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

Abstract

Spheroid-on-a-chip platforms are emerging as a promising in-vitro model that enables 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 labour- and cost-intensive. Gravity-induced flow using rocker platforms overcomes these challenges. Here, we develop a robust gravity-driven technique to culture arrays of cancer cell spheroids and dermal fibroblast spheroids in a high-throughput manner using a rocker platform. We benchmark the efficiency of the developed rocker-based platform to syringe pumps for generating multicellular spheroids and their use for screening biologically active ingredients. We study cell viability, internal spheroid structure, as well as the effect of vitamin C on the production of collagen type I and fibronectin by dermal fibroblast spheroids. We demonstrate that 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 it 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. This article is protected by copyright. All rights reserved.