Abstract
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.
Highlights
Parallelizing microfluidic cell culturing is essential for expanding the parameter screening space and increasing throughput in a wide variety of biological applications
We have previously reported a modular platform for microfluidics in which a single fluidic circuit board (FCB) connects multiple microfluidic building blocks (MFBBs) in a modular and standardized fashion[19,20]
We show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) in the chambers of an unmounted microfluidic large-scale integration (mLSI) MFBB as a first step toward applying this modular technology to create automated and highly parallelized yet versatile cell culture systems
Summary
Parallelizing microfluidic cell culturing is essential for expanding the parameter screening space and increasing throughput in a wide variety of biological applications. Zhang et al demonstrated a chip with an impressive number of 1500 independently addressable chambers[18] Such highly integrated chips are challenging to develop and set up, as this requires a complex design cycle, custom software for chip-specific operation and a highly optimized operating protocol. Flexible alterations to the design of these monolithic chips are not realizable when required by the experimental question To address this challenge in maintaining design flexibility while setting up a highly parallel mLSI cell culture system, we propose a modular approach to create a versatile system based on a library of standardized components
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