(712h) Evolution of Nanoparticle-Based Synthetic Molecular Recognition

Molecular recognition is fundamental to the design of therapeutics, diagnostics, and sensors. Many of these technologies rely on natural molecular recognition elements such as antibodies, which have evolved to be highly selective for their molecular targets. However, despite their exquisite selectivity, antibody-based molecular recognition suffers from limited stability outside narrow ranges of temperature, pH, and salt concentration, and have limited ex-vivo stability. Conversely, synthetic molecular recognition has enabled detection of molecular targets over a broad range of extraphysiological conditions with varying success in selective and sensitive detection of target analytes. Recent developments in synthetic molecular recognition include synthetic antibodies based on electrostatic pinning of bio-mimetic polymers to the surface of single-walled carbon nanotubes (SWNT), whereby the polymer serves as the molecular recognition element, and the SWNT provides a near-infrared fluorescent signal in response to analyte binding (1-3). In this and other embodiments of nanosensor platforms, the principal challenge lies in the laborious process of identifying synthetically-produced selective and sensitive molecular recognition elements. Herein, we describe a polymer evolution-based platform, in which 10^12 unique SWNT-pinned polynucleotide polymers can be screened for their ability to bind a target analyte and provide a selective near-infrared fluorescence signal. Iterative selection of analyte-binding polymers that form a SWNT-surface-adsorbed phase for target recognition are identified through ionic desorption of sub-optimal polymers, and exponential amplification of synthetic polymers that recognize the target analyte. Next-generation sequencing identifies SWNT-polynucleotide conjugates selective and sensitive for the desired analyte. We demonstrate the utility of this platform for the evolution of a SWNT-polymer conjugate for neuromodulator serotonin, which we show to be reversible, to have a detection limit of 100 nM, and to have a dynamic range appropriate for in vivo imaging of serotonergic neuromodulation. Our platform is fundamentally generic in enabling the evolution of molecular nanosensors from synthetic polymer-nanoparticle conjugates for any desired analyte.

(1) Smith et al., Nat. Nanotechnol. 2009, 4, (11), 710-711.

(2) Zhang et al., Nat. Nanotechnol. 2013, 8, (12), 959-968.

(3) Kruss, S. et al., J. Am. Chem. Soc. 2013, 136, (2), 713-724.