Hybrid Titania–Zirconia Nanoparticles Coated Adsorbent for Highly Selective Capture of Nucleosides from Human Urine in Physiological Condition

Modified nucleosides are important biomarkers of cancers. For their analysis, boronate adsorbents were widely used to selectively capture them from urine, but often suffered from serious secondary hydrophobic interaction and harsh alkaline extraction condition. In this work, the hybrid titania–zirconia nanoparticles coated on porous silica spheres (TiO₂–ZrO₂/SiO₂) were developed for the first time as a selective adsorbent for nucleosides under neutral conditions based on specific recognition of its Lewis acid sites to the cis-diol group. It was found here that TiO₂–ZrO₂ has higher binding constants than pure TiO₂ or ZrO₂, and a significant improvement of binding efficiencies was obtained by decreasing calcination temperature to 400 °C. Moreover, physiological pH of urine (pH 6–7) was found optimal to adsorb nucleosides and resist other Lewis base interferences. By self-assembly of TiO₂–ZrO₂ nanoparticles on silica, unprecedentedly high binding capacity (35 mg/g) for nucleosides was obtained due to high surface area (350 m²/g) and abundant Lewis acid sites on the surface. Due to efficient reduction of secondary hydrophobic interaction on the inorganic surface, cis-diol nucleosides could be captured from 500-fold non-cis-diol interferences. In the real sample application, nine nucleosides have been quantified with relative recoveries in 83%–126%, and 42 ribosylated metabolites had been identified with only 100 μL of urine at physiological pH. Among them, two nucleosides have never been identified in most previous studies using boronate adsorbents for capture

Fast Equilibrium Micro-Extraction from Biological Fluids with Biocompatible Core–Sheath Electrospun Nanofibers

Sample preparation methods with high temporal resolution and matrix resistance will benefit fast direct analysis of analytes in a complex matrix, such as drug monitoring in biofluids. In this work, the core–sheath biocompatible electrospun nanofiber was fabricated as a micro-solid phase extraction material. With the poly­(<i>N</i>-isopropylacrylamide) (PNIPAAm) as sheath polymer and polystyrene (PS) as core polymer, the fiber membrane was highly hydrophilic and exhibited good antifouling ability to proteins and cells. Its complete expansion in aqueous solution and its nanoscale fiber (100–200 nm) structure offered high mass transfer rate of analytes between liquid and solid phases. The equilibration time of microextraction with this membrane was all shorter than 2 min for eight drugs tested, and the linear ranges covered more than 3 orders of magnitude for most of them. This membrane could be applied to monitor free drugs in plasma and their protein binding kinetics by equilibrium–microextraction with a 2 min temporal resolution. The results showed that the core–sheath electrospun nanofiber membrane would be a better alternative of solid phase material for microextraction with good matrix-resistance ability and high temporal resolution

In Vivo Fast Equilibrium Microextraction by Stable and Biocompatible Nanofiber Membrane Sandwiched in Microfluidic Device

In vivo analysis poses higher requirements about the biocompatibility, selectivity and speed of analytical method. In this study, an in vivo fast equilibrium microextraction method was developed with a biocompatible core–sheath electrospun nanofiber membrane sandwiched within a microfluidic unit. The polystyrene/collagen core–sheath nanofiber membrane was coaxially electrospun and strengthened with in situ glutaraldehyde cross-linking. This membrane not only kept high mass transfer rate, large extraction capacity and biomatrix resistance as our previously proposed membrane (Anal. Chem. 2013, 85 (12), 5924–5932), but also got much better mechanical strength and stability in water. The microfluidic device was designed to sandwich the membrane, and the blood in vivo can be introduced into it and get contact with the membrane repetitively. With this membrane and device, a 2-min equilibrium in vivo extraction method was established, validated in a simulated blood circulation system, and was used to monitor the pharmacokinetic profiles of desipramine in rabbits. The free and total concentration of desipramine in vivo was monitored with 10-min interval almost without rabbit blood consumed. The results met well with those of in vitro extraction, and a correlation factor of 0.99 was obtained

Additive-Free Synthesis of In₂O₃ Cubes Embedded into Graphene Sheets and Their Enhanced NO₂ Sensing Performance at Room Temperature

In this report, we developed an additive-free synthesis of In₂O₃ cubes embedded into graphene networks with InN nanowires (InN-NWs) and graphene oxide (GO) as precursors by a facile one-step microwave-assisted hydrothermal method. In absence of GO, the InN-NWs maintained their chemical composition and original morphology upon the same treatment. At varying mass ratios of InN-NWs and GO, the different morphologies and distributions of In₂O₃ could be obtained on graphene sheets. The uniform distribution, which is usually considered favorable for enhanced sensing performance, was observed in In₂O₃ cubes/reduced graphene oxide (rGO) composites. The room-temperature NO₂ sensing properties of the In₂O₃ cubes/rGO composites-based sensor were systematically investigated. The results revealed that the sensor exhibited a significant response to NO₂ gas with a concentration lower to 1 ppm, and an excellent selectivity, even though the concentrations of interferential gases were 1000 times that of NO₂. The enhanced NO₂ sensing performances were attributed to the synergistic effect of uniformly distributed In₂O₃ cubes and graphene sheets in the unique hybrid architectures without the interfering of extra additives

Detection of Glutathione <i>in Vitro</i> and in Cells by the Controlled Self-Assembly of Nanorings

Taking advantage of a reduction-controlled biocompatible condensation reaction and self-assembly, we have developed a new method for the determination of glutathione (GSH) concentration <i>in vitro</i> and in HepG2 human liver cancer cells. Upon reduction by GSH under physiological conditions (pH 7.4 in buffer), the small molecule <b>CBT-Cys­(SEt)</b> condenses and self-assembles into nanorings, increasing the UV absorbance at 380 nm (with significant linear correlation in the 0–87 μM GSH range and a limit of detection of 1 μM). This method is also selective to GSH rather than cysteine in biological samples. Through the use of added internal standards, we successfully determined the concentration of GSH in HepG2 cells to be 14.96 μM (2.99 fmol/cell). To better understand the mechanism of nanoring self-assembly, the condensation product of <b>CBT-Cys­(SEt)</b> formed using different concentrations of GSH and different reaction times were characterized by transmission electron microscopy (TEM)