of Tg CRND8 mice compared to non-Tg littermates, indicating that Aβ toxicity functions neuroinflammation in hippocampal tissue and new theranostic opportunities might be offered by characterization of altered arachidonic acid metabolism for Alzheimer’s disease.      

Coupling of ultrasound‐assisted extraction and expanded bed adsorption for simplified medicinal plant processing and its theoretical model: Extraction and enrichment of ginsenosides from Radix Ginseng as a case study

A high‐efficient and environmental‐friendly method for the preparation of ginsenosides from Radix Ginseng using the method of coupling of ultrasound‐assisted extraction with expanded bed adsorption is described. Based on the optimal extraction conditions screened by surface response methodology, ginsenosides were extracted and adsorbed, then eluted by the two‐step elution protocol. The comparison results between the coupling of ultrasound‐assisted extraction with expanded bed adsorption method and conventional method showed that the former was better than the latter in both process efficiency and greenness. The process efficiency and energy efficiency of the coupling of ultrasound‐assisted extraction with expanded bed adsorption method rapidly increased by 1.4‐fold and 18.5‐fold of the conventional method, while the environmental cost and CO₂ emission of the conventional method were 12.9‐fold and 17.0‐fold of the new method. Furthermore, the theoretical model for the extraction of targets was derived. The results revealed that the theoretical model suitably described the process of preparing ginsenosides by the coupling of ultrasound‐assisted extraction with expanded bed adsorption system.     

A novel derivatization reagent possessing a bromoquinolinium structure for biological carboxylic acids in HPLC‐ESI‐MS/MS

A novel bromoquinolinium reagent, i.e. 1‐(3‐aminopropyl)‐3‐bromoquinolinium bromide (APBQ), was synthesized for the analysis of carboxylic acids. A simple and practical precolumn derivatization procedure using the APBQ in RP chromatography and MS (HPLC‐MS) has been developed using bile acids and free fatty acids, as the representative carboxylic acids in biological samples. The APBQ efficiently reacted with carboxylic acids at 60°C for 60 min in the presence of N,N‐dicyclohexylcarbodiimide and pyridine as the activation reagents. Because the APBQ possesses a bromine atom in the structure, the identification of a series of carboxylic acids was easily achieved due to the characteristic bromine isotope pattern in the mass spectra. The APBQ also has a quaternary amine structure, thus the positively charged derivatives are predominate for the highly sensitive detection of carboxylic acids. The APBQ was successfully applied to the selective determination of biological carboxylic acids in human plasma. The bile acids (chenodeoxycholic acid and deoxycholic acid) and several saturated (stearic acid and palmitic acid) and unsaturated free fatty acids (oleic acid and linoleic acid) were reasonably determined by HPLC‐MS under the proposed procedure. Based on the results of analyses of human plasma and saliva, the proposed procedure using APBQ seems to be applicable for the qualitative and quantitative analyses of a series of carboxylic acids in biological samples.     

Liquid chromatographic resolution of racemic rasagiline and its analogues on a chiral stationary phase based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

A liquid chromatographic chiral stationary phase based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid was applied to the resolution of 15 analytes, including racemic rasagiline, a chiral drug for the treatment of Parkinson's disease, and its analogues. The composition of mobile phase was optimized to be ethanol/acetonitrile/acetic acid/triethylamine (80:20:0.2:0.3, v/v/v/v) by evaluating the chromatographic results for the resolution of five selected analytes under various mobile phase conditions. Under the optimized mobile phase conditions, racemic rasagiline was resolved quite well with a separation factor of 1.48 and resolution of 2.71 and its 14 analogues were also resolved reasonably well with separation factors of 1.06–1.54 and resolutions of 0.54–2.11. Among 15 analytes, racemic rasagiline was resolved best except for just one analyte. The analyte structure–enantioselectivity relationship indicated that racemic rasagiline has the most appropriate structural characteristics for resolution on the chiral stationary phase.     

Adsorption in columns packed with porous adsorbent particles having partially fractal structures

