title: Line-scanning confocal microscopy for high-resolution imaging of upconverting rare-earth-based contrast agents.
abstract: Rare-earth (RE) doped nanocomposites emit visible luminescence when illuminated with continuous wave near-infrared light, making them appealing candidates for use as contrast agents in biomedical imaging. However, the emission lifetime of these materials is much longer than the pixel dwell times used in scanning intravital microscopy. To overcome this limitation, we have developed a line-scanning confocal microscope for high-resolution, optically sectioned imaging of samples labeled with RE-based nanomaterials. Instrument performance is quantified using calibrated test objects. NaYF4 : Er,Yb nanocomposites are imaged in vitro, and in ex vivo tissue specimens, with direct comparison to point-scanning confocal microscopy. We demonstrate that the extended pixel dwell time of line-scanning confocal microscopy enables subcellular-level imaging of these nanomaterials while maintaining optical sectioning. The line-scanning approach thus enables microscopic imaging of this emerging class of contrast agents for preclinical studies, with the potential to be adapted for real-time in vivo imaging in the clinic.
authors.affiliation: Rutgers University, Department of Biomedical Engineering, 599 Taylor Road, Piscataway, New Jersey 08854, United States.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Higgins
authors.affiliation: Rutgers University, Department of Biomedical Engineering, 599 Taylor Road, Piscataway, New Jersey 08854, United States.
authors.forename: Margot
authors.initials: M
authors.lastname: Zevon
authors.affiliation: Rutgers University, Department of Biomedical Engineering, 599 Taylor Road, Piscataway, New Jersey 08854, United States.
authors.forename: Vidya
authors.initials: V
authors.lastname: Ganapathy
authors.affiliation: Singapore University of Technology and Design, Engineering Product Development, 8 Somapah Road 487372, Singapore.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Singapore University of Technology and Design, Engineering Product Development, 8 Somapah Road 487372, Singapore.
authors.forename: Mei Chee
authors.initials: MC
authors.lastname: Tan
authors.affiliation: Rutgers University, Department of Materials Science and Engineering, 607 Taylor Road, Piscataway, New Jersey 08854, United States.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Riman
authors.affiliation: Rutgers University, Department of Biomedical Engineering, 599 Taylor Road, Piscataway, New Jersey 08854, United StatesdRutgers University, Department of Chemical and Biochemical Engineering, 98 Brett Road, Piscataway, New Jersey 08854, United States.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Roth
authors.affiliation: Rutgers University, Department of Biomedical Engineering, 599 Taylor Road, Piscataway, New Jersey 08854, United StatesdRutgers University, Department of Chemical and Biochemical Engineering, 98 Brett Road, Piscataway, New Jersey 08854, United States.
authors.forename: Prabhas V
authors.initials: PV
authors.lastname: Moghe
authors.affiliation: Rutgers University, Department of Biomedical Engineering, 599 Taylor Road, Piscataway, New Jersey 08854, United States.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Pierce
mesh_terms: D045744:Cell Line, Tumor / Q000737:chemistry* / Q000648:ultrastructure; D003287:Contrast Media / Q000737:chemistry; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D007089:Image Enhancement / Q000295:instrumentation*; D008674:Metals, Rare Earth; D008856:Microscopy, Fluorescence / Q000295:instrumentation*; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D008674:Metals, Rare Earth