Search

Traditional implanted drug delivery systems cannot easily change their release profile in real time to respond to physiological changes. Here we present a microfluidic aqueous two‐phase system to generate microcapsules that can release drugs on demand as triggered by focused ultrasound (FUS). The biphasic microcapsules are made of hydrogels with an outer phase of mixed molecular weight (MW) poly(ethylene glycol) diacrylate that mitigates premature payload release and an inner phase of high MW dextran with payload that breaks down in response to FUS. Compound release from microcapsules could be triggered as desired; 0.4 μg of payload was released across 16 on‐demand steps over days. We detected broadband acoustic signals amidst low heating, suggesting inertial cavitation as a key mechanism for payload release. Overall, FUS‐responsive microcapsules are a biocompatible and wirelessly triggerable structure for on‐demand drug delivery over days to weeks. [ABSTRACT FROM AUTHOR]

The subharmonic threshold for ultrasound contrast agents has been defined as a 20–25 dB difference between the fundamental and subharmonic (2/1) spectral components of the backscatter signal. However, this Fourier-based criterion assumes a linear time-invariant signal. A more appropriate criterion for short cycle and frequency-modulated waveforms is proposed with an adaptive signal-processing approach based on the empirical mode decomposition (EMD) method. The signal is decomposed into an orthogonal basis known as intrinsic mode functions (IMFs) and a subharmonic threshold is defined with respect to the energy ratio of the subharmonic IMF component to that of the incident signal. The method is applied to backscatter data acquired from two polymer-shelled contrast agents, Philips (#38, mean diameter 2.0 \mu \textm ) and Point Biomedical (#12027, mean diameter 3.9 \mu \textm ). The acoustic backscatter signals are investigated for a single contrast agent subjected to monofrequency (20 MHz, 20 cycles) and chirp (15–25 MHz, 20 cycles) forcing for incident pressures ranging from 0.5 to 2.4 MPa. In comparison to the spectral peak difference (20 dB) criterion, the EMD method is more sensitive in determining subharmonic signals. [ABSTRACT FROM PUBLISHER]