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Many solid-dose oral drug products are engineered to release their active ingredients into the body at a certain rate. Techniques for measuring the dissolution or degradation of a drug product in vitro play a crucial role in predicting how a drug product will perform in vivo. However, existing techniques are often labor-intensive, time-consuming, irreproducible, require specialized analytical equipment, and provide only “snapshots” of drug dissolution every few minutes. These limitations make it difficult for pharmaceutical companies to obtain full dissolution profiles for drug products in a variety of different conditions, as recommended by the US Food and Drug Administration. Additionally, for drug dosage forms containing multiple controlled-release pellets, particles, beads, granules, etc. in a single capsule or tablet, measurements of the dissolution of the entire multi-particle capsule or tablet are incapable of detecting pellet-to-pellet variations in controlled release behavior. In this work, we demonstrate a simple and fully-automated technique for obtaining dissolution profiles from single controlled-release pellets. We accomplished this by inverting the drug dissolution problem: instead of measuring the increase in the concentration of drug compounds in the solution during dissolution (as is commonly done), we monitor the decrease in the buoyant mass of the solid controlled-release pellet as it dissolves. We weigh single controlled-release pellets in fluid using a vibrating tube sensor, a piece of glass tubing bent into a tuning-fork shape and filled with any desired fluid. An electronic circuit keeps the glass tube vibrating at its resonance frequency, which is inversely proportional to the mass of the tube and its contents. When a pellet flows through the tube, the resonance frequency briefly changes by an amount that is inversely proportional to the buoyant mass of the pellet. By passing the pellet back-and-forth through the vibrating tube sensor, we can monitor its mass as it degrades or dissolves, with high temporal resolution (measurements every few seconds) and mass resolution (700 nanogram resolution). As a proof-of-concept, we used this technique to measure the single-pellet dissolution profiles of several commercial controlled-release proton pump inhibitors in simulated stomach and intestinal contents, as well as comparing name-brand and generic formulations of the same drug. In each case, vibrating tube sensor data revealed significantly different dissolution profiles for the different drugs, and in some cases our method also revealed differences between different pellets from the same drug product. By measuring any controlled-release pellets, particles, beads, or granules in any physiologically-relevant environment in a fully-automated fashion, this method can augment and potentially replace current dissolution tests and support product development and quality assurance in the pharmaceutical industry.

 

Pneumatically-actuated soft robots have advantages over traditional rigid robots in many applications. In particular, their flexible bodies and gentle air-powered movements make them more suitable for use around humans and other objects that could be injured or damaged by traditional robots. However, existing systems for controlling soft robots currently require dedicated electromechanical hardware (usually solenoid valves) to maintain the actuation state (expanded or contracted) of each independent actuator. When combined with power, computation, and sensing components, this control hardware adds considerable cost, size, and power demands to the robot, thereby limiting the feasibility of soft robots in many important application areas. In this work, we introduce a pneumatic memory that uses air (not electricity) to set and maintain the states of large numbers of soft robotic actuators without dedicated electromechanical hardware. These pneumatic logic circuits use normally-closed microfluidic valves as transistor-like elements; this enables our circuits to support more complex computational functions than those built from normally-open valves. We demonstrate an eight-bit nonvolatile random-access pneumatic memory (RAM) that can maintain the states of multiple actuators, control both individual actuators and multiple actuators simultaneously using a pneumatic version of time division multiplexing (TDM), and set actuators to any intermediate position using a pneumatic version of analog-to-digital conversion. We perform proof-of-concept experimental testing of our pneumatic RAM by using it to control soft robotic hands playing individual notes, chords, and songs on a piano keyboard. By dramatically reducing the amount of hardware required to control multiple independent actuators in pneumatic soft robots, our pneumatic RAM can accelerate the spread of soft robotic technologies to a wide range of important application areas. 

This paper introduces BioScript , a domain-specific language (DSL) for programmable biochemistry that executes on emerging microfluidic platforms. The goal of this research is to provide a simple, intuitive, and type-safe DSL that is accessible to life science practitioners. The novel feature of the language is its syntax, which aims to optimize human readability; the technical contribution of the paper is the BioScript type system. The type system ensures that certain types of errors, specific to biochemistry, do not occur, such as the interaction of chemicals that may be unsafe. Results are obtained using a custom-built compiler that implements the BioScript language and type system.