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Nature. 2019 Jan;565(7739):361-365. doi: 10.1038/s41586-018-0823-6. Epub 2019 Jan 2.

A wireless closed-loop system for optogenetic peripheral neuromodulation.

Mickle AD1,2, Won SM3, Noh KN3, Yoon J4, Meacham KW1,2, Xue Y5,6,7, McIlvried LA1,2, Copits BA1,2, Samineni VK1,2, Crawford KE8, Kim DH4, Srivastava P1,2, Kim BH4,7,9,10, Min S4, Shiuan Y1,2, Yun Y4, Payne MA2,11, Zhang J12, Jang H4, Li Y12, Lai HH1,2,11, Huang Y5,6,7, Park SI13, Gereau RW 4th14,15, Rogers JA16,17,18,19,20,21,22,23.

Author information

1
Washington University Pain Center and Department of Anesthesiology, Washington University, St Louis, MO, USA.
2
Washington University School of Medicine, St Louis, MO, USA.
3
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
4
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
5
Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL, USA.
6
Mechanical Engineering, Northwestern University, Evanston, IL, USA.
7
Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
8
Department of Materials Science and Engineering, University of Central Florida, Orlando, FL, USA.
9
Simpson Querrey Institute, Northwestern University, Chicago, IL, USA.
10
Center for Bio-integrated Electronics, Northwestern University, Evanston, IL, USA.
11
Washington University Department of Surgery - Division of Urologic Surgery, St Louis, MO, USA.
12
Institute of Solid Mechanics, Beihang University (BUAA), Beijing, China.
13
Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA.
14
Washington University Pain Center and Department of Anesthesiology, Washington University, St Louis, MO, USA. gereaur@wustl.edu.
15
Washington University School of Medicine, St Louis, MO, USA. gereaur@wustl.edu.
16
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA. jrogers@northwestern.edu.
17
Mechanical Engineering, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
18
Materials Science and Engineering, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
19
Simpson Querrey Institute, Northwestern University, Chicago, IL, USA. jrogers@northwestern.edu.
20
Center for Bio-integrated Electronics, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
21
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
22
Department of Chemistry, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
23
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. jrogers@northwestern.edu.

Abstract

The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system1-5. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome)4,6,7. Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency)8. Direct physical coupling of electrodes to the nerve can lead to injury and inflammation9-11. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.

PMID:
30602791
PMCID:
PMC6336505
DOI:
10.1038/s41586-018-0823-6
[Indexed for MEDLINE]
Free PMC Article

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