This research revolves around the development of laser scanning microscopy as a quantitative tool for cell biology and biophysics. To that end, the first three year grant was devoted to design and construction of a flexible instrument which would serve researchers as well as be a proving ground for new developments in scanned imaging. The goals of this phase of the project have nearly been achieved, and this competing continuation proposal addresses further scientific use of the instrument and several advanced technological issues related to the integration of optical design and digital postprocessing in the microscope system.
The specific aims of this continuation proposal are (1) To refine the optical and electronic design of the scanner and detector systems, in order to maximize signal-to-noise ratio with minimum optical dose to the specimen. (2) To use the laser scanning microscope in scientific investigations (neutrophil activation responses and cognate activation of B lymphocytes), to develop practical quantitative methods and test the instrument's performance; (3) To continue development of digital image processing methods for tomographic reconstruction from noisy (photon-limited) confocal image sets; (4) To investigate the fundamental limits and practical realization of so-called superresolving pupils for enhancing lateral or longitudinal resolution in the confocal microscope; and (5) To develop an integrated model for the microscope system which elucidates the roles played by optics and digital postprocessing, and which enables an optimum system to be designed. The results of this work will be applicable to other laser scanning microscopes, as well, and hence will further the general state of the art in scanning microscopy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM036594-04A1
Application #
3290886
Study Section
Special Emphasis Panel (SSS (B))
Project Start
1986-12-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
Schools of Engineering
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755