We report carbon nanotube network field-effect transistors (NTNFETs) that function as selective detectors of DNA immobilization and hybridization. NTNFETs with immobilized synthetic oligonucleotides have been shown to specifically recognize target DNA sequences, including H63D single-nucleotide polymorphism (SNP) discrimination in the HFE gene, responsible for hereditary hemochromatosis. The electronic responses of NTNFETs upon single-stranded DNA immobilization and subsequent DNA hybridization events were confirmed by using fluorescence-labeled oligonucleotides and then were further explored for label-free DNA detection at picomolar to micromolar concentrations. We have also observed a strong effect of DNA counterions on the electronic response, thus suggesting a charge-based mechanism of DNA detection using NTNFET devices. Implementation of label-free electronic detection assays using NTNFETs constitutes an important step toward low-cost, low-complexity, highly sensitive and accurate molecular diagnostics.hemochromatosis ͉ SNP ͉ biosensor T he development of nucleic acids diagnostics has become the subject of intense research, especially in the postgenome era. Current methods have mainly focused on optical detection using fluorescence-labeled oligonucleotides with dyes (1), quantum dots (2), or enhanced absorption of light by oligonucleotidemodified gold nanoparticles (3). On the other hand, label-free electronic methods promise to offer sensitivity, selectivity, and low cost for the detection of DNA hybridization (4). For example, microfabricated silicon field-effect sensors can monitor directly the increase in surface charge when DNA was hybridized on the sensor surface (5). Nanomaterials possess unique properties that are amenable to biosensor applications; they are one-dimensional structures that are extremely sensitive to electronic perturbations, readily functionalized with biorecognition layers, and compatible with many semiconducting manufacturing processes. Thus, one-dimensional silicon nanowires (6-8) and indium oxide nanowires (9) have shown promising performance, because their electronic conductance is more sensitive to DNA-associated charges as a result of their high surface-tovolume ratio. Using smaller nanowires with virtually all atoms on their surface, such as single-walled carbon nanotubes (SWNTs), will provide additional advantages in DNA detection. To date, there are several reports on electrochemical detection of DNA hybridization using multi-walled carbon nanotube electrodes (ref. 10 and references therein, and ref. 11). Whereas electrochemical methods rely on electrochemical behavior of the labels, measurement of direct electron transfer between SWNTs and DNA molecules paves the way for label-free DNA detection. SWNT-based field-effect transistors (12) have excellent operating characteristics (13), and they have already been explored for highly sensitive electronic detection of gases (14, 15) and biomolecules such as antibodies (16,17).Single-stranded DNA (ssDNA) has been recently demons...