Ultrasonic Selective Opening of Microcavities for Drug Delivery Microimplants

We present a fully passive, ultraminiaturized drug delivery microchip that enables wireless, on-demand release via ultrasonic actuation - a mechanism not previously demonstrated in implantable drug delivery systems. By eliminating the need for integrated power and control components, the device achieves sub-millimeter dimensions (<0.2 mm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times 0.5$</tex-math> </inline-formula> mm <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\times 1$</tex-math> </inline-formula> mm), enabling minimally invasive implantation in sensitive or hard-to-reach tissues. The system relies on ultrathin metallic membranes (<100<inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu $</tex-math> </inline-formula>m wide, <200 nm thick), engineered to rupture selectively at predefined ultrasonic resonance frequencies. Membrane behavior is optimized through analytical and numerical modeling, and the devices are fabricated using standard, scalable MEMS microfabrication techniques. Selective actuation enables precise release of up to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2~\mu $</tex-math> </inline-formula>g of powder payload from individual microcavities in response to specific frequencies (360/420/580kHz), with membrane rupture occurring in <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in vivo</i> conditions at ultrasonic intensities within clinically safe limits (<150 mW/cm<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> ² </i>). This platform represents a significant step toward precise, programmable drug delivery in anatomically constrained or delicate regions.[2025-0104]