Kui Li,Tian Li,Kefan Wang,Yifan Wang,Zixuan Wang,Bingxiao Cheng,Yusheng Ouyang,Panke Zhang,Shuo Huang
Urine, an easily accessible body fluid, contains rich metabolic compounds reflecting the human health condition. Though urine analysis can be carried out by many conventional analytical methods, direct, rapid, and simultaneous identification of a variety of urinary metabolites by a handheld device remains challenging. Recent developments in nanopore small molecule sensing may suggest direct urine analysis performed by an engineered nanopore. Here, a hetero-octameric Mycobacterium smegmatis porin A (MspA) nanopore immobilized with a single nickel ion is confirmed to be suitable for the simultaneous identification of six urinary metabolites: creatinine, taurine, histidine, 1-methylhistidine, 3-methylhistidine, and hypoxanthine. With the assistance of machine learning, an overall accuracy of 98.5% was reported. This urine sensing capacity was further applied in real-time urinary metabolite monitoring after diet and physical exercise. These proofs of concept suggest a variety of nanopore-based body fluid analyses for early diagnosis, health management, pharmacokinetic monitoring, and doping tests.
Isomers of some chemical compounds may be dynamically interconvertible. Due to a lack of sensing methods with a sufficient resolution, however, direct monitoring of such processes can be difficult. Engineered Mycobacterium smegmatis porin A (MspA) nanopores can be applied as nanoreactors so that chemical reactions can be directly monitored. Here, an MspA modified with a phenylboronic acid (PBA) adapter was prepared and was used to observe dynamic interconversion between chiral configurations of boronate esters, which appears as telegraphic switching on top of nanopore events. The mechanism of this behavior was further confirmed by trials with different halogenated catechols, dopamine, adenosine, 1,2-propanediol, and (2R,3R)-2,3-butanediol, and its generality has been demonstrated. These results suggest that an engineered MspA possesses an exceptional resolution in its monitoring of chemical reaction processes and may inspire the future design of nanopore small-molecule sensors.
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