Field effect transistor (FET) biosensors are capable of detecting various biomolecules, although challenges remain in the detection of uncharged molecules. In this study, the detection of uncharged cortisol was demonstrated by interfacial design using a technique to immobilize target-bound aptamers. The target-bound aptamers, which formed a higher-order structure than target-unbound aptamers, expanded the distance between adjacent aptamers and reduced the steric hindrance to the conformational change. The density-controlled aptamers efficiently induced their conformational changes with the cortisol binding, which resulted in the improvement of the sensitivity of FET biosensors.
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