Glutamate excitotoxicity is a pathology in which excessive glutamate can cause neuronal damage and degeneration. It has also been linked to secondary injury mechanisms in traumatic spinal cord injury. Conventional bioanalytical techniques used to characterize glutamate levels in vivo, such as microdialysis, have low spatiotemporal resolution, which has impeded our understanding of this dynamic event. In this study, we present an amperometric biosensor fabricated using a simple direct ink writing technique for the purpose of in vivo glutamate monitoring. The biosensor is fabricated by immobilizing glutamate oxidase on nanocomposite electrodes made of platinum nanoparticles, multi-walled carbon nanotubes, and a conductive polymer on a flexible substrate. The sensor is designed to measure extracellular dynamics of glutamate and other potential biomarkers during a traumatic spinal cord injury event. Here we demonstrate good sensitivity and selectivity of these rapidly prototyped implantable biosensors that can be inserted into a spinal cord and measure extracellular glutamate concentration. We show that our biosensors exhibit good flexibility, linear range, repeatability, and stability that are suitable for future in vivo evaluation.

The global cost of diabetes care exceeds $1 trillion each year with more than $327 billion being spent in the United States alone. Despite some of the advances in diabetes care including continuous glucose monitoring systems and insulin pumps, the technology associated with managing diabetes has largely remained unchanged over the past several decades. With the rise of wearable electronics and novel functional materials, the field is well‐poised for the next generation of closed‐loop diabetes care. Wearable glucose sensors implanted within diverse platforms including skin or on‐tooth tattoos, skin‐mounted patches, eyeglasses, contact lenses, fabrics, mouthguards, and pacifiers have enabled noninvasive, unobtrusive, and real‐time analysis of glucose excursions in ambulatory care settings. These wearable glucose sensors can be integrated with implantable drug delivery systems, including an insulin pump, glucose responsive insulin release implant, and islets transplantation, to form self‐regulating closed‐loop systems. This review article encompasses the emerging trends and latest innovations of wearable glucose monitoring and implantable insulin delivery technologies for diabetes management with a focus on their advanced materials and construction. Perspectives on the current unmet challenges of these strategies are also discussed to motivate future technological development toward improved patient care in diabetes management.

Nonenzymatic glucose biosensors have the potential for a more reliable in vivo functionality due to the reduced risk of biorecognition element degradation. However, these novel sensing mechanisms often are nanoparticle-based and have nonlinear responses, which makes it difficult to gauge their potential utility against more conventional enzymatic biosensors. Moreover, these nonenzymatic biosensors often suffer from poor selectivity that needs to be better addressed before being used in vivo. To address these problems, here we present an amperometric nonenzymatic glucose biosensor fabricated using one-step electrodeposition of Au and Ru nanoparticles on the surface of a carbon-nanotube-based platinum–nanoparticle hybrid in conductive polymer. Using benchtop evaluations, we demonstrate that the bimetallic catalyst of Au-Ru nanoparticles can enable the nonenzymatic detection of glucose with a superior performance and stability. Furthermore, our biosensor shows good selectivity against other interferents, with a nonlinear dynamic range of 1–19 mM glucose. The Au-Ru catalyst has a conventional linear range of 1–10 mM, with a sensitivity of 0.2347 nA/(μM mm2) ± 0.0198 (n = 3) and a limit of detection of 0.068 mM (signal-to-noise, S/N = 3). The biosensor also exhibits a good repeatability and stability at 37 °C over a 3 week incubation period. Finally, we use a modified Butler–Volmer nonlinear analytical model to evaluate the impact of geometrical and chemical design parameters on our nonenzymatic biosensor’s performance, which may be used to help optimize the performance of this class of biosensors.

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Simultaneous measurements of glucose, lactate, and neurotransmitters (e.g., glutamate) in cell culture over hours and days can provide a more dynamic and longitudinal perspective on ways neural cells respond to various drugs and environmental cues. Compared with conventional microfabrication techniques, direct writing of conductive ink is cheaper, faster, and customizable, which allows rapid iteration for different applications. Using a simple direct writing technique, we printed biosensor arrays onto cell culture dishes, flexible laminate, and glass to enable multianalyte monitoring. The ink was a composite of PEDOT:PSS conductive polymer, silicone, activated carbon, and Pt microparticles. We applied 0.5% Nafion to the biosensors for selectivity and functionalized them with oxidase enzymes. We characterized biosensors in phosphate-buffered saline and in cell culture medium supplemented with fetal bovine serum. The biosensor arrays measured glucose, lactate, and glutamate simultaneously and continued to function after incubation in cell culture at 37 °C for up to 2 days. We cultured primary human astrocytes on top of the biosensor arrays and placed arrays into astrocyte cultures. The biosensors simultaneously measured glucose, glutamate, and lactate from astrocyte cultures. Direct writing can be integrated with microfluidic organ-on-a-chip platforms or as part of a smart culture dish system. Because we print extrudable and flexible components, sensing elements can be printed on any 3D or flexible substrate.