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Fe3o4-Assisted Laser Desorption Ionization Mass Spectrometry For Journal of Hazardous Materials 388 (2020) 121817 Contents lists available at ScienceDirect Journal of Hazardous Materials journal homepage: www.elsevier.com/locate/jhazmat Fe3O4-assisted laser desorption ionization mass spectrometry for typical T metabolite analysis and localization: Influencing factors, mechanisms, and environmental applications Wen-Wen Weia,1, Yuanhong Zhongb,1, Ting Zoua, Xiao-Fan Chena, Li Renb, Zenghua Qia, Guoguang Liua, Zhi-Feng Chena,*, Zongwei Caia,c,** a Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou, 510006, China b School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China c State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China GRAPHICAL ABSTRACT ARTICLE INFO ABSTRACT Editor: R. Teresa Fe3O4 has been suggested as an efficient matrix for small-molecule analysis by laser desorption ionization Keywords: mass spectrometry (LDI-MS), but thus far there has been no systematic study exploring the influencing factors Fe3O4 of nano-Fe3O4 on the detection of typical metabolites, or the mechanism by which nano-Fe3O4 assists the Physicochemical property desorption and ionization of analytes after receiving laser energy. In this study, Fe3O4 nanoparticles with Small-molecule metabolite different physicochemical properties were synthesized and characterized. The results revealed that smaller Laser desorption ionization particle size and greater surface hydroxyl amount of nano-spherical Fe3O4 could improve the intensity and Time-of-flight mass spectrometry relative standard deviation of typical metabolites by LDI-MS. The thermally driven desorption process played a vital role in LDI performance, but the chemical interactions between nano-Fe3O4 and analytes did not. Good intra- or inter-spot repeatability and linearity of analytes were obtained by the optimum Fe3O4-assisted LDI- MS. Finally, the developed method was successfully used for the rapid analysis and localization of en- dogenous metabolites in biofluids and whole zebrafish tissue section samples. Our results not only elucidate ⁎ Corresponding author at: Guangdong University of Technology, Guangzhou, China. ⁎⁎ Corresponding author at: Hong Kong Baptist University, Hong Kong SAR, China. E-mail addresses: [email protected] (Z.-F. Chen), [email protected] (Z. Cai). 1 These authors contributed equally. https://doi.org/10.1016/j.jhazmat.2019.121817 Received 10 October 2019; Received in revised form 19 November 2019; Accepted 2 December 2019 Available online 03 December 2019 0304-3894/ © 2019 Elsevier B.V. All rights reserved. W.-W. Wei, et al. Journal of Hazardous Materials 388 (2020) 121817 the influencing factors and mechanisms of nano-Fe3O4 for the detection of typical metabolites in LDI-MS but also reveal an innovative tool for the imaging of chemicals in the regions of interest in terms of eco-tox- icological research. 1. Introduction nanomaterial, nano-Fe3O4 particle size can affect the detection sensi- tivity of metabolites in LDI-MS (Olaitan et al., 2018), suggesting that In the 1980s, matrix-assisted laser desorption ionization (MALDI) the physicochemical properties of nano-Fe3O4 influence method sensi- was proposed as a soft ionization technique (Karas and Hillenkamp, tivity and repeatability. 1988). The first application of nanoparticles as a matrix for laser des- In this study, we attempted to use microwave-assisted and copre- orption ionization coupled with time-of-flight mass spectrometry (LDI- cipitation methods for the synthesis of nano-Fe3O4 with different phy- MS) made Koichi Tanaka a Nobel laureate (Tanaka et al., 1988). sicochemical properties (e.g., morphologies, particle sizes, and surface MALDI-MS has been successfully used to detect biomacromolecules hydroxyl amounts). Based on peak intensities and relative standard (Cornett et al., 2007; Bouslimani et al., 2015; Dallongeville et al., 2016; deviations of target analytes, an ideal matrix was selected for LDI-MS in Cravatt et al., 2007; Bruno and Ruedi, 2006), including proteins, pep- positive ionization mode. We compared the performance between as- tides, and nucleic acids, in biological samples. The remarkable ad- prepared Fe3O4-assisted LDI-MS and traditional MALDI-MS and vali- vantages of MALDI-MS include simple operation, quick analysis, high dated the repeatability and calculation curves of analytes for the de- throughput, small sample consumption, and high salt tolerance (Karas veloped method. From the results of thermal desorption calculation and et al., 1987; Min et al., 2014). Traditional organic matrices that are the UV–vis absorption spectrum, the mechanisms of the desorption and used in MALDI-MS, such as α-cyano-4-hydroxycinnamic acid (CHCA), ionization of analytes after laser irradiation were tentatively proposed. 