Multiplexed quantitative measurements of field potential and contractility on biomimetically-matured hPSC-CMs

PROJECT SUMMARY The development of new drugs is a costly and time consuming process$billion overyearswith a very low success rate where onlyout ofcandidates will ever reaches the marketOne of the leading causes for this issue is the cardiotoxicity of drug candidateswherein a drug has an off target effect of causing cardiac arrhythmiasAs a resultsignificant effort and resources have been allocated to create more predictive preclinical and in vitro drug screening platformsHuman derived induced pluripotent cardiac myocyte stem cellshPSC CMsare a promising tool to address this problembut their relative lack of phenotypic maturity remains a barrier to their wide adoptionSome platforms focus on mimicking the structurale gbiomimetic culturewaremechanicale gcell and tissue stretching devicesand electrochemicale gmicroelectrode array platformscues of the extracellular matrix of the tissue to improve hPSC CM maturityWhile these cues are vital to the tissue developmentthey are oftentimes incompatible with the high throughput assays that are required by drug developersFurthermeasuring maturity within an assay is a challengeContractility is considered to be a highlyaccurate method of measuring maturitystate of differentiationand general health of cardiomyocytesThe currently available measurement tools cardiomyocytesCMscontractility can be generally grouped as either impedance based or microscopy basedsuch as traction force microscopyTFMImpedance based measurements are often fast and accurate but lacking in terms of capturing quantitative informationas impedance measures only cell shape changes and uses that as proxy of the cell contractionIn contrastTFM techniques are capable of quantifying CM contractionbut it is laborious and incompatible with high throughput platformsIndeeda critical need of the research community is a multiplexed platform that measures contractility in a high throughput and quantitative fashion in an environment that applies extracellular cues to drive the development and maturity of CMsNanoSurface Biomedical s mission is to develop a first of its kind microelectrode array device that provides a biomimetic culture environment and is multiplexed with quantitative contractility measurementWe term this device theMP ForceMEAThe MP ForceMEA will use an innovative strain gauge sensor with an MEA platform and will represent a novel instrument capable of simultaneous detection of electrophysiology and contractility in a highly parallelhigh throughputand scalable mannerPhaseactivities will result in the development of a single well novel platform compatible with standard end point assaysand this work will then serve as the basis for progression into Phasewhere the device will be scaled up to high throughput assay formatsThe resulting work will greatly improve the costefficiencyand safety of drug development and speed to market new lifesaving drugs PROJECT NARRATIVE We will develop and build a multiplexed biomimetic platform that is capable of quantitatively measuring the contractility and the electrophysiology of cell and tissue culturesThe device will integrate biomimetic cues that can drive more physiological cell phenotypesand can enhance the predictive power of cell based assaysThis novel platform will save time and resourcesimproving the translation of therapeutic technologies from the bench to the clinic