Acoustic microbubble propulsion, train-like assembly and cargo transport

Controlled manipulation of microparticles in viscous fluids is crucial for advancements in biologics, biotechnologies, and biomedical applications. Current methods often involve external field gradients (optical, magnetic, acoustic, electric) or nonreciprocal motion within microstructures. However, these techniques face challenges when applied to viscous gels or complex fluids, unlike natural microswimmers (bacteria, spirochetes, spermatozoa). This paper addresses this gap by investigating the behavior of microbubbles in a shear-thinning gel confined within a narrow slit under acoustic excitation. The research question focuses on whether acoustic manipulation can achieve controlled microparticle transport within a viscous gel, mimicking the functionality of a cargo train at the microscale. The study's importance lies in developing a novel technique for microparticle manipulation in challenging environments, thereby opening new avenues for microfluidic applications, single-cell analysis in gel-like media (e.g., exosome investigation), and targeted drug delivery.

Existing methods for microparticle manipulation primarily utilize external field gradients (optical, magnetic, acoustic, electric) or exploit nonreciprocal motion within designed microstructures. Optical tweezers, using light gradients, were among the earliest techniques demonstrated. Subsequently, magnetic, acoustic, and electric field gradients were also employed. Acoustic, electric, magnetic, and light-based approaches can also induce propulsion by leveraging nonreciprocity within or anchored to microstructures. However, most prior research focused on simple viscous fluids like water. Artificial microswimmers have struggled to navigate viscous fluids, unlike their natural counterparts. Only a few synthetic microswimmers have successfully navigated viscous fluids, often employing magnetic propulsion through reciprocal motion or exploiting acoustic vortex beams for trapping in agarose gels. This study aims to expand the capabilities of acoustic manipulation by addressing the challenge of microparticle manipulation in viscous gels.

The experimental setup consisted of a piezo disc transducer mounted on a glass slide, generating acoustic waves. A shear-thinning KY gel was applied, and a glass capillary was positioned on top, creating a narrow slit. The system was placed under an inverted microscope with a high-speed camera. A theoretical model was developed to simulate the acoustic pressure amplification within the narrow slit using a two-cylinder approximation (glass slide and capillary). The model, based on the Helmholtz equation, calculates the acoustic pressure distribution, revealing pressure amplification at the slit. The experimental procedure involved observing microbubble nucleation, migration, and propulsion under varying acoustic excitation parameters (frequency and amplitude). High-speed imaging captured microbubble oscillations and shape changes (spherical to ellipsoidal). The acoustic radiation force on the microbubbles was calculated using a formula involving the acoustic pressure gradient and bubble radius. Experiments explored the self-assembly of microbubbles into trains, their propulsion, and the subsequent trapping and transport of microparticles (polystyrene beads, yeast cells) introduced into the gel. The effects of acoustic voltage and frequency on train formation and inter-microbubble distance were also investigated. High-speed image acquisition (40,420 fps) with image rearrangement techniques allowed detailed analysis of bubble oscillations.

The study revealed several key findings: 1. **Acoustic Pressure Amplification:** A theoretical model confirmed the amplification of acoustic pressure within the narrow slit between the glass slide and capillary. 2. **Microbubble Nucleation and Migration:** Microbubbles nucleated at the slit due to the amplified acoustic pressure, exhibiting cross-migration behavior. 3. **Discoidal Microbubble Propulsion:** Individual ellipsoidal microbubbles showed controlled propulsion along the slit, driven by the superposition of volume and shape oscillation modes. 4. **Self-Assembly into Trains:** Multiple microbubbles self-assembled into train-like arrangements, moving in unison at uniform velocity. 5. **Trapping and Transport of Microparticles:** Solid microparticles (polystyrene beads, yeast cells) were effectively trapped between adjacent microbubbles in the train and transported along with the train. The microparticles became trapped at the center point between bubbles due to radial forces, sliding along the bubble surface to the equator before migrating forward and becoming trapped. 6. **Controlled Release:** Deactivating the acoustic field resulted in the release of the trapped microparticles. 7. The number of bubbles in a train varied between 5 and 6 and depended on the excitation voltage but not the frequency. The interparticle distance decreased with increasing voltage. Leading and trailing bubbles oscillated more freely compared to the inner ones. 8. The study demonstrated the system's ability to trap and transport microparticles in a shear-thinning gel, showcasing its potential for applications in various biological fluids.

The findings demonstrate a novel method for controlled microparticle manipulation in viscous fluids using acoustically propelled microbubble trains. The self-assembly of microbubbles into trains, their capacity for trapping and transporting cargo, and the ability to release the cargo on demand represent a significant advance in microfluidics and related fields. The observed propulsion mechanism, involving the interplay of volume and shape oscillation modes, provides valuable insights into the dynamics of acoustically driven microbubbles. The success of this technique in a shear-thinning gel highlights its potential for biological applications where viscous fluids are prevalent. The study addressed the limitations of existing methods for microparticle manipulation in complex fluids. The results open new possibilities for developing advanced microfluidic devices for particle separation, single-cell analysis, and controlled drug delivery.

This study successfully demonstrated the controlled propulsion of microbubbles in a viscous gel, their self-assembly into functional train-like arrangements, and their ability to trap and transport microparticles. The findings showcase a novel method for manipulating microparticles in challenging environments, with potential applications in various fields such as microfluidics, biology, and medicine. Future work could focus on optimizing the system for specific applications, investigating the effects of different gel properties on microbubble behavior, and exploring more complex geometries for directed particle transport.

The current study focused on a specific type of shear-thinning gel (KY gel) and a limited range of microparticle sizes. Further research is needed to investigate the generalizability of the findings to different gel types and particle sizes. The theoretical model uses a simplified two-cylinder approximation, and more sophisticated modeling might be needed to capture the full complexity of the acoustic field. The directionality of microbubble propulsion warrants further investigation, as it might be influenced by subtle variations in the experimental setup or acoustic field.