title: Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection.
abstract: 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.
authors.affiliation: Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Stephanie M W Y
authors.initials: SM
authors.lastname: van de Ven
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, IN, USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Bemis
authors.affiliation: Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lau
authors.affiliation: Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Ravali
authors.initials: R
authors.lastname: Adusumilli
authors.affiliation: Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.|Thermo Fisher Scientific, San Jose, CA, USA.
authors.forename: Uma
authors.initials: U
authors.lastname: Kota
authors.affiliation: Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Stolowitz
authors.affiliation: College of Science, College of Computer and Information Science, Northeastern University, Boston, MA, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Vitek
authors.affiliation: Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Parag
authors.initials: P
authors.lastname: Mallick
authors.affiliation: Canary Center at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.|Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.|Department of Bioengineering, Stanford University School of Medicine, Stanford, CA, USA.|Department of Materials Science & Engineering, Stanford, CA, USA.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D015415:Biomarkers; D006801:Humans; D057230:Limit of Detection; D051379:Mice; D010455:Peptides / Q000235:genetics* / Q000302:isolation & purification; D011506:Proteins / Q000235:genetics* / Q000302:isolation & purification; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015415:Biomarkers; D010455:Peptides; D011506:Proteins
keywords: Limit of detection; MALDI Imaging; Mass spectrometry; Protein biomarkers; Sensitivity; Technology