Heller, D. A. et al. Multimodal optical sensing and analyte specificity using single-walled carbon nanotubes. Nature Nanotech. 4, 114-120

Department of Physics, Harvard University, 02138, Cambridge, Massachusetts, USA
Nature Nanotechnology (Impact Factor: 34.05). 03/2009; 4(2):114-20. DOI: 10.1038/nnano.2008.369
Source: PubMed


Nanoscale sensing elements offer promise for single-molecule analyte detection in physically or biologically constrained environments. Single-walled carbon nanotubes have several advantages when used as optical sensors, such as photostable near-infrared emission for prolonged detection through biological media and single-molecule sensitivity. Molecular adsorption can be transduced into an optical signal by perturbing the electronic structure of the nanotubes. Here, we show that a pair of single-walled nanotubes provides at least four modes that can be modulated to uniquely fingerprint agents by the degree to which they alter either the emission band intensity or wavelength. We validate this identification method in vitro by demonstrating the detection of six genotoxic analytes, including chemotherapeutic drugs and reactive oxygen species, which are spectroscopically differentiated into four distinct classes, and also demonstrate single-molecule sensitivity in detecting hydrogen peroxide. Finally, we detect and identify these analytes in real time within live 3T3 cells, demonstrating multiplexed optical detection from a nanoscale biosensor and the first label-free tool to optically discriminate between genotoxins.

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    • "The chemical and physical structure of single-walled carbon nanotubes (SWCNTs) confers unique spatial, mechanical, pharmacokinetic, and electronic properties.1,2 Methods exist to conjugate SWCNTs to a variety of moieties, with the goal of modifying or exploiting these properties in fields such as circuitry, imaging,3 and drug delivery. For instance, the extensive π-system of carbon nanotubes allows noncovalent nucleotide wrapping and the adherence of other π-stacking molecules, such as aromatic pharmaceuticals.4–6 "
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    ABSTRACT: We aimed to create a more robust and more accessible standard for amine-modifying single-walled carbon nanotubes (SWCNTs). A 1,3-cycloaddition was developed using an azomethine ylide, generated by reacting paraformaldehyde and a side-chain-Boc (tert-Butyloxycarbonyl)-protected, lysine-derived alpha-amino acid, H-Lys(Boc)-OH, with purified SWCNT or C60. This cycloaddition and its lysine adduct provides the benefits of dense, covalent modification, ease of purification, commercial availability of reagents, and pH-dependent solubility of the product. Subsequently, SWCNTs functionalized with lysine amine handles were covalently conjugated to a radiometalated chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The (111)In-labeled construct showed rapid renal clearance in a murine model and a favorable biodistribution, permitting utility in biomedical applications. Functionalized SWCNTs strongly wrapped small interfering RNA (siRNA). In the first disclosed deployment of thermophoresis with carbon nanotubes, the lysine-modified tubes showed a desirable, weak SWCNT-albumin binding constant. Thus, lysine-modified nanotubes are a favorable candidate for medicinal work.
    Full-text · Article · Sep 2014 · International Journal of Nanomedicine
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    • "Chemical reactants at the nanotube surface can disturb the distribution of electrons within the nanotube, effectively protonating the sidewall of the nanotube and disturbing exciton-exciton recombination, which quenches fluorescence to some degree [63,95–97]. This quenching, measured as a decrease in the overall fluorescent signal of the nanotube, can be quantified using different algorithms to determine how many molecules are adsorbed to the surface of the nanotube and removing electrons, at any given moment [7,88,98]. This reaction, handily, is reversible. "
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    ABSTRACT: Reactive oxygen species (ROS) are increasingly being implicated in the regulation of cellular signaling cascades. Intracellular ROS fluxes are associated with cellular function ranging from proliferation to cell death. Moreover, the importance of subtle, spatio-temporal shifts in ROS during localized cellular signaling events is being realized. Understanding the biochemical nature of the ROS involved will enhance our knowledge of redox-signaling. An ideal intracellular sensor should therefore resolve real-time, localized ROS changes, be highly sensitive to physiologically relevant shifts in ROS and provide specificity towards a particular molecule. For in vivo applications issues such as bioavailability of the probe, tissue penetrance of the signal and signal-to-noise ratio also need to be considered. In the past researchers have heavily relied on the use of ROS-sensitive fluorescent probes and, more recently, genetically engineered ROS sensors. However, there is a great need to improve on current methods to address the above issues. Recently, the field of molecular sensing and imaging has begun to take advantage of the unique physico-chemical properties of nanoparticles and nanotubes. Here we discuss the recent advances in the use of these nanostructures as alternative platforms for ROS sensing, with particular emphasis on intracellular and in vivo ROS detection and quantification.
    Full-text · Article · Dec 2012 · International Journal of Molecular Sciences
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    • "Important biological metabolites are sometime difficult to measure in vitro or in real-time. Standard techniques such as immunoassays, gel electrophoresis and nuclear magnetic resonance typically cannot be performed in live cells and tissues, or at least they require preparation steps that inhibit real-time measurements [1]. Instead, electrochemical sensing based on oxidases is suitable for real-time monitoring of metabolites, such as glucose [2] and lactate [3]. "
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    ABSTRACT: Microdevices dedicated to monitor metabolite levels have recently enabled many applications in the field of cell analysis, to monitor cell growth and development of numerous cell lines. By combining the traditional technology used for electrochemical biosensors with nanoscale materials, it is possible to develop miniaturized metabolite biosensors with unique properties of sensitivity and detection limit. In particular, enzymes tend to adsorb onto carbon nanotubes and their optical or electrical activity can perturb the electronic properties. In the present work we propose multi-walled carbon nanotube-based biosensors to monitor a cell line highly sensitive to metabolic alterations, in order to evaluate lactate production and glucose uptake during different cell states. We achieve sensors for both lactate and glucose, with sensitivities of 40.1μAmM−1cm−2 and 27.7μAmM−1cm−2, and detection limits of 28μM and 73μM, respectively. This nano-biosensing technology is used to provide new information on cell line metabolism during proliferation and differentiation, which are unprecedented in cell biology.
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