Desorption Electrospray Ionization then MALDI Mass Spectrometry Imaging of Lipid and Protein Distributions in Single Tissue Sections

Analytical Chemistry (Impact Factor: 5.64). 11/2011; 83(22):8366-71. DOI: 10.1021/ac202016x
Source: PubMed


Imaging mass spectrometry (MS) is a powerful technique for mapping the spatial distributions of a wide range of chemical compounds simultaneously from a tissue section. Co-localization of the distribution of individual molecular species, including particular lipids and proteins, and correlation with the morphological features of a single tissue section are highly desirable for comprehensive tissue analysis and disease diagnosis. We now report on the use, in turn, of desorption electrospray ionization (DESI), matrix assisted laser desorption ionization (MALDI), and then optical microscopy to image lipid and protein distributions in a single tissue section. This is possible through the use of histologically compatible DESI solvent systems, which allow for sequential analyses of the same section by DESI then MALDI. Hematoxylin and eosin (H&E) staining was performed on the same section after removal of the MALDI matrix. This workflow allowed chemical information to be unambiguously matched to histological features in mouse brain tissue sections. The lipid sulfatide (24:1), detected at m/z 888.8 by DESI imaging, was colocalized with the protein MBP isoform 8, detected at m/z 14117 by MALDI imaging, in regions corresponding to the corpus callosum substructure of the mouse brain, as confirmed in the H&E images. Correlation of lipid and protein distributions with histopathological features was also achieved for human brain cancer samples. Higher tumor cell density was observed in regions demonstrating higher relative abundances of oleic acid, detected by DESI imaging at m/z 281.4, and the protein calcyclin, detected by MALDI at m/z 10085, for a human glioma sample. Since correlation between molecular signatures and disease state can be achieved, we expect that this methodology will significantly enhance the value of MS imaging in molecular pathology for diagnosis.

Download full-text


Available from: Sandro Santagata, Oct 12, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this paper, we propose a power supply with magnetic energy recovery current switch for pulsed magnets, such as the synchrotron accelerator bending magnets, magnetizer. The switch which consists of four MOSFET elements and one capacitor, generates a fast pulsed current with low voltage, and it improves the power factor. The switch absorbs the magnetic energy stored in the inductance of the load into the capacitor. And in next time on, it regenerates the energy to the load. In addition, this switch operates in zero-voltage switching and zero-current switching, and the switching loss is very small. In order to turn on the load current at high speed in the circuit with an inductance, high voltage of several times higher than the voltage which maintains steady current. Therefore, by adopting this switch in the power source for pulsed power supply, high-speed pulsed current is efficiently generated by recovering the magnetic energy which has been stored in the inductance to the load in the next time on. As an application of DC circuit, a semiconductor Marx-generator which generates the high voltage pulse composed of a multistage magnetic energy recovery is described.
    No preview · Article · Jul 2004 · IEEE Transactions on Applied Superconductivity
  • [Show abstract] [Hide abstract]
    ABSTRACT: Three-dimensional (3D) cell cultures have increased complexity compared to simple monolayer and suspension cultures, recapitulating the cellular architecture and molecular gradients in tissue. As such, they are popular for in vitro models in biological research. Classical imaging methodologies, like immunohistochemistry, are commonly used to examine the distribution of specific species within the spheroids. However, there is a need for an unbiased discovery-based methodology that would allow examination of protein/peptide distributions in 3D culture systems, without a need for prior knowledge of the analytes. We have developed a matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS)-based imaging approach to examine protein distributions in 3D cell culture models. Using colon carcinoma cell lines, we detect changes in the spatial distribution of proteins across 3D culture structures. To identify the protein species present, we are combining results from the MS/MS capabilities of MALDI-MS to sequence peptides in a de novo fashion and nanoflow liquid chromatography-tandem mass spectrometry (nLC-MS/MS) of homogenized cultures. As a proof-of-principle, we have identified cytochrome C and Histone H4 as two of the predominant protein species in the 3D colon carcinoma cultures.
    No preview · Article · Nov 2011 · Analytical Chemistry
  • Article: Lipidomics
    [Show abstract] [Hide abstract]
    ABSTRACT: Lipidomics characterizes the composition of intact lipid molecular species in biological systems and the field has been driven by some spectacular advances in mass spectrometry instrumentation and applications. This review will highlight these advances and outline their recent application to address clinical issues. This review first identifies recent advances in lipid detection and analysis by a variety of mass spectrometry techniques, then reviews specific application including stable isotope labelling of lipids, lipid mass spectrometry imaging, data analysis and bioinformatics, and finally presents examples of the application of lipidomics to selected disease states. Lipidomics so far has been principally concerned with identifying novel methodologies, but recent advances demonstrating applications in diabetes, neurodegenerative diseases, cystic fibrosis and other respiratory diseases clearly indicate the potential usefulness of lipidomics both to generate biomarkers of disease and to probe signalling and metabolic processes.
    No preview · Article · Mar 2012
Show more