Invasive Microelectrode Arrays (MEAs) have been a significant and useful tool for us to gain a fundamental understanding of how the brain works through high spatiotemporal resolution neuron-level recordings and/or stimulations. Through decades of research, various types of microwire, silicon, and flexible substrate-based MEAs have been developed using the evolving new materials, novel design concepts, and cutting-edge advanced manufacturing capabilities. Surgical implantation of the latest minimal damaging flexible MEAs through the hard-to-penetrate brain membranes introduces new challenges and thus the development of implantation strategies and instruments for the latest MEAs. In this paper, studies on the design considerations and enabling manufacturing processes of various invasive MEAs as in vivo brain-machine interfaces have been reviewed to facilitate the development as well as the state-of-art of such brain-machine interfaces from an engineering perspective. The challenges and solution strategies developed for surgically implanting such interfaces into the brain have also been evaluated and summarized. Finally, the research gaps have been identified in the design, manufacturing, and implantation perspectives, and future research prospects in invasive MEA development have been proposed.

3D bio-printing is an emerging technology to fabricate tissue scaffold in-vitro through the controlled allocation of biomaterial and cells, which can mimic the in-vivo counterpart of living tissue. Live cells are often encapsulated into the biomaterials (i.e., bio-ink) and extruded by controlling the printing parameters. The functionality of the bioink depends upon three factors: (a) printability, (b) shape fidelity, and (c) bio-compatibility. Increasing viscosity will improve the printability and the shape fidelity but require higher applied extrusion pressure, which is detrimental to the living cell dwelling in the bio-ink, which is often ignored in the bio-ink optimization process. This paper demonstrates a roadmap to develop and optimize bio-inks, ensuring printability, shape fidelity, and cell survivability. The pressure exerted on the bio-ink during extrusion processes is measured analytically, and the information is incorporated in the bio-ink's rheology design. Cell-laden filaments are fabricated with multiple cell lines, i.e., Human Embryonic Kidney (HEK 293), BxPC3, and prostate cancer cells which are analyzed for cell viability. The cross-sectional live-dead assay of the extruded filament demonstrates a spatial pattern for HEK 293 cell viability, which correlates with our analytical finding of the shear stress at the nozzle tip. All three cell lines were able to sustain a transient shear stress of 3.7 kPa and demonstrate 90% viability with our designed bio-ink after 15 days of incubation. Simultaneously, the shape fidelity and printability matrices show its suitability for 3D bio-printing process.

Fully metallic micrometer-scale 3D architectures can be fabricated via a hybrid additive methodology combining multi-photon lithography with electrochemical deposition of metals. The methodology - referred to as two-photon templated electrodeposition (2PTE) - has significant design freedom that enables the creation of complicated, traditionally difficult-to-make, high aspect ratio metallic structures such as microneedles. These complicated geometries, combined with their fully metallic nature, can enable precision surgical applications such as inner ear drug delivery or fluid sampling. However, the process involves electrochemical deposition of metals into complicated 3D lithography patterns thicker than 500 μm. This causes potential and chemical gradients to develop within the 3D template, creating limitations to what can be designed. These limitations can be explored, understood, and overcome via numerical modeling. Herein we introduce a numerical model as a design tool that can predict growth for manufacturing complicated 3D metallic geometries. The model is successful in predicting the geometric result of 2PTE, and enables extraction of insights about geometric constraints through exploration of its mechanics.

More than 1.2 million people worldwide require regular hemodialysis therapy to treat end stage renal failure. Current hemodialysis systems are too expensive to support at-home hemodialysis where more frequent and longer duration treatment can lead to better patient outcomes. The key cost driver for hemodialysers is the cost of the hemodialysis membrane. Microchannel hemodialysers are smaller providing the potential to use significantly less membrane. Prior work has demonstrated the use of sealing bosses to form compression seals in microchannel hemodialysers. In this paper, estimates show that the percentage of the membrane utilized for mass transfer is highly dependent on the design and registration accuracy of adjacent blood and dialysate laminae. Efforts here focus on the development of a self-registration method to align polycarbonate laminae compatible with compression sealing schemes for membrane separation applications. Self-nesting registration methods were demonstrated with average registration accuracies of 11.4 ± 7.2 μm measured over a 50 mm scale. Analysis shows that the registration accuracy is constrained by tolerances in the embossing process. A dialysis test article was produced using the self-nesting registration method showing a measured average one-dimensional misregistration of 18.5 μm allowing a potential 41.4% of the membrane to be utilized for mass transfer when considering both microchannel and header regions. Mass transfer results provide evidence of a twofold to threefold increase in membrane utilization over other designs in the existing literature.

Scale-up microsphere fabrication with controllable microsphere size has always been an exciting manufacturing challenge. The objective of this study is to experimentally study the effects of material properties and operating conditions on the formability of alginate microspheres and the microsphere size during drop-on-demand (DOD)-based single nozzle jetting. Alginate microspheres have been fabricated using bipolar wave-based drop-on-demand jetting, and its formability and size have been studied especially as a function of sodium alginate and calcium chloride concentrations, voltage rise/fall times, dwell and echo times, excitation voltage amplitudes, and frequency. It is found that 1) the formability is sensitive to the sodium alginate and calcium chloride concentrations, dwell and echo voltages, and voltage dwell time; and the formability decreases with the sodium alginate concentration but increases with the calcium chloride concentration, dwell and echo voltages, and voltage dwell time; 2) the size is not sensitive to the sodium alginate and calcium chloride concentrations but increases first with the dwell time and then decreases; and 3) the size increases with the dwell and absolute echo voltage amplitudes.

Powder thermal properties play a critical role in laser powder-bed fusion (LPBF) additive manufacturing, specifically, the reduced effective thermal conductivity compared to that of the solid significantly affects heat conduction, which can influence the melt pool characteristics, and consequently, the part mechanical properties. This study intends to indirectly measure the thermal conductivity of metallic powder, nickel-based super alloy 625 (IN625) and Ti-6Al-4V (Ti64), in LPBF using a combined approach that consists of laser flash analysis, finite element (FE) heat transfer modeling and a multivariate inverse method. The test specimens were designed and fabricated by a LPBF system to encapsulate powder in a hollow disk to imitate powder-bed conditions. The as-built specimens were then subjected to laser flash testing to measure the transient thermal response. Next, an FE model replicate the hollow disk samples and laser flash testing was developed. A multi-point optimization algorithm was used to inversely extract the thermal conductivity of LPBF powder from the FE model based on the measured transient thermal response. The results indicate that the thermal conductivity of IN625 powder used in LPBF ranges from 0.65 W/(m·K) to 1.02 W/(m·K) at 100 °C and 500 °C, respectively, showing a linear relationship with the temperature. On the other hand, Ti64 powder has a lower thermal conductivity than IN625 powder, about 35% to 40% smaller. However, the thermal conductivity ratio of the powder to the respective solid counterpart is quite similar between the two materials, about 4.2% to 6.9% for IN625 and 3.4% to 5.2% for Ti64.