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A wireless closed-loop system for optogenetic peripheral neuromodulation

Author

Listed:
  • Aaron D. Mickle

    (Washington University
    Washington University School of Medicine)

  • Sang Min Won

    (University of Illinois at Urbana-Champaign)

  • Kyung Nim Noh

    (University of Illinois at Urbana-Champaign)

  • Jangyeol Yoon

    (University of Illinois at Urbana-Champaign)

  • Kathleen W. Meacham

    (Washington University
    Washington University School of Medicine)

  • Yeguang Xue

    (Northwestern University
    Northwestern University
    Northwestern University)

  • Lisa A. McIlvried

    (Washington University
    Washington University School of Medicine)

  • Bryan A. Copits

    (Washington University
    Washington University School of Medicine)

  • Vijay K. Samineni

    (Washington University
    Washington University School of Medicine)

  • Kaitlyn E. Crawford

    (University of Central Florida)

  • Do Hoon Kim

    (University of Illinois at Urbana-Champaign)

  • Paulome Srivastava

    (Washington University
    Washington University School of Medicine)

  • Bong Hoon Kim

    (University of Illinois at Urbana-Champaign
    Northwestern University
    Northwestern University
    Northwestern University)

  • Seunghwan Min

    (University of Illinois at Urbana-Champaign)

  • Young Shiuan

    (Washington University
    Washington University School of Medicine)

  • Yeojeong Yun

    (University of Illinois at Urbana-Champaign)

  • Maria A. Payne

    (Washington University School of Medicine
    Washington University Department of Surgery - Division of Urologic Surgery)

  • Jianpeng Zhang

    (Beihang University (BUAA))

  • Hokyung Jang

    (University of Illinois at Urbana-Champaign)

  • Yuhang Li

    (Beihang University (BUAA))

  • H. Henry Lai

    (Washington University
    Washington University School of Medicine
    Washington University Department of Surgery - Division of Urologic Surgery)

  • Yonggang Huang

    (Northwestern University
    Northwestern University
    Northwestern University)

  • Sung-Il Park

    (Texas A&M University)

  • Robert W. Gereau

    (Washington University
    Washington University School of Medicine)

  • John A. Rogers

    (University of Illinois at Urbana-Champaign
    Northwestern University
    Northwestern University
    Northwestern University)

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.

Suggested Citation

  • Aaron D. Mickle & Sang Min Won & Kyung Nim Noh & Jangyeol Yoon & Kathleen W. Meacham & Yeguang Xue & Lisa A. McIlvried & Bryan A. Copits & Vijay K. Samineni & Kaitlyn E. Crawford & Do Hoon Kim & Paulo, 2019. "A wireless closed-loop system for optogenetic peripheral neuromodulation," Nature, Nature, vol. 565(7739), pages 361-365, January.
  • Handle: RePEc:nat:nature:v:565:y:2019:i:7739:d:10.1038_s41586-018-0823-6
    DOI: 10.1038/s41586-018-0823-6
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    Citations

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    Cited by:

    1. Tong Li & Zhidong Wei & Fei Jin & Yongjiu Yuan & Weiying Zheng & Lili Qian & Hongbo Wang & Lisha Hua & Juan Ma & Huanhuan Zhang & Huaduo Gu & Michael G. Irwin & Ting Wang & Steven Wang & Zuankai Wang , 2023. "Soft ferroelectret ultrasound receiver for targeted peripheral neuromodulation," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Woo Seok Kim & M. Ibrahim Khot & Hyun-Myung Woo & Sungcheol Hong & Dong-Hyun Baek & Thomas Maisey & Brandon Daniels & P. Louise Coletta & Byung-Jun Yoon & David G. Jayne & Sung Il Park, 2022. "AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Cheng Yang & Qianni Wu & Junqing Liu & Jingshan Mo & Xiangling Li & Chengduan Yang & Ziqi Liu & Jingbo Yang & Lelun Jiang & Weirong Chen & Hui-jiuan Chen & Ji Wang & Xi Xie, 2022. "Intelligent wireless theranostic contact lens for electrical sensing and regulation of intraocular pressure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Alp Timucin Toymus & Umut Can Yener & Emine Bardakci & Özgür Deniz Temel & Ersin Koseoglu & Dincay Akcoren & Burak Eminoglu & Mohsin Ali & Rasim Kilic & Tufan Tarcan & Levent Beker, 2024. "An integrated and flexible ultrasonic device for continuous bladder volume monitoring," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    5. Alban Guesdon-Vennerie & Patrick Couvreur & Fatoumia Ali & Frédéric Pouzoulet & Christophe Roulin & Immaculada Martínez-Rovira & Guillaume Bernadat & François-Xavier Legrand & Claudie Bourgaux & Cyril, 2022. "Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Pengcheng Sun & Chaochao Li & Can Yang & Mengchun Sun & Hanqing Hou & Yanjun Guan & Jinger Chen & Shangbin Liu & Kuntao Chen & Yuan Ma & Yunxiang Huang & Xiangling Li & Huachun Wang & Liu Wang & Sheng, 2024. "A biodegradable and flexible neural interface for transdermal optoelectronic modulation and regeneration of peripheral nerves," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Yunhui Liu & Lu Zhang & Nan Hu & Jie Shao & Dazhi Yang & Changshun Ruan & Shishu Huang & Liping Wang & William W. Lu & Xinzhou Zhang & Fan Yang, 2022. "An optogenetic approach for regulating human parathyroid hormone secretion," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Kyowon Kang & Seongryeol Ye & Chanho Jeong & Jinmo Jeong & Yeong-sinn Ye & Jin-Young Jeong & Yu-Jin Kim & Selin Lim & Tae Hee Kim & Kyung Yeun Kim & Jong Uk Kim & Gwan In Kim & Do Hoon Chun & Kiho Kim, 2024. "Bionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Jinhong Park & Duhwan Seong & Yong Jun Park & Sang Hyeok Park & Hyunjin Jung & Yewon Kim & Hyoung Won Baac & Mikyung Shin & Seunghyun Lee & Minbaek Lee & Donghee Son, 2022. "Reversible electrical percolation in a stretchable and self-healable silver-gradient nanocomposite bilayer," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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