A reconfigurable microfluidic building block platform for high-throughput nonhormonal contraceptive screening

Identifying nonhormonal contraceptives will have profound impacts on avoiding side effects of hormonal birth control methods, minimizing pregnancy complications and infant mortality rates, and promoting family planning. However, phenotypic screening of contraceptives is challenging due to the diverse procedures associated with oocyte culture, biochemical assays, and molecular imaging. This study reports a multifunctional microfluidic platform comprising reconfigurable building blocks and interfaces to implement various cell-based drug screening protocols. This versatile platform has three major layers. The top layer consists of interchangeable 3D microfluidic building blocks (e.g., branching microchannels, chemical gradient generators, pumpless flow controllers, and emulsion generators) or an open interface. The middle layer incorporates a multiwell array with embedded membrane filters for live cell culture, medium exchange, enzymatic cumulus cell removal, washing, and fluorescence staining. The bottom layer is also reconfigurable for waste collection, oocyte culture, plate reader measurement, and high-resolution microscopy. We demonstrate an 8 by 16 (128 wells) system for performing the cumulus-oocyte complex (COC) expansion and oocyte maturation assays for screening nonhormonal contraceptives. The microfluidic building block platform is scalable and can be reconfigured for a variety of drug screening applications in the future.