Development of Repetitive Mechanical Oscillation Needle-Free Injection through Electrically Induced Microbubbles

Abstract

We previously developed a novel needle-free reagent injection method based on electrically induced microbubbles. The system generates microbubbles and applies repetitive mechanical oscillation associated with microbubble dynamics to perforate tissue and introduce a reagent. In this paper, we propose improving the reagent injection depth by reflecting the shock wave through microbubble dynamics. Our results show that the developed shock wave reflection method improves the ability of the electrically induced microbubble injection system to introduce a reagent. The method extends the application potential of electrically induced microbubble needle-free injection.

Fig. 1.

Concept of repetitive mechanical oscillation needle-free injection based on electrically induced microbubbles. (A) Dynamics of the electrically induced microbubble, showing the formation, expansion, and shrinking of the microbubble and the shock wave and microjet from the microbubble. (B) Mechanism of the microbubble repetitive mechanical oscillation injection, microjet perforation of the target, shock wave expanding the wound, and the repeated process. (C) Mechanism of shock wave reflection enhancing perforation.

Fig. 2.

Experimental setup. (A) Schematic of the tissue injection experimental setup. (B) Photograph of a tissue injection experiment. (C) Schematic of the shock wave reflector. (D) Photograph of the microbubble injector integrated with the reflector. (E) Photograph of the schlieren photography experimental setup. (F) Schematic of the optical pathway of the schlieren photography.

Fig. 3.

Shock wave schlieren photography. (A) Shock wave generated from microbubble collapse and (B) shock wave generated by microbubble collapse and reflected by the reflector, where reflected shock waves are indicated by black arrows.

Fig. 4.

Tissue injection depth. (A and B) Injection depths without/with the reflector, with the first row showing bright-field images, the second row showing fluorescence images of tissue injected with fluorescent beads (used to measure the injection depth), and the third row showing binarized images (white part indicating fluorescence). (C and D) Injection depths at each power without and with reflector. *P < 0.05 versus sample without shock wave reflection (ANOVA using OriginLAB 2024).

Fig. 5.

Tissue injection wound area. (A and B) Wound areas without/with reflector, with the first row showing images of the wound and the second row showing binarized images (black part indicating the wound). (C and D) Wound areas at each power without/with the reflector. *P < 0.05 versus sample without shock wave reflection (ANOVA using OriginLAB 2024).

Fig. 6.

Injection depth and wound area versus (A) the distance from the microbubble generator tip to the tissue surface (*, &, and ^: P < 0.05 versus sample at a distance of 10 mm), (B) number of sets of pulses (* and &: P < 0.05 versus sample with 5 sets), and (C) focal distance (*, &, and ^: P < 0.05 versus sample with a focal distance of 10 mm) (ANOVA using OriginLAB 2024).