Microfluidic Chip with Integrated Electrophoretic Immunoassay for Investigating Cell-Cell Interactions.

Microfluidics have been used to create "body-on-chip" systems to mimic in vivo cellular interactions with a high level of control. Most such systems rely on optical observation of cells as a readout. In this work we integrated a cell-cell interaction chip with online microchip electrophoresis immunoassay to monitor the effects of the interaction on protein secretion dynamics. The system was used to investigate the effects of adipocytes on insulin secretion. Chips were loaded with 190 000 3T3-L1 adipocytes and a single islet of Langerhans in separate chambers. The chambers were perfused at 300-600 nL/min so that adipocyte secretions flowed over the islets for 3 h. Adipocytes produced 80 μM of nonesterified fatty acids (NEFAs), a factor known to impact insulin secretion, at the islets. After perfusion, islets were challenged with a step change in glucose from 3 to 11 mM while monitoring insulin secretion at 8 s intervals by online immunoassay. Adipocyte treatment augmented insulin secretion by 6-fold compared to controls. The effect was far greater than comparable concentrations of NEFA applied to the islets demonstrating that adipocytes release multiple factors that can strongly potentiate insulin secretion. The experiments reveal that integration of chemical analysis with cell-cell interaction can provide valuable insights into cellular functions.