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Orientation Independent DIC and Polarization Microscopy

Award Number: R01GM101701
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2005
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Orientation Independent DIC and Polarization Microscopy - Project Summary This project aims to develop and apply new quantitative differential interference contrast and polarized light microscope techniques, both of whose contrast is independent of specimen orientation. During the previous grant period we built the orientation-independent differential interference contrast (OI-DIC) microscope, which rapidly changes shear directions without any mechanically moved components. The OI-DIC technique, which we have developed, provides the highest quality of optical path length (dry mass) map of thin optical section of unstained and stained specimens with lateral resolution ~250-300nm, axial discrimination depth ~100nm, and optical path length sensitivity ~0.5nm at wavelength 546nm. We believe that images with such high level of resolution cannot be produced by any other currently available interference and phase microscopy techniques. We also built the polychromatic polarized light microscope (polscope), which employs new principle of generating interference color and produces a color image of the birefringent structures with retardances of several nm, which was not possible before. The hue of the structure indicates its slow axis orientation, and the brightness of the structure is proportional to its retardance. We will engineer the improved high-resolution OI- DIC with and exploit two principally new OI-DIC approaches. The new OI-DIC will be combined with the orientation-independent polarization (LC-polscope) and confocal fluorescence techniques. The improved OI- DIC and the combined setup will be used to study the architectural dynamics of live biological specimens, with emphasis on events associated with mitosis and meiosis. We will build an instantaneous OI-DIC, which will simultaneously capture 4 raw DIC images with the orthogonal shear directions. The instantaneous OI-DIC techniques will provide the best temporal resolution and allow the elimination of artifacts caused by movements of the cytosol and organelles. We will develop OI-DIC technique to restore the 3D distribution of both dry mass (phase-related information) and refractive index. With this technique, one will be able to determine the dry mass of chromosomes before division and observe its change during the division process. The new high- sensitive polychromatic polscope will visualize birefringent structures with retardances less than 1nm. The polychromatic polscope will be combined with phase contrast and dark field techniques, so that image brightness displays dry mass distribution and the color depicts molecular orientation. These combined techniques will be used to study metaphase of meiosis I, and analyze the correspondence between structural signatures in different live organisms, as well as their genetic background. We will create a quantitative polychromatic polscope, which will provide a two-dimensional distribution both the specimen’s retardance and slow axis orientation. The quantitative polychromatic polscope will be employed to study collagen fibers in cancer tissues.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$804 )
2025	2020	THE MARINE BIOLOGICAL LABORATORY	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	11	3/13/2025	NON-COMPETING CONTINUATION	-$804
														Subtotal = -$804

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	THE MARINE BIOLOGICAL LABORATORY	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	11	6/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	11	7/4/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $472,800 )
2020	2020	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	11	7/29/2020	NON-COMPETING CONTINUATION	$472,800
														Subtotal = $472,800

Issue Date FY: 2019 ( Subtotal = $512,800 )
2019	2019	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	10	7/30/2019	NON-COMPETING CONTINUATION	$512,800
														Subtotal = $512,800

Issue Date FY: 2018 ( Subtotal = $742,800 )
2018	2018	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	002	9	8/1/2018	NON-COMPETING CONTINUATION	$492,800
2018	2018	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	003	9	9/21/2018	SUPPLEMENT FOR EXPANSION	$250,000
2018	2017	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	001	8	5/10/2018	COMPETING CONTINUATION	$16,459
2018	2015	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	7	5/10/2018	NON-COMPETING CONTINUATION	-$16,459
														Subtotal = $742,800

Issue Date FY: 2017 ( Subtotal = $472,800 )
2017	2017	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	002	8	9/13/2017	COMPETING CONTINUATION	$472,800
2017	2015	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	001	7	9/13/2017	NON-COMPETING CONTINUATION	$0
2017	2015	MARINE BIOLOGICAL LABORATORY, THE	7 M B L ST	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	7	4/6/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $472,800

Issue Date FY: 2015 ( Subtotal = $381,402 )
2015	2015	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	7	3/17/2015	NON-COMPETING CONTINUATION	$381,402
														Subtotal = $381,402

Issue Date FY: 2014 ( Subtotal = $399,779 )
2014	2014	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	6	4/2/2014	NON-COMPETING CONTINUATION	$399,779
														Subtotal = $399,779

Issue Date FY: 2013 ( Subtotal = $370,347 )
2013	2013	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	5	5/20/2013	NON-COMPETING CONTINUATION	$370,347
														Subtotal = $370,347

Issue Date FY: 2012 ( Subtotal = $428,317 )
2012	2012	MARINE BIOLOGICAL LABORATORY	7 MBL STREET	WOODS HOLE	MA	02543	BARNSTABLE	USA	Biomedical Research and Research Training	000	4	6/4/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$428,317
														Subtotal = $428,317

Grand Total All Awards = $3,780,241

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Orientation Independent DIC and Polarization Microscopy

Award Number: R01GM101701

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2005

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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