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Abstract
Modular microfluidics offer the opportunity to combine the precise fluid control, rapid sample processing, low sample and reagent volumes, and relatively lower cost of conventional microfluidics with the flexible reconfigurability needed to accommodate the requirements of target applications such as drug toxicity studies. However, combining the capabilities of fully adaptable modular microelectromechanical systems (MEMS) assembly with the simplicity of conventional microfluidic fabrication remains a challenge. A hybrid polydimethylsiloxane (PDMS)-molding/photolithographic process is demonstrated to rapidly fabricate LEGO®-like modular blocks. The blocks are created with different sizes that interlock via tongue-and-groove joints in the plane and stack via interference fits out of the plane. These miniature strong but reversible connections have a measured resistance to in-plane and out-of-plane forces of up to >6000× and >1000× the weight of the block itself, respectively. The LEGO®-like interference fits enable O-ring-free microfluidic connections that withstand internal fluid pressures of >120 kPa. A single layer of blocks is assembled into LEGO®-like cell culture plates, where the in vitro biocompatibility and drug toxicity to lung epithelial adenocarcinoma cells and hepatocellular carcinoma cells cultured in the modular microwells are measured. A double-layer block structure is then assembled so that a microchannel formed at the interface between layers connects two microwells. Breast tumor cells and hepatocytes cultured in the coupled wells demonstrate interwell migration as well as the simultaneous effects of a single drug on the two cell types.
Highlights
The applications of microelectromechanical systems (MEMS) and microfluidic chip technologies have increased significantly with advances in soft lithography [1], system integration [2], and MEMS microassembly [3]
Modular microfluidic devices assembled from a variety of individual functional modules have been demonstrated in which each module consists of a unified standard interface for easy assembly [11,12]
Unlike monolithically fabricated microfluidic devices, modular microfluidic devices are assembled from a set of prefabricated units
Summary
The applications of microelectromechanical systems (MEMS) and microfluidic chip technologies have increased significantly with advances in soft lithography [1], system integration [2], and MEMS microassembly [3]. The resulting integration of multiple functions to manipulate, control, and/or analyze tiny volumes of fluids [4,5] have enabled the development of numerous miniature cell-based assay platforms These platforms, which can control multiple reagents in an automated manner in a single experiment, have been used for studies including genetic analysis [6], high-throughput. Each module with a specific function can be reconfigured and modified separately before being integrated to create different multiplexed applications and added functionality [13] Their ability to be reconfigured, precise control of fluids, rapid sample-processing time, lower sample/reagent consumption, lower cost, and portability have made modular microfluidic devices attractive tools for high-throughput screening assays for drug discovery [5,14] and other applications
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