Biomolecular detection with a thin membrane transducer

We present a thin membrane transducer (TMT) that can detect nucleic acid based biomolecular reactions including DNA hybridization and protein recognition by aptamers. Specific molecular interactions on an extremely thin and flexible membrane surface cause the deflection of the membrane due to surface stress change which can be measured by a compact capacitive circuit. A gold-coated thin PDMS membrane assembled with metal patterned glass substrate is used to realize the capacitive detection. It is demonstrated that perfect match and mismatch hybridizations can be sharply discriminated with a 16-mer DNA oligonucleotide immobilized on the gold-coated surface. While the mismatched sample caused little capacitance change, the perfectly matched sample caused a well-defined capacitance decrease vs. time due to an upward deformation of the membrane by a compressive surface stress. Additionally, the TMT demonstrated the single nucleotide polymorphism (SNP) capabilities which enabled a detection of mismatching base pairs in the middle of the sequence. It is intriguing that the increase of capacitance, therefore a downward deflection due to tensile stress, was observed with the internal double mismatch hybridization. We further present the detection of thrombin protein through ligand-receptor type recognition with 15-mer thrombin aptamer as a receptor. Key aspects of this detection such as the effect of concentration variation are investigated. This capacitive thin membrane transducer presents a completely new approach for detecting biomolecular reactions with high sensitivity and specificity without molecular labelling and optical measurement.