A successful drug development effort requires studying of compounds and targets in the correct disease context. Organ-on-a-Chip technology provides that context by comprehensively capturing human tissue physiology in healthy and diseased state. Thus far however, the technology was primarily positioned for preclinical studies as direct replacement of animal tests. Its potential to disrupt drug development by addressing compound and target discovery phases has been largely untapped.

Here, we describe screening of a library of 1546 protein kinase inhibitors on a perfused 3D angiogenesis model. The model comprises a perfused main blood vessel, grown against an extracellular matrix. Angiogenesis is triggered by exposure with a cocktail of angiogenic factors. Luminized microvessels sprout from the main vessel and have the tip-stalk hierarchy typical of the angiogenesis process. Automated robot handling was used for the various dispensing steps of the assay. Sprout and vessel morphology was recorded by high content imaging and analyzed utilizing machine learning algorithms. The assay was shown to have a robust z' factor and yielded a range of hits that were subsequently confirmed in dose response studies. The study demonstrates that Organ-on-a-Chip systems can be utilized in early-stage drug screening and target discovery efforts.