I-Corps: Human toxicity assay using synthetic embryo-like structures

Award ID: 2112458

The broader impact/commercial potential of this I-Corps project is the development of a controllable and scalable microfluidic technology in which synthetic human embryo-like structures may be derived from human stem cells for quantitative toxicity testing. The development of the proposed technology addresses the need for a cost-effective and highly predictive assay platform to determine embryo toxicology effects. The current assay is conducted using animal models such as rats or mice. These animal tests are costly and have ethical issues and limited predictive powers. The proposed technology offers human-relevant, organism-level toxicity testing. The method allows quantitative measurements and perturbations and is compatible with live imaging and high-throughput screens. The proposed technology may use disease- and patient-specific stem cells for disease modeling, and also may allow screening using stem cells derived from different age and racial/ethnic groups, thus modeling responses to pharmacological and chemical compounds of diverse populations. This I-Corps project is based on the development of a controllable and scalable microfluidic technology in which synthetic embryo-like structures derived from human stem cells may be utilized for embryo toxicity testing. The proposed microfluidic device allows precise positioning of human stem cell colonies in prescribed locations within the microfluidic device. In addition, the proposed device allows precise temporal delivery of soluble factors to drive these human stem cell colonies to develop and organize into multicellular structures whose molecular and cellular features bear significant similarities to early post-implantation human embryos. The proposed technology has been shown to be controllable, reproducible, scalable, and compatible with live imaging and immunocytochemistry, which may allow easy adoption into the existing high-throughput toxicity screening pipelines. The technology is designed to provide high-content phenotypic and morphological profiling of the effects of pharmacological compounds on embryo development based on colorimetric/fluorescent reagents. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

NSF Program Director: Ruth Shuman