Digital Manufacturing of Functional Ready‐to‐Use Microfluidic Systems

Abstract

Digital manufacturing (DM) strives for the seamless manufacture of a functional device from a digital file. DM holds great potential for microfluidics, but requirements for embedded conduits and high resolution beyond the capability of common manufacturing equipment, and microfluidic systems’ dependence on peripherals (e.g., connections, power supply, computer), have limited its adoption. Microfluidic capillaric circuits (CCs) are structurally‐encoded, self‐contained microfluidic systems that operate and self‐fill thanks to precisely tailored hydrophilicity. CCs were heretofore hydrophilized in a plasma chamber, but which only produces transient hydrophilicity, lacks reproducibility, and limits CC design to open surface channels sealed with a tape. Here we introduce the additive DM of monolithic, fully functional and intrinsically hydrophilic CCs. CCs were 3D printed with commonly available light engine‐based 3D printers using polyethylene(glycol)diacrylate‐based ink co‐polymerized with hydrophilic acrylic acid crosslinkers and optimized for hydrophilicity and printability. A new, robust capillary valve design and embedded conduits with circular cross‐sections that prevent bubble trapping are presented, and complex interwoven circuit architectures created, and their use illustrated with an immunoassay. Finally, the need for external paper capillary pumps is eliminated by directly embedding the capillary pump in the chip as a porous gyroid structure, realizing fully functional, monolithic CCs. Thence, a computer‐aided design file can be made into a CC by commonly available 3D printers in less than 30 min enabling low‐cost, distributed, DM of fully functional ready‐to‐use microfluidic systems.This article is protected by copyright. All rights reserved

Nanoporous PEGDA ink for High-Resolution Additive Manufacturing of Scaffolds for Organ-on-a-Chip

“…Beyond modeling organs with naturally occurring scaffold structures, we also speculate that 3D OoC models like ours may have a general advantage in promoting cell-cell interaction simply owing to the larger crosstalk interface between the cell chambers, given that 3D migration was observed in all three OoC cell types (i.e., IMR-90, MDA-MB-231, and HUVEC). Extending the design to multiple cell types can be foreseeable thanks to the customizability of 3D printing; while prior OoCs were limited to planar or multi-layered replica molded devices, here they can be designed to meet desired specifications and modified to contain multiple reservoirs for different cell types with CSVs and 3D-printed embedded channels to connect various reservoirs 36 . Media exchanges and perfusate can be studied downstream for proteomic analysis of compartmentalization and crosstalk.…”

“…The contact angle decreased from 67° contact angle for the nonporous objects to 29° contact angle for the objects 3D printed with 30% porogen. In our recent work 31 , we showed that a hydrophilic ink (CCInk) can be produced by adding acrylic acid to the formulation, reducing the contact angle to 35°. The P-PEGDA ink could potentially also be used for the fabrication of capillary microfluidic devices.…”

“…The interconnectivity of the gyroid facilitates cell migration and tissue integration which is advantageous for tissue engineering 42,43 . The dual CSV function of the microchannels allowed either the central chamber, or the surrounding gyroid to be filled selectively with a solution without leakage to the other part, Figure 5d-e To achieve three-dimensional seeding of stromal or endothelial cells throughout the entire gyroid structure in our OoC, we initially filled the gyroid with a cell-embedded Matrigel solution via capillary flow 31 , Subsequently, a MDA-MB-231 breast cancer spheroid was embedded in Matrigel and seeded in the central chamber. This assembly was then gelated in the cell incubator and filled with cell media, followed by bi-daily media changes and time-course imaging.…”

“…The contact angle decreased from 67° contact angle for the 0% porogen objects to 29° contact angle for the objects 3D printed with 30% porogen. In our recent work 36 , we showed that a hydrophilic ink (CCInk) can be produced by adding acrylic acid to the formulation, reducing the contact angle to 35°. The P-PEGDA ink could potentially also be used for the fabrication of capillary microfluidic devices, as an increase in surface roughness caused by surface nanoporosity increases the wettable area and subsequently decreases the water static contact angle, likely due to capillarity and hemiwicking 37,38 .…”

High-resolution low-cost LCD 3D printing of microfluidics

“…The design of PLInk was based on our prior ink formulations for 385 nm DLP 3D printing, 7,16 but adapted for LCD-based photopolymerization by considering the light heterogeneity, low irradiance, and 405 nm illumination wavelength. Based on our prior inks, PEGDA-250 was selected as the monomer due to its low viscosity, low protein adsorption, inherent cytocompatibility, and compatibility with solvents such isopropyl alcohol for efficient removal of uncured ink in embedded microchannels.…”