U-IMPACT: a universal 3D microfluidic cell culture platform

Abstract

The development of organs-on-a-chip has resulted in advances in the reconstruction of 3D cellular microenvironments. However, there remain limitations regarding applicability and manufacturability. Here, we present an injection-molded plastic array 3D universal culture platform (U-IMPACT) for various biological applications in a single platform, such as cocultures of various cell types, and spheroids (e.g., tumor spheroids, neurospheres) and tissues (e.g., microvessels). The U-IMPACT consists of three channels and a spheroid zone with a 96-well plate form factor. Specifically, organoids or spheroids (~500 μm) can be located in designated areas, while cell suspensions or cell-laden hydrogels can be selectively placed in three channels. For stable multichannel patterning, we developed a new patterning method based on capillary action, utilizing capillary channels and the native contact angle of the materials without any modification. We derived the optimal material hydrophilicity (contact angle of the body, 45–90°; substrate, <30°) for robust patterning through experiments and theoretical calculations. We demonstrated that the U-IMPACT can implement 3D tumor microenvironments for angiogenesis, vascularization, and tumor cell migration. Furthermore, we cultured neurospheres from induced neural stem cells. The U-IMPACT can serve as a multifunctional organ-on-a-chip platform for high-content and high-throughput screening.

Quantitative assessment of cardiomyocyte mechanobiology through high-throughput cantilever-based functional well plate systems

“…In the context of these challenges, three papers discuss and highlight the development and significance of organ-on-a-chip platforms for disease research and drug development. [31][32][33] These papers emphasize the limitations of traditional 2D cell culture models and underscore the pressing need for more accurate and reliable 3D models that can faithfully mimic human physiology's complexity. Engineering challenges and advancements in constructing platforms that integrate multiple aspects of human organ systems are also emphasized.…”

The Edifice of Vasculature-On-Chips: A Focused Review on the Key Elements and Assembly of Angiogenesis Models

“…Meanwhile, Nashimoto et al proposes that a sequential addition of fibroblasts to tumor spheroids may enhance vascularization and more accurately model the highly vascularized tumor microenvironment present in vivo . Lee and colleagues who developed a high-throughput microfluidic platform, referred to as U-IMPACT, implemented a similar coculture model to emulate the tumor microenvironment for angiogenesis, vasculogenesis, and tumor cell migration by having a designated spheroid zone sandwiched between parallel tissue channels . Beyond its high-content and high-throughput screening capabilities, the U-IMPACT platform possessed a unique characteristic wherein it employs a novel patterning method leveraging capillary action to create a tissue microchannel devoid of physical barriers.…”

“… 210 Lee and colleagues who developed a high-throughput microfluidic platform, referred to as U-IMPACT, implemented a similar coculture model to emulate the tumor microenvironment for angiogenesis, vasculogenesis, and tumor cell migration by having a designated spheroid zone sandwiched between parallel tissue channels. 211 Beyond its high-content and high-throughput screening capabilities, the U-IMPACT platform possessed a unique characteristic wherein it employs a novel patterning method leveraging capillary action to create a tissue microchannel devoid of physical barriers. The issue of vascularization remains a significant challenge in the field of tissue engineering, particularly in the context of engineering entire organs.…”

Manufactured tissue-to-tissue barrier chip for modeling the human blood–brain barrier and regulation of cellular trafficking

“…Several studies using injection mold-based MPS developed capillary guided liquid filling as a substitute for the micro-pillar array. 15,[36][37][38][39][40] However, these techniques are hard to be applied to our two-step perivascular unit construction process: 1) the hBVPs suspension injection; and 2) the injection of Matrigel with hAs, because they have been designed for one-time liquid filling.…”