| NSF Org: |
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems |
| Recipient: |
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| Initial Amendment Date: | July 31, 2019 |
| Latest Amendment Date: | June 9, 2021 |
| Award Number: | 1904921 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Aleksandr Simonian
asimonia@nsf.gov (703)292-2191 CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering |
| Start Date: | August 15, 2019 |
| End Date: | July 31, 2023 (Estimated) |
| Total Intended Award Amount: | $320,000.00 |
| Total Awarded Amount to Date: | $334,000.00 |
| Funds Obligated to Date: |
FY 2021 = $14,000.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
1500 HORNING RD KENT OH US 44242-0001 (330)672-2070 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
1 Summit Street KENT OH US 44242-0001 |
| 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): | BIOSENS-Biosensing |
| Primary Program Source: |
01002122DB NSF RESEARCH & RELATED ACTIVIT |
| 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
The research objective of this proposal is to take a multidisciplinary approach to innovate biosensing strategies with ultrahigh sensitivity to detect multiple chemical or biological targets. The detection will be accomplished by monitoring the variation of either tension or length of the sensing template upon binding of chemical or biochemical targets. To detect many targets simultaneously, which is an essential feature in next generation biosensors, the research team will incorporate different sensing units in a single template. Each sensing unit is designed to report the binding of specific targets. Successful completion of this project will provide new biosensing paradigms with great potential to transform single-molecule biosensors into viable devices with high sensitivity and superior efficiency compared to conventional biosensors. During this project, the investigator plans to integrate educational elements into research projects. The investigator's lab will train high-school and college students by recruiting them to carry out this NSF funded research. Research is modularly designed to facilitate participation of these students into the project. In addition, the research team will reach out to the public by helping K-12 students for scientific activities.
The intellectual merit of this project lies in the employment of single DNA molecules as sensing templates while detection of analytes is based on mechanochemical principles. Upon chemical binding of individual chemical or biochemical targets to the single-molecule DNA template, the mechanical property of the template such as its tensile force and/or extension will change. To detect such a tiny signal change on the order of picoNewton in force and nanometer in extension, single-molecule techniques such as optical tweezers and magnetic tweezers will be used. Since analyte detection is achieved at the single-molecule level, chemical amplification is not necessary, which increases the efficiency of materials usage in the mechanochemical sensing. To improve concentration detection limit, many sensing units will be incorporated in the template using molecular biology methods such as Rolling Circle Amplification (RCA). In addition, signal is amplified by spatial arrangement of localized sensing units, a feature that follows topochemical principles. To increase the throughput of the sensing, magnetic tweezers will be used so that hundreds of single-molecule sensing templates can be immobilized on a surface and monitored simultaneously. The topo chemical sensing strategies are anticipated to lead to viable single-molecule biosensors with high sensitivity and efficiency.
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.
Intellectual Merit. This grant has supported research to develop DNA copolymer-based sensing strategies at the single-molecule level. The sensing is based on the principle of mechanochemical coupling. Such a mechanochemical sensing exploits changes in mechanical force as an integral output signal to detect various targets on a single-molecule platform with high sensitivity and specificity. To increase sensing throughput, an ensemble set of DNA secondary structures has been introduced on a single-molecule template using rolling cycle amplification methods. The arrangement of 1D arrays allows simultaneous characterization of DNA structures such as DNA G-quadruplexes and hairpins, which provide accurate profiling of their structures and properties. Better understanding of these structures allow us to construct ultra-sensitive biosensors with shorter time window and lower concentration detection limit due to much increased detection area. As a result, as low as 1 fM target concentrations can be detected in tens of minutes. With this NSF support, we have also successfully demonstrated signal amplification can be achieved at single-molecule level, which has been rather challenging to accomplish due to the diffusive tendency of individual molecules in solution phase. All these strategies demonstrate a new direction for the force-based biosensing that would be instrumental for the development of next generation biosensors. During this grant period, we have published the following 25 peer-reviewed papers in various journals such as Nature Communications, Journal of the American Chemical Society, Journal of Visual Experiments, Biomacromolecules, Langmuir, Nucleic Acids Research, Angewandte Chemie International Edition, Journal of Physical Chemistry Letters, The Journal of Physical Chemistry B., Chemical Society Reviews, Accounts of Chemical Research, Analytical Biochemistry, Chemical Science, Nanoscale, Biochemistry, Bioconjugate Chemistry, Analytical Chemistry, ACS Sensors, and Nature Materials.
Broader Impact. This grant has allowed us to train three high school students: Andrew Hu, Victoria Martinez, and Evan Updegraff; four undergrad students: Benjamin Wales-McGrath, Jacob Haller, Dakota Smallridge, and Max Jansen; and six graduate students: Sagun Jonchhe, Shankar Pandey, Deepak Karna, Pravin Pokhrel, Jiayi Wang, and Rabia Tahir. All high school students gained research experience for the first time and most college students had few practical research experience before joining us. The NSF supported biosensing projects served to attract students to pursue scientific fields. For example, one of the undergrad students (Benjamin) joined biomedical graduate program at the University of Pennsylvania in Fall 2022. We anticipate the new mechanochemical sensing strategies will contribute to detecting biomarkers for various diseases as well as to facilitating development next generation biosensing, which may contribute the US economy in the long run.
Last Modified: 11/30/2023
Modified by: Hanbin Mao
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