In the last 10 years the field of molecular diagnostics has witnessed an explosion of interest in the use of nanomaterials in assays for gases, metal ions, and DNA and protein markers for many diseases. Intense research has been fueled by the need for practical, robust, and highly sensitive and selective detection agents that can address the deficiencies of conventional technologies. Chemists are playing an important role in designing and fabricating new materials for application in diagnostic assays. In certain cases assays based upon nanomaterials have offered significant advantages over conventional diagnostic systems with regard to assay sensitivity, selectivity, and practicality. Some of these new methods have recently been reviewed elsewhere with a focus on the materials themselves or as subclassifications in more generalized overviews of biological applications of nanomaterials.1-7 We intend to review some of the major advances and milestones in the field of detection systems based upon nanomaterials and their roles in biodiagnostic screening for nucleic acids, * To whom correspondence should be addressed. Phone: 847-4913907. Fax: 847-467-5123. E-mail: chadnano@northwestern.edu. Nathaniel L. Rosi earned his B.A. degree at Grinnell College (1999) and his Ph.D. degree from the University of Michigan (2003), where he studied the design, synthesis, and gas storage applications of metal−organic frameworks under the guidance of Professor Omar M. Yaghi. In 2003 he began postdoctoral studies as a member of Professor Mirkin’s group at Northwestern University. His current research focuses on the rational assembly of DNA-modified nanostructures into larger-scale materials.

/pdf/nanostructures-in-biodiagnostics-5553cs9yqw.pdf

Nanostructures in Biodiagnostics

Nanotechnology is a multidisciplinary field, which covers a vast and diverse array of devices derived from engineering, biology, physics and chemistry. These devices include nanovectors for the targeted delivery of anticancer drugs and imaging contrast agents. Nanowires and nanocantilever arrays are among the leading approaches under development for the early detection of precancerous and malignant lesions from biological fluids. These and other nanodevices can provide essential breakthroughs in the fight against cancer.

Cancer nanotechnology: opportunities and challenges.

Department of Materials Science, University of Patras, 26504 Rio Patras, Greece, Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vass. Constantinou Avenue, 116 35 Athens, Greece, Institut de Biologie Moleculaire et Cellulaire, UPR9021 CNRS, Immunologie et Chimie Therapeutiques, 67084 Strasbourg, France, and Dipartimento di Scienze Farmaceutiche, Universita di Trieste, Piazzale Europa 1, 34127 Trieste, Italy

Chemistry of Carbon Nanotubes

3.6.1. Polishing and Cleaning 2663 3.6.2. Vacuum and Heat Treatments 2664 3.6.3. Carbon Electrode Activation 2665 3.7. Summary and Generalizations 2666 4. Advanced Carbon Electrode Materials 2666 4.1. Microfabricated Carbon Thin Films 2666 4.2. Boron-Doped Diamond for Electrochemistry 2668 4.3. Fibers and Nanotubes 2669 4.4. Carbon Composite Electrodes 2674 5. Carbon Surface Modification 2675 5.1. Diazonium Ion Reduction 2675 5.2. Thermal and Photochemical Modifications 2679 5.3. Amine and Carboxylate Oxidation 2680 5.4. Modification by “Click” Chemistry 2681 6. Synopsis and Outlook 2681 7. Acknowledgments 2682 8. References 2682

/pdf/advanced-carbon-electrode-materials-for-molecular-2y6b22van0.pdf

Advanced carbon electrode materials for molecular electrochemistry.

This review addresses recent advances in carbon-nanotubes (CNT) based electrochemical biosensors. The unique chemical and physical properties of CNT have paved the way to new and improved sensing devices, in general, and electrochemical biosensors, in particular. CNT-based electrochemical transducers offer substantial improvements in the performance of amperometric enzyme electrodes, immunosensors and nucleic-acid sensing devices. The greatly enhanced electrochemical reactivity of hydrogen peroxide and NADH at CNT-modified electrodes makes these nanomaterials extremely attractive for numerous oxidase- and dehydrogenase-based amperometric biosensors. Aligned CNT “forests” can act as molecular wires to allow efficient electron transfer between the underlying electrode and the redox centers of enzymes. Bioaffinity devices utilizing enzyme tags can greatly benefit from the enhanced response of the biocatalytic-reaction product at the CNT transducer and from CNT amplification platforms carrying multiple tags. Common designs of CNT-based biosensors are discussed, along with practical examples of such devices. The successful realization of CNT-based biosensors requires proper control of their chemical and physical properties, as well as their functionalization and surface immobilization.

