Perfusable micro-vascularized 3D tissue array for high-throughput vascular phenotypic screening

Abstract

Microfluidic organ-on-a-chip technologies have enabled construction of biomimetic physiologically and pathologically relevant models. This paper describes an injection molded microfluidic platform that utilizes a novel sequential edge-guided patterning method based on spontaneous capillary flow to realize three-dimensional co-culture models and form an array of micro-vascularized tissues (28 per 1 × 2-inch slide format). The MicroVascular Injection-Molded Plastic Array 3D Culture (MV-IMPACT) platform is fabricated by injection molding, resulting in devices that are reliable and easy to use. By patterning hydrogels containing human umbilical endothelial cells and fibroblasts in close proximity and allowing them to form vasculogenic networks, an array of perfusable vascularized micro-tissues can be formed in a highly efficient manner. The high-throughput generation of angiogenic sprouts was quantified and their uniformity was characterized. Due to its compact design (half the size of a 96-well microtiter plate), it requires small amount of reagents and cells per device. In addition, the device design is compatible with a high content imaging machine such as Yokogawa CQ-1. Furthermore, we demonstrated the potential of our platform for high-throughput phenotypic screening by testing the effect of DAPT, a chemical known to affect angiogenesis. The MV-IMPACT represent a significant improvement over our previous PDMS-based devices in terms of molding 3D co-culture conditions at much higher throughput with added reliability and robustness in obtaining vascular micro-tissues and will provide a platform for developing applications in drug screening and development.

Integrated biosensors for monitoring microphysiological systems

“…Using microfluidics, several HT-MPSs have been recently reported. [151][152][153] They utilize multi-well plate and microscale manufacturing methods to achieve multi-cellular cell culture environments in one chip. During drug development, the companies need to screen a large library of compounds.…”

High-Resolution In Situ High-Content Imaging of 3D-Bioprinted Single Breast Cancer Spheroids for Advanced Quantification of Benzo(a)pyrene Carcinogen-Induced Breast Cancer Stem Cells

“…Gelatin and alginate hydrogel are water-soluble natural polymers and excellent substrates for cell culture in additive fabrication technologies owing to their outstanding rheological properties in a practical temperature range (normally 20–37 °C). , Moreover, the combination of sodium alginate and gelatin provides excellent biological properties, such as biocompatibility, biodegradability, and non-toxicity, and exhibits great structural integrity and extrusion uniformity owing to its high printability. Therefore, it has been universally applied in biosensors, diagnostics, and biomedical fields. − Additionally, gelatin provides a healthy environment for seeding cells as it allows for the adhesion of cells to polymers, which is lacking in hydrogel matrices produced using sodium alginate alone. , …”

All‐in‐one microfluidic design to integrate vascularized tumor spheroid into high‐throughput platform

“…From an end‐user perspective, the value of this microfluidics device is that it can allow for scalability, standardization, and high‐throughput screening. Lately, many platforms that are compatible with automated equipment such as liquid handling robotics or imaging system have been developed for high‐throughput drug screening (Du et al, 2018; Yu et al, 2022). And, the standardized All‐in‐One IMPACT can also allow for synergetic high‐throughput screening through compatibility with automated equipment.…”