Tandem metabolic reaction–based sensors unlock in vivo metabolomics
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (29)
Xuanbing Cheng
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Zongqi Li
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Jialun Zhu
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Jingyu Wang
Department of Engineering Science, University of Oxford
Ruyi Huang
Department of Neurosurgery, David Geffen School of Medicine, University of California
Lewis W. Yu
Department of Integrative Biology and Physiology, University of California
Shuyu Lin
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Sarah Forman
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Evelina Gromilina
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Sameera Puri
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Pritesh Patel
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Mohammadreza Bahramian
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Jiawei Tan
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032 China
Hannaneh Hojaiji
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
David Jelinek
Department of Molecular, Cell and Developmental Biology, University of California
Laurent Voisin
Department of Molecular, Cell and Developmental Biology, University of California
Kristie B. Yu
Department of Integrative Biology and Physiology, University of California
Ao Zhang
Connie Ho
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California
Lei Lei
Department of Molecular, Cell and Developmental Biology, University of California
Hilary A. Coller
Department of Molecular, Cell and Developmental Biology, University of California
Elaine Y. Hsiao
Department of Integrative Biology and Physiology, University of California
Beck L. Reyes
Division of Pediatric Neurology, Department of Pediatrics, University of California
Joyce H. Matsumoto
Division of Pediatric Neurology, Department of Pediatrics, University of California
Daniel C. Lu
Department of Neurosurgery, David Geffen School of Medicine, University of California
Chong Liu
Department of Chemistry and Biochemistry
Carlos Milla
The Stanford Cystic Fibrosis Center, Center for Excellence in Pulmonary Biology, Stanford University School of Medicine
Ronald W. Davis
Department of Biochemistry, School of Medicine, Stanford University
Sam Emaminejad
Interconnected and Integrated Bioelectronics Lab (I²BL), Department of Electrical and Computer Engineering, Samueli School of Engineering, University of California