Pancreatic islets, also known as islets of Langerhans, are cell clusters that specialize in the production of insulin and glucagon, two hormones that regulate blood glucose levels. Type 1 diabetes is caused by the autoimmune destruction of pancreatic cells, resulting in chronic hyperglycemia. The transplantation of pancreatic islets from a deceased donor became a standard of care in 2021, reimbursed by the French social security. However, these islets are extremely variable in their insulin production capacities. It would therefore be very useful if we could measure the insulin production of each islet, in order to choose the most efficient ones for transplantation.

Researchers at the Irig and the CEA-Leti have developed a microfluidic chip capable of trapping a single islet in a medium whose composition can be freely modified, using a set of hyper-elastic valves integrated into the chip. This makes it possible to stimulate the production of insulin by the entrapped islet, by increasing the glucose concentration. Thanks to a second network of hyper-elastic valves, the insulin secretions can be collected and quantified.

This last measurement has for now been performed off-chip, but developments are underway that will soon allow the measurement to be performed directly on the chip.

The next step will be to isolate about ten islets producing very little insulin and ten others that produce a lot of insulin, in order to identify by multi-omics analysis the molecular mechanisms behind this physiological difference.

The researchers hope to identify a biomarker that will then allow them to rapidly sort (5,000 islets/second) the best performing islets prior to their transplantation.

These developments are applicable to the secretome of any spheroid (a three-dimensional cell aggregate), whether or not it reproduces the micro-anatomy of an organ (organoid) or a tumor cell (tumoroid).