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A microfluidic trap array for longitudinal monitoring and multi-modal phenotypic analysis of individual stem cell aggregates

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Abstract

Three-dimensional pluripotent stem cell (PSC) cultures have the ability to undergo differentiation, self-organization, and morphogenesis to yield complex, in vitro tissue models that recapitulate key elements of native tissues. These tissue models offer a system for studying mechanisms of tissue development, investigating disease mechanisms, and performing drug screening. It remains challenging, however, to standardize PSC aggregate differentiation and morphogenesis methods due to heterogeneity stemming from biological and environmental sources. It is also difficult to monitor and assess large numbers of individual samples longitudinally throughout culture using typical batch-based culture methods. To address these challenges, we have developed a microfluidic platform for culture, longitudinal monitoring, and phenotypic analysis of individual stem cell aggregates. This platform uses a hydrodynamic loading principle to capture pre-formed stem cell aggregates in independent traps. We demonstrated that multi-day culture of aggregates in this platform reduces heterogeneity in phenotypic parameters such as size and morphology. Additionally, we showed that culture and analysis steps can be performed sequentially in the same platform, enabling correlation of multiple modes of analysis for individual samples. We anticipate this platform being applied to improve abilities for phenotypic analysis of PSC aggregate tissues and to facilitate research in standardizing culture systems in order to dually increase the yield and reduce the heterogeneity of PSC-derived tissues.

Graphical abstract: A microfluidic trap array for longitudinal monitoring and multi-modal phenotypic analysis of individual stem cell aggregates

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Publication details

The article was received on 21 Jul 2017, accepted on 18 Sep 2017 and first published on 19 Sep 2017


Article type: Paper
DOI: 10.1039/C7LC00763A
Citation: Lab Chip, 2017, Advance Article
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    A microfluidic trap array for longitudinal monitoring and multi-modal phenotypic analysis of individual stem cell aggregates

    E. L. Jackson-Holmes, T. C. McDevitt and H. Lu, Lab Chip, 2017, Advance Article , DOI: 10.1039/C7LC00763A

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