Jiyun Wang

MALDI-TOF MS Imaging of Metabolites with a N-(1-Naphthyl) Ethylenediamine Dihydrochloride Matrix and Its Application to Colorectal Cancer Liver Metastasis

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a label-free technique for identifying multiplex metabolites and determining both their distribution and relative abundance in situ. Our previous study showed that N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC) could act as a matrix for laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) detection of oligosaccharides in solution. In the present study, NEDC-assisted LDI-TOF MSI yielded many more endogenous compound peaks between m/z 60 and m/z 1600 than 9-aminoacridine (9-AA). Our results show that NEDC-assisted LDI-TOF MSI is especially well-suited for examining distributions of glycerophospholipids (GPs) in addition to low molecular weight metabolites below m/z 400. Particularly, NEDC matrix allowed the LDI-TOF MSI of glucose in animal tissue. Furthermore, NEDC-assisted LDI-TOF MSI was applied to a mouse model of colorectal cancer liver metastasis. We revealed the distinct spatio-molecular signatures of many detected compounds in tumor or tumor-bearing liver, and we found that taurine, glucose, and some GPs decreased in tumor-bearing liver as the tumor developed in liver. Importantly, we also found a glucose gradient in metastatic tumor foci for the first time, which further confirms the energy competition between tumors and liver remnant due to the Warburg effect. Our results suggest that NEDC-assisted LDI MSI provides an in situ label-free analysis of multiple glycerophospholipids and low molecular weight metabolites (including glucose) with abundant peaks and high spatial resolution. This will allow future application to in situ definition of biomarkers, signaling pathways, and disease mechanisms.

2,3,4,5-Tetrakis(3',4'-dihydroxylphenyl)thiophene: a new matrix for the selective analysis of low molecular weight amines and direct determination of creatinine in urine by MALDI-TOF MS.

Small organic matrixes are still the most commonly used ones in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) because of their advantages of high sensitivity, convenience, and cost-effectiveness. However, due to the matrix interference in the low mass region, the direct analysis of low molecular weight amines in complex surroundings with conventional organic matrixes remains a challenge. Here, a new Brønsted-Lowry acid compound 2,3,4,5-tetrakis(3,4-dihydroxylphenyl)thiophene (DHPT) was designed, synthesized, and applied as a matrix for analysis of low molecular weight amines by MALDI-TOF MS. DHPT displays good selectivity in the analysis of amines without matrix-related interference and the low picomole/femtomole limit-of-detection was obtained in positive ion mode. With DHPT, the metabolites including creatinine, glycine, alloxan, allantoin, and 3-hydroxyhippuric acid in human urine were directly analyzed by MALDI-TOF MS. The identity of these metabolites was confirmed by tandem mass spectrometry. Furthermore, the urine creatinine was quantitatively determined using isotope-labeled internal standard. This DHPT-assisted LDI MS method provides a general approach for both qualitative and quantitative analysis of low molecular weight amines.

Mo2Ga2C: a new ternary nanolaminated carbide

We report the discovery of a new hexagonal Mo2Ga2C phase, wherein two Ga layers – instead of one – are stacked in a simple hexagonal arrangement in between Mo2C layers. It is reasonable to assume this compound is the first of a larger family.

Isothermal oxidation of bulk Zr 2 Al 3 C 4 at 500 to 1000 °C in air

The isothermal oxidation behavior of Zr 2 Al 3 C 4 in the temperature range of 500 to 1000 °C for 20 h in air has been investigated. The oxidation kinetics follow a parabolic law at 600 to 800 °C and a linear law at higher temperatures. The activation energy is determined to be 167.4 and 201.2 kJ/mol at parabolic and linear stages, respectively. The oxide scales have a monolayer structure, which is a mixture of ZrO 2 and Al 2 O 3 . As indicated by x-ray diffraction and Raman spectra, the scales formed at 500 to 700 °C are amorphous, and at higher temperatures are α-Al 2 O 3 and t-ZrO 2 nanocrystallites. The nonselective oxidation of Zr 2 Al 3 C 4 can be attributed to the strong coupling between Al 3 C 2 units and ZrC blocks in its structure, and the close oxygen affinity of Zr and Al.

1,5-Diaminonaphthalene Hydrochloride Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Small Molecules in Tissues Following Focal Cerebral Ischemia

A sensitive analytical technique for visualizing small endogenous molecules simultaneously is of great significance for clearly elucidating metabolic mechanisms during pathological progression. In the present study, 1,5-naphthalenediamine (1,5-DAN) hydrochloride was prepared for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) of small molecules in liver, brain, and kidneys from mice. Furthermore, 1,5-DAN hydrochloride assisted LDI MSI of small molecules in brain tissue of rats subjected to middle cerebral artery occlusion (MCAO) was carried out to investigate the altered metabolic pathways and mechanisms underlying the development of ischemic brain damage. Our results suggested that the newly prepared matrix possessed brilliant features including low cost, strong ultraviolet absorption, high salt tolerance capacity, and fewer background signals especially in the low mass range (typically m/z < 500), which permitted us to visualize the spatial distribution of a broad range of small molecule metabolites including metal ions, amino acids, carboxylic acids, nucleotide derivatives, peptide, and lipids simultaneously. Nineteen endogenous metabolites involved in metabolic networks such as ATP metabolism, tricarboxylic acid (TCA) cycle, glutamate-glutamine cycle, and malate-aspartate shuttle, together with metal ions and phospholipids as well as antioxidants underwent relatively obvious changes after 24 h of MCAO. The results were highly consistent with the data obtained by MRM MS analysis. These findings highlighted the promising potential of the organic salt matrix for application in the field of biomedical research.

