Label-free, ultra-low detection limit DNA biosensor using high quality optical microcavity functionalized by DNA tetrahedral nanostructure probes

This study proposes and demonstrates a novel label-free DNA biosensor using high quality optical microcavity functionalized by 3D DNA nanostructure probes. To achieve ultra-low limit DNA biosensing, optical sensing interface of the hollow-core, thin wall-thickness microcavity was functionalized by self-assembled DNA tetrahedral nanostructure (DTN) probes with size of 17 bp and length of ∼5.8 nm. High efficiency binding of the DTN probes with the optical sensor interface and the target ssDNA are achieved. Whispering gallery mode (WGM) spectra with high-Q factor of >107 are excited and traced for DNA detection inside the microfluidic channel of the microcavity, with a small sample volume of nL. Incorporation of nanoscale DTN probes onto surface of the optical microcavity makes it an effective way for increasing efficient probe density and eliminating entanglement between DNA probes, thus ∼1000 times lower detection limit is achieved as compared to using 1D ssDNA probes. Due to its desirable merits of label-free, ultra-low LoD, real time and compact size, the proposed DNA biosensor has broad application prospects in bioengineering and medical diagnosis.