Comparison of Cu+, Ag+, and Au+ Ions as Ionization Agents of Volatile Organic Compounds at Subatmospheric Pressure.

Ionization of volatile organic compounds (VOCs) by coinage metal ions (Cu+, Ag+, and Au+) generated by laser desorption and ionization (LDI) of a metal nanolayer in subatmospheric conditions is explored. The study was performed in a commercial subatmospheric dual MALDI/ESI ion source. Five compounds representing different VOC classes were chosen for a detailed study of the metal ionization mechanism: ethanol, acetone, acetic acid, xylene, and cyclohexane. In the gas phase, ion molecular complexes of all three metal ions were formed, typically with two ligand molecules. The successful detection of the metal complexes with VOCs strongly depended on the applied voltages across the ion source, minimizing the in-source fragmentation. The employed orbital trap with ultrahigh resolving power and sub-parts-per-million mass accuracy allowed unambiguous identification of the formed complexes based on their molecular formulas. The detection limits of the studied compounds in the gas were in the range 0.1-1.4 nmol/L. Compared to Cu+ and Ag+ ions, Au+ ions exhibited the highest reactivity, often complicating spectra by side products of reactions. On the other hand, they also allowed detecting saturated hydrocarbons, which did not produce any signals with Ag+ and Cu+.

Detection of Single Ag Nanoparticles Using Laser Desorption/Ionization Mass Spectrometry.

The detection of a single entity (molecule, cell, particle, etc.) was always a challenging subject. Here we demonstrate the detection of single Ag nanoparticles (NPs) using subatmospheric pressure laser desorption/ionization mass spectrometry (LDI MS). The sample preparation, measurement conditions, generated ions, and limiting experimental factors are discussed here. We detected from 84 to 95% of the deposited 80 nm Ag NPs. The presented LDI MS platform is an alternative to laser ablation inductively coupled plasma mass spectrometry for imaging distribution of individual NPs across the sample surface and has a great potential for multiplexed mapping of low-abundance biomarkers in tissues.

Fate of Gold Nanoparticles in Laser Desorption/Ionization Mass Spectrometry: Toward the Imaging of Individual Nanoparticles.

This study focuses on mapping the spatial distribution of Au nanoparticles (NPs) by laser desorption/ionization mass spectrometry imaging (LDI MSI). Laser interaction with NPs and associated phenomena, such as change of shape, melting, migration, and release of Au ions, are explored at the single particle level. Arrays of dried droplets containing low numbers of spatially segregated NPs were reproducibly prepared by automated drop-on-demand piezo-dispensing and analyzed by LDI MSI using an ultrahigh resolution orbital trapping instrument. To enhance the signal from NPs, an in source gas-phase chemical reaction of generated Au ions with xylene was employed. The developed technique allowed the detecting, chemical characterization, and mapping of the spatial distribution of Au NPs; the ion signals were detected from as low as ten 50 nm Au NPs on a pixel. Furthermore, the Au NP melting dynamics under laser irradiation was monitored by correlative atomic force microscopy (AFM) and scanning electron microscopy (SEM). AFM measurements of Au NPs before and after LDI MSI analysis revealed changes in NP shape from a sphere to a half-ellipsoid and total volume reduction of NPs down to 45% of their initial volume.

Infrared Laser Desorption of Intact Nanoparticles for Digital Tissue Imaging.

We report a new technique for the digital mapping of biomarkers in tissues based on desorption and counting intact gold nanoparticle (Au NP) tags using infrared laser ablation single-particle inductively coupled plasma mass spectrometry (IR LA SP ICP MS). In contrast to conventional UV laser ablation, Au NPs are not disintegrated during the desorption process due to their low absorption at 2940 nm. A mass spectrometer detects up to 83% of Au NPs. The technique is demonstrated on mapping a proliferation marker, nuclear protein Ki-67, in three-dimensional (3D) aggregates of colorectal carcinoma cells, and the results are compared with confocal fluorescence microscopy and UV LA ICP MS. Precise counting of 20 nm Au NPs with a single-particle detection limit in each pixel by the new approach generates sharp distribution maps of a specific biomarker in the tissue. Advantageously, the desorption of Au NPs from regions outside the tissue is strongly suppressed. The developed methodology promises multiplex mapping of low-abundant biomarkers in numerous biological and medical applications using multielemental mass spectrometers.

Metal Oxide Laser Ionization Mass Spectrometry Imaging of Fatty Acids and Their Double Bond Positional Isomers.

We present a novel combination of a metal oxide laser ionization mass spectrometry imaging (MOLI MSI) technique with off-line lipid derivatization by ozone for the detection of fatty acids (FA) and their carbon-carbon double bond (C═C) positional isomers in biological tissues. MOLI MSI experiments were realized with CeO2 and TiO2 nanopowders using a vacuum matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometer in the negative mode. The catalytic properties of these metal oxides allow FA cleavage from phospholipids under UV laser irradiation. At the same time, fragile ozonides produced at the sites of unsaturation decomposed, yielding four diagnostic ions specific for the C═C positions. Advantageously, two MOLI MSI runs from a single tissue sprayed with the metal oxide suspension were performed. The first run prior to ozone derivatization revealed the distribution of FAs, while the second run after the reaction with ozone offered additional information about FA C═C isomers. The developed procedure was demonstrated on MSI of a normal mouse brain and human colorectal cancer tissues uncovering the differential distribution of FAs down to the isomer level. Compared to the histological analysis, MOLI MSI showed the distinct distribution of specific FAs in different functional parts of the brain and in healthy and cancer tissues pointing toward its biological relevance. The developed technique can be directly adopted by laboratories with MALDI TOF analyzers and help in the understanding of the local FA metabolism in tissues.

