Fig. 1: Schematic of in vivo acoustic manipulation of genetically engineered bacteria.

The E. coli BL21 was genetically engineered by introducing a gene cluster encoding GVs, endowing these bacteria (GVs@E. coli) with distinct acoustic impedance relative to water. When these GVs@E. coli were systemically administrated into mice, they could be trapped into clusters and programmatically manipulated by acoustic tweezers equipped with a 3 MHz 64-element (8 × 8) 2D matrix array transducer. By employing electronically controlled beam-steering techniques, multi-programmable acoustic beams could be generated by the phased-array 2D matrix transducer, achieving the counter flow or on-demand flow of these bacteria into the preset blood vessels in live mice. Using the fluorescence-labelled GVs@E. coli, the manipulation process could be clearly observed via the mouse dorsal skin-fold window chamber model under the inverted fluorescence microscopy.