Molecular charge contact biosensing based on the interaction of biologically modified magnetic beads with an ion-sensitive field effect transistor.

In this article, we report a novel method of biomolecular recognition based on the molecular charge contact (MCC). As one of the MCC biosensing method, the interaction between DNA-coated magnetic beads and a silicon-based semiconductor, an ion-sensitive field effect transistor (ISFET) could be detected for DNA molecular recognition events using the principle of the field effect, which enables detecting ionic or molecular charges. After DNA-coated magnetic beads had been introduced and brought in contact with the gate surface by a magnet, the threshold voltage of the ISFET was shifted in the positive direction by immobilization, hybridization and extension reaction of DNA molecules on magnetic beads. This positive shift was based on the increase in negative charges of the phosphate groups in them. Then, the ISFET device could be reused a couple of dozen times continuously and cost-effectively because the oligonucleotide probes were tethered to the magnetic beads, but this was not done directly on the gate surface of the ISFET. Moreover, the MCC biosensing method enabled discrimination of a single nucleotide polymorphism. By creating an interaction of magnetic beads with the semiconductor, we can expect enhancement of the reaction efficiency in a solution and reuse of the device by separating the reaction field from the sensing substrate.