Tandem metabolic reaction-based sensors unlock in vivo metabolomics

• 成果类型: Article
• 署名作者: Cheng, Xuanbing; Li, Zongqi; Zhu, Jialun; Wang, Jingyu; Huang, Ruyi; Yu, Lewis W.; Lin, Shuyu; Forman, Sarah; Gromilina, Evelina; Puri, Sameera; Patel, Pritesh; Bahramian, Mohammadreza; Tan, Jiawei; Hojaiji, Hannaneh; Jelinek, David; Voisin, Laurent; Yu, Kristie B.; Zhang, Ao; Ho, Connie; Lei, Lei; Coller, Hilary A.; Hsiao, Elaine Y.; Reyes, Beck L.; Matsumoto, Joyce H.; Lu, Daniel C.; Liu, Chong; Milla, Carlos; Davis, Ronald W.; Emaminejad, Sam
• 署名单位: University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Stanford University; Stanford University; University of California System; University of California Los Angeles
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12250
• DOI: 10.1073/pnas.2425526122
• 发表日期: 2025-03-04
• 关键词: transition-metal-complexes; electrochemical oxidation; nadh; 1; 10-phenanthroline-5; 6-dione; electrooxidation

摘要

Mimicking metabolic pathways on electrodes enables in vivo metabolite monitoring for decoding metabolism. Conventional in vivo sensors cannot accommodate underlying complex reactions involving multiple enzymes and cofactors, addressing only a fraction of enzymatic reactions for few metabolites. We devised a single- wall- carbon- nanotube- electrode architecture supporting tandem metabolic pathway-like reactions linkable to oxidoreductase- based electrochemical analysis, making a vast majority of metabolites detectable in vivo. This architecture robustly integrates cofactors, self- mediates reactions at maximum enzyme capacity, and facilitates metabolite intermediation/detection and interference inactivation through multifunctional enzymatic use. Accordingly, we developed sensors targeting 12 metabolites, with 100- fold- enhanced signal- to- noise ratio and days- long stability. Leveraging these sensors, we monitored trace endogenous metabolites in sweat/ saliva for noninvasive health monitoring, and a bacterial metabolite in the brain, marking a key milestone for unraveling gut microbiota-brain axis dynamics.