Integrating spheroid-on-a-chip with tubeless rocker platform: A high-throughput biological screening platform

Spheroid-on-a-chip platforms are emerging as promising in vitro models that enable screening of the efficacy of biologically active ingredients. Generally, the supply of liquids to spheroids occurs in the steady flow mode with the use of syringe pumps; however, the utilization of tubing and connections, especially for multiplexing and high-throughput screening applications, makes spheroid-on-a-chip platforms labor- and cost-intensive. Gravity-induced flow using rocker platforms overcomes these challenges. Here, a robust gravity-driven technique was developed to culture arrays of cancer cell spheroids and dermal fibroblast spheroids in a high-throughput manner using a rocker platform. The efficiency of the developed rocker-based platform was benchmarked to syringe pumps for generating multicellular spheroids and their use for screening biologically active ingredients. Cell viability, internal spheroid structure as well as the effect of vitamin C on spheroids' protein synthesis was studied. The rocker-based platform not only offers comparable or enhanced performance in terms of cell viability, spheroids formation, and protein production by dermal fibroblast spheroids but also, from a practical perspective, offers a smaller footprint, requires a lower cost, and offers an easier method for handling. These results support the application of rocker-based microfluidic spheroid-on-a-chip platforms for in vitro screening in a high-throughput manner with industrial scaling-up opportunities.