Exploiting binding-induced changes in probe flexibility for the optimization of electrochemical biosensors.

ABSTRACT: Electrochemical sensors employing redox-tagged, electrode-bound oligonucleotides have emerged as a promising new platform for the reagentless detection of molecular analytes. Signal generation in these sensors is linked to specific, binding-induced changes in the efficiency with which an attached redox tag approaches and exchanges electrons with the interrogating electrode. We present here a straightforward means of optimizing the signal gain of these sensors that exploits this mechanism. Specifically, using square-wave voltammetry, which is exquisitely sensitive to electrode reaction rates, we can tune the frequency of the voltammetric measurements to preferentially enhance the signal associated with either the unbound or target-bound conformations of the probe. This allows us to control not only the magnitude of the signal gain associated with target binding but also the sign of the signal change, generating "signal-on" or "signal-off" sensors. This optimization parameter appears to be quite general: we show here that tuning the square-wave frequency can significantly enhance the gain of the sensors directed against specific oligonucleotide sequences, small molecules, proteins, and protein-small molecule interactions.

SUBMITTER: White RJ 

PROVIDER: S-EPMC2802819 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature