A tissue-like neurotransmitter sensor for the brain and gut

Jinxing Li; Yuxin Liu; Lei Yuan; Baibing Zhang; Estelle Spear Bishop; Kecheng Wang; Jing Tang; Yu-Qing Zheng; Wenhui Xu; Simiao Niu; Levent Beker; Thomas L Li; Gan Chen; Modupeola Diyaolu; Anne-Laure Thomas; Vittorio Mottini; Jeffrey B-H Tok; James C Y Dunn; Bianxiao Cui; Sergiu P Pașca; Yi Cui; Aida Habtezion; Xiaoke Chen; Zhenan Bao

doi:10.1038/s41586-022-04615-2

A tissue-like neurotransmitter sensor for the brain and gut

Nature. 2022 Jun;606(7912):94-101. doi: 10.1038/s41586-022-04615-2. Epub 2022 Jun 1.

Authors

Jinxing Li^#^{1

2}, Yuxin Liu^#³, Lei Yuan^#⁴, Baibing Zhang⁴, Estelle Spear Bishop⁵, Kecheng Wang⁶, Jing Tang⁶, Yu-Qing Zheng¹, Wenhui Xu⁶, Simiao Niu¹, Levent Beker¹, Thomas L Li^{7

8}, Gan Chen⁶, Modupeola Diyaolu⁹, Anne-Laure Thomas⁹, Vittorio Mottini^{1

2}, Jeffrey B-H Tok¹, James C Y Dunn^{3

9}, Bianxiao Cui⁷, Sergiu P Pașca^{8

10}, Yi Cui⁶, Aida Habtezion⁵, Xiaoke Chen¹¹, Zhenan Bao¹²

Affiliations

¹ Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
² Department of Biomedical Engineering and Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
³ Department of Bioengineering, Stanford University, Stanford, CA, USA.
⁴ Department of Biology, Stanford University, Stanford, CA, USA.
⁵ Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
⁷ Department of Chemistry, Stanford University, Stanford, CA, USA.
⁸ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁹ Department of Surgery/Pediatric Surgery, Stanford University, Stanford, CA, USA.
¹⁰ Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute and Bio-X, Stanford University, Stanford, CA, USA.
¹¹ Department of Biology, Stanford University, Stanford, CA, USA. xkchen@stanford.edu.
¹² Department of Chemical Engineering, Stanford University, Stanford, CA, USA. zbao@stanford.edu.

^# Contributed equally.

Abstract

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract^1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease^1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

MeSH terms

Animals
Biosensing Techniques
Brain* / metabolism
Brain-Gut Axis
Elastomers
Enteric Nervous System* / metabolism
Gastrointestinal Tract* / innervation
Gastrointestinal Tract* / physiology
Graphite
Lasers
Mice
Nanoparticles
Neurotransmitter Agents* / analysis
Serotonin / analysis

Substances

Elastomers
Neurotransmitter Agents
Serotonin
Graphite

Abstract

MeSH terms

Substances

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