Graduate Seminar Series: Clinical Stream
Graduate Seminar Series for the Institute of Biomedical Engineering (BME). This day is for clinical stream presenters.
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Presentation Title: Design of an Islet-on-a-Chip Device to Dynamically Measure Insulin Secretion from Individual Islets
Abstract: Glucose-stimulated insulin secretion (GSIS) from pancreatic islets shows a biphasic pattern. Investigation of temporal dynamics and patterns of GSIS could give insights into mechanisms underlying β-cell function and dysfunction. Here, we present a novel microfluidic device to detect insulin secretion from individual islets on-chip through miniaturizing a fluorescence anisotropy immunoassay (FAIA). Insulin is co-secreted with c-peptide within ~5-10 min of glucose stimulation. Here we designed a c-peptide sensor with a fluorophore tagged to a synthetic c-peptide fragment and optimized assay parameters to maximize the sensitivity of the FAIA. Subsequently, a continuous-flow method was applied to monitor reaction kinetics to determine the equilibrium time of the assay. Using the maximum time required to reach equilibrium, we designed an islet-on-a-chip that captures the islet effluent and sufficiently mixes it with the reagents within the ~100 s residence time. This assay is downstream of the islet and leaves an ideal optical window to simultaneously image islet responses (e.g., Ca2+ activity). Ultimately, this device was used to measure c-peptide secretion from 4 individual mouse pancreatic islets simultaneously. The secretion detected on-chip shows the characteristic biphasic pattern and was further validated with pharmacological activators (ex. tolbutamide) for insulin secretion. In the future, the islet-on-a-chip could be coupled with other sensors, such as Ca2+ and oxygen consumption rate sensors to further probe β-cell metabolism.
Supervisor Name: Dr. Jonthan Rocheleau
Year of Study: 4
Program of Study: PhD
Zoom link: https://us02web.zoom.us/j/89610372821?pwd=azd4SCtYVWtreVovaGNPV1c2NGY2Zz09
Meeting ID: 896 1037 2821
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