Hara, Seth A.

AbstractA 3D‐printed array of hollow microneedles (HMNs) is designed and fabricated using a high‐resolution stereolithography 3D printer and assembled with a 3D‐printed reservoir that incorporates a Luer lock mechanism, ensuring standard and secure connection to syringes. The proof‐of‐concept needle designs consist of half‐eccentric and concentric conical tip shapes, each arrayed with two different interspacing values. After the geometrical features of the devices are characterized, the devices are tested ex vivo in porcine skin to evaluate the impact of tip shape and interspacing on the depth of penetration and the efficacy of the devices in delivering fluids (such as tattoo ink) into the dermis. Overall, the 3D‐printed HMNs can deliver fluids into the target layer of skin. Refinement of the design is ongoing with the ultimate aim to provide alternatives for intradermal drug delivery and diagnostic imaging, such as superficial lymphography.

Three-dimensional printing technology has been implemented in microfluidic mold fabrication due to its freedom of design, speed, and low-cost fabrication. To facilitate mold fabrication processes and avoid the complexities of the soft lithography technique, we offer a non-sacrificial approach to fabricate microscale features along with mesoscale features using Stereolithography (SLA) printers to assemble a modular microfluidic mold. This helps with addressing an existing limitation with fabricating complex and time-consuming micro/mesoscale devices. The process flow, optimization of print time and feature resolution, alignments of modular devices, and the advantages and limitations with the offered technique are discussed in this paper.

Abstract Additive manufacturing is a growing field, but its application in the fabrication of medical microdevices has not been fully explored. Traditionally, medical microdevices are manufactured via a combination of techniques such as photolithography, laser-cutting, and micromolding, which collectively have challenges such as multiple fabrication steps, limited design freedom, high fabrication cost, and significant fabrication time. Micro vat photopolymerization is presented here as an alternative method to produce four different microscale medical devices that have applications in microfluidics, drug delivery, and bioscaffolding. In terms of minimum feature size and resolution, the presented structures are comparable, if not superior, to literature quoted parts fabricated through conventional manufacturing methods. The fabrication steps, process parameters, design considerations, learnings, and future research directions are outlined.

Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good biocompatibility. Additionally, methods for processing and patterning diamond allow for high-throughput batch fabrication and customization of electrode arrays with unique architectures. While tradeoffs in sensitivity can undermine the advantages of BDD as a neurochemical sensor, there are numerous untapped opportunities to further improve performance, including anodic pretreatment, or optimization of the FSCV waveform, instrumentation, sp2/sp3 character, doping, surface characteristics, and signal processing. Here, we review the state-of-the-art in diamond electrodes for neurochemical sensing and discuss potential opportunities for future advancements of the technology. We highlight our team’s progress with the development of an all-diamond fiber ultramicroelectrode as a novel approach to advance the performance and applications of diamond-based neurochemical sensors.

Abstract Thin-film microelectrode arrays have a wide variety of applications in research and medical devices. Conventionally, these arrays are fabricated through the use of photolithography, which can be problematic for innovative medical device fabrication due to long process times, inflexibility to design changes, and the reliance on potentially harmful chemicals. Here, we present the use of laser micromachining as an alternative to photolithography processes to fabricate thin-film polyimide microelectrode arrays. This fabrication method lends itself to an iterative design process as it can reduce fabrication steps and is attractive for medical devices since it can be used without harmful chemicals. Several process parameters were explored and the performance of the fabricated electrodes was compared to similar electrodes that were fabricated with conventional photolithography processes.

Femtosecond laser ablation is a powerful tool for the fabrication of medical devices, especially with materials commonly used in implantable micro devices as these materials are often incompatible with traditional machining techniques. Laser machining quality is highly dependent not only on the laser parameters, but also on the material that is being machined and so the process must be characterized for each material of interest. In this work, process characterization is presented for two materials commonly used in implantable micro devices — polyimide and silicon. The ablation threshold and etch rate were determined for femtosecond laser machining with a UV wavelength.

Implantable devices to measure neurochemical or electrical activity from the brain are mainstays of neuroscience research and have become increasingly utilized as enabling components of clinical therapies. In order to increase the number of recording channels on these devices while minimizing the immune response, flexible electrodes under 10 µm in diameter have been proposed as ideal next-generation neural interfaces. However, the representation of motion artifact during neurochemical or electrophysiological recordings using ultra-small, flexible electrodes remains unexplored. In this short communication, we characterize motion artifact generated by the movement of 7 µm diameter carbon fiber electrodes during electrophysiological recordings and fast-scan cyclic voltammetry (FSCV) measurements of electroactive neurochemicals. Through in vitro and in vivo experiments, we demonstrate that artifact induced by motion can be problematic to distinguish from the characteristic signals associated with recorded action potentials or neurochemical measurements. These results underscore that new electrode materials and recording paradigms can alter the representation of common sources of artifact in vivo and therefore must be carefully characterized.

In an effort to determine the chronic stability, sensitivity, and thus the potential viability of various neurochemical recording electrode designs and compositions, we have developed a custom device called the Voltammetry Instrument for Neurochemical Applications (VINA). Here, we describe the design of the VINA and initial testing of its functionality for prototype neurochemical sensing electrodes. The VINA consists of multiple electrode fixtures, a flowing electrolyte bath, associated reservoirs, peristaltic pump, voltage waveform generator, data acquisition hardware, and system software written in National Instrument’s LabVIEW. The operation of VINA was demonstrated on a set of boron-doped diamond neurochemical recording electrodes, which were subjected to an applied waveform for a period of eighteen days. Each electrode’s cyclic voltammograms (CVs) were recorded, and sensitivity calibration to dopamine (DA) was performed. Results showed an initial decline with subsequent stabilization in the CV current measured during the voltammetric sweep, corresponding closely with changes in electrode sensitivity to DA. The VINA has demonstrated itself as a useful tool for the characterization of electrode stability and chronic electrochemical performance.