D Multi Organ Model Using Microfluidics to Mimic in vivo Compound Exposure

Project Summary Compounds from the pharmaceutical and other industries undergo safety and efficacy testing but the in vitro and animal models that are used often fail in their translation to human physiology resulting in late stage failures during development and significant costs There is a need to identify more physiologically relevant in vitro systems for both healthy and disease states that translates into the clinic This need is especially pronounced for pharmaceutical and therapeutic compounds where the dearth of human safety data particularly for preclinical evaluation of compounds is largely attributable to inadequate in vitro systems that cannot accurately predict the effects of compound or drug exposures on relevant cells tissues and organs There is a clear need for more life like systems which incorporate D cellular architecture fluid movement and mimic in vivo compound dosing with non linear compound and metabolite gradients that allow repeat low concentration dosing over time courses and amenable to running cell based assays The scope of this SBIR project is to develop a first in class fluidics bio tool that can promote highly functional D liver organoid formation link multiple organs and incorporate non linear compound and metabolite gradients The D organoid SciFlow system to be developed in this work will provide three major advances over current toxicological testing options Increased physiological relevance through promotion of D cellular architecture and multi organ systems Incorporation of non linear exposure gradient of compounds and metabolites across multi organ systems and a simple to use system with SBS format and broad compatibility with standard laboratory equipment including high content imagers and plate readers In Phase I we will complete the following Specific Aims Aim Characterize and select a non binding surface chemistry to promote non adherent cell culture and D spheroid formation Aim Establish a multi organ system with D liver cell cultures capable of increased bioactivation metabolism of therapeutic compounds resulting in an increased drug potency on downstream tumor cells Upon completion of the Phase I aims our Phase II work will focus on validating the system and scaling the unit for production Successful completion of this project will result in development of the SciSlick multi organ D system which will leverage the inter compartment flow with the ability to culture different cell types suitable for repeated dosing in long term to investigate parent compound metabolite complexities all in an easy to use accessible microfluidics device Project Narrative Thousands of pharmaceutical and therapeutic compounds are evaluated annually for effects on human physiology The early stages of compound testing are driven by safety and efficacy testing using in vitro tests followed by animal models While animal models are the standard for predicting outcomes they often fail in their translation to human physiology resulting in late stage failures at significant costs In this project SciKon is developing a novel in vitro microfluidic cell culture system capable of supporting D human cell architectures and linked multi organs to be used to investigate pre clinical compounds for metabolite safety and efficacy implications