Ensemble Modified Aptamer Based Pattern Recognition for Adaptive Target Identification

The difficulty of the molecular design and chemical synthesis of artificial sensing receptors restricts their diagnostic and proteomic applications. Herein, we report a concept of "ensemble modified aptamers" (EMAmers) that exploits the collective recognition abilities of a small set of protein-like side-chain-modified nucleic acid ligands for discriminative identification of molecular or cellular targets. Different types and numbers of hydrophobic functional groups were incorporated at designated positions on nucleic acid scaffolds to mimic amino acid side chains. We successfully assayed 18 EMAmer probes with differential binding affinities to seven proteins. We constructed an EMAmer-based chemical nose sensor and demonstrated its application in blinded unknown protein identification, giving a 92.9% accuracy. Additionally, the sensor is generalizable to the detection of blinded unknown bacterial and cellular samples, which enabled identification accuracies of 96.3% and 94.8%, respectively. This sensing platform offers a discriminative means for adaptive target identification and holds great potential for diverse applications.