Here we describe a method for the sensitive detection of a single-base mutation in DNA. We assembled a primer thiolated oligonucleotide, complementary to the target DNA as far as one base before the mutation site, on an electrode or a gold-quartz piezoelectric crystal. After hybridizing the target DNA, normal or mutant, with the sensing oligonucleotide, the resulting assembly is reacted with the biotinylated nucleotide, complementary to the mutation site, in the presence of polymerase. The labeled nucleotide is coupled only to the double-stranded assembly that includes the mutant site. Subsequent binding of avidin-alkaline phosphatase to the assembly, and the biocatalyzed precipitation of an insoluble product on the transducer, provides a means to confirm and amplify detection of the mutant. Faradaic impedance spectroscopy and microgravimetric quartz-crystal microbalance analyses were employed for electronic detection of single-base mutants. The lower limit of sensitivity for the detection of the mutant DNA is 1 x 10-14 mol/ml. We applied the method for the analysis of polymorphic blood samples that include the Tay-Sachs genetic disorder. The sensitivity of the method enables the quantitative analysis of the mutant with no PCR pre-amplification.

Detection of biological species is of great importance to numerous areas of medical and life sciences from the diagnosis of diseases to the discovery of new drugs. Essential to the detection mechanism is the transduction of a signal associated with the specific recognition of biomolecules of interest. Nanowire-based electrical devices have been demonstrated as a powerful sensing platform for the highly sensitive detection of a wide-range of biological and chemical species. Yet, detecting biomolecules in complex biosamples of high ionic strength (>100 mM) is severely hampered by ionic screening effects. As a consequence, most of existing nanowire sensors operate under low ionic strength conditions, requiring ex situ biosample manipulation steps, that is, desalting processes. Here, we demonstrate an effective approach for the direct detection of biomolecules in untreated serum, based on the fragmentation of antibody-capturing units. Size-reduced antibody fragments permit the biorecognition event to occur in closer proximity to the nanowire surface, falling within the charge-sensitive Debye screening length. Furthermore, we explored the effect of antibody surface coverage on the resulting detection sensitivity limit under the high ionic strength conditions tested and found that lower antibody surface densities, in contrary to high antibody surface coverage, leads to devices of greater sensitivities. Thus, the direct and sensitive detection of proteins in untreated serum and blood samples was effectively performed down to the sub-pM concentration range without the requirement of biosamples manipulation.

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The capability to detect traces of explosives sensitively, selectively and rapidly could be of great benefit for applications relating to civilian national security and military needs. Here, we show that, when chemically modified in a multiplexed mode, nanoelectrical devices arrays enable the supersensitive discriminative detection of explosive species. The fingerprinting of explosives is achieved by pattern recognizing the inherent kinetics, and thermodynamics, of interaction between the chemically modified nanosensors array and the molecular analytes under test. This platform allows for the rapid detection of explosives, from air collected samples, down to the parts-per-quadrillion concentration range, and represents the first nanotechnology-inspired demonstration on the selective supersensitive detection of explosives, including the nitro-and peroxide-derivatives, on a single electronic platform. Furthermore, the ultrahigh sensitivity displayed by our platform may allow the remote detection of various explosives, a task unachieved by existing detection technologies.