232 IEEE JOURNAL OF SOLID-STATE CIRCUITS, VOL. 49, NO. 1, JANUARY 2014 A Fully Integrated 8-Channel Closed-Loop Neural-Prosthetic CMOS SoC for Real-Time Epileptic Seizure Control Wei-Ming Chen, Member, IEEE, Herming Chiueh, Member, IEEE, Tsan-Jieh Chen, Member, IEEE, Chia-Lun Ho, Chi Jeng, Ming-Dou Ker, Fellow, IEEE, Chun-Yu Lin, Member, IEEE, Ya-Chun Huang, Chia-Wei Chou, Tsun-Yuan Fan, Ming-SengCheng, Yue-Loong Hsin, Sheng-Fu Liang, Member, IEEE, Yu-Lin Wang, Fu-Zen Shaw, Yu-Hsing Huang, Chia-Hsiang Yang, Member, IEEE, and Chung-Yu Wu, Fellow, IEEE Abstract—An 8-channel closed-loop neural-prosthetic SoC is presented for real-time intracranial EEG (iEEG) acquisition, seizure detection, and electrical stimulation in order to suppress epileptic seizures. The SoC is composed of eight energy-efficient analog front-end amplifiers (AFEAs), a 10-b delta-modulated SAR ADC (DMSAR ADC), a configurable bio-signal processor (BSP), and an adaptive high-voltage-tolerant stimulator. A wire- Manuscript received April 22, 2013; revised September 11, 2013; accepted September 12, 2013. Date of publication October 18, 2013; date of current version December 20, 2013. This paper was approved by Guest Editor Michiel Pertijs. This work was supported in part by the National Science Council (NSC), R.O.C., under Project 102-2220-E-009-001 and by the “Aim for the Top University Plan” of the National Chiao Tung University and Ministry of Education, Taiwan, R.O.C. W.-M. Chen, M.-D. Ker, C.-H. Yang, and C.-Y. Wu are with the Department of Electronics Engineering and the Institute of Electronics, National Chiao Tung University, Hsinchu 300, Taiwan, and also with the Biomedical Electronics Translational Research Center, National Chiao Tung University, Hsinchu 300, Taiwan (e-mail: peterwu@mail.nctu.edu.tw; mdker@ieee.org). H. Chiueh and T.-J. Chen are with the Department of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 300, Taiwan, and also with the Biomedical Electronics Translational Research Center, National Chiao Tung University, Hsinchu 300, Taiwan, and also with the Biomedical Elec- tronics Translational Research Center, National Chiao Tung University, Hsinchu 300, Taiwan (e-mail: chiueh@soclab.org). C.-L. Ho and C. Jeng are with the Department of Electrical and Computer Engineering, National Chiao Tung University, Hsinchu 300, Taiwan. C.-Y. Lin is with the Department of Applied Electronics Technology, Na- tional Taiwan Normal University, Taipei 106, Taiwan, and also with the Biomed- ical Electronics Translational Research Center, National Chiao Tung University, Hsinchu 300, Taiwan (e-mail: cy.lin@ieee.org). Y.-C. Huang, C.-W. Chou, T.-Y. Fan, and M.-S. Cheng are with the Depart- ment of Electronics Engineering and the Institute of Electronics, National Chiao Tung University, Hsinchu 300, Taiwan. Y.-L. Hsin is with Chung Shan Medical University Hospital, Taichung 402, Taiwan, and also with the Biomedical Electronics Translational Research Center, National Chiao Tung University, Hsinchu 300, Taiwan (e-mail: hsin.yloong@msa.hinet.net). S.-F. Liang is with the Department of Computer Science and Information Engineering and Institute of Medical Informatics, National Cheng Kung Uni- versity, Tainan 701, Taiwan, and also with the Biomedical Electronics Transla- tional Research Center, National Chiao Tung University, Hsinchu 300, Taiwan (e-mail: sfliang@mail.ncku.edu.tw). Y.-L. Wang is with the Biomedical Electronics Translational Research Center, National Chiao Tung University, Hsinchu 300, Taiwan (e-mail: daphne.yl.wang@gmail.com). F.-Z. Shaw is with the Department of Psychology and Institute of Geron- tology National Cheng Kung University, Tainan 701, Taiwan, and also with the Biomedical Electronics Translational Research Center, National Chiao Tung University, Hsinchu 300, Taiwan (e-mail: fzshaw@mail.ncku.edu.tw). Y.-H. Huang is with the Department of Psychology, National Cheng Kung University, Tainan 701, Taiwan (e-mail: lisa101173@yahoo.com.tw). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/JSSC.2013.2284346 less power-and-data transmission system is also embedded. By leveraging T-connected pseudo-resistors, the high-pass (low-pass) cutoff frequency of the AFEAs can be adjusted from 0.1 to 10 Hz (0.8 to 7 kHz). The noise-efficiency factor (NEF) of the AFEA is 1.77, and the DMSAR ADC achieves an ENOB of 9.57 bits. The BSP extracts the epileptic features from time-domain entropy and frequency spectrum for seizure detection. A constant 30- A stimulus current is delivered by closed-loop control. The acquired signals are transmitted with on-off keying (OOK) modulation at 4 Mbps over the MedRadio band for monitoring. A multi-LDO topology is adopted to mitigate the interferences across different power domains. The proposed SoC is fabricated in 0.18- m CMOS and occupies 13.47 mm . Verified on Long Evans rats, the proposed SoC dissipates 2.8 mW and achieves high detection accuracy 92% within 0.8 s. Index Terms—Closed-loop control, epilepsy, neuron modula- tion, neural prosthesis, system-on-Chip (SoC), wireless power transmission. I. INTRODUCTION E PILEPSY is a one of the common neurological disorders. Around 1% of the world population is affected. Epileptic seizures are caused by sudden excessive electrical discharges in a group of cortical neurons. It is characterized by recurrent seizures, which may vary from a brief lapse of attention and unnatural posturing to severe and prolonged convulsions. The unexpected seizures impact the quality of life for patients and their families. Currently, numerous anti-epileptic drugs are available for seizure control, but approximately 30% of epileptic patients remain either drug-resistant or develop limiting adverse effects [1]. Conventional resection surgery might be beneficial to pa- tients who respond poorly to medical treatment. However, only some patients are suitable for resection surgery. The possibility of obtaining undesired neurologic deficits is always a concern. Electrical neuromodulation to control drug-resistant epilepsy has been attempted due to several potential advantages over conventional surgery, such as its reversible characteristic [2], [3]. In addition to peripheral vagus nerve stimulation, prelimi- nary results show that electrical stimulation on the central ner- vous system is a promising solution, which is still under de- velopment. It delivers electrical impulses to a selected brain region in response to detected epileptic or pre-epileptic activi- ties [4]. Preferably, a neural-prosthetic device realizing a recip- 0018-9200 © 2013 IEEE