Graphene Biointerface for Cardiac Arrhythmia Diagnosis and Treatment

Abstract

Heart rhythm disorders, known as arrhythmias, cause signi cant morbidity and are one of the leading causes of mortality. Cardiac arrhythmias are primarily treated by implantable devices, such as pacemakers and de brillators, or by ablation therapy guided by electroanatomical mapping.Pharmacological treatments are mostly ineffective. Both implantable and ablation therapies require sophisticated biointerfaces for electrophysiological measurements of electrograms and delivery of therapeutic stimulation or ablation energy. In this work, we report for the rst time on graphene biointerface for in vivo cardiac electrophysiology. Leveraging sub-micrometer thick tissue-conformable graphene arrays, we demonstrate sensing and stimulation of the open mammalian heart both in vitro and in vivo. Furthermore, we demonstrate graphene pacemaker treatment of a pharmacologically-induced arrhythmia, AV block. The arrays show effective electrochemical properties, namely interface impedance down to 40 Ohm×cm 2 , charge storage capacity up to 63.7 mC/cm 2 , and charge injection capacity up to 704 µC/cm 2 . Transparency of the graphene structures allows for simultaneous optical mapping of cardiac action potentials and calcium transients while performing electrical measurements and stimulation. Our report presents evidence of the signi cant potential of graphene biointerfaces for the future clinical device-and catheter-based cardiac arrhythmias therapies.

2D Materials in Flexible Electronics: Recent Advances and Future Prospectives

“…Lin et al reported a sub-micrometer-thick graphene array for cardiac arrhythmia diagnosis, supporting sensing and stimulation of the mammalian heart in vitro and in vivo (Figure 26b). 41 The graphene arrays exhibit the ultralow interface impedance of 40 Ωcm 2 (at 1 kHz) with a charge storage capacity of up to 63.7 mC cm −2 . Besides, the transparency of the graphene array enables simultaneous optical mapping of cardiac action potentials, calcium transients, and optogenetic stimulation.…”

“…(b) Schematic illustration of the graphene array for recordings of cardiac electrophysiology and the treatment of cardiac arrhythmia. Adapted with permission from ref . Copyright 2023 Wiley-VCH.…”

“…Implantable devices with tissue-conformable bio-interfaces play an important role in the electrophysiological measurements of ECG. Lin et al reported a sub-micrometer-thick graphene array for cardiac arrhythmia diagnosis, supporting sensing and stimulation of the mammalian heart in vitro and in vivo (Figure b) . The graphene arrays exhibit the ultralow interface impedance of 40 Ωcm 2 (at 1 kHz) with a charge storage capacity of up to 63.7 mC cm –2 .…”

“…Various 2D materials, such as graphene, transition-metal dichalcogenides (TMDs), transition-metal oxides (TMOs), black phosphorous (BP), hexagonal boron nitride (h-BN), MXenes, and 2D perovskites, have been extensively studied and explored for various applications . Graphene has been widely used as an electrode material in flexible optoelectronics and wearable sensors due to its excellent mechanical flexibility, thermal conductivity, optical transparency, electrical transport, and surface sensitivity to chemical molecules. ,− However, its inherent zero-band gap limitation restricts its use as an electrode material in various applications. On the other hand, TMDs exhibit a semiconducting nature with versatile optical and electrical functions suitable for diverse high-performance applications such as flexible image sensors, logic circuits, and PN junctions. ,,,, Moreover, their good stability and compatibility in bio fluids and biological tissues make them promising for various neuromorphic applications. , …”

“…The CVD process has been successful in producing high-quality 2D materials over a large area with excellent thickness uniformity, leading to enormous flexible device applications such as optoelectronic devices, physical/chemical sensors, and bioelectronics devices with wireless connectivity (bottom panel of Figure ). ,,,,,− ,, However, the CVD approach suffers from low production yield and expensive processing, making a more efficient method necessary for the mass production of device-grade material. Solution-based exfoliation approaches offer the promise of a simple and cost-effective way to produce high-quality 2D materials, and ink technology is also developing at a fast pace parallel to CVD.…”