Abstract
An islet-on-chip system in the form of a completely transparent microscope slide optically accessible from both sides was developed. It is made from laser-structured borosilicate glass and enables the parallel perifusion of five microchannels, each containing one islet precisely immobilized in a pyramidal well. The islets can be in inserted via separate loading windows above each pyramidal well. This design enables a gentle, fast and targeted insertion of the islets and a reliable retention in the well while at the same time permitting a sufficiently fast exchange of the media. In addition to the measurement of the hormone content in the fractionated efflux, parallel live cell imaging of the islet is possible. By programmable movement of the microscopic stage imaging of five wells can be performed. The current chip design ensures sufficient time resolution to characterize typical parameters of stimulus-secretion coupling. This was demonstrated by measuring the reaction of the islets to stimulation by glucose and potassium depolarization. After the perifusion experiment islets can be removed for further analysis. The live-dead assay of the removed islets confirmed that the process of insertion and removal was not detrimental to islet structure and viability. In conclusion, the present islet-on-chip design permits the practical implementation of parallel perifusion experiments on a single and easy to load glass slide. For each immobilized islet the correlation between secretion, signal transduction and morphology is possible. The slide concept allows the scale-up to even higher degrees of parallelization.
Highlights
Pancreatic islets are functional mini-organs of the endocrine pancreas, containing multiple cell types
The glass chip was fabricated from laser structured halves of 700 μm thick BOROFLOAT substrates, which give a 1,400 μm thick monolithic glass slide with five parallel microchannels (Figure 1a)
The basic idea of the present islet-on-chip design was to fabricate a monolithic parallel glass chip, which is accessible from both sides
Summary
Pancreatic islets (islets of Langerhans) are functional mini-organs of the endocrine pancreas, containing multiple cell types. In addition to triggering signals the beta cell metabolism of glucose and other nutrient stimuli generates signals which amplify the secretory response (Sato and Henquin, 2014; Schulze et al, 2017b). The nature of these signals and the mechanisms by which they increase Ca2+ -triggered insulin secretion are not fully understood (Prentki et al, 2013). In addition to basic research on stimulus secretion coupling, perifusion of pancreatic islets is a useful technique to investigate mechanisms of beta cell damage, to characterize the function of islets prior to transplantation or to study the mechanisms of insulinotropic drugs (Castiello et al, 2015; Ullsten et al, 2015)
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