We report an integrated chip that senses nucleic acid biomarkers at exceptionally low concentrations. To achieve such sensitivities we exploit four concepts. (1) Nanostructured electrodes allow efficient display of probe sequences. (2) The use of uncharged probe sequences lowers the background signal in our read-out system. (3) Electrocatalysis provides built-in amplification of the electrical signal that reports hybridization events. (4) An optimal self-assembled monolayer of thiol-functionalized probe molecules is best achieved with the aid of a short spacer molecule to confer enhanced accessibility. We show herein that via joint optimization along these four axes we achieve attomolar sensitivity.
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