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Multi-stage fluidic reaction schemes for suspended particles (e.g., micro/nanospheres, cells, bacterial species, and extracellular vesicles) underly a diversity of chemical and biological applications. Conventional methods for executing such protocols can be exceedingly time, labor, and/or cost intensive. Microfluidic strategies can address these drawbacks; however, such technologies typically rely on clean room-based microfabrication that suffer from similar deficits for manufacturing the chips. To simultaneously overcome these challenges, here we explore the use of the submicron-scale additive manufacturing approach, “Two-Photon Direct Laser Writing (DLW)”, as a means for fabricating micro-fluidic “Deterministic Lateral Displacement (DLD)” arrays capable of passively guiding suspended particles across discrete, adjacent flow streams—the fundamental capability of continuous-flow multi-stage particle microreactors. Experimental results from microfluidic experimentation with 5 μm-in-diameter fluorescent particles revealed effective particle transport across flow streams, with 87.5% of fluorescent peaks detected in the designated, opposing outlet following the DLD array. These results suggest utility of the presented approach for micro- and nanoparticle-based microfluidic reactors targeting wide-ranging chemical and biological applications. 

The emergence of soft robots has presented new challenges associated with controlling the underlying fluidics of such systems. Here, we introduce a strategy for additively manufacturing unified soft robots comprising fully integrated fluidic circuitry in a single print run via PolyJet three-dimensional (3D) printing. We explore the efficacy of this approach for soft robots designed to leverage novel 3D fluidic circuit elements—e.g., fluidic diodes, “normally closed” transistors, and “normally open” transistors with geometrically tunable pressure-gain functionalities—to operate in response to fluidic analogs of conventional electronic signals, including constant-flow [“direct current (DC)”], “alternating current (AC)”–inspired, and preprogrammed aperiodic (“variable current”) input conditions. By enabling fully integrated soft robotic entities (composed of soft actuators, fluidic circuitry, and body features) to be rapidly disseminated, modified on demand, and 3D-printed in a single run, the presented design and additive manufacturing strategy offers unique promise to catalyze new classes of soft robots. 

Fluorescence imaging techniques such as fluorescein angiography and fundus autofluorescence are often used to diagnose retinal pathologies; however, there are currently no standardized test methods for evaluating device performance. Here we present microstructured fluorescent phantoms fabricated using a submicron-scale three-dimensional printing technology, direct laser writing (DLW). We employ anin situDLW technique to print 10 µm diameter microfluidic channels that support perfusions of fluorescent dyes. We then demonstrate how broadband photoresist fluorescence can be exploited to generate resolution targets and biomimetic models of retinal vasculature using standard DLW processes. The results indicate that these approaches show significant promise for generating better performance evaluation tools for fluorescence microscopy and imaging devices.

 

The ability to manufacture biodegradable structures at small scales is integral to a variety of applications in biological, medical, and pharmaceutical fields. Recent developments in additive manufacturing (or "three-dimensional (3D) printing") allow for biodegradable materials to be printed with high resolution; however, there is typically a limit with respect to a resolvable feature size (e.g., layer height) that dictates the minimum increments for tuning distinct degradation-mediated functionalities via print geometry. Here we investigate the potential to 3D print designs that afford additional degrees of control during intermediate stages between the complete biodegradation of microstructures that differ by a single layer height. Preliminary fabrication results revealed effective printing of tubular 3D biodegradable gelatin methacryloyl (GelMA) structures with outer diameters of 100 μm and wall thicknesses of 35 μm using two-photon direct laser writing (DLW)-based additive manufacturing. Simulation results for varying designs suggest that both the total degradation time as well as the diffusion dynamics through a microstructure during the final stage of biodegradation can be modulated via geometric means. Thus, the concepts presented in this work could open new avenues in areas including drug delivery and biomaterials. 

Additive manufacturing (or "three-dimensional (3D) printing") technologies offer unique means to expand the architectural versatility with which microfluidic systems can be designed and constructed. In particular, "direct laser writing (DLW)" supports submicron-scale 3D printing via two-photon (or multi-photon) polymerization; however, such high resolutions are poorly suited for fabricating the macro-to-micro interfaces (i.e., fluidic access ports) critical to microfluidic applications. To bypass this issue, here we present a novel strategy for using DLW to 3D print architecturally complex microfluidic structures directly onto-and notably, fully integrated with-macroscale fused silica tubes. Fabrication and experimental results for this "ex situ DLW (esDLW)" approach revealed effective structure-to-tube sealing, with fluidic integrity maintained during fluid transport from macroscale tubing, into and through demonstrative 3D printed microfluidic structures, and then out of designed outlets. These results suggest that the presented DLW-based printing approach for externally coupling microfluidic structures to macroscale fluidic systems holds promise for emerging applications spanning chemical, biomedical, and soft robotics fields. 

In situ direct laser writing ( is DLW) strategies that facilitate the printing of three-dimensional (3D) nanostructured components directly inside of, and fully sealed to, enclosed microchannels are uniquely suited for manufacturing geometrically complex microfluidic technologies. Recent efforts have demonstrated the benefits of using micromolding and bonding protocols for is DLW; however, the reliance on polydimethylsiloxane (PDMS) leads to limited fluidic sealing ( e.g. , operational pressures <50–75 kPa) and poor compatibility with standard organic solvent-based developers. To bypass these issues, here we explore the use of cyclic olefin polymer (COP) as an enabling microchannel material for is DLW by investigating three fundamental classes of microfluidic systems corresponding to increasing degrees of sophistication: (i) “2.5D” functionally static fluidic barriers (10–100 μm in height), which supported uncompromised structure-to-channel sealing under applied input pressures of up to 500 kPa; (ii) 3D static interwoven microvessel-inspired structures (inner diameters < 10 μm) that exhibited effective isolation of distinct fluorescently labelled microfluidic flow streams; and (iii) 3D dynamically actuated microfluidic transistors, which comprised bellowed sealing elements (wall thickness = 500 nm) that could be actively deformed via an applied gate pressure to fully obstruct source-to-drain fluid flow. In combination, these results suggest that COP-based is DLW offers a promising pathway to wide-ranging fluidic applications that demand significant architectural versatility at submicron scales with invariable sealing integrity, such as for biomimetic organ-on-a-chip systems and integrated microfluidic circuits.