Complementary Metal-Oxide-Semiconductor Integrated Carbon Nanotube Arrays: Toward Wide-Bandwidth Single-Molecule Sensing Systems

There is strong interest in realizing genomic molecular diagnostic platforms that are label-free, electronic, and single-molecule. One attractive transducer for such efforts is the single-molecule field-effect transistor (smFET), capable of detecting a single electronic charge and realized with a point-functionalized exposed-gate one-dimensional carbon nanotube field-effect device. In this work, smFETs are integrated directly onto a custom complementary metal-oxide-semiconductor chip, which results in an array of up to 6000 devices delivering a measurement bandwidth of 1 MHz. In a first exploitation of these high-bandwidth measurement capabilities, point functionalization through electrochemical oxidation of the devices is observed with microsecond temporal resolution, which reveals complex reaction pathways with resolvable scattering signatures. High-rate random telegraph noise is detected in certain oxidized devices, further illustrating the measurement capabilities of the platform

Novel Biologically Active Silver-Avidin Hybrids

Coupling of biologically active proteins, for example, enzymes and binding proteins, with metals carries huge potential inherent in the integration of these hybrids with miniaturized electronics, medical devices, and in vivo imaging. Here we propose and demonstrate feasibility of the preparation of novel, biologically active silver-avidin hybrids by electroless silver deposition directed to the surface of single, soluble avidin molecules, with retention of their solubility and highly specific biotin binding capacity. The process is based on conjugation of silver ions reducing polymers to avidin surface, followed by the addition of silver ions under mild physiological conditions. The partially overlapping silver patches thus obtained on the protein’s surface provided soluble, biologically active hybrids, retaining their specific biotin binding capability of both low-molecular-weight and high-molecular-weight biotinylated molecules and exhibiting enhanced thermal stability. The hybrids thus obtained were successfully used for molecular imaging of cancer cells prelabeled with biotinylated monoclonal antibody

Single-Molecule Reaction Chemistry in Patterned Nanowells

A new approach to synthetic chemistry is performed in ultraminiaturized, nanofabricated reaction chambers. Using lithographically defined nanowells, we achieve single-point covalent chemistry on hundreds of individual carbon nanotube transistors, providing robust statistics and unprecedented spatial resolution in adduct position. Each device acts as a sensor to detect, in real-time and through quantized changes in conductance, single-point functionalization of the nanotube as well as consecutive chemical reactions, molecular interactions, and molecular conformational changes occurring on the resulting single-molecule probe. In particular, we use a set of sequential bioconjugation reactions to tether a single-strand of DNA to the device and record its repeated, reversible folding into a G-quadruplex structure. The stable covalent tether allows us to measure the same molecule in different solutions, revealing the characteristic increased stability of the G-quadruplex structure in the presence of potassium ions (K⁺) versus sodium ions (Na⁺). Nanowell-confined reaction chemistry on carbon nanotube devices offers a versatile method to isolate and monitor individual molecules during successive chemical reactions over an extended period of time