494f Single-Walled Carbon Nanotube Optical Biosensors for Multi-Modal and Single Molecule Detection of Genotoxic Agents

Daniel A. Heller1, Hong Jin, and Michael S. Strano2. (1) Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 66-565, Cambridge, MA 02139, (2) 66-566 Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139

Reactive oxygen species (ROS) and active alkylating chemotherapeutics are important bioanalytes but difficult to measure selectively, in vivo, or in real time. A new nanoscale optical sensor platform under development can now detect as well as identify these analytes in situ and in single-molecule quantities.

Carbon nanotube-DNA complexes, formed by individually encapsulating nanotubes with oligonucleotides, respond in real time to genotoxins via multiple optical modes, giving each analyte a distinct optical signature. Single-walled carbon nanotubes are environmentally sensitive and emit tissue-transparent near-infrared fluorescence. By their encapsulation in short strands of synthetic DNA, we introduce a selective handle for changes in their emission, which responds to the polarity of the solvent medium. The complexes consequently respond to DNA-damaging oxygen species or alkylating agents, by red-shifts in emission energy as well as optical quenching, giving multiple detection modes which result in analyte specificity and up to single-molecule sensitivity.

The nanotube-DNA complexes exhibit uptake into mammalian cells via endocytosis without cytotoxic effects and emit from within live tissues. Upon introduction of alkylating agents and oxidative species, the complexes transduce analyte activity information live and in situ. This platform is being developed as a research and diagnostic tool for free radical biology, drug discovery, and pharmacodynamics.