/pdf/carbon-nanotube-based-electrochemical-biosensors-a-review-372j6kup7u.pdf

Carbon‐Nanotube Based Electrochemical Biosensors: A Review

A nanoelectrode array based on vertically aligned multiwalled carbon nanotubes (MWNTs) embedded in SiO2 is used for ultrasensitive DNA detection. Characteristic electrochemical behaviors are observed for measuring bulk and surface-immobilized redox species. Sensitivity is dramatically improved by lowering the nanotube density. Oligonucleotide probes are selectively functionalized to the open ends of nanotubes. The hybridization of subattomole DNA targets can be detected by combining such electrodes with Ru(bpy)32+ mediated guanine oxidation.

Carbon Nanotube Nanoelectrode Array for Ultrasensitive DNA Detection

We report a novel approach for the fabrication of nanoelectrode arrays using vertically aligned multi-walled carbon nanotubes (MWCNTs) embedded within a SiO2 matrix. Cyclic voltammetry and pulse voltammetry are employed to characterize the electrochemical properties of the MWCNT array. The unique graphitic structure of the novel MWCNT nanoelectrodes is compared with model systems such as highly oriented pyrolytic graphite and glassy carbon electrodes. Low-density MWCNT nanoelectrode arrays display independent nanoelectrode behavior showing diffusion-limited steady-state currents in cyclic voltammetry over a wide range of scan rates. Electroactive species can be detected at concentrations as low as a few nM. In addition, ultrasensitive DNA/RNA sensors are demonstrated using the low-density MWCNT arrays with selectively functionalized oligonucleotide probes. This platform can be widely used in analytical applications as well as fundamental electrochemical studies.

The fabrication and electrochemical characterization of carbon nanotube nanoelectrode arrays

We report the detection of DNA PCR amplicons using an ultrasensitive label-free electronic technique based on multiwalled carbon nanotube (MWNT) nanoelectrode arrays embedded in an SiO(2) matrix. Specific PCR amplicons are reliably detected using electrochemical (EC) methods through allele-specific oligonucleotide hybridization. The inherent guanine bases in the DNA amplicon target of [Formula: see text] bases serve as signal moieties with the aid of Ru(bpy)(3)(2+) mediators, providing an amplified anodic current associated with the oxidation of guanine groups at the nanoelectrode surface. The reduced size and density of the nanoelectrode array provided by MWNTs dramatically improves the sensitivity of EC detection. In addition, the abundant guanine bases in target DNA produce a large signal. Less than [Formula: see text] target amplicons can be detected on a microspot, approaching the sensitivity limit of conventional laser-based fluorescence techniques. This method also eliminates the labelling requirement and makes the measurements much simpler. This platform can be employed for developing highly automated electronic chips with multiplex nanoelectrode arrays for quick DNA analysis.

Ultrasensitive label-free DNA analysis using an electronic chip based on carbon nanotube nanoelectrode arrays.

We present an approach to tackle long-standing problems in contacts, thermal damage, pinhole induced short circuits and interconnects in molecular electronic device fabrication and integration. Our approach uses metallic nanowires as top electrodes to connect and interconnect molecular wires assembled on electrode arrays in crossbar architectures. Using this simple and reliable approach, we have revealed intriguing memory effects for several different molecular wires, and demonstrated their applications in molecular memory arrays. Our approach has great potential to be used for fast screening of molecular wire candidates and construction of molecular devices.

Fabrication approach for molecular memory arrays

The rapid development in nanomaterials and nanotechnologies has provided many new opportunities for electroanalysis. We review our recent results on the fabrication and electroanalytical applications of nanoelectrode arrays based on vertically aligned multi-walled carbon nanotubes (MWCNTs). A bottom-up approach is demonstrated, which is compatible with Si microfabrication processes. MWCNTs are encapsulated in SiO2 matrix leaving only the very end exposed to form inlaid nanoelectrode arrays. The electrical and electrochemical properties have been characterized, showing well-defined quasireversible nanoelectrode behavior. Ultrasensitive detection of small redox molecules in bulk solutions as well as immobilized at the MWCNT ends is demonstrated. A label-free affinity-based DNA sensor has shown extremely high sensitivity approaching that of fluorescence techniques. This platform can be integrated with microelectronics and microfluidics for fully automated microchips.

Jessica E. Koehne

Papers

Carbon Nanotube Nanoelectrode Array for Ultrasensitive DNA Detection

The fabrication and electrochemical characterization of carbon nanotube nanoelectrode arrays

Ultrasensitive label-free DNA analysis using an electronic chip based on carbon nanotube nanoelectrode arrays.

Fabrication approach for molecular memory arrays

Inlaid Multi-Walled Carbon Nanotube Nanoelectrode Arrays for Electroanalysis