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 & 5 others H. Henry Lai, Yonggang Huang, Sung Il Park, Robert W. Gereau, John A Rogers

Research output: Contribution to journalLetter

7 Citations (Scopus)

Abstract

The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system 1–5 . 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 inflammation 9–11 . 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.

Original languageEnglish (US)
Pages (from-to)361-365
Number of pages5
JournalNature
Volume565
Issue number7739
DOIs
StatePublished - Jan 17 2019

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Optogenetics
Urinary Bladder
Pain
Opsins
Interstitial Cystitis
Overactive Urinary Bladder
Organ Specificity
Peripheral Nervous System
Urinary Incontinence
Electric Stimulation
Electrodes
Medicine
Inflammation
Technology
Light
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Mickle, A. D., Won, S. M., Noh, K. N., Yoon, J., Meacham, K. W., Xue, Y., ... Rogers, J. A. (2019). A wireless closed-loop system for optogenetic peripheral neuromodulation. Nature, 565(7739), 361-365. https://doi.org/10.1038/s41586-018-0823-6
Mickle, Aaron D. ; Won, Sang Min ; Noh, Kyung Nim ; Yoon, Jangyeol ; Meacham, Kathleen W. ; Xue, Yeguang ; McIlvried, Lisa A. ; Copits, Bryan A. ; Samineni, Vijay K. ; Crawford, Kaitlyn E. ; Kim, Do Hoon ; Srivastava, Paulome ; Kim, Bong Hoon ; Min, Seunghwan ; Shiuan, Young ; Yun, Yeojeong ; Payne, Maria A. ; Zhang, Jianpeng ; Jang, Hokyung ; Li, Yuhang ; Lai, H. Henry ; Huang, Yonggang ; Park, Sung Il ; Gereau, Robert W. ; Rogers, John A. / A wireless closed-loop system for optogenetic peripheral neuromodulation. In: Nature. 2019 ; Vol. 565, No. 7739. pp. 361-365.
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abstract = "The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system 1–5 . 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 inflammation 9–11 . 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.",
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Mickle, AD, Won, SM, Noh, KN, Yoon, J, Meacham, KW, Xue, Y, McIlvried, LA, Copits, BA, Samineni, VK, Crawford, KE, Kim, DH, Srivastava, P, Kim, BH, Min, S, Shiuan, Y, Yun, Y, Payne, MA, Zhang, J, Jang, H, Li, Y, Lai, HH, Huang, Y, Park, SI, Gereau, RW & Rogers, JA 2019, 'A wireless closed-loop system for optogenetic peripheral neuromodulation' Nature, vol. 565, no. 7739, pp. 361-365. https://doi.org/10.1038/s41586-018-0823-6

A wireless closed-loop system for optogenetic peripheral neuromodulation. / Mickle, Aaron D.; Won, Sang Min; Noh, Kyung Nim; Yoon, Jangyeol; Meacham, Kathleen W.; Xue, Yeguang; McIlvried, Lisa A.; Copits, Bryan A.; Samineni, Vijay K.; Crawford, Kaitlyn E.; Kim, Do Hoon; Srivastava, Paulome; Kim, Bong Hoon; Min, Seunghwan; Shiuan, Young; Yun, Yeojeong; Payne, Maria A.; Zhang, Jianpeng; Jang, Hokyung; Li, Yuhang; Lai, H. Henry; Huang, Yonggang; Park, Sung Il; Gereau, Robert W.; Rogers, John A.

In: Nature, Vol. 565, No. 7739, 17.01.2019, p. 361-365.

Research output: Contribution to journalLetter

TY - JOUR

T1 - A wireless closed-loop system for optogenetic peripheral neuromodulation

AU - Mickle, Aaron D.

AU - Won, Sang Min

AU - Noh, Kyung Nim

AU - Yoon, Jangyeol

AU - Meacham, Kathleen W.

AU - Xue, Yeguang

AU - McIlvried, Lisa A.

AU - Copits, Bryan A.

AU - Samineni, Vijay K.

AU - Crawford, Kaitlyn E.

AU - Kim, Do Hoon

AU - Srivastava, Paulome

AU - Kim, Bong Hoon

AU - Min, Seunghwan

AU - Shiuan, Young

AU - Yun, Yeojeong

AU - Payne, Maria A.

AU - Zhang, Jianpeng

AU - Jang, Hokyung

AU - Li, Yuhang

AU - Lai, H. Henry

AU - Huang, Yonggang

AU - Park, Sung Il

AU - Gereau, Robert W.

AU - Rogers, John A

PY - 2019/1/17

Y1 - 2019/1/17

N2 - The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system 1–5 . 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 inflammation 9–11 . 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.

AB - The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system 1–5 . 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 inflammation 9–11 . 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.

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Mickle AD, Won SM, Noh KN, Yoon J, Meacham KW, Xue Y et al. A wireless closed-loop system for optogenetic peripheral neuromodulation. Nature. 2019 Jan 17;565(7739):361-365. https://doi.org/10.1038/s41586-018-0823-6