Grant: Research Tools and Instruments

We request a microelectrode array (MEA) system to develop and optimize an integrated and predictive cardiac screening assay using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), which can be validated and used in a commercially viable assay. This MEA system will be the first apparatus available at UBC to determine cardiac electrical and mechanical function using human cardiac cells in-vitro.*Need, urgency and suitability of equipment: The MEA technology is central to our research (NSERC DG: Biophysical elucidation of ion channel complex function (2016-21) and CHRP: Novel 3D bioprinted human cardiac tissue models for drug mechanism and efficacy testing (2018-21)). Use of the MEA will accelerate outcomes and improve impact from these NSERC programs as it provides a highly sensitive, data-rich method to study the electrical activity of 3D bioprinted cardiac tissue with spatiotemporal resolution in a high throughput manner. This technology records extracellular field potentials from cell monolayers or clusters, and generates field potential duration as an in vitro surrogate for the QT interval of the electrocardiogram. Currently, cardiac electrical function testing methods (i.e., cellular and animal models) do not accurately predict normal human cardiac physiology or allow sufficient throughput needed for drug discovery. Thus, there is a clear need to develop new and robust human experimental models that predict drug effects and facilitate high-throughput screening.*Merit of the research program and excellence of the research team: The unlimited source of hiPSC-CM provides new possibilities to create in vitro models of healthy human cardiac tissue that can be used in drug mechanism of action (MOA) and efficacy testing. The Food and Drug Administration (FDA) aims to improve current regulatory guidance by introducing predictive technologies, including commercially available hiPSC-CM, into assessment of drug MOA. The PI is a world leader in cardiac ion channel biophysics and this program will combine excellence in cardiac electrophysiology and cell biology with the development of novel bioprinted cell scaffolds and microfluidics to create patentable hiPSC-CM models in collaboration with Aspect Biosystems, a successful BC-based 3D bioprinting technology company. This research program will be supported by the well-characterized MEA system as an essential tool to validate novel cell models for application to high throughput screening. Integration of hiPSC-CM based 3D tissue with MEA will enable relevant, accurate, real-time, and flexible measurement of electrophysiological activity, thereby providing a versatile biological tool to assess drug MOA.*Highly qualified personnel (HQP): The team's equitable HQP training plan will train 1 MSc, 2 PhD, 3 undergrad, and 1 PDF. HQP will exemplify a diverse and representative combination of identities and various racial and ethnic backgrounds.*