| NSF Org: |
TI Translational Impacts |
| Recipient: |
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| Initial Amendment Date: | December 18, 2012 |
| Latest Amendment Date: | November 25, 2013 |
| Award Number: | 1248873 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Steven Konsek
TI Translational Impacts TIP Directorate for Technology, Innovation, and Partnerships |
| Start Date: | January 1, 2013 |
| End Date: | December 31, 2013 (Estimated) |
| Total Intended Award Amount: | $150,000.00 |
| Total Awarded Amount to Date: | $175,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
3415 COLORADO AVE BOULDER CO US 80303-1904 (303)735-4900 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
1815 Bluebell Ave Boulder CO US 80302-8021 |
| 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): | SBIR Phase I |
| 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): | 47.084 |
ABSTRACT
This Small Business Innovation Research Program (SBIR) Phase I project investigates the feasibility of a ground-breaking three-dimensional (3D) optical microscope with single-molecule sensitivity suitable for live cell studies and nanometer scale sensing. Several methods have recently shown resolution well beyond the optical diffraction limit, which restricts imaging to features larger than about 200 and 500 nm in the transverse and axial dimensions respectively. To date, these super-resolution techniques have been demonstrated in specialized labs but new developments are required to reach the fundamental limits on a regular basis at the typical biology lab. Therefore, this project focuses on fundamental technological developments to address the upcoming need for pervasive 3D superresolution single-molecule capabitlities. The instrument is based on a joint design of the illumination, optical response, data collection approach, and reconstruction algorithms for fluorescence imaging. The instrument makes use of tailored point spread functions that enable the determination of the 3D position of emitters with great precision, leading to better resolution and depth of field than competing methods. Preliminary laboratory experiments have shown 3D capability with resolutions below 20nm, which corresponds to one order of magnitude enhancement over most optical microscopes presently in use.
The broader impact/commercial potential of this project addresses a major opportunity in an expanding biological instrumentation market. If successful, it will enable 3D superresolution imaging capability to many biological laboratories currently limited by past technologies. The feasibility plan opens up opportunities for an accelerated commercialization path by implementing a cost-effective flexible solution compatible with existing microscopes. The extensive availability of superresolution imaging will impact several fields of science and engineering including 3D biophysical and biomedical optical imaging. During the project the company will generate synergistic relationships to rapidly transfer the technology into applications. The company has established partnerships for testing the instrument in significant biological problems that are expected to contribute to a better understanding of diseases. From a broader perspective, this project will increase scientific technical capabilities by providing nanoscale optical imaging for everyday biological research, thereby strengthening US presence in the worldwide optical microscopy industry.
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.
Optical microscopes are indispensable tools of laboratories in numerous fields including biology, medicine and pharmacology. They are used extensively to gain quantitative and visual data about single cell structures. However, the achievable resolution has historically been limited by diffraction of light that limits the smallest object that can be seen to about 200 nanometers. Recent breakthroughs in single-molecule microscopy have made it possible to overcome this limitation by one order of magnitude enhancement in resolution. This revolution in optical microscopy has, to date, seen a mismatch between the demonstrated potential for superresolution and the lack of widespread availability. Scientists, regularly marveled by reported images, do not have access to the proper instrumentation to create such images themselves, due to the complexity, cost and lack of user-friendly solutions. Moreover, most of the techniques are too specific to the problems investigated and hard to generalize for extensive use.
The Phase I SBIR project investigated the development of a compact, robust, and cost-effective three-dimensional superresolution microscopy module with advanced instrumentation capabilities for the biological and biophysics R&D community that can easily be integrated with the currently available scientific microscopes. This product will be the first of its type to enable high quality 3D imaging on a day-to-day basis achieved with existing conventional (research – level) microscopes currently in use in most biological labs.
The module uses the patented Double-HelixTM technology that has been shown to consistently provide nanometer scale resolution in three dimensions over a long depth region. Biologists are currently constrained by the limited resolution and/or lack of three-dimensional capabilities of existing optical microscopes, making the impact of the instrument far-reaching. The module addresses this constraint, having demonstrated capabilities for three-dimensional high-resolution imaging of biological samples. The image data was analyzed using fast and efficient algorithms that were developed for simultaneous acquisition and precise measurement of single-molecule live cells. Several ongoing scientific collaborations are in place to validate end user acceptance and to provide feedback towards future improvements.
The various accomplishments in this SBIR Phase I project have laid the foundation for bringing to market a new technology that addresses a major opportunity in an expanding biological instrumentation market. The module will make 3D superresolution imaging capability affordable to biological laboratories currently limited by past technologies and excluded today by the cost of limited available systems. In a broader sense, the project has contributed to a deeper scientific understanding of biological imaging at the subcellular level, improving the technical capabilities available to biological and biomedical researchers. The potential of high-resolution three-dimensional imaging could contribute to a fundamental understanding of how sub-cellular structures change impacting both disease discovery and disease diagnostics.
Last Modified: 05/27/2014
Modified by: Anurag Agrawal
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