Michael C. McAlpine’s research while affiliated with University of Minnesota, Duluth and other places

Devising an approach to deterministically position organisms can impact various fields such as bioimaging, cybernetics, cryopreservation, and organism‐integrated devices. This requires continuously assessing the locations of randomly distributed organisms to collect and transfer them to target spaces without harm. Here, an aspiration‐assisted adaptive printing system is developed that tracks, harvests, and relocates living and moving organisms on target spaces via a pick‐and‐place mechanism that continuously adapts to updated visual and spatial information about the organisms and target spaces. These adaptive printing strategies successfully positioned a single static organism, multiple organisms in droplets, and a single moving organism on target spaces. Their capabilities are exemplified by printing vitrification‐ready organisms in cryoprotectant droplets, sorting live organisms from dead ones, positioning organisms on curved surfaces, organizing organism‐powered displays, and integrating organisms with materials and devices in customizable shapes. These printing strategies can ultimately lead to autonomous biomanufacturing methods to evaluate and assemble organisms for a variety of single and multi‐organism‐based applications.

The ability to construct multiplexed micro-systems for fluid regulation could substantially impact multiple fields, including chemistry, biology, biomedicine, tissue engineering, and soft robotics, among others. 3D printing is gaining traction as a compelling approach to fabricating microfluidic devices by providing unique capabilities, such as 1) rapid design iteration and prototyping, 2) the potential for automated manufacturing and alignment, 3) the incorporation of numerous classes of materials within a single platform, and 4) the integration of 3D microstructures with prefabricated devices, sensing arrays, and nonplanar substrates. However, to widely deploy 3D printed microfluidics at research and commercial scales, critical issues related to printing factors, device integration strategies, and incorporation of multiple functionalities require further development and optimization. In this review, we summarize important figures of merit of 3D printed microfluidics and inspect recent progress in the field, including ink properties, structural resolutions, and hierarchical levels of integration with functional platforms. Particularly, we highlight advances in microfluidic devices printed with thermosetting elastomers, printing methodologies with enhanced degrees of automation and resolution, and the direct printing of microfluidics on various 3D surfaces. The substantial progress in the performance and multifunctionality of 3D printed microfluidics suggests a rapidly approaching era in which these versatile devices could be untethered from microfabrication facilities and created on demand by users in arbitrary settings with minimal prior training.

Bionic-engineered tissues have been proposed for testing the performance of cardiovascular medical devices and predicting clinical outcomes ex vivo. Progress has been made in the development of compliant electronics that are capable of monitoring treatment parameters and being coupled to engineered tissues; however, the scale of most engineered tissues is too small to accommodate the size of clinical-grade medical devices. Here, we show substantial progress toward bionic tissues for evaluating cardiac ablation tools by generating a centimeter-scale human cardiac disk and coupling it to a hydrogel-based soft-pressure sensor. The cardiac tissue with contiguous electromechanical function was made possible by our recently established method to 3D bioprint human pluripotent stem cells in an extracellular matrix-based bioink that allows for in situ cell expansion prior to cardiac differentiation. The pressure sensor described here utilized electrical impedance tomography to enable the real-time spatiotemporal mapping of pressure distribution. A cryoablation tip catheter was applied to the composite bionic tissues with varied pressure. We found a close correlation between the cell response to ablation and the applied pressure. Under some conditions, cardiomyocytes could survive in the ablated region with more rounded morphology compared to the unablated controls, and connectivity was disrupted. This is the first known functional characterization of living human cardiomyocytes following an ablation procedure that suggests several mechanisms by which arrhythmia might redevelop following an ablation. Thus, bionic-engineered testbeds of this type can be indicators of tissue health and function and provide unique insight into human cell responses to ablative interventions.

Photodetectors that are intimately interfaced with human skin and measure real‐time optical irradiance are appealing in the medical profiling of photosensitive diseases. Developing compliant devices for this purpose requires the fabrication of photodetectors with ultraviolet (UV)‐enhanced broadband photoresponse and high mechanical flexibility, to ensure precise irradiance measurements across the spectral band critical to dermatological health when directly applied onto curved skin surfaces. Here, a fully 3D printed flexible UV‐visible photodetector array is reported that incorporates a hybrid organic‐inorganic material system and is integrated with a custom‐built portable console to continuously monitor broadband irradiance in‐situ. The active materials are formulated by doping polymeric photoactive materials with zinc oxide nanoparticles in order to improve the UV photoresponse and trigger a photomultiplication (PM) effect. The ability of a stand‐alone skin‐interfaced light intensity monitoring system to detect natural irradiance within the wavelength range of 310–650 nm for nearly 24 h is demonstrated.

The ability to fully 3D-print active electronic and optoelectronic devices will enable unique device form factors via strategies untethered from conventional microfabrication facilities. Currently, the performance of 3D-printed optoelectronics can suffer from nonuniformities in the solution-deposited active layers and unstable polymer-metal junctions. Here, we demonstrate a multimodal printing methodology that results in fully 3D-printed flexible organic light-emitting diode displays. The electrodes, interconnects, insulation, and encapsulation are all extrusion-printed, while the active layers are spray-printed. Spray printing leads to improved layer uniformity via suppression of directional mass transport in the printed droplets. By exploiting the viscoelastic oxide surface of the printed cathode droplets, a mechanical reconfiguration process is achieved to increase the contact area of the polymer-metal junctions. The uniform cathode array is intimately interfaced with the top interconnects. This hybrid approach creates a fully 3D-printed flexible 8 × 8 display with all pixels turning on successfully.

Three-dimensional (3D) bioprinting strategies use computer-aided processes to enable automated simultaneous spatial patterning of cells and/or biomaterials. These technologies are suitable for a broad range of biomedical applications owing to their capability to produce structurally sophisticated and functionally relevant tissue constructs. Extrusion-based 3D bioprinting strategies were among the first modalities developed and are now arguably the most widely used for producing 3D tissue constructs. These technologies have rapidly evolved over the past two decades, providing a powerful tool set for the biofabrication of tissues that can facilitate translational efforts in the field. In this Primer, we describe the methodology of 3D extrusion bioprinting, focusing on the selection of hardware, software and bioinks. We expand upon recent advances in 3D extrusion bioprinting by illustrating the key variations that promote its biofabrication abilities. Finally, we provide an outlook on possible future refinements of the technology. 3D extrusion bioprinting methods can be used to produce tissue constructs in vitro and in situ and are arguably the most commonly used bioprinting strategies. In this Primer, Zhang and colleagues describe the variants of 3D extrusion bioprinting methods and their specific applications, considerations for the formulation of bioinks and strategies for assessing print quality. The authors conclude by looking to recent and upcoming developments in 4D printing and artificial intelligence-assisted dynamic printing strategies.