(335g) The Role of Nanosensors for Biodiagnostics and Bioprocess Monitoring

Our lab at MIT has been interested in how the 1D and 2D electronic structures of certain nano-materials can be utilized to advance new concepts in molecular detection, specifically for the real time monitoring of human physiology, feedback control of drug release, as well as bioprocessing monitoring to aid manufacturing. Our work demonstrates that nanosensors have a key advantage in their ability to achieve the ultimate detection limit of single molecules. Reducing a sensor transducer to nanometer scale dimensions lowers the detection limit until the stochastic fluctuations of single molecule can be detected. This level of sensitivity can be best capitalized on with concomitant advances in molecular recognition. To this end, our laboratory at MIT has introduced CoPhMoRe or Corona Phase Molecular Recognition¹ as a method of discovering synthetic antibodies, or nanotube-templated recognition sites from a heteropolymer library. We show that certain synthetic heteropolymers, once constrained onto a single-walled carbon nanotube by chemical adsorption, also form a new corona phase that exhibits highly selective recognition for specific molecules. To prove the generality of this phenomenon, we report three examples of heteropolymers–nanotube recognition complexes for riboflavin, L-thyroxine and estradiol. The platform opens new opportunities to create synthetic recognition sites for molecular detection. We have also extended this molecular recognition technique to neurotransmitters, producing the first fluorescent sensor for dopamine. Another area of advancement in biosensor development is the use of near infrared fluorescent carbon nanotube sensors for in-vivo detection². Our vision is the realization of multiplexed sensor arrays that can provide real time biochemical detection of physiological markers in humans. In our recent work, we show that PEG-ligated d(AAAT)₇ DNA wrapped SWNT are selective for nitric oxide, a vasodilator of blood vessels, and can be tail vein injected into mice and localized within the viable mouse liver. We use an SJL mouse model to study liver inflammation in vivo using the spatially and spectrally resolved nIR signature of the localized SWNT sensors. Lastly, we discuss new concepts for real time, bioprocess monitoring to aid pharmaceutical production and other applications.

1. Zhang, JQ et. al. Molecular recognition using corona phase complexes made of synthetic polymers adsorbed on carbon nanotubes. Nature Nanotechnology, 8, 12, 2013, 959-968

2. Iverson, NM, et. al. In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes. Nature Nanotechnology, 8, 11, 2013, 873-880