Authentic historic manuscripts fetch high sums, but establishing their authenticity is challenging, relies on a host of stylistic clues and requires expert knowledge. High resolution mass spectrometry has not, until now, been applied to guide the authentication of historic manuscripts. Robert Burns is a well-known Scottish poet, whose fame, and the eponymous ‘Burns Night’ are celebrated world-wide. Authenticity of his works is complicated by the ‘industrial’ production of fakes by Alexander Smith in the 1890s, many of which were of good quality and capable of fooling experts. This study represents the first analysis of the inks and paper used in Burns poetry, in a minimally destructive manner that could find application in many areas. Applying direct infusion mass spectrometry to a panel of selected authenticated Burns and Smith manuscripts, we have produced a Support Vector Machine classifier that distinguishes Burns from Smith with a 0.77 AUC. Using contemporary recipes for inks, we were also able to match features of each to the inks used to produce some of Burns’ original manuscripts. We anticipate the method and classifier having broad application in authentication of manuscripts, and our analysis of contemporary inks to provide insights into the production of written works of art.
Daniel J. Ryan, David Nei, Boone M. Prentice, Kristie L. Rose, Richard M. Caprioli, Jeffrey M. Spraggins
Robotic liquid surface extractions can be used to interrogate discrete regions of tissue to provide protein identifications with high throughput, accuracy, and robustness. The direct coupling of tissue surface extractions and liquid chromatography, offers a new and effective approach to provide spatial proteomics data in an imaging experiment.
Tissue extractions were completed using the TriVersa NanoMate® (Advion, Inc., Ithaca, NY, USA) modified to include a glass capillary (LESA Plus) for improved spatial resolution and online integration with LC-based experiments. 36 Scanned images of thaw-mounted samples were uploaded to the ChipSoft Software (Advion, Inc.) to allow histological regions of interest to be selected for analysis.
Lieke Lamont, Mark Baumert, Nina Ogrinc Potočnik, Mark Allen, Rob Vreefken, Ron M. A. Heeren, and Tiffany Porta
Direct analysis by mass spectrometry (imaging) has become increasingly deployed in preclinical and clinical research due to its rapid and accurate readouts. However, when it comes to biomarker discovery or histopathological diagnostics, more sensitive and in-depth profi ling from localized areas is required. We developed a comprehensive, fully automated online platform for high-resolution liquid extraction surface analysis (HR-LESA) followed by micro−liquid chromatography (LC) separation and a data-independent acquisition strategy for untargeted and low abundant analyte identifi cation directly from tissue sections. Applied to tissue sections of rat pituitary, the platform demonstrated improved spatial resolution, allowing sample areas as small as 400 μ m to be studied, a major advantage over conventional LESA.
The LESA extraction was performed using the automated TriVersa NanoMate® The LESA extraction was controlled by a beta version of the LESA Plus software (Advion, UK)
Rian L. Griffiths, Emma K. Sisley, Andrea F. Lopez-Clavija, Anna L. Simmonds, Iain B. Styles, Helen J. Cooper
Here, researchers present native liquid extraction surface analysis (LESA) mass spectrometry imaging of proteins and protein complexes from mouse brain and liver tissue. Intact proteins were detected in characteristically low charge states, indicating that the proteins remain folded. In brain, abundant proteins such as ubiquitin and β thymosin 4 were detected homogeneously across the tissue whereas other proteins, such as neurogranin, were localised in specific anatomical regions.
In liver, imaging of a protein complex (tetrameric hemoglobin) is demonstrated, as well as fatty acid binding protein. Interestingly, the use of native-like solvents enables extraction of proteins which have not previously been observed in LESA experiments employing denaturing solvents, i.e., native LESA can be applied to extend the range of proteins observed. In addition native LESA ion mobility spectrometry is presented and shows that the collision cross sections of proteins extracted from tissue may be determined by travelling wave ion mobility spectrometry. The collision cross section of the 5+ ion of ubiquitin was calculated as 1047 Å2, in good agreement with measurements of ubiquitin protein standard solutions. Collision cross sections for the 4+ ions of β-thymosin 4, β-thymosin 10 and two unidentified proteins were also calculated, together with that of a 10+ ion of an unidentified protein of molecular weight 15660 Da.
For mass spectrometry and mass spectrometry imaging, the samples were introduced to the mass spectrometer via nanoESI using a TriVersa NanoMate® (Advion Biosciences, Ithaca, USA). The exact location to be sampled was selected using the LESA® Points software (Advion).
ABSTRACT: Large-scale metabolic profiling requires the development of novel economical high-throughput analytical methods to facilitate characterization of systemic metabolic variation in population phenotypes. We report a fit-forpurpose direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) method with time-of-flight detection for rapid targeted parallel analysis of over 40 urinary metabolites. The newly developed 2 min infusion method requires <10 μL of urine sample and generates high-resolution MS profiles in both positive and negative polarities, enabling further data mining and relative quantification of hundreds of metabolites. Here we present optimization of the DI-nESI-HRMS method in a detailed step-by-step guide and provide a workflow with rigorous quality assessment for large-scale studies.
From the Journal of Proteome Research, Published February 2017
The TriVersa NanoMate® LESA® is the latest in chip-based electrospray ionization technology from Advion Interchim Scientific®. It combines the benefits of liquid chromatography, mass spectrometry, chip-based infusion, fraction collection and direct surface analysis into one integrated ion source platform. It allows scientists to obtain more information from complex samples than LC/MS alone.
The early stages of nonalcoholic fatty liver disease (NAFLD) are characterized by the accumulation of fat in the liver (steatosis). This can lead to cell injury and inflammation resulting in nonalcoholic steatohepatitis (NASH). To determine whether lipid profiling of liver tissue can identify metabolic signatures associated with disease presence and severity, we explored liquid extraction surface analysis mass spectrometry (LESA−MS, Advion TriVersa NanoMate with LESA PLUS) as a novel sampling tool. Using LESA−MS, lipids were extracted directly from the surface of ultrathin slices of liver tissue prior to detection by high-resolution mass spectrometry (MS).
We compared the data obtained by LESA− MS to that from liquid chromatography (LC)− MS and matrix-assisted laser desorption ionization MS. Advantages of LESA− MS include rapid analysis, minimal sample preparation, and high lipid coverage.
Furthermore, since tissue slices are routinely used for diagnostics in clinical settings, LESA− MS is ideally placed to complement traditional histology. Overall LESA− MS is found to be a robust, fast, and discriminating approach for determining NAFLD presence and severity in clinical samples.
Infusion based lipidomics analysis (shotgun Lipidomics) is an analysis strategy that involves the liquid extraction of lipids from samples such as blood, tissue homogenates or dried blood spots. This approach is suitable for a wide range of biomedical questions of lipid differentiation and lipid flux in the field of metabolic disease, neurological disorders, cancers or eye diseases. See how utilizing the Advion Interchim Scientific TriVersa NanoMate® can be used for high throughput shotgun Lipidomics analysis.