A mathematical model is constructed and solved that could describe the dynamic behavior of the adsorption of a solute of interest in single and stratified columns packed with partially fractal porous adsorbent particles. The results show that a stratified column bed whose length is the same as that of a single column bed, provides larger breakthrough times and a higher dynamic utilization of the adsorptive capacity of the particles than those obtained from the single column bed, and the superior performance of the stratified bed becomes especially more important when the superficial velocity of the flowing fluid stream in the column is increased to accommodate increases in the system throughput. This occurs because the stratified column bed provides larger average external and intraparticle mass transfer and adsorption rates per unit length of packed column. It is also shown that increases in the total number of recursions of the fractal and the ratio of the radii between larger and smaller microspheres that make up the partially fractal particles, increase the intraparticle mass transfer and adsorption rates and lead to larger breakthrough times and dynamic utilization of the adsorptive capacity of the particles. The results of this work indicate that highly efficient adsorption separations could be realized through the use of a stratified column comprised from a practically reasonable number of sections packed with partially fractal porous adsorbent particles having reasonably large (i) total number of recursions of the fractal and (ii) ratio of the radii between larger and smaller microspheres from which the partially fractal particles are made from. It is important to mention here that the physical concepts and modeling approaches presented in this work could be, after a few modifications of the model, applied in studying the dynamic behavior of chemical catalysis and biocatalysis in reactor beds packed with partially fractal porous catalyst particles.     

Facile Fabrication of Multi‐targeted and Stable Biochemical SERS Sensors

The direct transfer of single‐crystalline Au nanowires (NWs) onto Au substrates was achieved by a simple attachment and detachment process. In the presence of a lubricant, Au NWs grown vertically on a sapphire substrate were efficiently moved to an Au substrate through van der Waals interactions. We demonstrate that the transferred Au NWs on the Au substrate can act as sensitive, reproducible, and long‐term‐stable surface‐enhanced Raman scattering (SERS) sensors by detecting human α‐thrombin as well as Pb²⁺ and Hg²⁺ ions. These three biochemically and/or environmentally important analytes were successfully detected with high sensitivity and selectivity by Au NW‐SERS sensors bound by a thrombin‐binding aptamer. Furthermore, the as‐prepared sensors remained in working order after being stored under ambient conditions at room temperature for 80 days. Because Au NWs can be routinely transferred onto Au substrates and because the resultant Au NW‐SERS sensors are highly stable and provide with high sensitivity and reproducibility of detection, these sensors hold potential for practical use in biochemical sensing.     

Sensitive detection of human breast cancer cells based on aptamer–cell–aptamer sandwich architecture

Breast cancer is one of the most critical threats to the health of women, and the development of new methods for early diagnosis is urgently required, so this paper reports a method to detect Michigan cancer foundation-7 (MCF-7) human breast cancer cells with considerable sensitivity and selectivity by using electrochemical technique. In this method, a mucin 1 (MUC1)-binding aptamer is adopted to recognize MCF-7 human breast cancer cells, while enzyme labeling is employed to produce amplified catalytic signals. The molecular recognition and the signal amplification are elaborately integrated by fabricating an aptamer–cell–aptamer sandwich architecture on an electrode surface, thus a biosensor for the detection of MCF-7 is fabricated based on the architecture. The detection range can be from 100 to 1 × 10⁷ cells, and the detection limit can be as low as 100 cells. The method is also cost-effective and conveniently operated, implying potential help for the development of early diagnosis of breast cancer.     

Simultaneous,real-time measurement of nitric oxide and oxygen dynamics during cardiac ischemia-reperfusion of the rat utilizing sol-gel-derived electrochemical microsensors

In this study, we simultaneously measured nitric oxide (NO) and oxygen (O₂) dynamics in the myocardium during myocardial ischemia-reperfusion (IR) utilizing sol-gel modified electrochemical NO and O₂ microsensors. In addition, we attempted to clarify the correlation between NO release in the ischemic period and O₂ restoration in the myocardium after reperfusion, comparing a control heart with a remote ischemic preconditioning (RIPC)-treated heart as an attractive strategy for myocardial protection. Rat hearts were randomly divided into two groups: a control group (n = 5) and an RIPC group (n = 5, with RIPC treatment). Myocardia that underwent RIPC treatment (182 ± 70 nM, p < 0.05) released more NO during the ischemic period than those of the control group (63 ± 41 nM). The restoration value of oxygen tension (pO₂) in the RIPC group significantly increased and was restored to pre-ischemic levels (92.6 ± 36.8%); however, the pO₂ of the control group did not increase throughout the reperfusion period (5.7 ± 7.5%, p = 0.001). Myocardial infarct size measurements revealed a significant decrease in cell death in the myocardium region of the RIPC group (41.44 ± 6.42%, p = 0.001) compared with the control group (60.05 ± 10.91%). As a result, we showed that the cardioprotective effect of RIPC could be attributed to endogenous NO production during the ischemic period, which subsequently promoted reoxygenation in post-ischemic myocardia during early reperfusion. Our results suggest that the promotion of endogenous formation during an ischemic episode might be helpful as a therapeutic strategy for protecting the myocardium from IR injury. Additionally, our NO and O₂ perm-selective microsensors could be utilized to evaluate the effect of drug or treatment.