A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals

Wei Ouyang; Wei Lu; Yamin Zhang; Yiming Liu; Jong Uk Kim; Haixu Shen; Yunyun Wu; Haiwen Luan; Keith Kilner; Stephen P Lee; Yinsheng Lu; Yiyuan Yang; Jin Wang; Yongjoon Yu; Amy J Wegener; Justin A Moreno; Zhaoqian Xie; Yixin Wu; Sang Min Won; Kyeongha Kwon; Changsheng Wu; Wubin Bai; Hexia Guo; Tzu-Li Liu; Hedan Bai; Giuditta Monti; Jason Zhu; Surabhi R Madhvapathy; Jacob Trueb; Maria Stanslaski; Elizabeth M Higbee-Dempsey; Iwona Stepien; Nayereh Ghoreishi-Haack; Chad R Haney; Tae-Il Kim; Yonggang Huang; Roozbeh Ghaffari; Anthony R Banks; Thomas C Jhou; Cameron H Good; John A Rogers

doi:10.1038/s41551-023-01029-x

A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals

Nat Biomed Eng. 2023 Oct;7(10):1252-1269. doi: 10.1038/s41551-023-01029-x. Epub 2023 Apr 27.

Authors

Wei Ouyang^#¹, Wei Lu^#¹, Yamin Zhang^#¹, Yiming Liu², Jong Uk Kim^{1

3}, Haixu Shen⁴, Yunyun Wu¹, Haiwen Luan¹, Keith Kilner⁵, Stephen P Lee^{1

5}, Yinsheng Lu⁴, Yiyuan Yang⁶, Jin Wang⁴, Yongjoon Yu⁵, Amy J Wegener^{7

8}, Justin A Moreno^{7

8

9}, Zhaoqian Xie^{4

6

10}, Yixin Wu⁴, Sang Min Won¹¹, Kyeongha Kwon¹², Changsheng Wu¹, Wubin Bai^{1

4

13}, Hexia Guo⁴, Tzu-Li Liu⁶, Hedan Bai¹, Giuditta Monti¹⁴, Jason Zhu^{15

16}, Surabhi R Madhvapathy⁴, Jacob Trueb¹, Maria Stanslaski⁵, Elizabeth M Higbee-Dempsey¹⁷, Iwona Stepien¹⁷, Nayereh Ghoreishi-Haack¹⁷, Chad R Haney¹⁸, Tae-Il Kim^{3

19}, Yonggang Huang^{1

4

6

10}, Roozbeh Ghaffari^{1

5}, Anthony R Banks^{1

5}, Thomas C Jhou²⁰, Cameron H Good^{21

22

23

24}, John A Rogers^{25

26

27

28

29

30}

Affiliations

¹ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA.
² Department of Electrical and Computer Engineering, Northwestern University, Evanston, IL, USA.
³ School of Chemical Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
⁴ Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
⁵ Neurolux Inc., Northfield, IL, USA.
⁶ Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA.
⁷ US Army Research Laboratory, Aberdeen Proving Ground, MD, USA.
⁸ US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA.
⁹ SURVICE Engineering, Belcamp, MD, USA.
¹⁰ Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL, USA.
¹¹ Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
¹² School of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
¹³ Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁴ Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
¹⁵ Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA.
¹⁶ Department of Chemistry, Northwestern University, Evanston, IL, USA.
¹⁷ Developmental Therapeutics Core, Northwestern University, Evanston, IL, USA.
¹⁸ Center for Advanced Molecular Imaging, Northwestern University, Evanston, IL, USA.
¹⁹ Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon, Republic of Korea.
²⁰ Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA. jhou@musc.edu.
²¹ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA. cameron.good@northwestern.edu.
²² Neurolux Inc., Northfield, IL, USA. cameron.good@northwestern.edu.
²³ US Army Research Laboratory, Aberdeen Proving Ground, MD, USA. cameron.good@northwestern.edu.
²⁴ US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD, USA. cameron.good@northwestern.edu.
²⁵ Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
²⁶ Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
²⁷ Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
²⁸ Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
²⁹ Department of Chemistry, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.
³⁰ Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Evanston, IL, USA. jrogers@northwestern.edu.

^# Contributed equally.

PMID: 37106153
DOI: 10.1038/s41551-023-01029-x

Abstract

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.