Integrated valves enable automated control in microfuidic systems,as they can be applied for mixing,pumping and compartmentalization purposes.Such automation would be highly valuable for applications in organ-on-chip(...Integrated valves enable automated control in microfuidic systems,as they can be applied for mixing,pumping and compartmentalization purposes.Such automation would be highly valuable for applications in organ-on-chip(OoC)systems.However,OoC systems typically have channel dimensions in the range of hundreds of micrometers,which is an order of magnitude larger than those of typical microfluidic valves.The most-used fabrication process for integrated,normally open polydimethylsiloxane(PDMS)valves requires a reflow photoresist that limits the achievable channel height.In addition,the low stroke volumes of these valves make it challenging to achieve flow rates of microliters per minute,which are typically required in OoC systems.Herein,we present a mechanical'macrovalve'fabricated by multilayer soft lithography using micromilled direct molds.We demonstrate that these valves can close off rounded channels of up to 700μm high and 1000μm wide.Furthermore,we used these macrovalves to create a peristaltic pump with a pumping rate of up to 48μL/min and a mixing and metering device that can achieve the complete mixing of a volume of 6.4μL within only 17 s.An initial cell culture experiment demonstrated that a device with integrated macrovalves is biocompatible and allows the cell culture of endothelial cells over multiple days under continuous perfusion and automated medium refreshment.展开更多
基金This project was funded by a Building Blocks of Life grant from the Netherlands Organization for Scientific Research(NWO),grant no.737.016.003by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no.853988.This Joint Undertaking received support from the European Union's Horizon 2020 research and innovation programme and EFPIA and JDRF International.
文摘Integrated valves enable automated control in microfuidic systems,as they can be applied for mixing,pumping and compartmentalization purposes.Such automation would be highly valuable for applications in organ-on-chip(OoC)systems.However,OoC systems typically have channel dimensions in the range of hundreds of micrometers,which is an order of magnitude larger than those of typical microfluidic valves.The most-used fabrication process for integrated,normally open polydimethylsiloxane(PDMS)valves requires a reflow photoresist that limits the achievable channel height.In addition,the low stroke volumes of these valves make it challenging to achieve flow rates of microliters per minute,which are typically required in OoC systems.Herein,we present a mechanical'macrovalve'fabricated by multilayer soft lithography using micromilled direct molds.We demonstrate that these valves can close off rounded channels of up to 700μm high and 1000μm wide.Furthermore,we used these macrovalves to create a peristaltic pump with a pumping rate of up to 48μL/min and a mixing and metering device that can achieve the complete mixing of a volume of 6.4μL within only 17 s.An initial cell culture experiment demonstrated that a device with integrated macrovalves is biocompatible and allows the cell culture of endothelial cells over multiple days under continuous perfusion and automated medium refreshment.