Experimental study of active control of microbubbles in blood flow by forming their aggregations

Masuda, Kohji; Koda, Ren; Watarai, Nobuyuki; Shigehara, Nobuhiko; Ito, Tetsuo; Kakimoto, Takashi; Miyamoto, Yoshitaka; Enosawa, Shin; Chiba, Tadatoshi

doi:10.1109/ultsym.2011.0503

Cited by 18 publications

(18 citation statements)

References 9 publications

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“…The propulsion direction can be tuned, i.e., with or against the flow, by positioning the piezo actuator facing or opposite the flow direction. Although microswarm formation and migration towards the wall are consistent with previous findings (45)(46)(47), we devise a strategy that apply these phenomena in developing an efficient navigation platform that can execute cross-stream and upstream motion against physiological flow conditions.…”

Section: Mechanism Of Acoustic Microswarm Formation and Its Translati...supporting

confidence: 79%

“…However, while resonating microbubbles confined in cylindrical shells generate large propulsive forces, the microbubbles are typically not stable, i.e., they grow over time; as such, driving them becomes a fundamental challenge. Researchers have also investigated the self-assembly of microbubbles (45)(46)(47), and to date, most such studies involve only trapping of microbubbles or microparticles when exposed to an external flow (48,49). Despite the interest in and potential of acousticbased microrobots of all types, a thorough investigation of how they navigate when exposed to physiological flow rates has yet to be made.…”

Section: Introductionmentioning

confidence: 99%

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Navigation of Ultrasound-controlled Swarmbots under Physiological Flow Conditions

Fonseca

Kohler

Ahmed

2022

Preprint

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Navigation of microrobots in living vasculatures is essential in realizing targeted drug delivery and advancing non-invasive surgeries. We developed acoustically-controlled swarmbots based on the self-assembly of clinically-approved microbubbles. Ultrasound is noninvasive, penetrates deeply into the human body, and is well-developed in clinical settings. Our propulsion strategy relies in two forces: the primary radiation force and secondary Bjerknes force. Upon ultrasound activation, the microbubbles self-assemble into microswarms, which migrate towards and anchor at the containing vessels wall. A second transducer, which produces an acoustic field parallel to the channel, propels the swarms along the wall. We demonstrated cross- and upstream navigation of the swarmbots at 3.27 mm/s and 0.53 mm/s, respectively, against physiologically-relevant flow rates of 4.2 to 16.7 cm/s. Additionally, we showed swarm controlled manipulation within mice blood and under pulsatile flow conditions of 100 beats per minute. This capability represents a much-needed pathway for advancing preclinical research.

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Section: Mechanism Of Acoustic Microswarm Formation and Its Translati...supporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Navigation of Ultrasound-controlled Swarmbots under Physiological Flow Conditions

Fonseca

Kohler

Ahmed

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…[40][41][42][43][44][45][46][47][48][49][50][51][52] Specially, MBs filled with gas are excellent for focusing ultrasound, and in response to ultrasound, MBs typically form aggregations. [53][54][55][56][57][58] Dayton et al demonstrated the use of acoustic radiation forces to trap groups of MBs when they were exposed to a flow field. [59] In a similar experiment, Masuda et al demonstrated preliminary result that ultrasound could manipulate MB clusters across a bifurcated channel.…”

Section: Introductionmentioning

confidence: 99%

“…[59] In a similar experiment, Masuda et al demonstrated preliminary result that ultrasound could manipulate MB clusters across a bifurcated channel. [54] However, these studies mainly focus on trapping MBs, [60][61][62][63] and still none of them take advantage of the wall condition to demonstrate manipulation. Despite the interest in and potential of acoustic-based microrobots of all types, a thorough investigation of how they can be navigated when exposed to physiological flow rates has yet to be made.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound‐Controlled Swarmbots Under Physiological Flow Conditions

Fonseca

Kohler

Ahmed

2022

Adv Materials Inter

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Navigation of microrobots in living vasculatures is essential in realizing targeted drug delivery and advancing non‐invasive surgeries. Acoustically‐controlled “swarmbots” are developed based on the self‐assembly of clinically‐approved microbubbles (MBs). Ultrasound is noninvasive, penetrates deeply into the human body, and is well‐developed in clinical settings. This propulsion strategy relies on two forces: the primary radiation force and the secondary Bjerknes force. Upon ultrasound activation, the MBs self‐assemble into microswarms, which migrate toward and anchor at the containing vessel's wall. A second transducer, which produces an acoustic field parallel to the channel, propels the swarms along the wall. Noting that human arteries have a blood flow 5–19 cm s−1, powerful features of cross‐ and upstream swarmbot navigation are demonstrated against physiologically‐relevant flow rates that reach 16.7 cm s−1. Additionally, controlled navigation of swarmbots is shown within mice blood and under pulsatile flow conditions of 100 beats per minute (bpm); an adult human heart at rest executes between 60 and 100 bpm. This capability represents a much‐needed pathway for advancing preclinical research.

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“…If microbubbles can be controlled in vivo, their ef ciency and ef cacy would be sigini cantly improved. To address this issue, we have proposed a technique that controls microbubble behavior in blood vessels using ultrasound emitted from the body surface [3][4][5]. In previous in vitro studies, we have con rmed and clari ed that microbubbles can be aggregated, induced, and trapped in vessels.…”

Section: Introductionmentioning

confidence: 99%

Automatic Doppler Volume Fusion of 3D Ultrasound using Point-based Registration of Shared Bifurcation Points

Onogi

Phan

Mochizuki

et al. 2015

ABE

Self Cite

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We previously proposed the use of acoustic microbubble delivery in blood vessels as a therapeutic application of microbubbles to improve the ef ciency of high-intensity focused ultrasound and the ef cacy of acoustic targeted drug therapy. Among the technical requirements for this technique is detailed visualization of the blood vessel network for navigation around a target such as a tumor. For this purpose, three-dimensional (3D) Doppler volumes, which can be acquired by matrix array imaging probes, are quite convenient because they allow the blood vessel structure to be extracted without segmentation. However, the acquirable volume is limited and incomplete because the Doppler signal depends on ow direction. To compensate for these issues, an ultrasound volume fusion technique is required. In this study, we propose a blood vessel volume fusion method by automatic registration among shared bifurcations. In addition, we propose a novel 3D ultrasound calibration method, which is needed to determine the initial transformation. Several optical markers are used as ducial markers in this calibration. To examine the feasibility of the proposed methods, calibration accuracy and volume fusion accuracy assessments were conducted using an arti cial blood vessel and in human subjects. Regarding calibration accuracy, the target registration error of the proposed method was 2.2 mm. Regarding volume fusion accuracy in the arti cial blood vessel, the mean distance between the shared bifurcations was reduced from 2.4 mm (initial transformation by tracking data) to 0.5 mm (registration of shared bifurcations). Regarding the volume fusion of blood vessels in human subjects, the distance was also reduced from 10.4 mm to 0.3 mm. The results demonstrate that the proposed methods are accurate for constructing large and complete blood vessel networks for navigation of microbubble delivery. Moreover, the methods may also be useful for extracting intraoperative blood vessel network to support minimally invasive surgery or therapy.

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Experimental study of active control of microbubbles in blood flow by forming their aggregations

Cited by 18 publications

References 9 publications

Navigation of Ultrasound-controlled Swarmbots under Physiological Flow Conditions

Navigation of Ultrasound-controlled Swarmbots under Physiological Flow Conditions

Ultrasound‐Controlled Swarmbots Under Physiological Flow Conditions

Automatic Doppler Volume Fusion of 3D Ultrasound using Point-based Registration of Shared Bifurcation Points

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