Single-cell Imaging Mass Spectrometry
Imaging mass spectrometry technologies will be used to map the distribution of biomolecules and pharmaceuticals in tissue at sub-cellular resolutions. Spatial ‘omics experiments will be used to examine metabolomics alterations resulting from cellular activation/differentiation, drug perturbation, and diseases.
The research program will:
Utilize single-cell ‘omics signatures to characterize the role of macrophage polarization and T-cell activation in tissue inflammation.
Develop a method for evaluating drug efficacy and toxicity via intracellular drug concentration and ‘omics perturbation measurements.
Develop IMS-based diagnostic applications for cancer; use heterogeneity and microenvironment characteristics to predict patient outcomes and develop ex-vivo methods for testing treatment strategies.
Mass Spectrometry-based Intracellular Drug Measurements
•We are investigating the cellular uptake of pharmaceutical compounds and examining their biochemical effects at therapeutic and toxic levels.
•In order to evaluate intracellular drug levels, we are developing a multi-modal analytical approach that combined live-cell atomic force microscopy (AFM) and single-cell mass spectrometry (MS).
Fundamental studies to improve multi-modal IMS (NSERC-DG)
To ensure the advancement of multi-modal IMS in both clinical and pharmacological research it is necessary to understand and optimize the analytical workflow. In these studies we will collect complimentary SIMS images from adjacent tissue sections in an independent workflow (a) or in series with MALDI-IMS using the same sample (b). Moreover, SIMS imaging can be utilized as an investigative tool to characterize matrix application (i.e. analytes/matrix co-localization and crystal size, c), examine the footprint of the laser after MALDI analysis (d) and improve the lateral resolution of MALDI images via computational data fusion techniques (e). SIMS imaging can also assess changes in the tissue bimolecular signature before and after washing, on-tissue derivatization, and on-tissue digestions steps.