Olfactory Projections to Locomotor Control Centers in the Sea Lamprey.

Although olfaction is well known to guide animal behavior, the neural circuits underlying the motor responses elicited by olfactory inputs are poorly understood. In the sea lamprey, anatomical evidence shows that olfactory inputs project to the posterior tuberculum (PT), a structure containing dopaminergic (DA) neurons homologous to the mammalian ventral tegmental area and the substantia nigra pars compacta. Olfactory inputs travel directly from the medial olfactory bulb (medOB) or indirectly through the main olfactory bulb and the lateral pallium (LPal).

Hydrodynamic considerations for spring-driven autoinjector design.

In recent years, significant progress has been made in the studies of the spring-driven autoinjector, leading to an improved understanding of this device and its interactions with tissue and therapeutic proteins. The development of simulation tools that have been validated against experiments has also enhanced the prediction of the performance of spring-driven autoinjectors. This paper aims to address critical hydrodynamic considerations that impact the design of spring-driven autoinjectors, with a specific emphasis on sloshing and cavitation.

The role of liquid rheological properties on the injection process of a spring-driven autoinjector.

Accurate injection time prediction is essential in developing spring-driven autoinjector devices since the drug delivery is expected to finish within seconds to bring convenience, reduce the risk for early lift-off, and provide a consistent experience to users. The Carreau model captures the liquid's shear-dependent viscosity measured in our experiments. Thus, a quasi-steady model, which uses the Carreau model to describe the liquid's viscosity, is developed to predict the injection time of spring-driven autoinjectors.

The air entrainment and hydrodynamic shear of the liquid slosh in syringes.

Understanding the interface motion and hydrodynamic shear induced by the liquid sloshing during the insertion stage of an autoinjector can help improve drug product administration. We perform experiments to investigate the interfacial motion and hydrodynamic shear due to the acceleration and deceleration of syringes. The goal is to explore the role of fluid properties, air gap size, and syringe acceleration on the interface dynamics caused by autoinjector activation.

Assessment of Cavitation Intensity in Accelerating Syringes of Spring-Driven Autoinjectors.

Purpose: Cavitation is an undesired phenomenon that may occur in certain types of autoinjectors (AIs). Cavitation happens because of rapid changes of pressure in a liquid, leading to the formation of small vapor-filled cavities, which upon collapsing, can generate an intense shock wave that may damage the device container and the protein drug molecules. Cavitation occurs in the AI because of the syringe-drug relative displacement as a result of the syringe's sudden acceleration during needle insertion and the ensuing pressure drop at the bottom of the container.

Modeling cavitation bubble dynamics in an autoinjector and its implications on drug molecules.

The collapse of cavitation bubbles induced by abrupt acceleration of the syringe in an autoinjector device can lead to protein aggregation. The details of bubble dynamics are investigated using an axisymmetric, three-dimensional simulation with passive tracers to illustrate the transport of protein molecules. When a bubble near the syringe wall collapses, protein molecules are concentrated in the re-entrant jet, pushed towards the syringe wall, and then spread across the wall, potentially leading to protein adsorption on the syringe wall and aggregation.

The Interface Motion and Hydrodynamic Shear of the Liquid Slosh in Syringes.

Purpose: Interface motion and hydrodynamic shear of the liquid slosh during the insertion of syringes upon autoinjector activation may damage the protein drug molecules. Experimentally validated computational fluid dynamics simulations are used in this study to investigate the interfacial motion and hydrodynamic shear due to acceleration and deceleration of syringes. The goal is to explore the role of fluid viscosity, air gap size, syringe acceleration, syringe tilt angle, liquid-wall contact angle, surface tension and fill volume on the interface dynamics caused by autoinjector activation.

An experimentally validated dynamic model for spring-driven autoinjectors.

This study focuses on developing a predictive dynamic model for spring-driven autoinjectors. The values of unknown physical parameters, such as the heat convection coefficient and the friction force between the plunger and the syringe barrel, are obtained by fitting the experimentally measured displacements of the plunger and the syringe barrel. The predicted kinematics of the components, such as the displacement and velocity of the syringe barrel, agree well with the experiments with a l-norm error smaller than 10%.

Performance characterization of spring actuated autoinjector devices for Emgality and Aimovig.

Autoinjectors are a convenient and efficient way to self-administer subcutaneous injections of biopharmaceuticals. Differences in device mechanical design can affect the autoinjector functionality and performance. This study investigates the performance differences of two single-spring-actuated autoinjectors.

Pressure and stress transients in autoinjector devices.

Spring-actuated autoinjectors delivering viscous drug solutions resulting from large drug concentrations require large spring forces which can create high peak pressures and stresses within syringes. The high peak pressures and stresses can lead to device failure. Measurements with a suite of novel instrumentation and analysis using numerical simulation explain the peak pressures and peak stresses as originating from mechanical impacts between moving components, the large acceleration of the components, and surprisingly, the production of tension waves in the liquid resulting in cavitation.