Integrated biocompatible 3D printed isoporous membranes with 7 µm pores.

In this work, we present a new 3D printing technique that enables the realization of native digital micro-mirror device (DMD) resolution in negative features of a 3D printed part without improving 3D printer hardware and demonstrate the fabrication of fully integrated, biocompatible isoporous membranes with pore sizes as small as 7 µm. We utilize this technique to construct a microfluidic device that mimics an established organ-on-a-chip configuration, including an integrated isoporous membrane. Two cell populations are seeded on either side of the membrane and imaged as a proof of concept for other organ-on-a-chip applications. These 3D printed isoporous membranes can be leveraged for a wide variety of other mechanical and biological applications, creating new possibilities for seamlessly integrated, 3D printed microfluidic devices.

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

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.

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

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.

3D-Printed Microfluidic One-Way Valves and Pumps.

New microfluidic lab-on-a-chip capabilities are enabled by broadening the toolkit of devices that can be created using microfabrication processes. For example, complex geometries made possible by 3D printing can be used to approach microfluidic design and application in new or enhanced ways. In this paper, we demonstrate three distinct designs for microfluidic one-way (check) valves that can be fabricated using digital light processing stereolithography (DLP-SLA) with a poly(ethylene glycol) diacrylate (PEGDA) resin, each with an internal volume of 5-10 nL. By mapping flow rate to pressure in both the forward and reverse directions, we compare the different designs and their operating characteristics. We also demonstrate pumps for each one-way valve design comprised of two one-way valves with a membrane valve displacement chamber between them. An advantage of such pumps is that they require a single pneumatic input instead of three as for conventional 3D-printed pumps. We also characterize the achievable flow rate as a function of the pneumatic control signal period. We show that such pumps can be used to create a single-stage diffusion mixer with significantly reduced pneumatic drive complexity.

Spatially and optically tailored 3D printing for highly miniaturized and integrated microfluidics.

Traditional 3D printing based on Digital Light Processing Stereolithography (DLP-SL) is unnecessarily limiting as applied to microfluidic device fabrication, especially for high-resolution features. This limitation is due primarily to inherent tradeoffs between layer thickness, exposure time, material strength, and optical penetration that can be impossible to satisfy for microfluidic features. We introduce a generalized 3D printing process that significantly expands the accessible spatially distributed optical dose parameter space to enable the fabrication of much higher resolution 3D components without increasing the resolution of the 3D printer. Here we demonstrate component miniaturization in conjunction with a high degree of integration, including 15 µm × 15 µm valves and a 2.2 mm × 1.1 mm 10-stage 2-fold serial diluter. These results illustrate our approach's promise to enable highly functional and compact microfluidic devices for a wide variety of biomolecular applications.

Post-fabrication tuning of microring resonators using 3D-printed microfluidics.

We demonstrate a method of tuning the resonant frequencies of silicon microring resonators using a 3D-printed microfluidic chip overlaid directly on the photonic circuit with zero energy consumption following the initial tuning. Aqueous solutions with different concentrations of NaCl are used in experimentation. A shift of a full free spectral range is observed at a concentration of 10% NaCl. On a 60 µm microring resonator, this equals a resonant wavelength shift of 1.514 nm when the index of the cladding changes by 0.017 refractive index units (RIUs), or at a rate of 89.05 nm/RIU.

Self-Sustaining 3D Thin Liquid Films in Ambient Environments.

Thin liquid films (TLF) have fundamental and technological importance ranging from the thermodynamics of cell membranes to the safety of light-water cooled nuclear reactors. The creation of stable water TLFs, however, is very difficult. In this paper, the realization of thin liquid films of water with custom 3D geometries that persist indefinitely in ambient environments is reported. The wetting films are generated using microscale "mounts" fed by microfluidic channels with small feature sizes and large aspect ratios. These devices are fabricated with a custom 3D printer and resin, which were developed to print high resolution microfluidic geometries as detailed in Reference 26. By modifying the 3D-printed polymer to be hydrophilic and taking advantage of well-known wetting principles and capillary effects, self-sustaining microscale "water fountains" are constructed that continuously replenish water lost to evaporation while relying on surface tension to stabilize their shape. To the authors' knowledge, this is the first demonstration of stable sub-micron thin liquid films (TLFs) of pure water on curved 3D geometries.