Colin Nuckolls, Department of Chemistry, Columbia University Kenneth Shepard, Department of Electrical Engineering, Columbia University Philip Kim, Department of Physics, Columbia University Qiao Lin, Department of Mechanical Engineering, Columbia University Matthew Francis, Department of Chemistry, University of California Berkeley
The objective of this research is to develop a new class of nanoscale biosensors based on molecular electronic devices that utilize carbon nanotube and graphene-based electrodes. The approach centers around using chemistry to incorporate biological macromolecules as recognition domains on molecular bridges and to further develop these molecular-electronic devices as sensors. These biosensors will be fabricated on active complementary metal-oxide-semiconductor microelectronic substrates to provide true single-molecular sensitivities with potentially submicrosecond temporal resolution. The intellectual merit of the proposed effort is centered on the sensitivity and specificity that can be achieved using this approach. Because these sensors do not rely on temporal or ensemble averaging to achieve sensitivity, they monitor individual events at a true single-molecule level, providing measurement of rich stochastic dynamics of probe-target interactions. In particular, the research effort involves new scientific investigations involving nucleic acid hybridization, protein-protein interactions, and protein conformation changes with single-molecule sensitivity, yielding new insight into processes such as folding and catalysis. These highly integrated devices will have broad practical application in medical diagnostics (genomics and proteomics), drug discovery, and environmental monitoring. This integrated program of research and education has broad impact in training graduate and undergraduate students in a cross-disciplinary research environment. The research has broad impact to a range of science and technology including medicine, pharmacology, semiconductors, homeland security, and environmental monitoring. Significant effort will be made for K-12 outreach by systematically training highly motivated high school students within the program and also enhancing the interaction with local K-12 educators.
Intellectual Merit: In this proposal we created and investigated a new class of molecular electronic devices made from molecules wired with either carbon-based electrodes, in the form of either carbon nanotubes (CNT) or graphene sheets. There have been several significant achievements that should be highlighted: (1) We have devised methods to study these processes in real time using a microfluidic system. (2) We have developed single molecule sensors that can detect DNA hybridization at the single molecule level. Since then we have been able to elucidate the mechanism of their activity as single molecule sensors. (3) We have developed methods to use the CNT-DNA-CNT devices as an electronic device that can detect methyltransferase activity. The research program was centered around four major activities: (1) To create molecular electronic devices with carbon based electrodes utilizing covalent contacts which allow a fundamental study of charge transport properties in these low-dimensional hybrid systems. (2) To develop the chemistries to allow functionalization of molecular bridges and use these to attach nucleic acids and proteins. (3) To develop techniques for fabrication of these devices on active CMOS substrates allowing the incorporation of low-noise, high-bandwidth electronics for detection. (4) To develop this platform for real-time studies of the stochastic dynamics of single-molecule interactions. Broader Impacts: In the area of ultrasensitive biosensors, this project created intellectual property and high quality research publications. As a result of this project, the training of a diverse group students and post-doctoral scientists in interdisciplinary research and education was made possible. In addition, his project created and implemented tools for outreach and public education in the Harlem area of New York.
