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Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21427-21437. doi: 10.1073/pnas.1909850116. Epub 2019 Oct 10.

Battery-free, lightweight, injectable microsystem for in vivo wireless pharmacology and optogenetics.

Zhang Y1,2, Castro DC3, Han Y4,5,6, Wu Y2, Guo H2, Weng Z1, Xue Y2,7,8, Ausra J9, Wang X10, Li R11,12, Wu G1, Vázquez-Guardado A13, Xie Y2, Xie Z7,8,11, Ostojich D2, Peng D14, Sun R15, Wang B16, Yu Y17, Leshock JP2, Qu S18, Su CJ2, Shen W19, Hang T20, Banks A2, Huang Y2,7,8,13, Radulovic J4, Gutruf P21, Bruchas MR22,23,24, Rogers JA25,13,26,27,28,29.

Author information

1
Department of Biomedical, Biological, and Chemical Engineering, University of Missouri, Columbia, MO 65211.
2
Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208.
3
Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195.
4
Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL 60611.
5
Department of Anesthesiology, Eye & ENT Hospital, Fudan University, 200031 Shanghai, China.
6
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 221004 Xuzhou, China.
7
Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL 60208.
8
Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208.
9
Biomedical Engineering, College of Engineering, The University of Arizona, Tucson, AZ 85721.
10
Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, MO 65211.
11
State Key Laboratory of Structural Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, 116024 Dalian, China.
12
International Research Center for Computational Mechanics, Dalian University of Technology, 116024 Dalian, China.
13
Center for Bio-Integrated Electronics, Northwestern University, Evanston, IL 60208.
14
College of Optoelectronic Engineering, Shenzhen University, 518060 Shenzhen, China.
15
Bristol Composites Institute, University of Bristol, BS8 1TR Bristol, United Kingdom.
16
Department of Civil and Environmental Engineering, University of Missouri, Columbia, MO 65211.
17
NeuroLux, Inc., Evanston, IL 60201.
18
Department of Materials Science and Engineering, Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
19
Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, TX 76019.
20
School of Materials Science and Engineering, Shanghai Jiao Tong University, 200240 Shanghai, China.
21
Biomedical Engineering, College of Engineering, The University of Arizona, Tucson, AZ 85721; pgutruf@email.arizona.edu mbruchas@uw.edu jrogers@northwestern.edu.
22
Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195; pgutruf@email.arizona.edu mbruchas@uw.edu jrogers@northwestern.edu.
23
Center for Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA 98195.
24
Department of Pharmacology, University of Washington, Seattle, WA 98195.
25
Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208; pgutruf@email.arizona.edu mbruchas@uw.edu jrogers@northwestern.edu.
26
Simpson Querrey Institute, Northwestern University, Chicago, IL 60611.
27
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208.
28
Department of Chemistry, Northwestern University, Evanston, IL 60208.
29
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.

Abstract

Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.

KEYWORDS:

neuroscience; optogenetics; pharmacology

PMID:
31601737
PMCID:
PMC6815115
[Available on 2020-04-10]
DOI:
10.1073/pnas.1909850116

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