Pixelated microfluidics for drug screening on tumour spheroids and ex vivo microdissected primary tissue

Abstract

Anti-cancer drugs have the lowest success rate of approval in drug development programs. Thus, preclinical assays that closely predict the clinical responses to drugs are of utmost importance in both clinical oncology and pharmaceutical research. 3D tumour models preserve the tumoural architecture and are cost-, labour-, and time-efficient. However, the short-term longevity, limited throughput, and limitations to live imaging of these models have so far driven researchers towards simpler, less realistic tumour models such as monolayer cell cultures. Here, we present a static open-space microfluidic drug screening platform that enables the formation, culture, and multiplexed delivery of several reagents to various 3D tumour models, namely cancer cell line spheroids and ex vivo primary tumour fragments. Our platform utilizes an open-space microfluidic technology, a pixelated chemical display, which creates fluidic "pixels" of biochemical reagents that stream over tumour models in a contact-free fashion. Up to 9 different treatment conditions can be tested over 144 samples in a single experiment. We provide a proof-of-concept application by staining fixed and live tumour models with multiple cellular dyes. Furthermore, we demonstrate that the various responses of the tumour models to biological stimuli can be assessed using the proposed drug screening platform. The platform is amenable to various 3D tumour models, such as tumour organoids. Upscaling of the microfluidic platform to larger areas can lead to higher throughputs, and thus will have a significant impact on developing treatments for cancer.