Microinstrumentation for Brain Organoids.

Brain organoids are three-dimensional aggregates of self-organized differentiated stem cells that mimic the structure and function of human brain regions. Organoids bridge the gaps between conventional drug screening models such as planar mammalian cell culture, animal studies, and clinical trials. They can revolutionize the fields of developmental biology, neuroscience, toxicology, and computer engineering. Conventional microinstrumentation for conventional cellular engineering, such as planar microfluidic chips; microelectrode arrays (MEAs); and optical, magnetic, and acoustic techniques, has limitations when applied to three-dimensional (3D) organoids, primarily due to their limits with inherently two-dimensional geometry and interfacing. Hence, there is an urgent need to develop new instrumentation compatible with live cell culture techniques and with scalable 3D formats relevant to organoids. This review discusses conventional planar approaches and emerging 3D microinstrumentation necessary for advanced organoid-machine interfaces. Specifically, this article surveys recently developed microinstrumentation, including 3D printed and curved microfluidics, 3D and fast-scan optical techniques, buckling and self-folding MEAs, 3D interfaces for electrochemical measurements, and 3D spatially controllable magnetic and acoustic technologies relevant to two-way information transfer with brain organoids. This article highlights key challenges that must be addressed for robust organoid culture and reliable 3D spatiotemporal information transfer.

Untethered shape-changing devices in the gastrointestinal tract.

INTRODUCTION: Advances in microfabrication, automation, and computer engineering seek to revolutionize small-scale devices and machines. Emerging trends in medicine point to smart devices that emulate the motility, biosensing abilities, and intelligence of cells and pathogens that inhabit the human body. Two important characteristics of smart medical devices are the capability to be deployed in small conduits, which necessitates being untethered, and the capacity to perform mechanized functions, which requires autonomous shape-changing. AREAS COVERED: We motivate the need for untethered shape-changing devices in the gastrointestinal tract for drug delivery, diagnosis, and targeted treatment. We survey existing structures and devices designed and utilized across length scales from the macro to the sub-millimeter. These devices range from triggerable pre-stressed thin film microgrippers and spring-loaded devices to shape-memory and differentially swelling structures. EXPERT OPINION: Recent studies demonstrate that when fully enabled, tether-free and shape-changing devices, especially at sub-mm scales, could significantly advance the diagnosis and treatment of GI diseases ranging from cancer and inflammatory bowel disease (IBD) to irritable bowel syndrome (IBS) by improving treatment efficacy, reducing costs, and increasing medication compliance. We discuss the challenges and possibilities associated with ensuring safe, reliable, and autonomous operation of these smart devices.

Capillary Flow-Driven and Magnetically Actuated Multi-Use Wax Valves for Controlled Sealing and Releasing of Fluids on Centrifugal Microfluidic Platforms.

Compact disc (CD)-based centrifugal microfluidics is an increasingly popular choice for academic and commercial applications as it enables a portable platform for biological and chemical assays. By rationally designing microfluidic conduits and programming the disc's rotational speeds and accelerations, one can reliably control propulsion, metering, and valving operations. Valves that either stop fluid flow or allow it to proceed are critical components of a CD platform. Among the valves on a CD, wax valves that liquify at elevated temperatures to open channels and that solidify at room temperature to close them have been previously implemented on CD platforms. However, typical wax valves on the CD fluidic platforms can be actuated only once (to open or to close) and require complex fabrication steps. Here, we present two new multiple-use wax valve designs, driven by capillary or magnetic forces. One wax valve design utilizes a combination of capillary-driven flow of molten wax and centrifugal force to toggle between open and closed configurations. The phase change of the wax is enabled by heat application (e.g., a 500-mW laser). The second wax valve design employs a magnet to move a molten ferroparticle-laden wax in and out of a channel to enable reversible operation. A multi-phase numerical simulation study of the capillary-driven wax valve was carried out and compared with experimental results. The capillary wax valve parameters including response time, angle made by the sidewall of the wax reservoir with the direction of a valve channel, wax solidification time, minimum spin rate of the CD for opening a valve, and the time for melting a wax plug are measured and analyzed theoretically. Additionally, the motion of the molten wax in a valve channel is compared to its theoretical capillary advance with respect to time and are found to be within 18.75% of the error margin.

Fabrication of patterned graphitized carbon wires using low voltage near-field electrospinning, pyrolysis, electrodeposition, and chemical vapor deposition.

We herein report a high-resolution nanopatterning method using low voltage electromechanical spinning with a rotating collector to obtain aligned graphitized micro and nanowires for carbon nanomanufacturing. A small wire diameter and a small inter-wire spacing were obtained by controlling the electric field, the spinneret-to-collector distance, the pyrolysis parameters, the linear speed of the spinneret, the rotational speed of the collector. Using a simple scaling analysis, we show how the straightness and the diameter of the wires can be controlled by the electric field and the distance of the spinneret to the collector. A small inter-wire spacing, as predicted by a simple model, was achieved by simultaneously controlling the linear speed of the spinneret and the rotational speed of the collector. Rapid drying of the polymer nanowires enabled the facile fabrication of suspended wires over various structures. Patterned polyacrylonitrile wires were carbonized using standard stabilization and pyrolysis to obtain carbon nanowires. Suspended carbon nanowires with a diameter of <50 nm were obtained. We also established a method for making patterned, highly graphitized structures by using the aforementioned carbon wire structures as a template for chemical vapor deposition of graphite. This patterning technique offers high throughput for nano writing, which outperforms other existing nanopatterning techniques, making it a potential candidate for large-scale carbon nanomanufacturing.

Fabrication of polymer and carbon polyhedra through controlled cross-linking and capillary deformations.

Fabrication of polymer polyhedral structures is achieved by first producing origami sheets with dissimilar stiffness levels at their folds and faces via multi-step photolithography. Subsequent capillary folding of the sheets towards permanently folded target shapes is realized by thermally controlling, simultaneously, the compliance of the sheets and the volume of the deposited droplets. This fabrication method allows us to create millimeter and sub-millimeter polyhedral structures with arbitrary levels of folding, to manufacture permanently folded polymer polyhedra using single-material monolayer sheets, and to produce carbon shapes from these carbon-rich polymer polyhedra through pyrolysis.

Nitrogen-Rich Polyacrylonitrile-Based Graphitic Carbons for Hydrogen Peroxide Sensing.

Catalytic substrate, which is devoid of expensive noble metals and enzymes for hydrogen peroxide (H2O2), reduction reactions can be obtained via nitrogen doping of graphite. Here, we report a facile fabrication method for obtaining such nitrogen doped graphitized carbon using polyacrylonitrile (PAN) mats and its use in H2O2 sensing. A high degree of graphitization was obtained with a mechanical treatment of the PAN fibers embedded with carbon nanotubes (CNT) prior to the pyrolysis step. The electrochemical testing showed a limit of detection (LOD) 0.609 µM and sensitivity of 2.54 µA cm-2 mM-1. The promising sensing performance of the developed carbon electrodes can be attributed to the presence of high content of pyridinic and graphitic nitrogens in the pyrolytic carbons, as confirmed by X-ray photoelectron spectroscopy. The reported results suggest that, despite their simple fabrication, the hydrogen peroxide sensors developed from pyrolytic carbon nanofibers are comparable with their sophisticated nitrogen-doped graphene counterparts.