A whole-thermoplastic microfluidic chip with integrated on-chip micropump, bioreactor and oxygenator for cell culture applications

Abstract

Microfluidics provides enabling platforms for various cell culture, drug testing and synthesis of drug carriers using chip-based microsystems. In this study, we present a novel integrated whole-thermoplastic microfluidic chip to provide a platform for on-chip cell culture at static and dynamic conditions. The whole chip was made of polymethyl methacrylate (PMMA) and thermoplastic polyurethane (TPU) using high precision micromilling and laser micromachining, assembled by thermal fusion bonding. Prior to fabricate the integrated microchip, a pneumatic solo diffuser-nozzle micropump was fabricated and characterized to evaluate its functionality for on-chip pumping. Then the micropump was integrated with a microbioreactor and an oxygenator in a microchip for flow pumping required for on-chip cell culture. Oxygenator, made of a thin TPU membrane and a reservoir, was implemented in the microchip because of low oxygen permeability of PMMA. To design the oxygenator for sufficient oxygen delivery to the chip, numerical simulation was performed using COMSOL Multiphysics® to evaluate oxygen concentration distribution inside the microchip. Finally, the diffuser-nozzle micropump was integrated with the oxygenator and a bioreactor on the microchip for cell culture with on-chip pumping. Culture of DFW cells was performed on the integrated chip for three days, and cell survival was evaluated with Trypan Blue assay. The findings reveal that the proposed integrated chip with on-chip pumping could be employed for conducting various cell culture studies.