Multilayer Counterflow Microdialysis Chips for Scalable Buffer Exchange and Sample Purification

In this study, we present a scalable multilayer platform enabling rapid buffer exchange and sample purification by counterflow microdialysis. The microfluidic system features a compact design employing polycarbonate substrates that contain integrated microchannels, with mixed cellulose ester membrane filters bonded between the mating polycarbonate layers. The unique design allows microdialysis layers to be stacked within a single device while employing standard membrane filters to increase the transport of ions and small molecules between the buffer compartments to enhance microdialysis performance. Devices with up to 4 microdialysis layers are demonstrated using a manufacturing process that supports an arbitrary level of scaling. Performance of the fabricated multilayer microdialysis chips is evaluated for application to continuous-flow buffer exchange for pH shifting and lipid nanoparticle purification.