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Electrical transduction of DNA hybridization events is a major challenge in genoelectronics. Here we report on a new strategy for amplifying electrical DNA sensing based on the use of microsphere tags loaded internally with a redox marker. The resulting “electroactive beads” are capable of carrying a huge number of the ferrocenecarboxaldehyde marker molecules and hence offer a remarkable amplification of single hybridization events. This allows chronopotentiometric detection of target DNA down to the 5.1 × 10-21 mol level (∼31 000 molecules) in connection to 20 min of hybridization and “release” of the marker in an organic medium. The dramatic signal amplification advantage is combined with a remarkable discrimination against a huge excess (107) of noncomplementary nucleic acids. Such electroactive beads hold great promise for multitarget detection (in connection to spheres loaded with different redox markers) and for enhancing the sensitivity of other bioassays.