Modular operation of microfluidic chips for highly parallelized cell culture and liquid dosing via a fluidic circuit board

Microfluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing.To achieve this,systems typically integrate all functions into a single,monolithic device as a“one size fits all”solution.However,this approach limits the end users’(re)design flexibility and complicates the addition of new functions to the system.To address this challenge,we propose and demonstrate a modular and standardized plug-and-play fluidic circuit board(FCB)for operating microfluidic building blocks(MFBBs),whereby both the FCB and the MFBBs contain integrated valves.A single FCB can parallelize up to three MFBBs of the same design or operate MFBBs with entirely different architectures.The operation of the MFBBs through the FCB is fully automated and does not incur the cost of an extra external footprint.We use this modular platform to control three microfluidic large-scale integration(mLSI)MFBBs,each of which features 64 microchambers suitable for cell culturing with high spatiotemporal control.We show as a proof of principle that we can culture human umbilical vein endothelial cells(HUVECs)for multiple days in the chambers of this MFBB.Moreover,we also use the same FCB to control an MFBB for liquid dosing with a high dynamic range.Our results demonstrate that MFBBs with different designs can be controlled and combined on a single FCB.Our novel modular approach to operating an automated microfluidic system for parallelized cell culture will enable greater experimental flexibility and facilitate the cooperation of different chips from different labs.

Systematic characterization of cleanroom-free fabricated macrovalves,demonstrating pumps and mixers for automated fluid handling tuned for organ-on-chip applications

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.

Biofabrication of natural hydrogels for cardiac,neural,and bone Tissue engineering Applications

Natural hydrogels are one of the most promising biomaterials for tissue engineering applications,due to their biocompatibility,biodegradability,and extracellular matrix mimicking ability.To surpass the limitations of conventional fabrication techniques and to recapitulate the complex architecture of native tissue structure,natural hydrogels are being constructed using novel biofabrication strategies,such as textile techniques and three-dimensional bioprinting.These innovative techniques play an enormous role in the development of advanced scaffolds for various tissue engineering applications.The progress,advantages,and shortcomings of the emerging biofabrication techniques are highlighted in this review.Additionally,the novel applications of biofabricated natural hydrogels in cardiac,neural,and bone tissue engineering are discussed as well.