“Drills” and Nanodroplets prove to be ultrasonic and effective in fighting hard blood clots

A new technique developed by researchers at NC State, UNC, and Michigan uses an ultrasonic “drill” to explode nanodroplets into and around hard blood clots. As nanodroplets explode into microbubbles, ultrasound causes the microbubbles to oscillate, disrupting the physical structure of the clot. Credit: Leela Goel

Engineering researchers have developed a new technique for removing particularly hard blood clots, using engineered nano-drops and an ultrasonic “drill” to distribute the clots inside. The technique has not yet undergone clinical examination. In vitro tests have shown promising results.

Specifically, the new approach is designed to treat delayed blood clots that arise over a long period of time and are particularly dense. These clots are particularly difficult to treat because they are less porous than other clots, so it is difficult for drugs that dissolve blood clots to enter the clot.

The new technique has two key components: nano drops and an ultrasonic drill.

Nano droplets are made up of tiny lipid spheres filled with liquid perfluorocarbon (PFC). Specifically, nano droplets are filled with low-boiling point PFCs, which means that a small amount of ultrasonic energy will cause the liquid to convert to gas. When converted to gas, PFCs expand rapidly, evaporating nano-droplets and forming microscopic bubbles.

“We insert nanodroplets into the clot site, and because the nanodroplets are very small, they are able to insert and convert microbubbles inside the clots when they are under the influence of ultrasound,” says Leela Goel. lana. Dr. Goel is. student in the joint department of biomedical engineering North Carolina State University and the University of North Carolina at Chapel Hill.

Once the microbubbles have formed inside the clots, the fact that the clots are in succession to the ultrasound oscillates the microbubbles. The rapid vibration of the microbubbles causes them to act like small marches, disrupting the physical structure of the clot and helping the clots to dissolve. This vibration creates larger holes in the clot mass so that anti-clotting drugs can penetrate deep into the clot through the bloodstream and break it further.

The technique is achieved by means of an ultrasonic drill, which is an ultrasonic transducer that is small enough to enter the blood vessel through a catheter. The drill can direct the ultrasound directly, which makes it very accurate. It is also capable of activating nanodroplets to a sufficiently focused ultrasonic energy site without causing damage to surrounding healthy tissues. The drill has a tube that allows users to inject nano droplets.

In in vitro tests, researchers have used a variety of drug treatment combinations, microbubbles and ultrasound to remove clots and compared the new technique using nanodroplets and ultrasound.

“We found that the use of nanotubes, ultrasound, and drug treatment was the most effective, reducing the clot size by 40% or 9%,” says Xiaoning Jiang, Professor of Mechanical and Aerospace Engineering at Dean F. Duncan. At NC State and author of the corresponding writer. “Using nanodroplets and ultrasound alone, the mass was reduced by 30%, by 8% plus or minus. The next best treatment was drug treatment, microbubbles and ultrasound, which reduced the mass of clots by only 17%, by 9% plus or minus. The 30-minute treatment was performed at the same time.

“These initial test results are very promising.”

“The use of ultrasound to disrupt blood clots has been studied over the years, including major studies in several European patients, with little success,” says author Paul Dayton, William R. Kenan Jr. Professor of Biomedical Engineering at UNC and NC state. “However, the addition of low-boiling nano-drops, combined with ultrasonic drilling, has been a significant advance in this technology.”

“The following steps will help us evaluate technical models for how safe and effective the treatment of deep vein thrombosis can be in animal models,” says Zhen Xu, a professor and co-author of biomedical engineering at the University of Michigan. of paper.

The article, “Nanodroplet-Mediated Catheter-Directed Sonothrombolysis of Retracted Blood Clots,” is published in open access journal Microsystems and Nanoengineering. The document is by Dr. Huaiyu Wu and Dr. Bohua Zhang. NC State students; and Jinwook Kim, a postdoctoral fellow in the United States Department of Biomedical Engineering at UNC and NC.

The work was carried out with the support of the National Institutes of Health, with a grant of R01HL141967.

Reference: Leela Goel, Huaiyu Wu, Bohua Zhang, Jinwook Kim, Paul A. Dayton, Zhen Xu, and Xiaoning Jiang, January 6, 2021, “Nanodroplet-Oriented Catheters for Sonotrombolysis sonotrombolysis of blood clots “. Microsystems and Nanoengineering.
DOI: 10.1038 / s41378-020-00228-9

SonoVascular, Inc., created by Jiang. a startup called NC State’s ultrasonic “drill” technology. SonoVascular and NC State hope to work with industry partners to advance the technology. Low-boiling nano-drops, invented by Dayton, have also been granted a U.S. patent. Triangle Biotechnology, Inc. the company has licensed this technology created by Dayton. Research authors Dayton, Kim, Xu and Jiang have also filed a patent application related to sonotrombolysis using nanodroplets.

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