Vat photopolymerization 3D printed microfluidic devices for organ-on-a-chip applications

Abstract

Organs-on-a-chip, or OoCs, are microfluidic tissue culture devices with micro-scaled architectures that repeatedly achieve biomimicry of biological phenomena. They are well positioned to become the primary pre-clinical testing modality as they possess high translational value. Current methods of fabrication have facilitated the development of many custom OoCs that have generated promising results. However, the reliance on microfabrication and soft lithographic fabrication techniques has limited their prototyping turnover rate and scalability. Additive manufacturing, known commonly as 3D printing, shows promise to expedite this prototyping process, while also making fabrication easier and more reproducible. We briefly introduce common 3D printing modalities before identifying two sub-types of vat photopolymerization - stereolithography (SLA) and digital light processing (DLP) - as the most advantageous fabrication methods for the future of OoC development. We then outline the motivations for shifting to 3D printing, the requirements for 3D printed OoCs to be competitive with the current state of the art, and several considerations for achieving successful 3D printed OoC devices touching on design and fabrication techniques, including a survey of commercial and custom 3D printers and resins. In all, we aim to form a guide for the end-user to facilitate the in-house generation of 3D printed OoCs, along with the future translation of these important devices.

Fig. 1

Anatomy of a DLP-SLA 3D printer: (A) Build platform for containing printed objects, a resin tray to house the printing resin, turning mirror to guide the light projection and optical engine as light source. (B) Close-up of an object being 3D printed through a bottom-up approach (‘bat’ configuration) by cured resin along a plane where the x-, y-resolution is determined by the pixel resolution of the light source and the z-resolution is determined by the optical penetration depth through the resin.

Fig. 1

Anatomy of a DLP-SLA 3D printer: (A) Build platform for containing printed objects, a resin tray to house the printing resin, turning mirror to guide the light projection and optical engine as light source. (B) Close-up of an object being 3D printed through a bottom-up approach (‘bat’ configuration) by cured resin along a plane where the x-, y-resolution is determined by the pixel resolution of the light source and the z-resolution is determined by the optical penetration depth through the resin.

Fig. 2

Key features and functional requirements of OoC microfluidic devices for 2D cultures relevant to barrier tissues e.g. epithelium and endothelium, and 3D cultures relevant to parenchyma and connective tissues e.g. liver, bone, heart. Connections between the fluidic networks to external pumps, valves and other devices are typically facilitated via commercial fitting (e.g. Luer fittings) at the cost of device footprint due to their larger liquid volume. Customized slip-fit connectors can be utilized to reduce device footprint.

Fig. 3

Process flow chart for SLA/DLP 3D printing for a microfluidic OoC device.

Fig. 4

Identification of priority controllable parameters for SLA/DLP 3D printed OoC device design, fabrication and post-processing. To pinpoint the important controllable parameters for a SLA/DLP 3D printed OoC, researchers must identify their desired OoC characteristics in the first column, prioritize key printing features in the second column, and adjust the controllable parameters in the third column accordingly.

Fig. 5

Publications relating to 3D printed microfluidics over time. Search parameters on PubMed as follows, updated 04/14/23: “(microfluidic OR microfluidics) AND (“3D printing” OR “3D printed” OR “3D print” OR “additive manufacturing”), Last 10 years”.