2,5-dihydroxybenzoic acid (DHB), and sinapic acid (SA), exhibit good Finally, the developed method was successfully applied in order to performance in the analysis of biomacromolecules. However, severe identify and localize the potential metabolites in biofluids and whole background noise in the low-mass range and heterogeneous cocrys- zebrafish tissue section samples, respectively. tallization between traditional organic matrices and small-molecule analytes can limit the practicability of traditional MALDI-MS in vital 2. Experimentation endogenous metabolite analysis (Tholey and Heinzle, 2006; Weidner and Falkenhagen, 2009; Kawasaki et al., 2012; Kinumi et al., 2000; Lin 2.1. Synthesis and characterization of Fe3O4 nanoparticles et al., 2015a; Shi et al., 2017; Lopez de laorden et al., 2015). Endogenous metabolites play an essential role in the growth, de- Based on our previous work (Zhong et al., 2017), a type of nano- velopment, and reproduction of humans and other organisms (Patti spherical Fe3O4 particle (M2) was synthesized via the standard copre- et al., 2012; Shevchenko and Simons, 2010). For the accurate quanti- cipitation method, and 9 types of nano-Fe3O4 particles (M1, M3–M10) fication of metabolites with molecular weights below 1000 Da,gas with different morphologies, particle sizes, and surface hydroxyl chromatography coupled with mass spectrometry (GC–MS) (Robles amounts were synthesized using a microwave-assisted technique. M11 et al., 2017) and liquid chromatography coupled with mass spectro- was a commercial nano-Fe3O4 particle, while nano-Fe3O4 (M12) was metry (LC–MS) (Teleki and Takors, 2019) are the commonly used synthesized using a method from Yagnik et al. (Yagnik et al., 2016). The analytical instrument combinations, both of which require sample XRD patterns of the as-prepared Fe3O4 nanoparticles were obtained by preparation and extra time for chromatographic separation. In contrast an Aeris benchtop X-ray diffractometer (PANalytical B.V., Netherlands) to GC–MS and LC–MS, MALDI-MS not only enables the rapid detection with a tube voltage of 40 kV and a current of 15 mA at room tem- of analytes but also visually displays the distribution of endogenous perature. The range of angles was set from 10° to 80° (2θ) with a metabolites in tissue sections combined with an imaging technique (Liu scanning step width of 0.02° and a speed of 5°/min. The morphologies et al., 2014; Mainini et al., 2015; Wang et al., 2015; Ye et al., 2013). and particle sizes were determined from scanning electron microscope MALDI-MS imaging has shown potential for the elucidation of tox- images (SEM). SEM measurements were performed on a Hitachi icological mechanisms (Bruinen et al., 2016; Cobice et al., 2015; Liu SU8000 with 3-kV accelerating voltage and 9,400-nA emission current et al., 2017). (Hitachi Ltd., Japan). The surface hydroxyl amount of nano-Fe3O4 was In the past few years, various types of nanostructured matrices measured using a SDT Q600 simultaneous TGA-DSC thermal analyzer containing silica- and silicon-based substrates (Dupre et al., 2012; (TA Instruments, USA). The data were recorded from room temperature Zhang et al., 1999), metal nanoparticles (e.g., gold (Tang et al., 2011; to 800 °C with a heating rate of 10 °C/min and a nitrogen flow rate of Amendola et al., 2013), silver (Muller et al., 2015), and platinum(Nitta 50 mL/min. Specific heat measurements were conducted in azero et al., 2013)), metal oxides (e.g., TiO2 (Shrivas et al., 2011), Fe3O4 magnetic field with a temperature region of 271–306 K and apressure (Chiang et al., 2010; Bi et al., 2015), and ZnO (Gedda et al., 2014)), and of 9.9 × 10−6 Torr, using the specific heat option of a Quantum Design carbon-based materials (e.g., colloidal graphite (Gedda et al., 2014; Cha physical property measurement system (Quantum Design, China). The and Yeung, 2007), graphene oxide (Kim et al., 2011), and carbon dots UV–vis absorption spectrum (200−800 nm) of nano-Fe3O4 was ob- (Lin et al., 2018)) have been developed for the surface-assisted analysis tained from a MAPADA UV-3200 Spectrophotometer (Shanghai Ma- of small molecules. Due to superior optical and charge-transfer per- pada Instruments Co. Ltd., China). The detailed synthesis approaches formance, carbon-based materials (Shiea et al., 2003; Lu et al., 2016) (Text S1 and Table S1) and information (Table S2) of the nano-Fe3O4 in have attracted an enormous amount
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