High-resolution low-cost LCD 3D printing for microfluidics and organ-on-a-chip devices.

The fabrication of microfluidic devices has progressed from cleanroom manufacturing to replica molding in polymers, and more recently to direct manufacturing by subtractive (e.g., laser machining) and additive (e.g., 3D printing) techniques, notably digital light processing (DLP) photopolymerization. However, many methods require technical expertise and DLP 3D printers remain expensive at a cost ∼15-30 K USD with ∼8 M pixels that are 25-40 µm in size. Here, we introduce (i) the use of low-cost (∼150-600 USD) liquid crystal display (LCD) photopolymerization 3D printing with ∼8-58 M pixels that are 18-35 µm in size for direct microfluidic device fabrication, and (ii) a poly(ethylene glycol) diacrylate-based ink developed for LCD 3D printing (PLInk). We optimized PLInk for high resolution, fast 3D printing and biocompatibility while considering the illumination inhomogeneity and low power density of LCD 3D printers. We made lateral features as small as 75 µm, 22 µm-thick embedded membranes, and circular channels with a 110 µm radius. We 3D printed microfluidic devices previously manufactured by other methods, including an embedded 3D micromixer, a membrane microvalve, and an autonomous capillaric circuit (CC) deployed for interferon-γ detection with excellent performance (limit of detection: 12 pg mL-1, CV: 6.8%). We made PLInk-based organ-on-a-chip devices in 384-well plate format and produced 3420 individual devices within an 8 h print run. We used the devices to co-culture two spheroids separated by a vascular barrier over 5 days and observed endothelial sprouting, cellular reorganization, and migration. LCD 3D printing together with tailored inks pave the way for democratizing access to high-resolution manufacturing of ready-to-use microfluidic and organ-on-a-chip devices by anyone, anywhere.

High-Resolution Additive Manufacturing of a Biodegradable Elastomer with A Low-Cost LCD 3D Printer.

Artificial organs and organs-on-a-chip (OoC) are of great clinical and scientific interest and have recently been made by additive manufacturing, but depend on, and benefit from, biocompatible, biodegradable, and soft materials. Poly(octamethylene maleate (anhydride) citrate (POMaC) meets these criteria and has gained popularity, and as in principle, it can be photocured and is amenable to vat-photopolymerization (VP) 3D printing, but only low-resolution structures have been produced so far. Here, a VP-POMaC ink is introduced and 3D printing of 80 µm positive features and complex 3D structures is demonstrated using low-cost (≈US$300) liquid-crystal display (LCD) printers. The ink includes POMaC, a diluent and porogen additive to reduce viscosity within the range of VP, and a crosslinker to speed up reaction kinetics. The mechanical properties of the cured ink are tuned to match the elastic moduli of different tissues simply by varying the porogen concentration. The biocompatibility is assessed by cell culture which yielded 80% viability and the potential for tissue engineering illustrated with a 3D-printed gyroid seeded with cells. VP-POMaC and low-cost LCD printers make the additive manufacturing of high resolution, elastomeric, and biodegradable constructs widely accessible, paving the way for a myriad of applications in tissue engineering and 3D cell culture as demonstrated here, and possibly in OoC, implants, wearables, and soft robotics.

Digital Manufacturing of Functional Ready-to-Use Microfluidic Systems.

Digital manufacturing (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 peripheralshave limited its adoption. Capillaric circuits (CCs) are structurally encoded, self-contained microfluidic systems that operate and self-fill via precisely tailored hydrophilicity. CCs  are  heretofore hydrophilized in a plasma chamber, but which offers only transient hydrophilicity, lacks reproducibility, and limits CC design to open surface channels subsequently sealed with tape. Here, the additive DM of monolithic, fully functional, and intrinsically hydrophilic CCs is reported. CCs are 3D printed with commonly available light-engine-based 3D printers using poly(ethylene 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, interwoven circuit architectures created, and CC use illustrated with an immunoassay. Finally, the external paper capillary pumps are eliminated by directly embedding the capillary pump in the chip as a porous gyroid structure, realizing fully functional, monolithic CCs. Thence, a digital 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.

Direct sound printing.

Photo- and thermo-activated reactions are dominant in Additive Manufacturing (AM) processes for polymerization or melting/deposition of polymers. However, ultrasound activated sonochemical reactions present a unique way to generate hotspots in cavitation bubbles with extraordinary high temperature and pressure along with high heating and cooling rates which are out of reach for the current AM technologies. Here, we demonstrate 3D printing of structures using acoustic cavitation produced directly by focused ultrasound which creates sonochemical reactions in highly localized cavitation regions. Complex geometries with zero to varying porosities and 280 µm feature size are printed by our method, Direct Sound Printing (DSP), in a heat curing thermoset, Poly(dimethylsiloxane) that cannot be printed directly so far by any method. Sonochemiluminescnce, high speed imaging and process characterization experiments of DSP and potential applications such as remote distance printing are presented. Our method establishes an alternative route in AM using ultrasound as the energy source.

Emerging Technologies in Multi-Material Bioprinting.

Bioprinting, within the emerging field of biofabrication, aims at the fabrication of functional biomimetic constructs. Different 3D bioprinting techniques have been adapted to bioprint cell-laden bioinks. However, single-material bioprinting techniques oftentimes fail to reproduce the complex compositions and diversity of native tissues. Multi-material bioprinting as an emerging approach enables the fabrication of heterogeneous multi-cellular constructs that replicate their host microenvironments better than single-material approaches. Here, bioprinting modalities are reviewed, their being adapted to multi-material bioprinting is discussed, and their advantages and challenges, encompassing both custom-designed and commercially available technologies are analyzed. A perspective of how multi-material bioprinting opens up new opportunities for tissue engineering, tissue model engineering, therapeutics development, and personalized medicine is offered.

Upcoming Methods and Specifications of Continuous Intraocular Pressure Monitoring Systems for Glaucoma.

Glaucoma is the leading cause of irreversible blindness and vision loss in the world. Although intraocular pressure (IOP) is no longer considered the only risk factor for glaucoma, it is still the most important one. In most cases, high IOP is secondary to trabecular meshwork dysfunction. High IOP leads to compaction of the lamina cribrosa and subsequent damage to retinal ganglion cell axons. Damage to the optic nerve head is evident on funduscopy as posterior bowing of the lamina cribrosa and increased cupping. Currently, the only documented method to slow or halt the progression of this disease is to decrease the IOP; hence, accurate IOP measurement is crucial not only for diagnosis, but also for the management. Due to the dynamic nature and fluctuation of the IOP, a single clinical measurement is not a reliable indicator of diurnal IOP; it requires 24-hour monitoring methods. Technological advances in microelectromechanical systems and microfluidics provide a promising solution for the effective measurement of IOP. This paper provides a broad overview of the upcoming technologies to be used for continuous IOP monitoring.