Ultrasound-stimulated Brownian ratchet enhances diffusion of molecules retained in hydrogels

We demonstrate that low-frequency ultrasonic stimulation applied directly to a hydrogel, at energy levels below the cavitation threshold, can control the release of a therapeutic molecule. The hydrogel that contained the molecules was enclosed within a hollow acoustic horn. The harmonic modes in the acoustic horn combined with the physical gel structure to induce a flashing ratchet that released all of the retained molecules in less than 90 s at an intensity of 1.5 W cm−2 (applied energy of 135 J cm−2, ultrasound center frequency of 27.9 ± 1.5 kHz). In contrast, ultrasound is used currently as a remote stimulus for drug-delivery systems, at energy levels above the cavitation threshold. The low-energy flashing ratchet approach that we describe is applicable to drive the diffusion of molecules in a range of gels that are ubiquitous in biomedical systems, including for example in drug delivery, molecule identification and separation systems. Low-frequency ultrasound stimulation was applied directly to a hydrogel contained within a hollow acoustic horn at energy levels below the cavitation threshold. This stimulation generated harmonic modes within the acoustic horn that induced a flashing-ratchet, which quickly directed the diffusion and release of a therapeutic molecule retained in the hydrogel. This flashing ratchet approach can be applied to drive the diffusion of molecules in a range of gels that are ubiquitous in biomedical systems, including for example in drug delivery, molecule identification and separation systems. [Display omitted]