In-vivo programmable acoustic manipulation of genetically engineered bacteria

Abstract

Acoustic tweezers can control target movement through the momentum interaction between an acoustic wave and an object. This technology has advantages over optical tweezers for in-vivo cell manipulation due to its high tissue penetrability and strong acoustic radiation force. However, normal cells are difficult to acoustically manipulate because of their small size and the similarity between their acoustic impedance and that of the medium. In this study, we use the heterologous expression of gene clusters to generate genetically engineered bacteria that can produce numerous sub-micron gas vesicles in the bacterial cytoplasm. We show that the presence of the gas vesicles significantly enhances the acoustic sensitivity of the engineering bacteria, which can be manipulated by ultrasound. We find that by employing phased-array-based acoustic tweezers, the engineering bacteria can be trapped into clusters and manipulated in vitro and in vivo via electronically steered acoustic beams, enabling the counter flow or on-demand flow of these bacteria in the vasculature of live mice. Furthermore, we demonstrate that the aggregation efficiency of engineering bacteria in a tumour is improved by utilizing this technology. This study provides a platform for the in-vivo manipulation of live cells, which will promote the progress of cell-based biomedical applications.

Acoustic Trapping and Manipulation of Hollow Microparticles under Fluid Flow Using a Single-Lens Focused Ultrasound Transducer

“…Additionally, if this method were to be applied to drug carrier systems, then it would be necessary to test its performance in biological fluids, such as blood. 54,55 There are other materials such as polymeric particles 56,57 and gas vesicles 58,59 in the literature with negative acoustic contrast factor. It would be worthwhile to compare the values of the expected negative contrast factor and range of acoustic radiation force between them.…”

“…There are other materials such as polymeric particles , and gas vesicles , in the literature with negative acoustic contrast factor. It would be worthwhile to compare the values of the expected negative contrast factor and range of acoustic radiation force between them.…”

Recent Advances in Acoustofluidics for Point‐of‐Care Testing

“…Further Optimization and exploration of existing acoustic technologies . The current acoustic devices demonstrate excellent performance in the manipulation of microparticles; however, it still remains a challenge for acoustofluidics to realize nanoparticle manipulation (e. g., bacteria, [58] viruses, exosomes, biomolecules) with high robustness level. In this scenario, the combination with immunoaffinity method [59] may provide new solution for the manipulation of bionanoparticles.…”

Applications of Serine Integrases in Synthetic Biology over the Past Decade

“…For example, two tyrosine recombinases Cre and FLP could be redesigned to respond to light and worked as optogenetic tools [94,95]. Although other physical factors have not been utilized as inducers for regulating integrase, the well-optimized designs that respond to sound [96], temperature [97], electricity [98], and magnetism [99] have been reported and may be potentially utilized.…”