Carbon nanotubes (CNT) – field effect transistor (FET) sensors are promising candidates for label-free, sensitive detection of biological molecules. In this study, we have developed a proof-of-concept biosensor for the detection of microRNA (miRNA) in which designer oligonucloetide (ODN) probes covalently attached to CNTs serve as a highly specific molecular recognition function and FET device that translate changes in CNT electric properties serves as a signal transduction function. MicroRNA-21 was selected in this study as a model miRNA molecule. Basic research has shown that over-expression of miRNA-21 is associated with development of leukemia, breast cancer and prostate cancer. CNTs were functionalized with designer oligionucleotide (ODN) probes having conformational structures and sequences that are highly specific for hybridization with target miRNA-21. Conjugation of ODN probes with CNTs was examined using zeta potential surface charge measurements, fluorescent labeling, and atomic force and scanning electron microscopies. Biological activity and hybridization of immobilized ODN probe with miRNA 21 were further monitored using quartz crystal monitor measurements and fluorescent labeling. Subsequently, CNT-ODN network films were deposited using dielectrophoretic technique. Thin and wide metal electrodes that allow for increased Schottky contact areas were fabricated by magnetron sputter deposition of metals for source and drain electrodes using a shadow mask and tilted angle. Electrical impedance spectroscopy and current-gate voltage measurements were used to study the effect of ODN attachment and hybridization event on CNT electronic properties. In this presentation, we will discuss the fabrication and characterization of the developed sensor along with challenges of meeting the required specificity and sensitivity for real-world applications such as in vitro medical diagnostics.