Tunable Gas Bubbles within Gas-Encapsulating Microcapsules (GEMs) for Buoyancy-Driven Purification.

Certain aquatic microorganisms regulate buoyancy by producing intracellular gas vesicles. Separately, cavitation in drought-stressed plants illustrates how negative pressure can spontaneously generate gas bubbles. Inspired by both natural phenomena, we present gas bubble-encapsulating microcapsules (GEMs) that combine these principles, mimicking the buoyancy regulation of microbial gas vesicles and cavitation within plants by leveraging negative pressure to nucleate and control the size of gas bubbles. GEMs are derived from poly(d,l-lactide--glycolide) (PLGA) microcapsules with an aqueous core and a solid polymeric shell. Microcapsules experience a phenomenon known as osmosis-induced cavitation when transferred into an environment with high osmotic pressure. In this phenomenon, the internal aqueous phase experiences a large negative pressure, triggering cavitation, where gas bubbles nucleate and grow from dissolved air to form GEMs. This cavitation-based approach enables precise postfabrication control of bubble size by simply modulating the external salt concentration. We demonstrate that the buoyancy imparted by these internal gas bubbles allows for the effective purification of GEMs from impurities, such as polymer debris and defective microcapsules. Our strategy offers a straightforward, scalable, and highly controllable approach for producing GEMs. It also establishes a synthetic analogue to microbial gas vesicle systems with potential applications in purification, ultrasound theranostics, gastric drug delivery, and pressure-responsive delivery of active agents.