Enhanced Sensitivity in Nanopore Sensing of Cancer Biomarkers in Human Blood via Click Chemistry. Issue 2 (6th November 2018) - Zhang, Zehui
Abstract: Cancer biomarkers are expected to be indicative of the occurrence of certain cancer diseases before the tumors form and metastasize. However, many biomarkers can only be acquired in extremely low concentrations, which are often beyond the limit of detection (LOD) of current instruments and technologies. A practical strategy for nanopore sensing of cancer biomarkers in raw human blood down to the femtomolar level is developed here. This strategy first converts the detection of cancer biomarkers to the quantification of copper ions by conducting a sandwich assay involving copper oxide nanoparticles. The released Cu 2+ is then taken to catalyze the "click" reaction which ligates a host–guest modified DNA probe. Finally, this DNA probe is subjected to single‐channel recordings to afford the translocation events that can be used to derive the concentrations of the original biomarkers. Due to the amplification effects of nanoparticle loadings and the "click" reaction, the LOD of this strategy can be as low as the subfemtomolar level. Further, the acid treatment step could effectively eliminate the interferences from plasma proteins in raw human blood and make the strategy highly suitable for the detection of cancer biomarkers in clinical samples. Abstract : A new strategy for the ultrasensitive detection of cancer biomarkers is developed based on the combination of a sandwich assay, "click" chemistry, and DNA‐assisted nanopore sensing. The limit of detection of the strategy can be as low as the femtomolar level. Furthermore, it can effectively eliminate interferences from plasma proteins and be applied in the clinical detection of cancer biomarkers.