Journal
BIOMEDICAL MICRODEVICES
Volume 19, Issue 3, Pages -Publisher
SPRINGER
DOI: 10.1007/s10544-017-0186-z
Keywords
Microfluidic perfusion system; Borosilicate glass; Femtosecond laser-structuring; Islet of Langerhans; Calcium; Insulin secretion; NAD(P)H autofluorescence; Organ-on-a-chip
Funding
- Niedersachsisches Ministerium fur Wissenschaft und Kultur within the collaborative project SynFoBiA - Novel synthesis and formulation methods for poorly soluble drugs and sensitive biopharmaceuticals
- Niedersachsisches Ministerium fur Wissenschaft und Kultur within graduate program mu-Props: Processing of Poorly Soluble Drugs at Small Scale
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Microfluidic perfusion systems (MPS) are well suited to perform multiparametric measurements with small amounts of tissue to function as an Organ on Chip device (OOC). Such microphysiolgical characterization is particularly valuable in research on the stimulus-secretion-coupling of pancreatic islets. Pancreatic islets are fully functional competent mini-organs, which serve as fuel sensors and transduce metabolic activity into rates of hormone secretion. To enable the simultaneous measurement of fluorescence and oxygen consumption we designed a microfluidic perfusion system from borosilicate glass by 3D femtosecond laser ablation. Retention of islets was accomplished by a plain well design. The characteristics of flow and shear force in the microchannels and wells were simulated and compared with the measured exchange of the perfusion media. Distribution of latex beads, MIN6 cell pseudo islets and isolated mouse islets in the MPS was characterized in dependence of flow rate and well depth. Overall, the observations suggested that a sufficient retention of the islets at low shear stress, together with sufficient exchange of test medium, was achieved at a well depth of 300 mu m and perfusion rates between 40 and 240 mu l/min. This enabled multiparametric measurement of oxygen consumption, NAD(P) H autofluorescence, cytosolic Ca2+ concentration, and insulin secretion by isolated mouse islets. After appropriate correction for different lag times, kinetics of these processes could be compared. Such measurements permit a more precise insight into metabolic changes underlying the regulation of insulin secretion. Thus, rapid prototyping using laser ablation enables flexible adaption of borosilicate MPS designs to different demands of biomedical research.
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