| NSF Org: |
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems |
| Recipient: |
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| Initial Amendment Date: | December 15, 2017 |
| Latest Amendment Date: | December 15, 2017 |
| Award Number: | 1752405 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Adam Wax
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering |
| Start Date: | June 1, 2018 |
| End Date: | May 31, 2023 (Estimated) |
| Total Intended Award Amount: | $500,000.00 |
| Total Awarded Amount to Date: | $500,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
341 PINE TREE RD ITHACA NY US 14850-2820 (607)255-5014 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
237 Tower Road Ithaca NY US 14853-7202 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | BioP-Biophotonics |
| Primary Program Source: |
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| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.041 |
ABSTRACT
Optical microscopy has played a key role in biomedical discoveries for clinical management of disease, but significant challenges remain for applications that require rapid, non-invasive imaging over large volumes, particularly when imaging deep into optically dense biological media. This proposal addresses these limitations by developing new ways of splitting up, and sharing the work of image formation between state-of-the-art computational and hardware approaches. These methods will be demonstrated by imaging biological phenomena that cannot be studied with existing methods. The accompanying education and outreach activities will foster a broader appreciation for biomedical optics and imaging, and train scientists and engineers to effectively interact with, and engage the public. Outreach aspects of this proposal will create experiential and interactive inquiry-based workshops for middle and high school students, develop interactive demonstrations for the Ithaca Sciencenter and train graduate students to effectively communicate their science with the public.
High-throughput volumetric microscopy deep in biological media is important for the study of dynamic biological processes, such as the biophysical interactions associated with collective cell migration, or neural network activity in the mouse brain. Optical coherence microscopy (OCM) and three-photon microscopy (3PM) are currently the modalities that enable the deepest microscopic imaging in scattering biological samples. However, their volumetric imaging speed and penetration depth is currently limited by depth-dependent photon collection, or by wavefront distortions due to aberrations and multiple scattering. This proposal will synergistically combine hardware adaptive optics (AO) and computational adaptive optics (CAO), to dramatically improve the speed and imaging depth range of volumetric OCM and 3PM.This hybrid AO approach will be used to launch new avenues of investigation, including studies on inter-cell coordination of cell traction forces during 3D migration, and investigations on the connection between behavior and spatiotemporal patterns of neural network activity deep in the mouse brain.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
This project has developed new ways of integrating optical wavefront shaping with computational methods to enable faster and deeper imaging in scattering biological samples. Faster imaging is important for studying how a population of cells interact with each other as well as their 'local neighborhood' known as the extracellular matrix. In particular, we have demonstrated volumetric time-lapse imaging of these dynamic interactions without the need for fluorescent labeling that can be toxic when when used for long-term continuous imaging studies. Imaging deeper into scattering samples (tissues or engineered cell cultures) is a significant problem since scattering distorts the wavefront of light propaging into the sample, degrading the ability to form high quality images deep into the sample. (This problem is analoigous to trying to see through fog, which can severly limit the range of visibility when driving.) Our integrated optical wavefront shaping and computational approach has shown that the diffuse (or 'hazy') part of the measured light signal can actually be suppressed, thereby improving image quality when imaging deep into a scatttering sample. Our advances enable us to 'see' more of the 3D microstructure of the sample, and how cell populations interact with each other and their neighbourhood. This could lead to new discoveries about how diseases like cancer develop, and also provide a way to design and test new approaches to treating disease.
The outreach aspects of this project have resulted in the training of tens of graduate or undergraduate students on how to effectively engage a general audience (especially K-12 students), to get them excited about the 'world of optics and imaging'. As part of the Principlal Investigators Modern Biomedical Microsocpy class, during a science communication module that was run in collaboration with the Ithaca Sciencenter and Cornell's Center for Teaching Innovation, students in the class developed interactive activities that were subsequently presented to visitors at the Ithaca Sciencenter. This has helped share some of the excitemtent of doing science (in particular optics and imaging research) with non-specialists, and helped train potential future leaders in science to continue to engage with the public.
Last Modified: 02/19/2024
Modified by: Steven G Adie
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