A modular 3D printed microfluidic system: a potential solution for continuous cell harvesting in large-scale bioprocessing

Abstract

Microfluidic devices have shown promising applications in the bioprocessing industry. However, the lack of modularity and high cost of testing and error limit their implementation in the industry. Advances in 3D printing technologies have facilitated the conversion of microfluidic devices from research output to applicable industrial systems. Here, for the first time, we presented a 3D printed modular microfluidic system consisting of two micromixers, one spiral microfluidic separator, and one microfluidic concentrator. We showed that this system can detach and separate mesenchymal stem cells (MSCs) from microcarriers (MCs) in a short time while maintaining the cell’s viability and functionality. The system can be multiplexed and scaled up to process large volumes of the industry. Importantly, this system is a closed system with no human intervention and is promising for current good manufacturing practices. Graphical Abstract

Advancing Tissue Culture with Light-Driven 3D-Printed Microfluidic Devices

“…Hence, SLA’s precision and high-resolution output make it cost-effective for fabricating complex structures, especially microfluidic devices for tissue-related research [ 36 , 37 , 38 , 39 ]. L. Ding et al used an SLA 3D printer to rapidly print modular microfluidic systems for detaching and separating mesenchymal stem cells (MSCs) from microcarriers (MCs) [ 40 ]. Direct SLA printing was used to create each module, resulting in inexpensive and easy-to-manufacture high-precision 3D objects [ 40 ].…”

Rapid and Continuous Cryopreservation of Stem Cells with a 3D Micromixer

“…The micromixer was fabricated as previously described [13]. Briefly, SolidWorks 2018 × 64 (SolidWorks Corporation, Waltham, MA, USA) was used to design the micromixer.…”

“…Microfluidic devices can be the perfect solution to mix CPA and cells. They are miniaturised channels used to manipulate fluids inside the channels, possessing low-cost, disposable, and simple operation features and can be easily implemented in different conditions [12,13]. There were attempts to implement sheath flow-added straight channels to replace the media of the cells to CPA-added media.…”

“…Although we demonstrate the application of the device here with a small sample size (<5 mL cells), the 3D-printed micromixer has the potential to perform large-scale cryopreservation. It can also be easily integrated into other microfluidic systems [6,13] or the current industry system at a low cost.…”

A Modified-Herringbone Micromixer for Assessing Zebrafish Sperm (MAGS)

“…Most reported microdevices utilizing high-dilution or combinatorial mixing methods are focused on biochemical applications [ 40 , 41 ] rather than for use with live cells. In the microdevices where cells travel through the micromixers or diluting arrays, they have been designed for disruption such as cell lysis to access cytosolic contents [ 42 ] or cell removal from microcarrier beads [ 43 ].…”