Mechanism for invalid detection of microcantilever-DNA biosensors due to environmental changes

Microcantilever-DNA biosensors can lose recognition signals under specific hybridization conditions; this could be termed as a type of invalid detection. Using a multiscale energy method, this paper presents an alternative mechanism for this invalid detection induced by bio-interactions and environmental changes in temperature and ionic strength. First, a scaling law for the nanoscale thickness of the DNA film, and a mesoscopic empirical potential for bio-interactions in DNA liquid crystal solution, were combined to update a multiscale analytical model revealing the relation between cantilever motion, temperature, ionic strength, elastic properties of multilayered cantilevers, and nanoscopic properties of DNA molecules. Second, we carried out isothermal and non-isothermal experiments for the bending motion during the formation of a self-assembled monolayer of thiolated single-stranded DNA covalently immobilized on the gold-coated side of the cantilevers, and during the subsequent hybridization with the complementary nucleic acid, in order to obtain the relevant model parameters, and also to validate the proposed analytical model. Third, the effects of temperature and ionic strength on the microcantilever deflections were investigated. Numerical results show that the competing interplay among electrostatic force, hydration force, and configurational entropy generates an invalid point of detection at a grafting density of about 0.05 chain nm⁻². In the grafting density interval of 0.02–0.05 chain nm⁻², the thermal effect induces distortion of signals; in the grafting density interval of 0.05–0.097 chain nm⁻², fluctuations in ionic strength make detection fail. These findings will help to design and improve microcantilever-based biosensors with high sensitivity and robustness. (paper)