title: A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications.
abstract: There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type - the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels. Here we describe an arrayed version of the platform that incorporates multiple vascularized micro-organs (VMOs) on a 96-well plate. Each VMO is independently-addressable and flow through the micro-organ is driven by hydrostatic pressure. The platform is easy to use, requires no external pumps or valves, and is highly reproducible. As a proof-of-concept we have created arrayed vascularized micro tumors (VMTs) and used these in a blinded screen to assay a small library of compounds, including FDA-approved anti-cancer drugs, and successfully identified both anti-angiogenic and anti-tumor drugs. This 3D platform is suitable for efficacy/toxicity screening against multiple tissues in a more physiological environment than previously possible.
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA. cchughes@uci.edu.
authors.forename: Duc T T
authors.identifier: 0000-0003-3827-1490
authors.initials: DTT
authors.lastname: Phan
authors.affiliation: Department of Micro/Nano Electronics, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA. cchughes@uci.edu.
authors.forename: Brianna M
authors.initials: BM
authors.lastname: Craver
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA. cchughes@uci.edu.
authors.forename: Agua
authors.initials: A
authors.lastname: Sobrino
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. aplee@uci.edu.
authors.forename: Da
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA. cchughes@uci.edu.
authors.forename: Jerry C
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA. cchughes@uci.edu.
authors.forename: Lilian Y N
authors.initials: LYN
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Washington University in St. Louis, MO 63130, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: George
authors.affiliation: Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. aplee@uci.edu and Department of Mechanical and Aerospace Engineering, University of California, Irvine, CA 92697, USA.
authors.forename: Abraham P
authors.initials: AP
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA. cchughes@uci.edu and Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA. aplee@uci.edu and The Edwards Lifesciences Center for Advanced Cardiovascular Technology, Irvine, CA 92697, USA.
authors.forename: Christopher C W
authors.initials: CCW
authors.lastname: Hughes
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000295:instrumentation*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009374:Neoplasms, Experimental / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D046888:Tissue Array Analysis / Q000295:instrumentation* / Q000379:methods
chemical_list: D000970:Antineoplastic Agents