Abstract
Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes in heart beat kinetics. In traditional 2D cultures, beating kinetics can be measured by electrode arrays, but in some 3D constructs, quantifying beating kinetics can be more challenging. For example, real time measurements of calcium flux or contractile forces are possible, yet rather complex. In this communication article, we demonstrate a simple sensing system based on software code that optically analyzes video capture files of beating cardiac organoids, translates these files in representations of moving pixels, and quantifies pixel movement activity over time to generate beat kinetic plots. We demonstrate this system using bioengineered cardiac organoids under baseline and drug conditions. This technology offers a non-invasive, low-cost, and incredibly simple method for tracking and quantifying beating behavior in cardiac organoids and organ-on-a-chip systems for drug and toxicology screening.
Highlights
Bioengineered organoid models and organ-on-a-chip, known as microphysiological systems, have rapidly advanced in recent years for applications such as disease modeling and pharmacology/toxicology screening [1,2]
We demonstrate a simple cardiac beat kinetic sensing system based on software code that analyzes imaging of beating cardiac organoids, translates these files into representations of moving pixels, and quantifies pixel movement activity over time to generate beat kinetics plots
We first developed cardiac organoids by inducing cell–cell aggregation in round bottom non-adherent 96-well plates. These spherical cardiac organoids (Figure 1A) were formed using induced pluripotent stem cell-derived cardiomyocytes that were cultured for four days prior to use in the subsequent studies
Summary
Bioengineered organoid models and organ-on-a-chip, known as microphysiological systems, have rapidly advanced in recent years for applications such as disease modeling and pharmacology/toxicology screening [1,2]. Further development of bioengineered organ systems [3,4], combined with advanced microfluidic hardware, has resulted in organ-on-a-chip platforms that produce physiologically relevant responses to drugs and toxins These platforms take a variety of forms, from single cell analysis devices to complex integrated organoid systems that can be employed for drug testing, toxicology [5], high throughput screens, and disease modeling [6,7]. While a variety of tissues have been represented in these organoid and organ-on-a-chip systems, liver and cardiac platforms dominate the current research and development landscape This is due to the fact that liver and cardiac toxicities account for the majority of drug candidate failures in human trials [8,9,10]. A lack of models that accurately predict human drug toxicity drives up the cost of drug development [11]
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