Transforming a well into a chip: A modular 3D-printed microfluidic chip.

Rossana Rauti,Adi Ess,Mark Epshtein,Baptiste Le Roi,Yevgeniy Kreinin,Ben M Maoz,Netanel Korin

doi:10.1063/5.0039366

Rossana Rauti, Adi Ess + Show 5 more

Open Access

https://doi.org/10.1063/5.0039366

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Abstract

Organ-on-a-Chip platforms provide rich opportunities to observe interactions between different cell types under in vivo-like conditions, i.e., in the presence of flow. Yet, the costs and know-how required for the fabrication and implementation of these platforms restrict their accessibility. This study introduces and demonstrates a novel Insert-Chip: a microfluidic device that provides the functionality of an Organ-on-a-Chip platform, namely, the capacity to co-culture cells, expose them to flow, and observe their interactions—yet can easily be integrated into standard culture systems (e.g., well plates or multi-electrode arrays). The device is produced using stereolithograpy 3D printing and is user-friendly and reusable. Moreover, its design features overcome some of the measurement and imaging challenges characterizing standard Organ-on-a-Chip platforms. We have co-cultured endothelial and epithelial cells under flow conditions to demonstrate the functionality of the device. Overall, this novel microfluidic device is a promising platform for the investigation of biological functions, cell–cell interactions, and response to therapeutics.

Highlights

This study introduces and demonstrates a novel Insert-Chip: a microfluidic device that provides the functionality of an Organon-a-Chip platform, namely, the capacity to co-culture cells, expose them to flow, and observe their interactions—yet can be integrated into standard culture systems
These platforms include Transwell (TW) cell culture inserts, which enable cells to be co-cultured over a membrane;17–19 microfluidic devices (Organs-on-a-Chip), which allow for both coculturing and the application of flow and other mechanical forces;20 organoids, which mimic 3D tissue structure; and other 3D-systems that recreate a 3D microenvironment
To achieve straightforward integration into standard culture platforms, we designed the Insert-Chip to be self-supported on four short legs with the membrane positioned below the cell culture surface (Fig. 1) in any orientation desi (2) co-culture: A key feature of Organs-on-a-Chip is the capacity to scitation.org/journal/apb accommodate cell–cell interaction and diffusion between compartments (Fig. 2 and supplementary material Fig. 1)

Summary

Introduction

Several in vitro modeling platforms have been developed with the capacity to capture many of these features.4,14–16 These platforms include Transwell (TW) cell culture inserts, which enable cells to be co-cultured over a membrane; microfluidic devices (Organs-on-a-Chip), which allow for both coculturing and the application of flow and other mechanical forces; organoids, which mimic 3D tissue structure; and other 3D-systems that recreate a 3D microenvironment.. These platforms include Transwell (TW) cell culture inserts, which enable cells to be co-cultured over a membrane; microfluidic devices (Organs-on-a-Chip), which allow for both coculturing and the application of flow and other mechanical forces; organoids, which mimic 3D tissue structure; and other 3D-systems that recreate a 3D microenvironment.4,21,22 Though these platforms constitute significant advancements toward faithfully recapitulating in vivo environments, each has certain shortcomings that hinder its universal application. As yet, no one system fulfills all of the following criteria: modular, low cost, easy to use, applicable to high-throughput experiments, captures cell– cell interactions, capable of inducing flow, and compatible with highmagnification imaging procedures

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