title: A scalable microfluidic device for the mass production of microencapsulated islets.
abstract: The objective of this research was to test the viability and function of islets microencapsulated using a scalable microfluidic device that is suitable for the mass production of encapsulated islets for transplantation. A 3-D microfluidic device consisting of eight outlets with an inner fluid inlet and an outer concentric inlet to the device has been designed and fabricated using the stereolithography rapid prototyping technique. Islets were isolated from normal Wistar-Furth rat pancreas using the procedure of collagenase digestion of pancreatic tissue. Following purification, islet suspensions in 1.5% sodium alginate were pumped into the fluid inlet of the microfluidic device, which distributed the flow equally to all the eight channels according to the design. The air plenum distributed compressed air uniformly through the eight concurrent outlets, and with one fluid pump and air source, the device produced eight microencapsulations simultaneously. After encapsulation, the islets were tested for functionality using the dynamic perifusion procedure with low- and high-glucose concentrations. The device is capable of producing eight channels of steady stream of monodisperse microencapsulations of a range of diameters depending on the design and process parameters. Using this prototype device, encapsulated islets were shown to be viable in the functional tests that we performed. Thus, the mean ± standard deviation rate of insulin secretion increased from a basal rate of 0.165 ± 0.059 ng/10 islets/min to a stimulated rate of 0.422 ± 0.095 ng/10 islets/min (P < .05, n = 3), when the glucose concentration was changed from 5.5 mmol/L to 27.5 mmol/L, and this glucose stimulation index was not different from that observed with unencapsulated islets under same conditions. In summary, the high-throughput prototype device that we have designed can produce encapsulated islets that are viable and suitable for transplantation studies.
authors.affiliation: Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina 27695-7910, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tendulkar
authors.forename: J P
authors.initials: JP
authors.lastname: McQuilling
authors.forename: C
authors.initials: C
authors.lastname: Childers
authors.forename: R
authors.initials: R
authors.lastname: Pareta
authors.forename: E C
authors.initials: EC
authors.lastname: Opara
authors.forename: M K
authors.initials: MK
authors.lastname: Ramasubramanian
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002470:Cell Survival; D017364:Collagenases / Q000378:metabolism; D004339:Drug Compounding; D005947:Glucose / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007328:Insulin / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics / Q000379:methods; D008863:Microspheres; D010179:Pancreas / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D007328:Insulin; D020723:Glucuronic Acid; D017364:Collagenases; D005947:Glucose
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