Mass Spectrometry Imaging Techniques Enabling Visualization of Lipid Isomers in Biological Tissues.

This Feature focuses on a review of recent developments in mass spectrometry imaging (MSI) of lipid isomers in biological tissues. The tandem MS techniques utilizing online and offline chemical derivatization procedures, ion activation techniques such as ozone-induced dissociation (OzID), ultraviolet photodissociation (UVPD), or electron-induced dissociation (EID), and other techniques such as coupling of ion mobility with MSI are discussed. The importance of resolving lipid isomers in diseases is highlighted.

Metal Ionization in Sub-atmospheric Pressure MALDI Interface: A New Tool for Mass Spectrometry of Volatile Organic Compounds.

A novel approach for the analysis of volatile organic compounds (VOCs) based on chemical ionization by Au+ ions has been proposed. The ionization is carried out in a commercially available dual sub-atmospheric pressure MALDI/ESI interface without any modifications. The Au+ ions are generated by laser ablation of a gold nanolayer with the MALDI laser, and VOCs are infused via the ESI capillary. The ultrahigh resolving power and sub-ppm mass accuracy of the employed mass spectrometer allow straightforward identification of the formed ion-molecule complexes and other products of Au+ interactions with VOCs in the gas phase. The performance of the technique is demonstrated on the analysis of various classes of organic molecules, namely, alkanes, alkenes, alcohols, aldehydes, ketones, aromatic compounds, carboxylic acids, ethers, or organosulfur compounds, expanding the portfolio of currently available methods for the analysis of VOCs such as secondary electrospray ionization, proton-transfer reaction, and selected ion flow tube mass spectrometry.

Gas-aggregated Ag nanoparticles for detection of small molecules using LDI MS.

Several reports demonstrate that silver nanomaterials can serve as surface-assisted laser desorption ionization mass spectrometry (SALDI MS) substrates for low molecular weight analytes. Substrate with tailored silver nanostructures, primarily representing the upmost layer of the bulk, i.e., occurring beneath the analyzed medium, limits the use of silver only for desorption enhancement; the charge transfer progresses through atoms from the absorbing analyte or an additional matrix (resulting in the formation of analyte/hydrogen, sodium, or potassium adducts in the most cases). In the presented approach, we utilize a homogeneous layer of silver nanoparticles, prepared under low-pressure conditions, deposited onto a dried analyte. We demonstrate that the nanoparticle layer can fully replace a matrix typically used for the detection of small molecules by laser desorption/ionization mass spectrometry-based technique (LDI MS) and can be applied to the already prepared samples. Various chemical species were detected as [M + Ag]+ adduct ions employing the proposed technique. The normalized signal of the analyte/silver adduct can be utilized to characterize a quantitative presence of analytes on the surface similar to signal-to-noise value, here demonstrated by the detection of trimethoprim molecule. This study also includes a detailed description of additional features one needs to take into account, such as a formation of [Mx + Agy]+ adducts, presence of silver ions (can be used for m/z calibration), analyte fragmentation, and influence of deposited nanoparticles quantity on the signal intensity. Graphical abstract.

Formation of aluminium, aluminium nitride and nitrogen clusters via laser ablation of nano aluminium nitride. Laser Desorption Ionisation and Matrix-Assisted Laser Desorption Ionisation Time-of-Flight Mass Spectrometry.

Laser Desorption Ionisation (LDI) and Matrix-Assisted Laser Desorption Ionisation (MALDI) Time-of-Flight Mass Spectrometry (TOFMS) were used to study the pulsed laser ablation of aluminium nitride (AlN) nano powder. The formation of Al(m)(+) (m=1-3), N(n)(+) (n=4, 5), AlN(n)(+) (n=1-5, 19, 21), Al(m)N(+) (m=2-3), Al(3)N(2)(+), Al(9)N(n)(+) (n=5, 7, 9, 11 and 15), Al(11)N(n)(+) (n=4, 6, 10, 12, 19, 21, 23, and 25), and Al(13)N(n)(+) (n=25, 31, 32, 33, 34, 35, and 36) clusters was detected in positive ion mode. Similarly, Al(m)(-) (m=1-3), AlN(n)(-) (n=1-3, 5), Al(m)N(-) (n=2, 3), Al(2)N(n)(-) (n=2-4, 28, 30), N(n)(-) (n=2, 3), Al(4)N(7)(-) Al(8)N(n)(-) (n=1-6), and Al(13)N(n)(-) (n=9, 18, 20, 22, 24, 26, 28, 33, 35, 37, 39, 41 and 43) clusters were observed in negative ion mode. The formation of the stoichiometric Al(10) N(10) cluster was shown to be of low abundance. On the contrary, the laser ablation of nano-AlN led mainly to the formation of nitrogen-rich Al(m)N(n) clusters in both negative and positive ion mode. The stoichiometry of the Al(m)N(n) clusters was determined via isotopic envelope analysis and computer modelling.