Nanofabrication technologies should be useful for developing highly sensitive, reproducible nanobiosensors. This letter presents a nanometric system that is composed of well-oriented nanowells. The geometry permits only one or a few biomolecules to enter and become attached to nanosized gold dots. This nanoarray is easily fabricated using current nanolithography technology. When the authors applied this array to highly sensitive electrochemical DNA detection, they obtained a two-orders-of-magnitude enhancement in sensitivity. This nanometric system could be applied to numerous other integrated digital biosensors.

Scanning near-¢eld optical microscopy (SNOM) imaging was performed to allow for the direct visualization of damaged sites on individual DNA molecules to a scale of a few tens of nanometers. Fluorescence in situ hybridization on extended DNA molecules was modi¢ed to detect a single abasic site. Abasic sites were speci¢cally labelled with a biotinlylated aldehyde-reactive probe and £uorochrome-conjugated streptavidin. By optimizing the performance of the SNOM technique, we could obtain high contrast near-¢eld optical images that enabled high-resolution near-¢eld £uorescence imaging using optical ¢ber probes with small aperture sizes. High-resolution near-¢eld £uorescence imaging demonstrated that two abasic sites within a distance of 120 nm are clearly obtainable, something which is not possible using conventional £uorescence in situ hybridization combined with far-¢eld £uorescence microscopy.

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