Wu, YuqiangZhang, David YuYin, PengVollmer, Frank2015-07-102015-07-102014Wu, Yuqiang, Zhang, David Yu, Yin, Peng, et al.. "Ultraspecific and Highly Sensitive Nucleic Acid Detection by Integrating a DNA Catalytic Network with a Label-Free Microcavity." <i>Small,</i> 10, no. 10 (2014) Wiley: 2067-2076. http://dx.doi.org/10.1002/smll.201303558.https://hdl.handle.net/1911/80891Nucleic acid detection with label-free biosensors circumvents costly fluorophore functionalization steps associated with conventional assays by utilizing transducers of impressive ultimate detection limits. Despite this technological prowess, molecular recognition at a surface limits the biosensors' sensitivity, specificity, and reusability. It is therefore imperative to integrate novel molecular approaches with existing label-free transducers to overcome those limitations. Here, we demonstrate this concept by integrating a DNA strand displacement circuit with a micron-scale whispering gallery mode (WGM) microsphere biosensor. The integrated biosensor exhibits at least 25-fold improved nucleic acid sensitivity, and sets a new record for label-free microcavity biosensors by detecting 80 pM (32 fmol) of a 22nt oligomer; this improvement results from the catalytic behavior of the circuit. Furthermore, the integrated sensor exhibits extremely high specificity; single nucleotide variants yield 40- to 100-fold lower signal. Finally, the same physical sensor was demonstrated to alternatingly detect 2 different nucleic acid sequences through 5 cycles of detection, showcasing both its reusability and its versatility.engThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Wiley.Journal articlebiosensorDNA catalytic circuitoligonucleotidesoptical microcavitysingle-nucleotide polymorphism detectionhttp://dx.doi.org/10.1002/smll.201303558