The addition of nano-scale organisms could potentially expand the range of medical conditions diagnosed with noninvasive ultrasound.
The technology opens the door to a variety of potential imaging applications where the nanometer size is advantageous, such as labeling targets outside the bloodstream, detecting tumors, and monitoring the gastrointestinal system.
To create the nano-scale organisms, Mikhail Shapiro at the California Institute of Technology and colleagues turned to nature for inspiration. The result is the first ultrasound imaging agent based on genetically encoded gas-containing structures.
Shapiro’s team utilized photosynthetic micro-organisms that form gas nanostructures called “gas vesicles,” which the researchers discovered were excellent imaging agents for ultrasound, with several unique properties making them especially useful in biomedical applications.
Better than microbubbles
Previously, most ultrasound imaging agents were based on small gas bubbles, which ultrasound can detect because they have a different density than their surroundings and can resonate with sound waves.
Unfortunately, these “microbubbles” could only be synthesized at sizes of several microns (or larger) because of their fundamental physics: the smaller you tried to make them, the less stable they became. As a result, they were always confined to the bloodstream and could only image a limited number of biological targets.
The researchers wanted to find another way of making gas-filled structures that could be nanoscale. In particular, certain photosynthetic micro-organisms regulate their buoyancy by forming protein-shelled gas nanostructures called “gas vesicles” inside the cell body.
These structures interact with gas in a way that is fundamentally different from microbubbles, allowing them to have nanometer size. In this study, they discovered that gas vesicles are excellent imaging agents for ultrasound.
The researchers showed that they were able to easily attach biomolecules to the gas vesicle surface to enable targeting. In addition, because these structures are encoded as genes, they now have a chance to modify these genes to optimize gas vesicles’ ultrasound properties.
Already the team has shown that gas vesicles from different species, which vary in genetic sequence, exhibit different properties that can be used to, for example, distinguish them from each other in an ultrasound image.
The journal Nature Nanotechnology reported the team’s findings.