The current standards for compound screening are animal models; while representing human tissues of interest, these models are expensive, scarce, and carry ethical challenges. On the other end, 2D in vitro assays poorly mimic native cellular environments and thus human in vivo response, but offer high-throughput testing with ease. There is a demand for in vitro assays that are both predictive of human in vivo response and high-throughput.
As a result, we developed a viability assay, the BiO Assay. Based on magnetic 3D bioprinting, cells magnetized with NS (NanoShuttle™-PL) are printed into spheroids and rings. Immediately after printing, these structures will shrink or close, as a function of cell migration, viability, cell-cell interaction, and / or proliferation, and varies with dosage. Ring closure can be captured using a compact imaging kit (n3Dock) with an iPod™ programmed by a freely available app (Experiment Assistant) to image whole plates at specific intervals, forgoing the need to image well-by-well under a microscope. Culture contraction is generally complete within 24 hours and images are batch processed to rapidly yield toxicity data. Moreover, as the assay is label-free, the remaining rings or spheroids are available for further experimentation (IHC, genomics, Western blot, etc).
The BiO Assay can be used to track the culture contraction of both rings and spheroids representing different situations. For rings, closure of the ring can represent wound-healing, wherein cells are working to close the void in the middle of the ring. Additionally, rings can represent similarly shaped tissues, like blood vessels, where dilation and contraction can be assayed. For Spheroids, contraction is related to spheroid assembly, with the assay macroscopically measuring how well the cells are interacting and migrating to build a competent structure.
The BiO Assay combines 3D cell culture environments with high-throughput and high-content testing to effectively predict in vivo response in vitro.