Biocompatible High-Resolution 3D-Printed Microfluidic Devices: Integrated Cell Chemotaxis Demonstration

Abstract

We demonstrate a method to effectively 3D print microfluidic devices with high-resolution features using a biocompatible resin based on avobenzone as the UV absorber. Our method relies on spectrally shaping the 3D printer source spectrum so that it is fully overlapped by avobenzone’s absorption spectrum. Complete overlap is essential to effectively limit the optical penetration depth, which is required to achieve high out-of-plane resolution. We demonstrate the high resolution in practice by 3D printing 15 μm square pillars in a microfluidic chamber, where the pillars are separated by 7.7 μm and are printed with 5 μm layers. Furthermore, we show reliable membrane valves and pumps using the biocompatible resin. Valves are tested to 1,000,000 actuations with no observable degradation in performance. Finally, we create a concentration gradient generation (CG) component and utilize it in two device designs for cell chemotaxis studies. The first design relies on an external dual syringe pump to generate source and sink flows to supply the CG channel, while the second is a complete integrated device incorporating on-chip pumps, valves, and reservoirs. Both device types are seeded with adherent cells that are subjected to a chemoattractant CG, and both show clear evidence of chemotactic cellular migration. Moreover, the integrated device demonstrates cellular migration comparable to the external syringe pump device. This demonstration illustrates the effectiveness of our integrated chemotactic assay approach and high-resolution biocompatible resin 3D printing fabrication process. In addition, our 3D printing process has been tuned for rapid fabrication, as printing times for the two device designs are, respectively, 8 and 15 min.

Integrated biocompatible 3D printed isoporous membranes with 7 μm pores

“…Membranes with various pore sizes were designed and printed on a custom 3D printer reported in ref. 10 and 17 which is based on a DMD with 7.6 μm pixels and uses 1 : 1 projection optics, yielding square 7.6 μm pixels in the image plane. We used a custom photopolymerizable resin consisting of poly(ethylene glycol) diacrylate (PEGDA, MW258) with a 1% (w/w) phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure 819) photoinitiator and a 0.38% (w/w) Avobenzone UV absorber, the same resin reported in ref.…”

“…We used a custom photopolymerizable resin consisting of poly(ethylene glycol) diacrylate (PEGDA, MW258) with a 1% (w/w) phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure 819) photoinitiator and a 0.38% (w/w) Avobenzone UV absorber, the same resin reported in ref. 9 and 10. The devices were printed on 25 mm square silanized glass substrates, prepared as described in ref.…”

“…No further integration processes or materials are required as the entire print is made from a single, biocompatible resin. 9,10 We begin with a treatment of what can be accomplished with traditional 3D printing techniques and then develop a new exposure approach that can realize voids with native micro-mirror dimensions in a 3D printed part, resulting in porous membranes with 7 μm pores. Pores this size are relevant for many organ-on-chip applications including lung 11,12 and pancreas 13 models, among others.…”

Evolution of 3d printing technology in fabrication of microfluidic devices and biological applications: a comprehensive review

“…High-resolution (10-15 μm) features have been developed by DLP-SLA technology for biomedical applications such as micropillars, valves, pumps and microchannels. Utilising the absorption range of the biocompatible resin Avobenzone, Boaks et al 95 demonstrated cellular migration through their lab-on-chip device (Figure 13A). Enclosed serpentine microchannels have been fabricated through DLP-SLA by Tzivelekis et al 94 to carry out two-step polymerase chain reaction (PCR) thermocycling.…”

“…DLP-SLA printed microfluidic chip developed for (A) cellular migration and (B) two-step PCR thermocycling set-up. (a) Open microchannel geometry with a serpentine pattern, (b) 3D model assembly of PCR chip, (c) Schematic of the two-step PCR thermocycling, (d) Peltier pairs for thermocycling setup and (e) PCR sample pressurisation.Source: (A) Ref 95. ; (B) reprinted with permission94 Copyright © 2021 IOP Publishing Ltd.…”