Abstract

Conventional in vitro assays and many microphysiological systems struggle to generate time-dependent drug exposure profiles because medium replacement simultaneously removes or re-adds drugs in the culture compartment. Here, we developed an Open-access Dialysis Membrane-integrated Microfluidic Device (O-DMiMD) that uses molecular weight-dependent transport across a dialysis membrane to decouple nutrient supply from drug exposure control. The device comprises a cell culture compartment (CCC) and a donor compartment (DC) separated by a dialysis membrane. Transport functions were evaluated using Lucifer Yellow, FITC-dextran, and glucose, followed by drug-response studies using SN-38 and T-DM1 under different medium change conditions. Lucifer Yellow and glucose permeated through the dialysis membrane, whereas FITC-dextran was retained. DC medium change supplied glucose to the CCC and maintained A549/HepG2 co-culture proliferation comparably to direct CCC medium replacement. For SN-38, partial transport to the DC and retention in the CCC generated time-dependent exposure profiles; in A549/HepaRG co-culture, medium change conditions altered A549 viability. For T-DM1, conditions with or without re-addition to the CCC produced different SK-BR-3 responses, suggesting exposure-dependent effects for high-molecular-weight drugs. The O-DMiMD provides an open-access in vitro platform for evaluating drug responses under exposure profiles governed by molecular weights, protein binding, medium changes, and metabolic cell contexts.

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