Zeptomole detection of DNA based on microparticle dissociation from a glass plate in a combined acoustic-gravitational field

Abstract

In this study, we propose a novel detection principle based on the dissociation of microparticles immobilized on a glass plate through weak hybridization involving 4–6 base pairs (bps) in a combined acoustic-gravitational field. Particle dissociation from the glass plate occurs when the resultant of the acoustic radiation force (Fac) and the sedimentation force (Fsed) exerted on the particle exceeds the binding force owing to the weak hybridization (Fbind). Because Fac and Fsed can be controlled by the microparticle density, and Fac is a function of the applied voltage to the transducer (V), an increase in V induces particle dissociation. The binding of gold nanoparticles (AuNPs) onto silica microparticles (SPs) resulting from the strong hybridization of 20 bps induces an increase in the density of SPs, leading to an increase in Fac and Fsed; consequently, the voltage V required for dissociation becomes lower than that required without AuNP binding. We demonstrate that the dependence of the binding number of AuNPs per SP on V follows the theoretical prediction. The binding of 7500 AuNPs per SP can be detected as a 10 V change in V. The present approach allows the detection of 2000 DNA molecules involved in the strong hybridization between AuNPs and SP.