Direct analysis and profiling of a complex endotoxin without any prior purification or sample treatment techniques using chitosan nanomagnets coupled with MALDI-MS techniques has been demonstrated. Surface modified magnetic nanoparticles such as Fe3O4 and CuFeO2 with chitosan were synthesized and characterized by using UV, TEM, and FTIR. Endotoxin (lipopolysaccharides (LPS)) was spiked into human urine and recovery enabled using chitosan nanomagnets. For the first time, the use of CuFeO2@chitosan and Fe3O4@chitosan nanomagnets for affinity based separation and enrichment of trace levels of endotoxin and direct detection using MALDI-MS has been successfully achieved. The chitosan nanomagnet based recovery of endotoxin from urine samples showed a high degree of sensitivity compared to the conventional MALDI-MS analysis, where the lowest detectable endotoxin concentration was 30 mg mL−1 (0.15 mg, 5 μL). The Fe3O4@chitosan nanomagnet approach has 67 times higher sensitivity at 450 μg mL−1 (2.25 μg, 5 μL) compared to the direct MALDI-MS analysis. However, CuFeO2@chitosan nanomagnets appeared to be more effective than Fe3O4@chitosan nanomagnets (about 4 times) and 250 times more sensitive for separation at 120 μg mL−1 (0.6 μg, 5 μL) and detection of endotoxin from urine. The current approach proposes a novel MALDI-MS platform using the chitosan nanomagnets for extraction/detection of endotoxin from clinical samples such as human urine which can be further applied for biomedicine/clinical application for rapid, sensitive, direct and effective detection for bacterial infections.

Chitosan modified CdS quantum dots (CdS@CTS) can be used as an effective bacterial biosensor due to their good bioaffinity among chitosan molecules and bacterial membranes. CdS@CTS is an ultrafast, sensitive, direct and biocompatible biosensor for pathogenic bacteria (Pseudomonas aeruginosa and Staphylococcus aureus). Chitosan biopolymer of CdS@CTS provides bioaffinity sites that can be employed for the assembly on pathogen bacteria cells due to the chemical similarity of the chitosan and the bacteria membranes. Thus, S. aureus and P. aeruginosa cells were detected at low concentrations of 150 and 200 cfu mL−1, respectively, in an extremely short time (1 min). The CdS@CTS–bacteria interaction is noncovalent. From the thermodynamic results, the van der Waals force and hydrogen bonding formation are characterized by negative enthalpy (ΔH), while positive entropy (ΔS) is considered as the evidence for typical hydrophobic interactions. Moreover, negative ΔH and positive ΔS might play a role in the electrostatic interactions. The negative free energy (ΔG) shows that the binding events were spontaneous processes. Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) and transmission electron microscopy (TEM) were performed to evaluate the interactions and the biocompatibility of CdS@CTS toward bacteria cells. Their biocompatibility, together with the high sensitivity and the presence of multifunctional forces, making these quantum dots (CdS@CTS) an excellent and novel biosensor which can be widely applied in the near future.

A new method was proposed to probe the interactions between transition metals of Fe(II), Fe(III), Cu(II) with a non steroidal anti-inflammatory drug (NSAID), flufenamic acid (FF) using graphene as a matrix for Graphene assisted laser desorption ionization mass spectrometry (GALDI-MS). Metal–drug complexation was confirmed via UV absorption spectroscopy, fluorescence spectroscopy, pH meter, and change in solution conductivity. The optimal molar ratios for these complexation interactions are stoichiometry 1:2 in both Cu(II) and Fe(II) complexes, and 1:3 in Fe(III) complexes at physiological pH (7.4). Metal complexation of the drug could enhance fluorescence for 20 fold which is due to the charge transfer reaction or increase rigidity of the drug. The main interaction between graphene and flufenamic acid is the П–П interaction which allows us to probe the metal–drug complexation. The GALDI-MS could sensitively detect the drug at m/z 281.0 Da (protonated molecule) with detection limit 2.5 pmol (1.0 μM) and complexation at m/z 661.0, 654.0 and 933.0 Da corresponding to [Cu(II)(FF)2(H2O)2 + H]+, [Fe(II)(FF)2(H2O)2 + H]+ and [Fe(III) (FF)3(H2O)2 + H]+, respectively (with limit of detection (LOD) 2.0 pmol (10.0 μM). Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) spectra show change in the protein profile of intact pathogenic bacteria (Pseudomonas aeroginosa, Staphylococcus aureus). The change in the ionization ability (mainly proton affinity) of pathogenic bacteria may be due to the interactions between the bacteria with the drug (or its complexes). Shielding carboxylic group by metals and increase the hydrophilicity could enhance the biocompatibility of complexes toward the pathogenic bacteria which can be used as biosensors with high sensitivity and lowest detectable concentrations are in the range of 3.3 × 103–3.9 × 104 cfu mL−1 with large linear dynamic range.

Application of two new series of ionic liquid matrices (ILMs) based on the two most predominantly used conventional organic matrices (Sinapinic acid and 2,5-DHB) in conjugation with various bases (aniline (ANI), dimethyl aniline (DMANI), diethylamine (DEA), dicyclohexylamine (DCHA), pyridine (Pyr), 2-picoline(2-P), 3-picoline(3-P)) for bacterial analysis in matrix assisted laser desorption/ionisation mass spectrometry (MALDI-MS) are reported. The results reveal that ionic liquid matrices could significantly enhance the protein signals, reduce spot-to-spot variation and increase spot homogeneity. More importantly, these novel matrices would not produce any interference during MALDI-MS analysis. Among these ILMs, 2,5-DHB/ANI, 2,5-DHB/DMANI and 2,5-DHB/Pyr can be successfully applied to intact bacterial studies compared with other ILMs. Base molecules when added to conventional matrix can promote proton transfer between the bacterial lysate and the matrices. Due to the enhanced proton transfer efficiency by the ionic liquid matrices, almost all the biomolecules of the intact bacterial cells can be ionized and detected in the MALDI-MS. All synthesized ILMs were characterized using ESI (+)/MS and UV-spectroscopy.

