The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier.

While identifying acute HIV infection is critical to providing prompt treatment to HIV-positive individuals and preventing transmission, existing laboratory-based testing methods are too complex to perform at the point of care. Specifically, molecular techniques can detect HIV RNA within 8–10 days of transmission but require laboratory infrastructure for cold-chain reagent storage and extensive sample preparation performed by trained personnel. Here, we demonstrate our point-of-care microfluidic rapid and autonomous analysis device (microRAAD) that automatically detects HIV RNA from whole blood. Inside microRAAD, we incorporate vitrified amplification reagents, thermally-actuated valves for fluidic control, and a temperature control circuit for low-power heating. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) products are visualized using a lateral flow immunoassay (LFIA), resulting in an assay limit of detection of 100 HIV-1 RNA copies when performed as a standard tube reaction. Even after three weeks of room-temperature reagent storage, microRAAD automatically isolates the virus from whole blood, amplifies HIV-1 RNA, and transports amplification products to the internal LFIA, detecting as few as 3 × 10⁵ HIV-1 viral particles, or 2.3 × 10⁷ virus copies per mL of whole blood, within 90 minutes. This integrated microRAAD is a low-cost and portable platform to enable automated detection of HIV and other pathogens at the point of care.

The demand for wearable and point-of-care devices has led to an increase in electrochemical sensor development to measure an ever-increasing array of biological molecules. In order to move from the benchtop to truly portable devices, the development of new biosensors requires miniaturized instrumentation capable of making highly sensitive amperometric measurements. To meet this demand, we have developed KickStat, a miniaturized potentiostat that combines the small size of the integrated Texas Instruments LMP91000 potentiostat chip (Texas Instruments, Dallas, TX, USA) with the processing power of the ARM Cortex-M0+ SAMD21 microcontroller (Microchip Technology, Chandler, AZ, USA) on a custom-designed 21.6 mm by 20.3 mm circuit board. By incorporating onboard signal processing via the SAMD21, we achieve 1 mV voltage increment resolution and an instrumental limit of detection of 4.5 nA in a coin-sized form factor. This elegant engineering solution allows for high-resolution electrochemical analysis without requiring extensive circuitry. We measured the faradaic current of an anti-cocaine aptamer using cyclic voltammetry and square wave voltammetry and demonstrated that KickStat’s response was within 0.6% of a high-end benchtop potentiostat. To further support others in electrochemical biosensors development, we have made KickStat’s design and firmware available in an online GitHub repository.

Objectives: No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implications of muscle‐derived motor‐endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury.Methods: Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post‐injury. Harvested porcine larynges were examined for volume, gene expression, and histology.Results: MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of videolaryngoscopy post‐injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE‐injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post‐mortem, the MEE‐injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR.Conclusions: Minimally invasive MEE injection appears to establish an early molecular and microenvironmental framework to encourage innate RLN regeneration. Longer follow‐up is needed to determine if early findings will translate into functional contraction.Level of Evidence: NA Laryngoscope, 134:272–282, 2024