Graphene Biointerface for Cardiac Arrhythmia Diagnosis and Treatment

Abstract

The human heart is an efficient electromechanical pump which provides oxygen and nutrients to all human organs. Each heartbeat is ignited and synchronized by an electrical action potential initiating and rapidly propagating through the heart's electrical system. Cardiovascular diseases, a leading cause of death in humans, disrupt this synchronous excitation. Heart rhythm disorders, known as arrhythmias, are particularly deadly. Cardiac arrhythmias are primarily treated by implantable pacemakers and defibrillators because pharmacological treatments are mostly ineffective. In this work, we report on graphene-only cardiac pacemakers as advanced cardiac biointerfaces. Leveraging sub-micrometer thick tissue-conformable graphene arrays, we are able to sense from and stimulate the heart, altering its functions, suggesting that the devices can be used for high-density functional interfacing with the heart. The arrays show effective electrochemical properties, namely interface impedance down to 40 Ohm x cm2, charge storage capacity up to 63.7 mC/cm2, and charge injection capacity up to 704 uC/cm2. Transparency of the structures allows for simultaneous optical mapping of cardiac action potentials and calcium transients while performing electrical measurements. Upon validating the graphene-based cardiac pacing in ex vivo mouse hearts, we performed in vivo cardiac pacing in a rat model with clinically induced arrhythmia. The condition was successfully diagnosed and treated using graphene biointerfaces.

Graphene-based cardiac sensors and actuators

“…American Chemical Society; (D) , ( Kireev et al, 2021 ), Springer Nature Ltd.; (E) , ( Kireev et al, 2022b ), Springer Nature Ltd. Panels reproduced from open-access publications: (A,B) , ( Lou et al, 2016 ), MDPI; (F) , ( Lin et al, 2022 ), Wiley.…”

“…The increase in the technical complexity of GETs may allow their use for recording of electrical signals directly from the surface of the heart ( Figure 5F ). To achieve this goal, previously described GETs were modified to include additional components such as two transparent and flexible silicon elastomer support layers with an electrode opening of 1, 1.5, 2, or 3 mm, and a flexible adhesive ultrathin (10-µm) conductive gold tape to connect GET with the data acquisition and stimulation hardware ( Lin et al, 2022 ). Three-layer GETs with smaller electrode openings provided the most reproducible qualities, including the lowest sheet resistance and lower interface impedance.…”

“…To improve the spatial resolution of the cardiac electrical mapping, a novel array of micropatterned GETs (mGETs) was fabricated ( Lin et al, 2022 ) where the layer of graphene was patterned into multiple feedlines and individually addressed; an extended PMMA substrate was providing the support at the bottom; and the top passivated PMMA layer only had openings at the contact and electrode opening sites. The architecture of this PMMA-graphene-PMMA device is similar to classic MEAs, while offering a thickness below 500 nm.…”

“…(C,D) , demonstrate the ability to use the graphene electrodes for sensing (C) electrical activity of the heart with a disorder (AV Block) and ability to treat the disorder by applying electrical stimulation pulses (D) . Panels reproduced from open-access publication Lin et al (2022) , Wiley.…”

“… Lin et al (2022) used GET-electrodes to perform cardiac actuating by connecting them to a cardiac stimulator. Cardiac pacing was performed using pulses of 0.5–2 ms in duration, resulting in a faster heart rate.…”