By Joseph Nuffer Cavalier Daily Senior Writer
In the past, there has been a stark difference between human innovation and nature's ways of solving similar problems. As Janine M. Benyus chronicles in "Biomimicry: Innovation Inspired by Nature," scientists are now attempting to apply nature's methods to diverse fields such as agriculture, materials, computing and business.
"That ability to recognize the genius in the natural world is where biomimicry begins," Benyus says.This approach to problem solving has been adopted by some researchers at the University's biomedical engineering department. Dr. Shasha Klibanov, Dr. Jonathan Lindner and graduate student Jack Rychack are applying this school of thought to microbubbles, an emerging new contrast agent.
The goal of microbubbles is to identify where a pathology, like a tumor or inflammation, is located within the body. Other options for identifying pathologies currently include invasive surgery and MRIs. Surgery obviously is not a practical solution because of the difficulty and risks associated with it. MRIs, while capable imaging devices, are time-consuming and not widespread.
Since it is prevalent among physicians, ultrasound provides an ideal technique to couple with microbubbles. According to Rychak, "The microbubbles appear as a highlighted signal within the tissue or organ, enhancing the image." Additionally, the gas inside the bubbles oscillates and reflects additional light to provide a highlighted region.
Despite the great promise shown by microbubbles in ultrasound, the technique is not without problems. "Bubbles typically have low binding, pass the target site, and adhesion efficiency is low," Rychack said. Wall shear stress is another problem, causing the bubbles to break. Bubbles bind only during a narrow range of wall shear stresses. To solve this problem, researchers have looked to the way in which the body accomplishes a similar process with leukocytes, Dr. Klaus Ley's specialty here at the University.
Leukocytes are the white blood cells the body uses to fight infection. Leukocytes cruise through the blood stream very quickly and then have to bind to the area of infection. "It is similar to traveling 180 mph in a car and having to come to a complete stop," Rychack said.
A recent presentation given by Rychak, Lindner, Ley and other collaborators reported on advances in microbubbles. According to their presentation, to bind at these very high speeds, the "arms" of the white blood cells actually deform when contacting the wall. These blood cells form a tear drop shape that increases the contact area with the infected area. This deformation helps the blood cell to establish firm adhesion to the vessel wall. Additionally, the leukocytes have "arms" that also help binding to the surface.
Applying this to microbubbles, the bubbles were deformed with a syringe, creating an excess surface area. "These new microbubbles appear wrinkled and look like a partially inflated balloon," Rychack said during an interview. This excess surface area around the gas is key to binding to the surface, nearly doubling the binding efficiency at most wall shear stresses. These wrinkled microbubbles also formed attachments greater than 10 seconds more often in vivo and in vitro.
Also, micron projections can be added to the microbubbles, similar to arms.The addition of arms to the spherical microbubbles had a similar impact as the wrinkles. These microbubbles had around 50 percent more sustained attachments than spherical ones.Besides arms, ligands also have been added to microbubbles to enhance attachment. These work best at high target density and offer improvements at higher shear stresses. By mimicking the leukocytes traveling through the body, researchers have been able to improve diagnostic capabilities of microbubbles.
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