Single-walled carbon nanotubes (SWNT) are ideal substrates for optical sensing, due to their large Raman scattering cross-sections and photoluminescence in the near infrared (nIR). The latter occurs where absorption, scattering, and auto-fluorescence from biological media such as whole blood, are minimized. Because the electrons are confined in a one dimensional, cylindrical geometry, carbon nanotubes exhibit intriguing sensitivity to molecular adsorption on their surface, yielding sizable responses for several classes of chemical and biological moieties. The optical modulation of single walled carbon nanotubes is an area that we have pioneered exclusively over past three year project. We were the first to create biomedical implantable sensors for nIR glucose detection (Nature Materials 4, 86, 2005). We demonstrated optical transduction of DNA hybridization (Nano Letters 6, 371, 2006). Recently, in pioneering work, we demonstrated successful operation in live cells for toxic ion detection (Science 311, 508, 2006). In this renewal proposal, we describe a program of continued innovation in this new area by investigating fundamental mechanisms of signal transduction, and using engineering principles to further develop these technologies. The renewal program will answer central questions regarding these systems, and solve major limitations uncovered in our research. We find that many adsorption processes involving DNA/RNA on SWNT possess substantially enhanced thermodynamic barriers over free solution values which translate into exceedingly long transduction times. We show some success in modeling these effects using the theory of polyelectrolyte adsorption on curved surfaces. These models will be utilized to form hypotheses about the influence of length and sequence on adsorption processes to be validated by experiment. Dielectric modulation is a new modality of detection we have uncovered for SWNT. Here, the fluorescence is shifted to a higher energy upon DNA hybridization, and to a lower energy when divalent metal cations are introduced as the surface coverage on the SWNT is changed. The former mechanism is operative only for the (6,5) nanotube for a reason to be uncovered. In this renewal program, we also intend to extend this platform to the measurement of DNA-genotoxins with high sensitivity. We show preliminary data indicating that we can measure the flux of melphalan, a model genotoxic agent, in real time within single living cells. Imagine a universal assay capable of indicating whether an unknown agent in the environment can immediately damage DNA within live cells and tissues. This work will advance the scientific understanding of DNA interactions with other DNA, proteins and polymer adsorbates on carbon nanotube substrates.
Intellectual Merit of Proposed Activity: The proposed research renewal will continue to advance the scientific understanding of electron transfer and induced dielectric modulation of 1-D quantum nanotubes using carbon as a model system. The science explored in this work will produce optically-queried sensor molecules with high sensitivity and selectivity for environmentally important analytes. Applications include operation from within strongly scattering, near-infrared transparent media such as the human body. The goal is a new set of engineering tools that have the ability to be used in previously intractable optical media such as whole blood serum, thick tissue and live, unprocessed cell cultures.
Broader Impacts of the Proposed Activity: The economic and societal benefits of developing passive, noninvasive sensors for pathogen recognition or medical screening applications are enormous. Imagine being able to screen individuals, clothing and the surrounding environment for small pox contamination by labeling a selective binding agent with a nIR fluorophore sensor as outlined in this proposal and irradiating the suspected person or area with nIR light. This sensing technology will also find applications as injectable, vascular or trans-dermal implants, giving the medical community a remote means of sensing biochemical process at the nanoscale with unprecedented detail. Outreach efforts include active participation with the IMPRINT program at UIUC, where minority students are paired with research labs in the first year of their tenure. The project will also work with W. Hammack on issues of engineering education and societal outreach. An inquiry-based nanotechnology course is also proposed as part of this project.