1-naphthylhydrazine hydrochloride: a new matrix for the quantification of glucose and homogentisic acid in real samples by MALDI-TOF MS.

BACKGROUNDnDue to its strong ultraviolet absorption and low background interference in the low molecular weight region, 1-naphthylhydrazine hydrochloride (NHHC) has been selected as an ideal matrix to detect small molecules by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).nnnRESULTSnThis salt-tolerant matrix could be applied for the high sensitive glucose analysis with an ultra-low limit of detection of 1 amol, and the [glucose+Cl](-) signal can be found even in saturated NaCl solution. With NHHC, glucose in serum and the biomarker homogentisic acid in urine were successfully determined by MALDI-TOF MS in negative ion mode.nnnCONCLUSIONnThis NHHC-assisted laser desorption/ionization MS method provided a fast and high through-put approach for the small molecule analysis in complex samples, and have a great potential in clinical applications.

Induced Dual-Nanospray: A Novel Internal Calibration Method for Convenient and Accurate Mass Measurement

AbstractAccurate mass information is of great importance in the determination of unknown compounds. An effective and easy-to-control internal mass calibration method will dramatically benefit accurate mass measurement. Here we reported a simple induced dual-nanospray internal calibration device which has the following three advantages: (1) the two sprayers are in the same alternating current field; thus both reference ions and sample ions can be simultaneously generated and recorded. (2) It is very simple and can be easily assembled. Just two metal tubes, two nanosprayers, and an alternating current power supply are included. (3) With the low-flow-rate character and the versatility of nanoESI, this calibration method is capable of calibrating various samples, even untreated complex samples such as urine and other biological samples with small sample volumes. The calibration errors are around 1xa0ppm in positive ion mode and 3xa0ppm in negative ion mode with good repeatability. This new internal calibration method opens up new possibilities in the determination of unknown compounds, and it has great potential for the broad applications in biological and chemical analysis.n

Quantitative Assessment of Protein Adsorption on Microparticles with Particle Mass Spectrometry

In this paper, particle mass spectrometry (PMS), which consists of an aerodynamic desorption/ionization (AD) source, a quadrupole ion trap (QIT) mass analyzer, and a charge detector, was exploited to characterize the protein adsorption on microparticles based on the mass variations of microparticles before and after protein adsorption. This method is simple and has low sample cost. Importantly, its mass resolution is good enough to distinguish the microparticles with and without protein. For the adsorption of bovine serum albumin (BSA) on 3 μm porous poly styrene-divinylbenzene (poly S-DVB), the minimum mass increase that can be resolved by PMS corresponds to 128 fg (1.8 ng/cm(2)) or 1.17 × 10(6) BSA molecules on each poly S-DVB particle. With PMS, the adsorption process of BSA on poly S-DVB spheres was successfully characterized, and the obtained maximum adsorption capacity qm and dissociation constant Kd were consistent with that determined by the conventional depletion method. In addition, the influence of surface modification of silica particles on the enzyme immobilization was evaluated. Compared with C4 (propyldimethylsilane), C8 (octyldimethylsilane), and Ph (phenyldimethylchlorosilane), the CN (cyanoethyldimethylchlorosilane) functionalized silica particles were screened to be most beneficial for the immobilization of both lysozyme and trypsin.

Mass Spectrometry Imaging of Kidney Tissue Sections of Rat Subjected to Unilateral Ureteral Obstruction

Chronic kidney disease (CKD) poses a serious threat to the quality of human life and health with an increasing incidence worldwide. Renal fibrosis is closely related to CKD and regarded as the final common pathophysiological pathway in most cases of end-stage renal diseases. Elucidating the mechanisms underlying renal fibrosis and developing novel therapeutic strategies are of great importance. Herein, matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) based on 1, 5-diaminonaphthalene hydrochloride was applied to the rat model of unilateral ureteral obstruction (UUO) to investigate metabolic changes during renal fibrosis. Among identified endogenous compounds, twenty-one metabolites involved in metabolic networks such as glycolysis, tricarboxylic acid (TCA) cycle, ATP metabolism, fatty acids metabolism, antioxidants, and metal ions underwent relatively obvious changes after 1 and 3 weeks of UUO. Unique distribution of the metabolites was obtained, and metabolic changes of kidneys during renal fibrosis were investigated simultaneously for the first time. These findings once again highlighted the promising potential of the organic salt matrix for application in small molecule in situ MSI and in the field of biomedical research.

Fluorographene nanosheets: a new carbon-based matrix for the detection of small molecules by MALDI-TOF MS

Fluorographene nanosheets (FG) were synthesized via one-pot chloroform-mediated sonochemical exfoliation under ambient conditions. For the first time, this material served as a novel matrix for the detection of small molecules by negative ion MALDI-TOF MS. The structural characterization and ionization mechanism of FG were illustrated. The unique properties of FG endow it with properties such as low background, excellent chemical compatibility and homogeneity over conventional carbon based matrices. Most significantly, application of FG as matrix resolved the contamination problem of conventional carbon based matrices to ion source. With the association of FG, a variety of small molecules containing amino acids, peptides, small metabolites, drugs and organonitrogen compounds were analyzed. The developed method was found to have excellent feasibility with biosystems. Based on this, qualitative analysis of sialic acid in human saliva, melatonin in human urine and in situ analysis of MCF-7 cells were done, besides, quantification of anti-cancer drug in human serum and uric acid in human urine were displayed. This work extends the application fields of FG and provides a good candidate of matrix for MALDI-TOF MS detection of small molecules.