Hybridization kinetics and thermodynamics of DNA adsorbed to individually dispersed single-walled carbon nanotubes.

Hybridization of DNA adsorbed to single-walled carbon nanotubes in solution has much slower kinetics than free solution DNA, and can be detected through a blue shift in the near-infrared nanotube fluorescence. Adsorption of the receptor DNA strand to the nanotube surface is consistent with models of polyelectrolyte adsorption on charged surfaces, introducing both entropic (46.8 cal mol(-1) K(-1)) and activation energy (20.4 kcal mol(-1)) barriers to the hybridization, which are greater than free solution values (31.9 cal mol(-1) K(-1) and 12.9 kcal mol(-1)) at 25 degrees C. The increased hybridization barriers on the nanotube result in exceedingly slow kinetics for hybridization with t(1/2)=3.4 h, compared to the free solution value of t(1/2)=4 min. These results have significant implications for nanotube and nanowire biosensors.

In vivo biosensing via tissue-localizable near-infrared-fluorescent single-walled carbon nanotubes.

Single-walled carbon nanotubes are particularly attractive for biomedical applications, because they exhibit a fluorescent signal in a spectral region where there is minimal interference from biological media. Although single-walled carbon nanotubes have been used as highly sensitive detectors for various compounds, their use as in vivo biomarkers requires the simultaneous optimization of various parameters, including biocompatibility, molecular recognition, high fluorescence quantum efficiency and signal transduction. Here we show that a polyethylene glycol ligated copolymer stabilizes near-infrared-fluorescent single-walled carbon nanotubes sensors in solution, enabling intravenous injection into mice and the selective detection of local nitric oxide concentration with a detection limit of 1 µM. The half-life for liver retention is 4 h, with sensors clearing the lungs within 2 h after injection, thus avoiding a dominant route of in vivo nanotoxicology. After localization within the liver, it is possible to follow the transient inflammation using nitric oxide as a marker and signalling molecule. To this end, we also report a spatial-spectral imaging algorithm to deconvolute fluorescence intensity and spatial information from measurements. Finally, we demonstrate that alginate-encapsulated single-walled carbon nanotubes can function as implantable inflammation sensors for nitric oxide detection, with no intrinsic immune reactivity or other adverse response for more than 400 days.

Molecular recognition using corona phase complexes made of synthetic polymers adsorbed on carbon nanotubes.

Understanding molecular recognition is of fundamental importance in applications such as therapeutics, chemical catalysis and sensor design. The most common recognition motifs involve biological macromolecules such as antibodies and aptamers. The key to biorecognition consists of a unique three-dimensional structure formed by a folded and constrained bioheteropolymer that creates a binding pocket, or an interface, able to recognize a specific molecule. Here, we show that 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 heteropolymer-nanotube recognition complexes for riboflavin, L-thyroxine and oestradiol. In each case, the recognition was predicted using a two-dimensional thermodynamic model of surface interactions in which the dissociation constants can be tuned by perturbing the chemical structure of the heteropolymer. Moreover, these complexes can be used as new types of spatiotemporal sensors based on modulation of the carbon nanotube photoemission in the near-infrared, as we show by tracking riboflavin diffusion in murine macrophages.

Sequential delivery of dexamethasone and VEGF to control local tissue response for carbon nanotube fluorescence based micro-capillary implantable sensors.

In this study, we examined the in vivo pharmacological effects of the sequential delivery of dexamethasone (DX) followed by vascular endothelial growth factor (VEGF) on the immune response and localized vascular network formation around a hydrogel-coated, micro-capillary implant for single-walled carbon nanotube based fluorescence sensors. We demonstrate, for the first time, imaging of an SWNT fluorescence device implanted subcutaneously in a rat. For tissue response studies, the chick embryo chorioallantoic membrane (CAM) was used as a tissue-model for an 8-day implantation period. The average vascular density of the tissue surrounding a hydrogel-coated microdialysis capillary sensor with simultaneous, sequential, or no delivery of DX and VEGF was 1.24+/-0.35x10(-3)vessels/microm(2), 1.15+/-0.30x10(-3)vessels/microm(2) and 0.71+/-0.20x10(-3)vessels/microm(2), respectively. Calculation of the therapeutic index (vasculature/inflammation ratio), which reflects promotion of angiogenesis versus the host immune response, demonstrates that sequential DX/VEGF delivery was 60.3% and 139.3% higher than that of VEGF and DX release alone, respectively, and was also 32.1% higher when compared to simultaneous administration, proving to be a more effective strategy in utilizing the pharmacological impact of DX and VEGF around the biosensor-model implant.