MALDI imaging mass spectrometry of lipids by adding lithium salts to the matrix solution

Abstract

Mass spectrometry imaging of lipids using MALDI-TOF/TOF mass spectrometers is of growing interest for chemical mapping of organic compounds at the surface of tissue sections. Many efforts have been devoted to the best matrix choice and deposition technique. Nevertheless, the identification of lipid species desorbed from tissue sections remains problematic. It is now well-known that protonated, sodium- and potassium-cationized lipids are detected from biological samples, thus complicating the data analysis. A new sample preparation method is proposed, involving the use of lithium salts in the matrix solution in order to simplify the mass spectra with only lithium-cationized molecules instead of a mixture of various cationized species. Five different lithium salts were tested. Among them, lithium trifluoroacetate and lithium iodide merged the different lipid adducts into one single lithium-cationized species. An optimized sample preparation protocol demonstrated that the lithium trifluoroacetate salt slightly increased desorption of phosphatidylcholines. Mass spectrometry images acquired on rat brain tissue sections by adding lithium trifluoroacetate showed the best results in terms of image contrast. Moreover, more structurally relevant fragments were generated by tandem mass spectrometry when analyzing lithium-cationized species.

MALDI Imaging of Lipid Biochemistry in Tissues by Mass Spectrometry

“…37 Some research groups have added lithium salt with the matrix in order to produce lithiated PC ions from tissues since the CID of [M+Li] + of PC molecular species results in structurally relevant product ions that are indicative of the fatty acid chains esterified to the glycerol backbone of PC lipids. 24 In two studies, 2,6-dihydroxyacetophenone matrix was modified with 100 mM lithium chloride and this mixture was applied onto rat brain 38 and mouse embryo implantation sites. 39 In a recent study, many different lithium salts, including lithium citrate, lithium acetate, lithium trifluoroacetate, lithium iodide, and lithium chloride, were evaluated at a concentration of 1-2 mg/mL.…”

“…2,3 Similar development and implementation of instrumentation for MALDI IMS has leveraged lipid diversity, abundance and contrast in rodent brain samples to achieve advancements in technology. 4-8 The development of different matrices useful for MALDI IMS, 9-16 different methods of matrix application 17-23 and different matrix modifiers 24,25 have been employed in MALDI IMS experiments to establish the value and parameters of these method modifications for lipid analysis.…”

Gas-Phase Lithium Cation Basicity: Revisiting the High Basicity Range by Experiment and Theory

“…Analytical mass spectrometry makes use of the formation of gas-phase adducts with metal cations (a process often called cationization), and Li + has been extensively examined in this regard. Lithium adduct generation occurs easily, starting in general from a condensed phase, when polar functional groups are present in analytes [21][22][23][24][25]. Another specific tool, which emerged from the observation of direct gas-phase cationization by Li + , the so-called ion attachment mass spectrometry (IAMS) [26][27][28][29], makes use of the attachment of the cation to neutral species in the gas phase.…”

Selective or Class-wide Mass Fingerprinting of Phosphatidylcholines and Cerebrosides from Lipid Mixtures by MALDI Mass Spectrometry

“…[3][4][5] For example, with the addition cesium ions, spectral complexity was reduced and sensitivity was enhanced in lipid mass profiles.…”

“…5,6 Recently, Griffiths and Bunch systematically explored this salt additive effect in MALDI MS of lipids with a DHB matrix.…”