Larry A. Nagahara

Considerations in the development of circulating tumor cell technology for clinical use

This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC) technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development–analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA) and the US National Cancer Institute (NCI).

Directed placement of suspended carbon nanotubes for nanometer-scale assembly

Single-wall carbon nanotubes (SWNTs) suspended in an aqueous solution have been placed selectively between two metal electrodes separated by a few tens of nanometers. After the initial patterning of the metal electrodes by electron beam lithography, no further fine-line lithography steps are necessary to achieve directed placement of SWNTs at these dimensions. An ac bias is applied between the two electrodes and the “nanoscale wiring” is completed within seconds. An additional advantage of using ac bias is the enhancement for selectively placing SWNTs between the electrode gap over competing contaminant species in the solution.

Electrical measurements of a dithiolated electronic molecule via conducting atomic force microscopy

We describe a method of measuring the electrical properties of a molecule via conducting atomic force microscopy (AFM). A dithiolated molecule is chemically inserted into defect sites in an insulating self-assembled monolayer formed on an epitaxial Au substrate and the top thiol terminus of the molecule is reacted with a Au nanoparticle. A Au-coated AFM probe is used to contact the molecule through the nanoparticle, thus electrical data can be obtained. We report preliminary transport measurements of two test molecules. Our data shows qualitative agreement with previously published results for similar molecules deposited in a nanopore containing approximately a thousand molecules. This work indicates that the measured negative differential resistance is not an intermolecular phenomenon.

A Hybrid Nanosensor for TNT Vapor Detection

Real-time detection of trace chemicals, such as explosives, in a complex environment containing various interferents has been a difficult challenge. We describe here a hybrid nanosensor based on the electrochemical reduction of TNT and the interaction of the reduction products with conducting polymer nanojunctions in an ionic liquid. The sensor simultaneously measures the electrochemical current from the reduction of TNT and the conductance change of the polymer nanojunction caused from the reduction product. The hybrid detection mechanism, together with the unique selective preconcentration capability of the ionic liquid, provides a selective, fast, and sensitive detection of TNT. The sensor, in its current form, is capable of detecting parts-per-trillion level TNT in the presence of various interferents within a few minutes.

Structure determination of individual single-wall carbon nanotubes by nanoarea electron diffraction

In this letter, we report an electron diffraction determination of chiral vectors (n,m) of individual single-wall carbon nanotubes (SWNTs). Electron diffraction patterns from individual SWNTs were recorded on imaging plates using a parallel electron beam over a section of tube of ∼50 nm long. Using two tubes of 1.39 and 3.77 nm in diameter, we show that the details of electron diffuse scattering can be detected for both the small and large tubes. The quality of diffraction patterns allows the accurate measurement of both the diameters and chiral angles of SWNTs for a direct determination of chiral vectors. The electron diffraction technique is general and applicable to other forms of individual nanostructures.

An approach to transport measurements of electronic molecules

We present a hybrid assembly technique to facilitate the transport measurements of electronic molecules. The technique consists of forming a self-assembled monolayer of the investigated molecule on prepatterned electrodes and then bridging the electrodes with nanoparticles using an alternating electric field. This technique can potentially provide a quick and simple way to screen a large number of electronic molecules. As an example, we report preliminary transport measurements of 1-nitro-2,5-di(phenylethynyl-4*-thioacetyl)benzene as a test molecule. The data show qualitative agreement with previously published results for a similar molecule.

In situ detection of cytochrome c adsorption with single walled carbon nanotube device

We report on the in situ detection of cytochrome c adsorption onto individual SWNT transistors via the changes in the electron transport properties of the transistors.

Self-orientation of short single-walled carbon nanotubes deposited on graphite

In view of practical handling of single-walled carbon nanotubes (SWNTs), here we present cutting procedures and spontaneous ordering of SWNTs deposited on highly oriented pyrolytic graphite (HOPG). Purified SWNTs were cut by ultrasonication in H2SO4/HNO3 mixture and further in de-ionized water. Thus, prepared short SWNTs were resuspended in methanol and dropped on a freshly cleaved HOPG surface. Scanning tunneling microscopy under a vacuum revealed that the short tubes of 20–100 nm in length were aligned along the basal axis of the HOPG lattice. Tunneling spectroscopy obtained from the oriented tubes indicated a semiconducting behavior, which was characterized in relation to their helical structure. The observed orientation of SWNTs was attributed to their one-dimensional electronic nature along the tube axis with the HOPG lattice.

Chemical sensors using peptide-functionalized conducting polymer nanojunction arrays

We demonstrate a heavy metal-ion sensor for drinking water analysis using a conducting polymer nanojunction array. Each nanojunction is formed by bridging a pair of nanoelectrodes separated with a small gap (<60nm) with electrodeposited peptide-modified polyanilines. The signal transduction mechanism of the sensor is based on the change in the nanojunction conductance as a result of polymer conformational changes induced by the metal-ion chelating peptide. The nanojunction sensor allows real-time detection of Cu2+ and Ni2+ at ppt range.

A Breath Ammonia Sensor Based on Conducting Polymer Nanojunctions

We present an ammonia sensor for human breath analysis based on electrically conducting polymer nanojunctions. Each nanojunction is formed by bridging a pair of gold nanoelectrodes on a silicon chip separated by a small gap (<60 nm) with electrodeposited polyaniline. The signal transduction mechanism of the sensor is the change in the nanojunction conductance as a result of polymer dedoping by ammonia. The sensor response to human breath is validated by comparison with a reference method for detection of ammonium ion combined with an optimized breath ammonia trapping system. The nanojunction sensor is capable of in situ detection of parts per billion (ppb) levels of ammonia in human breath.