Anchor‐IMPACT: A standardized microfluidic platform for high‐throughput antiangiogenic drug screening

• Published in: Biotechnology and bioengineering Vol. 118; no. 7; pp. 2524 - 2535
• Main Authors: Kim, Suryong, Ko, Jihoon, Lee, Seung‐Ryeol, Park, Dohyun, Park, Seunghyuk, Jeon, Noo Li
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2021
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Antiangiogenic agents; Antiangiogenics; Anticancer properties; Antineoplastic drugs; Antitumor agents; Arrays; Biochips; Biopharmaceuticals; Capillary flow; Cell culture; Cell Line, Tumor; colorectal cancer; Colorectal carcinoma; Drug Evaluation, Preclinical; Drug screening; Experimentation; high‐throughput screening; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hydrogels; Injection; Lab-On-A-Chip Devices; Material properties; Microenvironments; Microfluidic Analytical Techniques; Microfluidics; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; organ‐on‐a‐chip; Paracrine signalling; Pattern formation; Screening; organ-on-a-chip; colorectal cancer; microfluidics; angiogenesis; high-throughput screening
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.27765

In vitro models are becoming more advanced to truly present physiological systems while enabling high‐throughput screening and analysis. Organ‐on‐a‐chip devices provide remarkable results through the reconstruction of a three‐dimensional (3D) cellular microenvironment although they need to be further developed in terms of multiple liquid patterning principle, material properties, and scalability. Here we present a 3D anchor‐based microfluidic injection‐molded plastic array culture platform (Anchor‐IMPACT) that enables selective, space‐intensive patterning of hydrogels using anchor‐island for high‐throughput angiogenesis evaluation model. Anchor‐IMPACT consists of a central channel and an anchor‐island, integrating the array into an abbreviated 96‐well plate format with a standard microscope slide size. The anchor‐island enables selective 3D cell patterning without channel‐to‐channel contact or any hydrogel injection port using an anchor structure unlike conventional culture compartment. The hydrogel was patterned into defined regions by spontaneous capillary flow under hydrophilic conditions. We configured multiple cell patterning structures to investigate the angiogenic potency of colorectal cancer cells in Anchor‐IMPACT and the morphological properties of the angiogenesis induced by the paracrine effect were evaluated. In addition, the efficacy of anticancer drugs against angiogenic sprouts was verified by following dose‐dependent responses. Our results indicate that Anchor‐IMPACT offers not only a model of high‐throughput experimentation but also an advanced 3D cell culture platform and can significantly improve current in vitro models while providing the basis for developing predictive preclinical models for biopharmaceutical applications. The authors present a 3D anchor‐based microfluidic injection‐molded plastic array culture platform (Anchor‐IMPACT) that enables selective, space‐intensive 3D hydrogel patterning and high‐throughput quantitative assessment. Anchor‐IMPACT establishes co‐cultures using anchor‐island to develop tumor angiogenesis for various carcinomas. The platform evaluates the potential of angiogenesis for various colorectal cancers and the efficacy against representative anticancer drugs