Amplified Magnetic Resonance Sensing via Enzyme-Mediated Click Chemistry and Magnetic Separation

Magnetic resonance sensing (MRS) assays with simple pretreatment have drawn increasing attention for the development of biosensors, whereas conventional MRS is not competent for analyzing trace targets due to its relative low sensitivity. In this work, we employ alkaline phosphatase-mediated click chemistry as a signal transformation and amplification technique that effectively enhances the magnetic signal for amplified MRS. We outline two strategies by modulating either the aggregation state or the number of the magnetic probes based on click chemistry-triggered aggregation of nanoparticles and their ability for magnetic separation. The experimental results show that the combination of magnetic nanoprobe number-based modulation and magnetic separation outcompetes nanoprobe aggregation-based strategy for an enhanced sensitivity, providing an attractive platform for MRS-based analysis of small molecules. For proof of application, we apply this click chemistry-based approach for the detection of clenbuterol, an illegally used drug to promote growth in livestock. It shows a linear detection range from 0.1 ng mL^-1 to 500 ng mL^-1 with a limit of detection of 0.02 ng mL^-1, revealing that the click chemistry-mediated amplified MRS can act as a promising magnetic platform to detect trace levels of small molecules in authentic samples.