In this application, we propose to demonstrate the feasibility of spectral domain phase microscopy (SDPM) as a new tool for non-invasive, non-contact, far-field optical characterization of static and dynamic nanoscale structures including living cell membranes. SDPM is a functional extension of spectral domain optical coherence tomography which allows for the detection of structural surface profiles, motions and dynamics with nanometer-scale sensitivity in the axial dimension in real time. Nanometer-scale sensitivity in the axial direction is obtained by using a newly developed implementation of exquisitely phase stable self-referencing interferometry, while maintaining the non-contact advantages of working in the optical far field. Lateral resolution in this technique is limited by physical optics to the micrometer scale. Although our proposed technique has many potential applications in static and dynamic structural analysis of living and non-living nanoscale materials and machines, in this R21 application we concentrate primarily on initial SDPM technology development and feasibility demonstrations of its applications in cell biology. The particular cell biology questions we propose to address with this technology include measuring mechanical activity in developing cardiomyocytes and assessing the magnitude and kinetics of cell migration in neural crest cells.
The specific aims of this proposal are as follows: 1. Develop novel technology implementations for high-speed temporally- and spatially- resolved nanoscale axial displacement measurements using spectral domain phase microscopy (SDPM); 2. Develop signal and image processing approaches for improving the accuracy of SDPM displacement quantitation; 3. Apply temporally and spatially-resolved SDPM for static and dynamic nanoscale measurements in living cells. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB006338-02
Application #
7230296
Study Section
Special Emphasis Panel (ZRG1-BCMB-R (50))
Program Officer
Zhang, Yantian
Project Start
2006-05-01
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
2
Fiscal Year
2007
Total Cost
$183,814
Indirect Cost
Name
Duke University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Hendargo, Hansford C; Bower, Bradley A; Reinstein, Alex S et al. (2011) Depth-Encoded Spectral Domain Phase Microscopy for Simultaneous Multi-Site Nanoscale Optical Measurements. Opt Commun 284:4847-4851
Skala, Melissa C; Fontanella, Andrew; Lan, Lan et al. (2010) Longitudinal optical imaging of tumor metabolism and hemodynamics. J Biomed Opt 15:011112
Davis, Anjul; Izatt, Joseph; Rothenberg, Florence (2009) Quantitative measurement of blood flow dynamics in embryonic vasculature using spectral Doppler velocimetry. Anat Rec (Hoboken) 292:311-9
Hendargo, Hansford C; Zhao, Mingtao; Shepherd, Neal et al. (2009) Synthetic wavelength based phase unwrapping in spectral domain optical coherence tomography. Opt Express 17:5039-51
Skala, Melissa C; Fontanella, Andrew; Hendargo, Hansford et al. (2009) Combined hyperspectral and spectral domain optical coherence tomography microscope for noninvasive hemodynamic imaging. Opt Lett 34:289-91
Skala, Melissa C; Crow, Matthew J; Wax, Adam et al. (2008) Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres. Nano Lett 8:3461-7
Tao, Yuankai K; Davis, Anjul M; Izatt, Joseph A (2008) Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform. Opt Express 16:12350-61
Davis, A M; Rothenberg, F G; Shepherd, N et al. (2008) In vivo spectral domain optical coherence tomography volumetric imaging and spectral Doppler velocimetry of early stage embryonic chicken heart development. J Opt Soc Am A Opt Image Sci Vis 25:3134-43
Ellerbee, Audrey K; Izatt, Joseph A (2007) Phase retrieval in low-coherence interferometric microscopy. Opt Lett 32:388-90