A wireless closed-loop system for optogenetic peripheral neuromodulation

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, Paulome Srivastava, Bong Hoon Kim, Seunghwan Min, Young Shiuan, Yeojeong Yun, Maria A. Payne, Jianpeng Zhang, Hokyung Jang, Yuhang Li, H. Henry Lai, Yonggang Huang, Sung-Il Park, Robert W. Gereau () and John A. Rogers ()
Additional contact information
Aaron D. Mickle: Washington University
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
Yeguang Xue: Northwestern University
Lisa A. McIlvried: Washington University
Bryan A. Copits: Washington University
Vijay K. Samineni: Washington University
Kaitlyn E. Crawford: University of Central Florida
Do Hoon Kim: University of Illinois at Urbana-Champaign
Paulome Srivastava: Washington University
Bong Hoon Kim: University of Illinois at Urbana-Champaign
Seunghwan Min: University of Illinois at Urbana-Champaign
Young Shiuan: Washington University
Yeojeong Yun: University of Illinois at Urbana-Champaign
Maria A. Payne: Washington University School of Medicine
Jianpeng Zhang: Beihang University (BUAA)
Hokyung Jang: University of Illinois at Urbana-Champaign
Yuhang Li: Beihang University (BUAA)
H. Henry Lai: Washington University
Yonggang Huang: Northwestern University
Sung-Il Park: Texas A&M University
Robert W. Gereau: Washington University
John A. Rogers: University of Illinois at Urbana-Champaign

Nature, 2019, vol. 565, issue 7739, 361-365

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-018-0823-6

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