Real-Time Conformational Change Monitoring of G-Quadruplex Using Capillary-Based Biocompatible Whispering Gallery Mode Microresonator

In this paper, a capillary-based microfluidic whispering gallery mode (WGM) microresonator is proposed to dynamically monitor the conformation change of G-quadruplex driven by K + ion. We have theoretically analyzed the resonance wavelength shift mechanism for the DNA folding process, and the resonance mode with the largest wavelength sensitivity of 995.63 nm/RIU according to our simulation result is selected for monitoring of the DNA folding as well as the PGQS immobilization processes. The experimentally observed resonance wavelength shift caused by the immobilization of streptavidin is in accordance with our theoretical analysis on the WGM properties of the proposed microresonator. Moreover, experimental results indicate that PGQS could be folded with a KCl concentration down to 1~\mu \text{M} and a resonance wavelength shift rate of 18.85\times 10^{-5} nm/s, which decreases to 2.03\times 10^{-5} nm/s when the KCl concentration increases to 10 mM due to the reduction of available PGQS folding sites. Our proposed WGM-microresonator-based measurement platform possesses many desirable merits such as high sensitivity, high integration, microfluidic, label-free and real-time monitoring operation, which make it a promising candidate for DNA sensing, measurement of trivial amount biochemical analyte and related applications.