Journal ArticlePhotonic crystal enhanced fluorescence emission and blinking suppression for single quantum dot digital resolution biosensingXiong, Yanyu; Huang, Qinglan; Canady, Taylor D.; Barya, Priyash; Liu, Shengyan; Arogundade, Opeyemi H.; Race, Caitlin M.; Che, Congnyu; Wang, Xiaojing; Zhou, Lifeng; Wang, Xing; Kohli, Manish; Smith, Andrew M.; Cunningham, Brian T.Abstract While nanoscale quantum emitters are effective tags for measuring biomolecular interactions, their utilities for applications that demand single-unit observations are limited by the requirements for large numerical aperture (NA) objectives, fluorescence intermittency, and poor photon collection efficiency resulted from omnidirectional emission. Here, we report a nearly 3000-fold signal enhancement achieved through multiplicative effects of enhanced excitation, highly directional extraction, quantum efficiency improvement, and blinking suppression through a photonic crystal (PC) surface. The approach achieves single quantum dot (QD) sensitivity with high signal-to-noise ratio, even when using a low-NA lens and an inexpensive optical setup. The blinking suppression capability of the PC improves the QDs on-time from 15% to 85% ameliorating signal intermittency. We developed an assay for cancer-associated miRNA biomarkers with single-molecule resolution, single-base mutation selectivity, and 10-attomolar detection limit. Additionally, we observed differential surface motion trajectories of QDs when their surface attachment stringency is altered by changing a single base in a cancer-specific miRNA sequence.2022-12-0110428315Nature Communications1312041-1723https://doi.org/10.1038/s41467-022-32387-w1900277National Science Foundation