Soft Nanomembrane Sensors and Flexible Hybrid Bioelectronics for Wireless Quantification of Blepharospasm

Blepharospasm (BL) is characterized by involuntary closures of the eyelids due to spasms of the orbicularis oculi muscle. The gold standard for clinical evaluation of BL involves visual inspection for manual rating scales. This approach is highly subjective and error prone. Unfortunately, there are currently no simple quantitative systems for accurate and objective diagnostics of BL. Here, we introduce a soft, flexible hybrid bioelectronic system that offers highly conformal, gentle lamination on the skin, while enabling wireless, quantitative detection of electrophysiological signals. Computational and experimental studies of soft materials and flexible mechanics provide a set of key fundamental design factors for a low-profile bioelectronic system. The nanomembrane soft electrodes, mounted around the eyes, are capable of accurately measuring clinical symptoms, including the frequency of blinking, the duration of eye closures during spasms, as well as combinations of blinking and spasms. The use of a deep-learning, convolutional neural network, with the bioelectronics offers objective, real-time classification of key pathological features in BL. The wearable bioelectronics outperform the conventional manual clinical rating, as shown by a pilot study with 13 patients. In vivo demonstration of the bioelectronics with these patients indicates the device as an easy-to-use solution for objective quantification of BL.

[1]  Dong Sup Lee,et al.  Soft, conformal bioelectronics for a wireless human-wheelchair interface. , 2017, Biosensors & bioelectronics.

[2]  Shinjae Kwon,et al.  Skin-conformal, soft material-enabled bioelectronic system with minimized motion artifacts for reliable health and performance monitoring of athletes. , 2020, Biosensors & bioelectronics.

[3]  W. Yeo,et al.  Soft Material‐Enabled, Active Wireless, Thin‐Film Bioelectronics for Quantitative Diagnostics of Cervical Dystonia , 2019, Advanced materials technologies.

[4]  K. Wohlfarth,et al.  Low-Dose Treatment of Cervical Dystonia, Blepharospasm and Facial Hemispasm with Albumin-Diluted Botulinum Toxin Type A under EMG Guidance , 2000, European Neurology.

[5]  Woon-Hong Yeo,et al.  All‐in‐One, Wireless, Stretchable Hybrid Electronics for Smart, Connected, and Ambulatory Physiological Monitoring , 2019, Advanced science.

[6]  Trevor Darrell,et al.  Fully Convolutional Networks for Semantic Segmentation , 2017, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[7]  Dumitru Erhan,et al.  Going deeper with convolutions , 2014, 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[8]  E. Buckley,et al.  Botulinum toxin for blepharospasm: single-fiber EMG studies , 1986, Neurology.

[9]  Todd P. Coleman,et al.  Scalable Manufacturing of Solderable and Stretchable Physiologic Sensing Systems , 2017, Advanced materials.

[10]  E D Louis,et al.  Reliability between two observers using a protocol for diagnosing essential tremor , 1998, Movement disorders : official journal of the Movement Disorder Society.

[11]  Woosik Lee,et al.  Fractal design concepts for stretchable electronics , 2014, Nature Communications.

[12]  C. Marsden,et al.  Pathophysiology of blepharospasm and oromandibular dystonia. , 1985, Brain : a journal of neurology.

[13]  Jae‐Woong Jeong,et al.  Advanced Soft Materials, Sensor Integrations, and Applications of Wearable Flexible Hybrid Electronics in Healthcare, Energy, and Environment , 2019, Advanced materials.

[14]  G. Defazio,et al.  Frequency of apraxia of eyelid opening in the general population and in patients with extrapyramidal disorders , 2002, Neurological Sciences.

[15]  James J. S. Norton,et al.  Materials and Optimized Designs for Human‐Machine Interfaces Via Epidermal Electronics , 2013, Advanced materials.

[16]  Dong Sup Lee,et al.  Wireless, intraoral hybrid electronics for real-time quantification of sodium intake toward hypertension management , 2018, Proceedings of the National Academy of Sciences.

[17]  Mark Hallett,et al.  Development and validation of a clinical scale for rating the severity of Blepharospasm , 2015, Movement disorders : official journal of the Movement Disorder Society.

[18]  Xingyu Wang,et al.  Frequency Recognition in SSVEP-Based BCI using Multiset Canonical Correlation Analysis , 2013, Int. J. Neural Syst..

[19]  M. Hallett Blepharospasm , 2002, Neurology.

[20]  Woon-Hong Yeo,et al.  Soft Material-Enabled, Flexible Hybrid Electronics for Medicine, Healthcare, and Human-Machine Interfaces , 2018, Materials.

[21]  Yonggang Huang,et al.  Multifunctional Epidermal Electronics Printed Directly Onto the Skin , 2013, Advanced materials.

[22]  M. Hallett,et al.  Blepharospasm 40 years later , 2017, Movement disorders : official journal of the Movement Disorder Society.

[23]  K. Digre,et al.  The evaluation of light sensitivity in benign essential blepharospasm. , 2006, American journal of ophthalmology.

[24]  Moongee Cho,et al.  Fabric-based stretchable electronics with mechanically optimized designs and prestrained composite substrates , 2014 .

[25]  J Jankovic,et al.  Botulinum A toxin for cranial‐cervical dystonia , 1987, Neurology.

[26]  Stretch reflex blepharospasm , 1985, Neurology.

[27]  A. Bentivoglio,et al.  Analysis of blink rate in patients with blepharospasm , 2006, Movement disorders : official journal of the Movement Disorder Society.