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Measurement of insulin production in a single pancreatic islet using a microfluidic chip


Pancreatic islets are clusters of cells that produce two hormones (insulin and glucacon) that regulate blood sugar. Researchers at our laboratory [collaboration] have developed a microfluidic chip made of thermoplastic with an automated control of fluxes for the stimulation and secretion collection of pancreatic islet. This chip, which allows them to measure and monitor insulin secretion from a single islet, can also be adapted to study a wide variety of biological tissues and secretomes.

Published on 8 March 2022
Islets of Langerhans or pancreatic islets are clusters of cells specialized in the production of insulin and glucacon, two hormones regulating blood glucose levels. Type 1 diabetes is a chronic metabolic disease related to an active autoimmune destruction of insulin-secreting pancreatic cells, resulting in total insulinopenia responsible for chronic hyperglycemia. The transplantation of pancreatic islets from a deceased donor is now standard of care reimbursed by social security since 2021. However, these islets have extremely variable insulin production capacities. It would be very useful to be able to measure the insulin production of each islet in order to choose the most efficient ones before their transplantation.

Researchers at our laboratory, in collaboration with Leti's Technologies for Biology and Health Department at CEA-Grenoble, have developed a microfluidic chip (Figure) that traps a single islet of Langerhans at a dedicated site on the chip. Once trapped, the composition of the medium can be changed at will using a set of highly elastic valves incorporated into the chip. Thus, by switching from a low concentration of glucose to a high concentration, the production of insulin by the entrapped islet can be stimulated. Thanks to a second network of hyper-elastic valves, the secretions from the islet can be collected and the quantity of insulin produced measured. At this stage of the project, this measurement has been performed outside the chip, but developments are underway to be able to dose insulin directly on the chip. Beyond the measurement of insulin from a tissue explant (here a pancreatic islet), the organ-on-chip that has been developed demonstrates the ability that researchers now have to measure secretions from a single spheroid, organoid, tumoroid, automatically trapped in a chip, thus opening up a wide field of possible applications.

The next step will be to isolate, thanks to the chip, about ten islets producing very little insulin and about ten others producing a lot of insulin, in order to identify by multi-omics analysis the still unknown molecular mechanisms that are at the origin of this physiological difference. The researchers hope to be able to identify a biomarker, which will then allow us to sort out very quickly (5,000 islets/second thanks to a large particle FACS) the best performing islets before their transplantation into the patient.

In cell culture, spheroids are three-dimensional cellular aggregates.
An organoid is a three-dimensional multicellular structure that mimics the micro-anatomy of an organ and recapitulate at least one physiological function of the organ; it is therefore an in vitro model of the organ (or a mini-organ).
When the organoids are cancer cells, they are called tumoral organoids or tumoroids.


Architecture of a microfluidic chip to measure glucose-stimulated insulin secretion (GSIS) from a single pancreatic islet. Scheme showing an overview of the GSIS assay protocol on a serpentine chip using a pneumatic valve array.

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