We have explored all-electronic chemical detectors based on bio-nano hybrids, where the biomolecule (DNA or protein) provides chemical recognition and a carbon nanotube (NT) or graphene transistor is used for electronic readout. This sensor class has numerous favorable properties and is a promising approach towards ultrasensitive detection of liquid- and vapor-phase anayltes. NT or graphene transistors are functionalized with proteins through an amide bond using a reliable and robust process based on carboxylated diazonium salts. If desired, control of protein orientation is achieved through the use of a Ni-nitrilotriacetic acid (Ni-NTA) chemistry with affinity for the histidine tag on an engineered protein. We have used this approach to create a nanoelectronic interface to olfactory receptor proteins (ORs) that were embedded in synthetic nanoscale cell membrane analogues. Olfactory receptor proteins (ORs) are the most numerous class of G-protein coupled receptors (GPCRs), a large family of membrane proteins whose roles in the detection of molecules outside eukaryotic cells and initiation of cascades of intracellular responses make them important pharmaceutical targets.

We have also very recently used similar methods based on an engineered antibody to demonstrate detection of a cancer biomarker at levels of 1 pgm/mL, 500 times smaller than the antibody dissociation constant. Non-covalent functionalization of carbon nanotube transistors is achieved through self-assembly of monolayers of single-stranded DNA on the NT sidewall. The DNA is used not for its self-recogntion properties but rather for its chemical recognition for small molecule analytes. We will discuss the possible use of this system for an "electronic tongue" system for detection of small molecule targets in aqueous media. Finally I will describe progress towards high-yield fabrication of large arrays of nanotube-based chemical sensors.