Many properties of single-walled carbon nanotubes (SWCNTs) make them ideal candidates for sensors, particularly for biological systems. Both their fluorescence in the near-infrared range of 820-1600 nm, where absorption by biological tissues is often minimal, and their inherent photostability are desirable attributes for the design of in vitro and in vivo sensors. The mechanisms by which a target molecule can selectively alter the fluorescent emission include primarily changes in emission wavelength (i.e., solvatochromism) and intensity, including effects such as charge-transfer transition bleaching and exciton quenching. The central challenge lies in engineering the nanotube interface to be selective for the analyte of interest. In this work, we review the recent development in this area over the past few years, and describe the design rules that we have developed for detecting various analytes, ranging from stable small molecules and reactive oxygen species (ROS) or reactive nitrogen species (RNS) to macromolecules. Applications to in vivo sensor measurements using these sensors are also described. In addition, the emerging field of SWCNT-based single-molecule detection using band gap fluorescence and the recent efforts to accurately quantify and utilize this unique class of stochastic sensors are also described in this article.

Excessive sample volumes continue to be a major limitation in the analysis of protein-protein interactions, motivating the search for label-free detection methods of greater sensitivity. Herein, we report the first chemical approach for selective protein recognition using fluorescent single-walled carbon nanotubes (SWNTs) enabling label-free microarrays capable of single protein detection. Hexahistidine-tagged capture proteins directly expressed by cell-free synthesis on SWNT/chitosan microarray are bound to a Ni(2+) chelated by Nα,Nα-bis(carboxymethyl)-L-lysine grafted to chitosan surrounding the SWNT. The Ni(2+) acts as a proximity quencher with the Ni(2+)/SWNT distance altered upon docking of analyte proteins. This ability to discern single protein binding events decreases the apparent detection limit from 100 nM, for the ensemble average, to 10 pM for an observation time of 600 s. This first use of cell-free synthesis to functionalize a nanosensor extends this method to a virtually infinite number of capture proteins. To demonstrate this, the SWNT microarrays are used to analyze a network of 1156 protein-protein interactions in the staurosporine-induced apoptosis of SH-SY5Y cells, confirming literature predictions.

Discrete DNA nanostructures allow simultaneous features not possible with traditional DNA forms: encapsulation of cargo, display of multiple ligands, and resistance to enzymatic digestion. These properties suggested using DNA nanostructures as a delivery platform. Here, DNA pyramids displaying antisense motifs are shown to be able to specifically degrade mRNA and inhibit protein expression in vitro, and they show improved cell uptake and gene silencing when compared to linear DNA. Furthermore, the activity of these pyramids can be regulated by the introduction of an appropriate complementary strand. These results highlight the versatility of DNA nanostructures as functional devices.

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We demonstrate the use of hydrogel swelling as a mechanism to reversibly induce solvatochromic shifting in single-walled carbon nanotube (SWNT) near-infrared emission within a biocompatible hydrogel. The optical sensor reports the degree of the swelled state and glucose concentration when apo-glucose oxidase is used to cross-link the hydrogel. Photoluminescence emission maxima from dispersed nanotubes in a poly(vinyl alcohol) hydrogel shift as cross-linking is increased, with a maximum of -48 meV for the (6,5) nanotube. The Raman tangential mode also red shifts up to 17 cm(-1), indicative of nanotube lattice strain equivalent to an effective hydrostatic pressure of 3 GPa. While the electronic band gaps of SWNTs are known to either increase or decrease with uniaxial strain or lattice deformation depending on chiral vector, we show that the mechanism of detection is counterintuitively non-strain-dependent. Instead, the data are well-described by a model that accounts for changes in dielectric screening of the 1-D exciton, as the osmotic pressure forces conformational distortions in the PVA by rotating more polar groups to the nanotube surface. The model describes observed changes with hydration state and cross-linking density variation from 0 to 14%. Cross-linking with apo-glucose oxidase renders the hydrogel glucose responsive, and we demonstrate rapid and reversible detection of glucose from these systems after repeated cycling of 10 mM glucose. We also demonstrate detection and imaging in the near-infrared of implanted hydrogel sensors in a mouse tissue model, showing excellent signal-to-noise of 8.6 and contrast with integration times of 60 s.