Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells. Issue 22 (28th October 2022)

• Record Type: Journal Article
• Authors: Goswami, Ishan; de Klerk, Eleonora; Carnese, Phichitpol; Hebrok, Matthias; Healy, Kevin E.
• Is Part Of: Lab on a chip. Volume 22:Issue 22(2022)
• Page Start: 4430
• Page End: 4442
• Publication Date: 2022-10-28
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/d2lc00468b
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : Multiplexed microphysiological system as a high-content, higher throughput device for stem cell-derived β cell culture and drug screening. Abstract : Stem cell-derived β cells offer an alternative to primary islets for biomedical discoveries as well as a potential surrogate for islet transplantation. The expense and challenge of obtaining and maintaining functional stem cell-derived β cells calls for a need to develop better high-content and high-throughput culture systems. Microphysiological systems (MPS) are promising high-content in vitro platforms, but scaling for high-throughput screening and discoveries remain a challenge. Traditionally, simultaneous multiplexing of liquid handling and cell loading poses a challenge in the design of high-throughput MPS. Furthermore, although MPS for islet β culture/testing have been developed, studies on multi-day culture of stem-cell derived β cells in MPS have been limited. We present a scalable, multiplexed islet β MPS device that incorporates microfluidic gradient generators to parallelize fluid handling for culture and test conditions. We demonstrated the viability and functionality of the stem cell-derived enriched β clusters (eBCs) for a week, as assessed by the ∼2 fold insulin release by the clusters to glucose challenge. To show the scalable multiplexing for drug testing, we demonstrated the loss of stimulation index after long-term exposure to logarithmic concentration range of glybenclamide. The MPS cultured eBCs also confirmed a glycolytic bottleneck as inferred by insulin secretion responses to metabolites methyl succinate and glyceric acid. Thus, we present an innovative culture platform for eBCs with a balance of high-content and high-throughput characteristics.