We are requesting funding to upgrade our Olympus FV1000 confocal microscope at the Optical Imaging Core (OIC) to a fully capable fluorescence lifetime (FLT) imaging microscope (FLIM) using system-specific upgrade kit from PicoQuant. FLIM measures FLT in cell microenvironment. Unlike fluorescence intensity, FLT is exquisitely sensitive to local probe environment through perturbation of excited state properties. Washington University in St. Louis (WUSTL) and surrounding research community do not have access to a FLIM system that provides easy-to-use interface and performs diverse wavelength imaging with the capability of detecting fluorescence in multiple channels. The FLIM system will support 17+ NIH-funded projects, initially consisting of 3 major and 11 minor users from WUSTL, Saint Louis University (SLU), and University of Missouri at St. Louis (UMSL). All the investigators have substantially published work in molecular imaging and demonstrable ongoing need for FLIM. Planned studies will focus on discovering novel molecular interactions that result in changes in the FLT of reporter molecules, designing new class of FLT contrast agents, quantitatively determining the sub-cellular distribution of target biomolecules, establishing the behavior of different fluorescent molecular probes and cancer drugs in cell compartments, understanding the complex dynamics of macromolecules in cells, unraveling the biochemical roles of proteins of unknown functions, and elucidating the bio-significance of FLT heterogeneity observed in noninvasive small animal imaging studies with high resolution FLIM. Not only will this system perform FLT and conventional fluorescence intensity measurement, it will also provide spatio-temporal information of a target biomolecule or process in response to cell microenvironmental changes stimulated by factors such as pH, lipophilicity, cell metabolic state, presence of free radicals, and hypoxia. The proposed system upgrade will enhance the services available in OIC for molecular imaging of biological processes and advance the research of many growing research groups at St. Louis. It will facilitate new collaborations and generate new concepts to advance our understanding of complex biological systems at cell level. Because of OIC's location in the heart of the medical center, the system will be available to all current and future users, as is the current practice with other instruments housed in OIC. Highly experienced personnel will manage the instrument, train new users, and help conduct new projects. The proximity of the instrument to research laboratories at WUSTL, SLU, and UMSL will attract new user and facilitate training of students and fellows using the state-of-the-art technology platform.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Levy, Abraham
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Miller, Jessica; Wang, Steven T; Orukari, Inema et al. (2018) Perfusion-based fluorescence imaging method delineates diverse organs and identifies multifocal tumors using generic near-infrared molecular probes. J Biophotonics 11:e201700232
Zheleznyak, Alexander; Shokeen, Monica; Achilefu, Samuel (2018) Nanotherapeutics for multiple myeloma. Wiley Interdiscip Rev Nanomed Nanobiotechnol 10:e1526
Gilson, Rebecca C; Black, Kvar C L; Lane, Daniel D et al. (2017) Hybrid TiO2 -Ruthenium Nano-photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions. Angew Chem Int Ed Engl 56:10717-10720
Miller, Jessica P; Habimana-Griffin, LeMoyne; Edwards, Tracy S et al. (2017) Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores. J Biomed Opt 22:66007
Mondal, Suman B; Gao, Shengkui; Zhu, Nan et al. (2017) Optical See-Through Cancer Vision Goggles Enable Direct Patient Visualization and Real-Time Fluorescence-Guided Oncologic Surgery. Ann Surg Oncol 24:1897-1903
Miller, Jessica P; Egbulefu, Christopher; Prior, Julie L et al. (2016) Gradient-Based Algorithm for Determining Tumor Volumes in Small Animals Using Planar Fluorescence Imaging Platform. Tomography 2:17-25
Som, Avik; Bloch, Sharon; Ippolito, Joseph E et al. (2016) Acidic extracellular pH of tumors induces octamer-binding transcription factor 4 expression in murine fibroblasts in vitro and in vivo. Sci Rep 6:27803
Sarder, Pinaki; Maji, Dolonchampa; Achilefu, Samuel (2015) Molecular probes for fluorescence lifetime imaging. Bioconjug Chem 26:963-74
Gilson, Rebecca C; Tang, Rui; Som, Avik et al. (2015) Protonation and Trapping of a Small pH-Sensitive Near-Infrared Fluorescent Molecule in the Acidic Tumor Environment Delineate Diverse Tumors in Vivo. Mol Pharm 12:4237-46
Tsen, Shaw-Wei D; Kingsley, David H; Kibler, Karen et al. (2014) Pathogen reduction in human plasma using an ultrashort pulsed laser. PLoS One 9:e111673