Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection.
MALDI mass spectrometry imaging (MSI) is emerging as a tool for protein and peptide imaging across tissue sections. Despite extensive study, there does not yet exist a baseline study evaluating the potential capabilities for this technique to detect diverse proteins in tissue sections. In this study, we developed a systematic approach for characterizing MALDI-MSI workflows in terms of limits of detection, coefficients of variation, spatial resolution, and the identification of endogenous tissue proteins. Our goal was to quantify these figures of merit for a number of different proteins and peptides, in order to gain more insight in the feasibility of protein biomarker discovery efforts using this technique. Control proteins and peptides were deposited in serial dilutions on thinly sectioned mouse xenograft tissue. Using our experimental setup, coefficients of variation were <30% on tissue sections and spatial resolution was 200 μm (or greater). Limits of detection for proteins and peptides on tissue were in the micromolar to millimolar range. Protein identification was only possible for proteins present in high abundance in the tissue. These results provide a baseline for the application of MALDI-MSI towards the discovery of new candidate biomarkers and a new benchmarking strategy that can be used for comparing diverse MALDI-MSI workflows.
['van de Ven|Stephanie M W Y|SM|', 'Bemis|Kyle D|KD|', 'Lau|Kenneth|K|', 'Adusumilli|Ravali|R|', 'Kota|Uma|U|', 'Stolowitz|Mark|M|', 'Vitek|Olga|O|', 'Mallick|Parag|P|', 'Gambhir|Sanjiv S|SS|']
D000818:Animals D015415:Biomarkers D006801:Humans D057230:Limit of Detection D051379:Mice D010455:Peptides D011506:Proteins D040901:Proteomics D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization D023041:Xenograft Model Antitumor Assays
Protein biomarkers Mass spectrometry Limit of detection MALDI Imaging Sensitivity Technology