Single-Molecule Mechanochemical Sensing for Multiplexed Tasks: A Topochemical Strategy

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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.