Drugs and metabolites are transported in the blood by plasma proteins, such as human serum albumin (HSA). The uridine analog 2'dFUrd, which is a cytotoxic prodrug metabolite of capecitabine, has remarkable activity against solid tumors when administered orally. We report the results of an in vitro experimental study on the interactions of 2'-dFUrd with the N-isoform (at pH 7.4) and B-isoform (at pH 9.0) of HSA, investigated using fluorescence spectroscopy, circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and molecular docking. The binding constant (Kb) was higher for the N-isoform than for the B-isoform. Thermodynamic parameters, such as enthalpy change (ΔH°), entropy change (ΔS°), and Gibbs free energy change (ΔG°), were also calculated for both isoform interactions using calorimetric techniques. The thermostabilities of HSA and the HSA-2'dFUrd complex were found to be higher for the N-isoform. The interaction of 2'dFUrd with HSA was also explored in molecular docking studies, which revealed that 2'dFUrd was bound to the Sudlow site I in subdomain IIA through multiple modes of interaction, such as hydrophobic interactions and hydrogen bonding. These results suggest that 2'dFUrd has higher binding affinity for the N-isoform of HSA.

Drugs and metabolites are transported in the blood by plasma proteins, such as human serum albumin (HSA). The uridine analog 2'dFUrd, which is a cytotoxic prodrug metabolite of capecitabine, has remarkable activity against solid tumors when administered orally. We report the results of an in vitro experimental study on the interactions of 2'-dFUrd with the N-isoform (at pH 7.4) and B-isoform (at pH 9.0) of HSA, investigated using fluorescence spectroscopy, circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and molecular docking. The binding constant (Kb) was higher for the N-isoform than for the B-isoform. Thermodynamic parameters, such as enthalpy change (ΔH°), entropy change (ΔS°), and Gibbs free energy change (ΔG°), were also calculated for both isoform interactions using calorimetric techniques. The thermostabilities of HSA and the HSA-2'dFUrd complex were found to be higher for the N-isoform. The interaction of 2'dFUrd with HSA was also explored in molecular docking studies, which revealed that 2'dFUrd was bound to the Sudlow site I in subdomain IIA through multiple modes of interaction, such as hydrophobic interactions and hydrogen bonding. These results suggest that 2'dFUrd has higher binding affinity for the N-isoform of HSA.

Multifunctional graphene magnetic nanosheet decorated with chitosan (GMCS) is demonstrated as a promising biosensor for fluorescence spectroscopy and it can be also applied for matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) for sensitive pathogenic bacteria detection. Graphene-magnetic@chitosan (GMCS) can be applied for multiple applications such as fluorescence biosensor, fluorescence background suppressor, acting as co-matrix, enriching nanoprobe, and separation by external magnets for pathogenic bacteria (Pseudomonas aeruginosa and Staphylococcus aureus) present in aqueous suspension or blood colloids. GMCS has been prepared and characterized using various techniques including TEM, UV, FTIR, XRD, Raman and fluorescence spectroscopy. Due to the non-covalent interactions among the pathogenic bacteria with the GMCS, fluorescence enhancement takes place as a function of bacterial cell number with a low number of cell detection (4.5 × 102 to 5.0 × 102 cfu mL−1) and wide linear dynamic range which indicates that the GMCS approach is an excellent quantitative methodology and highly sensitive approach for detection of bacteria cells. Graphene works intrinsically as a fluorescence quencher for blood fluorophores and cell autofluorescence as graphene typically has a long life time, which allows detection of the bacteria signals by direct fluorescence measurements. Because of the high fluorescence enhancement efficiency, and large surface area (to volume ratio) of graphene, GMCS exhibits extraordinarily high sensitivity for complex (blood) sample analysis. GMCS also can be applied as an efficient separation and preconcentration nanoprobe for surface assisted laser desorption/ionization (SALDI) and enhances the ionization of bacterial biomolecules during MALDI-MS analysis. The bacterial cell suspension was concentrated from 1 mL to 10 μL via an external magnetic field, thus it can enhance bacteria detection for MALDI-MS analysis. GMCS is an outstanding approach which is a rapid, sensitive, culture free technique and low cost biosensor for pathogenic bacteria detection.

This review surveys all the state-of-art applications of quantum dots (QDs) in conventional and modern analytical methods in proteomic studies. A brief introduction of QDs and their properties is initially presented followed by outlining the application of QDs in fluorescence, MS, imaging, and cancer-based proteomics. The in-depth application of QDs in MALDI-MS and surface assisted laser desorption/ionization-MS has been elaborately discussed, summarizing the speculated mechanism behind the protein–QDs interactions during QD matrix applications leading to enhanced detection sensitivity.

We analyze the convergence of the Mann-type double sequence iteration process to the solution of a Lipschitz pseudocontractive operator equation on a bounded closed convex subset of arbitrary real Banach space into itself. Our results extend the result in (Moore in Comp. Math. Appl. 43: 1585-1589, 2002).

We disprove Strichartz estimates for the solution of the inhomogeneous Schrödinger equation in a certain range of the Lebesgue exponents values.