With approximately 48,000 attributed deaths in 2017, the opioid overdose is now the leading cause of death amongst Americans under the age of 50. The overdose process can be interrupted by the administration of naloxone, a safe and effective opiate antagonist that can reverse the effects of overdose and minimizing the delay in administering the antidote is critical in preventing permanent damage to patients. A closed-loop implantable drug delivery system is an ideal solution to minimize the response time, however, they often feature complex designs that are expensive to fabricate and require a more invasive surgical implantation. Here we propose a simple, low-cost, minimally-invasive automatic antidote delivery device (A2D2) that can administer a large dose of naloxone upon detection of overdose-induced respiratory failure. The subcutaneously placed device can be activated using an externally applied time varying magnetic field from a wearable device. Using a custom magnetic field generator, we were able to release the drug within 10 s. Our bench-top evaluation showed that A2D2 can release 1.9 mg of powdered drug within 60 s and up to 8.8 mg in 600 s. We also performed in vivo evaluation to demonstrate rapid drug releasing capability in the subcutaneous space of mice. However, we saw a small amount of leakage (1.75% of payload) over the course of 1000 h of simulated implantation. Thus, additional research is needed to verify the long term stability of our device and to demonstrate the closed-loop release mechanism to revive overdosed animals. Nevertheless, our preliminary results show the potential of using a simple, low-cost, subcutaneous device for emergency drug delivery application.
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.
Glutamate, one of the main neurotransmitters in the brain, plays a critical role in communication between neurons, neuronal development, and various neurological disorders. Extracellular measurement of neurotransmitters such as glutamate in the brain is important for understanding these processes and developing a new generation of brain–machine interfaces. Here, we demonstrate the use of a perovskite nickelate–Nafion heterostructure as a promising glutamate sensor with a low detection limit of 16 nM and a response time of 1.2 s via amperometric sensing. We have designed and successfully tested novel perovskite nickelate–Nafion electrodes for recording of glutamate release ex vivo in electrically stimulated brain slices and in vivo from the primary visual cortex (V1) of awake mice exposed to visual stimuli. These results demonstrate the potential of perovskite nickelates as sensing media for brain–machine interfaces.
COMMUNICATION (1 of 7)A λ ε λIn this paper, a novel strategy to control the orientation of nano wrinkles by applying a thickness-gradient to a bilayer-system is presented. Surface modification by plasma treatment on ultraviolet light-curable polysiloxanebased resin applies biaxial compressive strain, resulting in the formation of randomly oriented nanowrinkles over a large-area. The thickness-gradient of the resin, given by the meniscus formed between the groove made with patterned polydimethylsiloxane (PDMS) after spin-coating of the resin, directed wrinkle propagation. Given the propagation orientation, nanowrinkles were well aligned over a large-area using a simple and accessible method.
Here we demonstrate a simple and scalable nanotexturing method for both planar (films) and nonplanar (tubes) polytetrafluoroethylene (PTFE) surfaces using a commercial desktop oxygen plasma etcher. The simple process can generate semiordered nanopillar structures on both tubular and planar samples with high radial and axial uniformity. We found that the resulting surfaces exhibit good in vitro bactericidal and in vivo anti-inflammatory properties. When tested against Staphylococcus aureus, the nanotextured surfaces showed significantly decreased live bacteria coverage and increased dead bacteria coverage, demonstrating significant bactericidal functionality. Moreover, the etched planar PTFE films exhibited better healing and inflammatory responses in the subcutis of C57BL/6 mice over 7 and 21 days, evidenced by a thinner inflammatory band, lower collagen deposition, and decreased macrophage infiltration. Our results suggest the possibility of using this simple process to generate large scale biomimetic nanotextured surfaces with good antibiofouling properties to enhance the functionality of many implantable and other biomedical devices.
For legged robots, collecting tactile information is essential for stable posture and efficient gait. However, mounting sensors on small robots weighing less than 1 kg remain challenges in terms of the sensor’s durability, flexibility, sensitivity, and size. Crack-based sensors featuring ultra-sensitivity, small-size, and flexibility could be a promising candidate, but performance degradation due to crack growing by repeated use is a stumbling block. This paper presents an ultra-stable and tough bio-inspired crack-based sensor by controlling the crack depth using silver nanowire (Ag NW) mesh as a crack stop layer. The Ag NW mesh inspired by skin collagen structure effectively mitigated crack propagation. The sensor was very thin, lightweight, sensitive, and ultra-durable that maintains its sensitivity during 200,000 cycles of 0.5% strain. We demonstrate sensor’s feasibility by implementing the tactile sensation to bio-inspired robots, and propose statistical and deep learning-based analysis methods which successfully distinguished terrain type.
Vagus nerve stimulation (VNS) has the potential to treat various peripheral dysfunctions, but the traditional cuff electrodes for VNS are susceptible to off‐target effects. Microelectrodes may enable highly selective VNS that can mitigate off‐target effects, but they suffer from the increased impedance. Recent studies on microelectrodes with non‐Euclidean geometries have reported higher energy efficiency in neural stimulation applications. These previous studies use electrodes with mm/cm‐scale dimensions, mostly targeted for myelinated fibers. This study evaluates fractal microelectrodes for VNS in a rodent model (N = 3). A thin‐film device with fractal and circle microelectrodes is fabricated to compare their neural stimulation performance on the same radial coordinate of the nerve. The results show that fractal microelectrodes can activate C‐fibers with up to 52% less energy (p = 0.012) compared to circle microelectrodes. To the best of the knowledge, this work is the first to demonstrate a geometric advantage of fractal microelectrodes for VNS in vivo.
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