University of Cambridge, NIHR BCR Metabolomics and Lipidomics Facility

What is the focus of your lab’s research?

Almost exclusively high throughput lipid profiling of samples from large epidemiological studies, where we study gene-lifestyle interactions. The method works with plasma samples as well as dried blood spots. The method is also applied to small-scale studies of specific disease groups, dietary interventions and model systems such as yeast. The TriVersa NanoMate® is also used to study the lipid composition of tissues analyzed by LESA®.

Why did you incorporate the TriVersa NanoMate® into your laboratory?

The TriVersa NanoMate® is essential to efficiently analyze large-scale studies. It offers a really robust method for high throughput studies with minimal carryover.

Who would you recommend to purchase the TriVersa NanoMate®?

I recommend the TriVersa NanoMate® to laboratories with a large number of samples requiring a robust and reliable delivery system. The TriVersa NanoMate® eliminates typical nanoelectrospray ionization challenges.

Do you have any publications or presentations using the TriVersa NanoMate®?

Publication Highlight:
Development and Application of High-Throughput Single Cell Lipid Profiling: A Study of SNCA-A53T Human Dopamine Neurons
Snowden, et al. iScience, 2020, 23(10), 101703

Combining FACS and LESA-MS to establish high-throughput single cell lipid profiling. Research identifies lipid differences found within and between populations of human dopamine neurons.

Other Publications:
  • Snowden et al. Combining lipidomics and machine learning to measure clinical lipids in dried blood spots. Metabolomics. DOI: 10.1007/s11306-020-01703-0
  • Koulman et al. The development and validation of a fast and robust dried blood spot based lipid profiling method to study infant metabolism. Metabolomics. DOI: 10.1007/s11306-014-0628-z
  • Furse et al. A high-throughput platform for detailed lipidomic analysis of a range of mouse and human tissues. Analytical and Bioanalytical Chemistry. DOI: 10.1007/s00216-020-02511-0
  • Harshfield et al. An unbiased lipid phenotyping approach to study the genetic determinants of lipids and their associations with coronary heart disease risk factors. J Proteom Res. DOI: 10.1021/acs.jproteome.8b00786
  • Mann et al. Insights into genetic variants associated with NASH-fibrosis from metabolite profiling. Hum Mol Genet. DOI: 10.1093/hmg/ddaa162

Liquid Extraction Surface Analysis Mass Spectrometry (LESA-MS): Examples of a New Surface Probing Technique for Clinical and Pre-Clinical Applications

Executive Summary:

  • LESA and LESAplus liquid chromatography provide novel surface analysis tools for the spatial resolution of analytes from a wide variety of surfaces.
  • Whole body or organ sections in particular can be probed for small molecules, lipids and proteins with a resolution of 400 – 1000μm.
  • Commercial solution allows for automated processing of samples (Advion TriVersa NanoMate® LESA®).

This poster was presented at MSACL 2018 US in Palm Springs, CA.

Optimization and Application of Direct Infusion Nanoelectrospray HRMS Method for Large-Scale Urinary Metabolic Phenotyping in Molecular Epidemiology

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

TriVersa NanoMate® LESA® with ESI Chip® Technology

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.

Liquid Extraction Surface Analysis Mass Spectrometry Method for Identifying the Presence and Severity of Nonalcoholic Fatty Liver Disease

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.

Analysis of urine, oral fluid and fingerprints by liquid extraction surface analysis coupled to high resolution MS and MS/MS – opportunities for forensic and biomedical science

Published by the Royal Society of Chemistry

Liquid Extraction Surface Analysis (LESA) is a new, high throughput tool for ambient mass spectrometry. A solvent droplet is deposited from a pipette tip onto a surface and maintains contact with both the surface and the pipette tip for a few seconds before being re-aspirated. The technique is particularly suited to the analysis of trace materials on surfaces due to its high sensitivity and low volume of sample removal. In this work, we assess the suitability of LESA for obtaining detailed chemical profiles of fingerprints, oral fluid and urine, which may be used in future for rapid medical diagnostics or metabolomics studies. We further show how LESA can be used to detect illicit drugs and their metabolites in urine, oral fluid and fingerprints. This makes LESA a potentially useful tool in the growing field of fingerprint chemical analysis, which is relevant not only to forensics but also to medical diagnostics. Finally, we show how LESA can be used to detect the explosive material RDX in contaminated artificial fingermarks.

LESA plus: Liquid Extraction Surface Analysis PLUS LC Separation

The Liquid Extraction Surface Analysis (LESA) capability of the TriVersa NanoMate enables simple, direct nanoESI mass spectrometric analysis from a variety of surfaces.

The new LESAPLUS allows for automated LESA experiments plus additional nano-LC separation through the ChipSoftX operating software with Developers Kit. This enhancement is ideal for direct tissue analysis.

CHIPSOFT 10.0 WITH DEVELOPERS KIT: Customized method development for the TriVersa Nanomate

ChipSoftX is an entirely new operating software for the TriVersa NanoMate automated nanoelectrospray source. Besides improvement in program compatibility with Windows and integration of existing software features, it also provides access to the new Developers Kit – a platform for customized method development with direct access to robot controls allowing entirely novel analysis workflows such as LESAPLUS.


LESA – Liquid Extraction Surface Analysis

More analytes and higher sensitivity

Developed in collaboration with Oak Ridge National Laboratory*, the liquid extraction surface analysis (LESA) capability of the TriVersa Nanomate® enables simple, direct ESI mass spectrometric analysis from a variety of surfaces.