Multi-Scale and Topology Graphene-based Nanomaterials for Investigation and Modulation of Electrical Activity of Excitable Cells

Investigation and modulation of the electrical activity of neurons and cardiomyocytes is essential to understand the underlying mechanisms and treatment of neurological and cardiac diseases. Furthermore, having two-way interfaces with cells is crucial for brain-machine interfacing and engineering of more effective tissue regenerative scaffolds. Development of various optical and bioelectronics platforms over the decades has enabled probing of excitable cells to monitor and modulate their electrical activity. Ideally, the recording/stimulating platform should enable long-term stable interfaces and multi-site recordings/stimulation with sub-millisecond temporal and sub-cellular spatial resolution. Even though significant progress has been made, the current technologies are still limited on various fronts. Specifically, (i) patch clamp technique is limited by its recording sites, (ii) metal-based microelectrode array (MEA) are incapable to record at a single cell or sub-cellular level, (iii) high rigidity of Si-based probes lead to mechanical mismatch with the tissue thus impeding long-term stable interfaces, (iv) planar field effect transistors (FETs) are limited by the charge storage and injection capacities needed to stimulate cells, (v) voltage/ion sensitive dyes are limited in temporal resolution especially for volume measurements, and (vi) optogenetics is limited by the need of genetic modification of cells.
In this thesis work, the limitations of current techniques were addressed by developing platforms using an extraordinary carbon-based nanomaterial called graphene. Graphene’s physical, chemical and electrical properties were tuned by tailoring its morphology and structure. The high transparency of two-dimensional planar graphene was leveraged to develop transparent MEA platform that enabled simultaneous optical and electrical recordings, thus integrating the high spatial and temporal advantages of both the techniques. The high surface area of out-of-plane grown three-dimensional (3D) graphene was leveraged to develop ultra-microelectrode arrays that enabled recordings at sub-cellular spatial and sub-msec temporal resolutions. The high photo-absorbance and photo-thermal efficiency of nanowire-templated 3D graphene was leveraged to enable non-genetic photo-stimulation of neurons with high precision and sub-cellular spatial resolution. The tools developed in this thesis push the limits of the current technology which will further enhance our understanding of the tissue functioning both in healthy and disease states. Furthermore, it will enable development of better diagnostic and therapeutic platforms for both cardiac and neurological disorders.