Being small is good. Being very small is better. This is the philosophy of Mark Kester, professor of biomedical engineering, pharmacology, molecular physiology and biophysics at the University of Virginia.
Kester’s research focuses on particles smaller than 100 nanometers, called nanoparticles, which can be engineered to have new properties that cannot be explained by conventional physics. By harnessing these properties – which is the mission of UVA’s nanoSTAR institute – nanotechnology can produce more efficient drugs and vaccines, faster computers, better batteries for the next generation of electric cars, wings of lighter aircraft and countless other possibilities.
Kester heads the institute, which reports to AVU’s School of Engineering, but is a collaborative research effort that incorporates professors from all backgrounds.
This summer, the institute added another layer to its undergraduate summer research program, which has historically placed rising sophomores in nanotechnology labs that match their academic interests. After a year of delay due to the pandemic, Kester and the institute organized the nanoSTAR Summer Program for Entrepreneurial Engineering at the Nanoscale. With the help of Dr. Bernie Carlson, Director of Engineering Programs at AVU, and supported by a $ 100,000 grant from the Jefferson Trust, nine students had the opportunity to develop their own intellectual property while acquiring the entrepreneurial skills to eventually bring it to market. .
Ziyuan Wang, a third-year physics and psychology student, was one such student. Through her nanoscale research, under the supervision of Dr. Bellave Shivaram, associate professor of physics, Wang plans to explore the peculiar behaviors of superfluidity – a state of matter that is neither gaseous, liquid nor solid – using superfluid helium droplets. With zero viscosity and the ability to flow endlessly, Wang describes matter as magical, as it can crawl over walls and pass through containers undisturbed.
“We’re studying superfluid, like a lot of labs around the world, because it’s a very good model of the quantum world,” Wang said. “This project may one day provide us with more information about the properties of the quantum world that we can observe macroscopically.”
(Superfluid can also help explain the origins of the universe, but we’ll get to that later.)
Before Wang, alongside his two undergraduate colleagues Maxwell Wisnieski and Rose Knight, could explore the special properties of superfluid helium, they first had to design a device to observe these droplets at the nanoscale. . This was in the form of a metal vacuum chamber containing a window covered with a thin layer of cesium only a few atoms wide. At the start of the summer program, Wang began to assemble the chamber while his teammates began to develop a laser beam controller system and a power supply to operate the device. By early September, the group had completed their separate tasks and will soon begin using the laser system to draw patterns on the cesium surface.
“Upon entering, I had no idea what a vacuum chamber looked like,” Wang said. “You have to go through a lot of datasheets and manuals to see how it all works, because nothing we received came with very specific instructions. … But we figured it out along the way.
Since cesium reacts violently with oxygen and water, the group’s biggest challenge has been to reduce the vacuum to a pressure low enough, to the point that neither oxygen nor water remains inside. Many screws and five vacuum pumps later, Wang was able to achieve a sufficiently low pressure by wrapping the vacuum in heating bands for an eight-hour slow cooking to 150 degrees Celsius.
“In our next step, we will place cesium dispensers in the vacuum and form a thin layer of cesium on this mirror,” Wang said. “We will then be directing lasers at it to draw pictures, to make sure we can later manipulate helium droplets on the surface.”
Rather than having a directly marketable end product, Wang explained that the cesium coating they are working on has applications in many areas, from coatings on eyeglass lenses and furniture surfaces to military machinery and solar panels. energy efficient. Additionally, the knowledge they hope to gain can create vistas for furthering the prospect of quantum computing – a method of computation that outperforms supercomputers, with the ability to analyze massive amounts of data to solve complex problems. and find optimal combinations.
When it comes to explaining the origins of the universe, two discoveries have led to theories that put superfluid helium at the start. The first is that unlike normal fluids which have a tornado-like vortex when rotated, superfluid helium creates multiple vortices. The second is that the universe had a uniform density when it started, just like the superfluid.
“Scientists speculated that these vortices that are present when you spin a superfluid droplet could be how the first galaxies formed in a universe,” Wang said. “This is something that we may be able to observe in the future. “
While Wang was working on nanomaterials, Christopher Nguyen, third-year major in biochemistry and ROTC Army cadet, used the eight-week summer program to advance a nanomedicine project called Manifold. As part of the Virginia iGEM team, led by UVA biology professor Dr Keith Kozminski, the group is developing a biosynthetic device that it hopes will help alleviate drug shortages, especially for complex drugs that save lives.
For their proof of concept, the group uses an over-the-counter heart drug, resveratrol. Since drugs of similar complexity cannot be synthesized as efficiently as simpler drugs, such as aspirin, many pharmacies do not stock them, often resulting in restricted access for patients.
The problem of scarcity arises from the long and inefficient processes of plant and then chemical synthesis, by which complex drugs are mainly produced. Plant synthesis requires a lot of space and resources, while chemical synthesis consists of many reactions and purification steps, producing low yields and high impurities.
To counter these inefficiencies, Manifold is introducing a more sustainable approach to prokaryotic biosynthesis – the process by which bacterial cells “grow” a desired drug – to the pharmaceutical industry. Unlike plant and chemical synthesis, biosynthesis places drug-producing bacteria in bioreactors in which temperature, pH, and growth medium can be controlled for large volumes of cells. With higher temperatures and ideal growing conditions, the rate of biosynthesis increases, allowing these bacteria to mass produce the desired drug.
“Cells are very special in that they have undergone billions of years of evolution, which allows them to create complicated structures very efficiently,” Nguyen said. “Many of these complex drugs are already encoded in their genome. All you have to do is find a way to mass-produce these drugs beyond what [bacterial cells] normally do.
To make a biosynthesis process even more efficient, Nguyen’s group tackles four issues, all of which arise from the fact that biosynthesis occurs in the cytosol, or the liquid interior, of bacterial cells. With such a large reaction space, biosynthesis encounters a loss of intermediates and flow imbalance, where the intermediates diffuse anywhere in the cell and prevent reactions; as well as competition pathways, in which intermediates are used in bad reactions to produce unwanted products. In addition, the generation of toxic products is quite common and can damage or even kill the bacterial cell due to the lack of natural compartmentalization. All of these problems inhibit industrial biosynthesis.
Using special organelles called bacterial microcompartments, which are only found in specific types of bacteria, Nguyen’s group designs artificial DNA scaffolds that locate certain enzymes inside these organelles to solve the four problems. of biosynthesis. Using bacterial microcompartments 40 to 200 nanometers in diameter, biosynthetic reactions occur in a smaller and better organized space; the intermediates are sequestered from the cytosol, the toxic substances are encapsulated inside the organelle and the inability of the intermediates to diffuse outside the microcompartments prevents competition of the pathways.
“Essentially, we are trying to create a bacterial cell capable of sustainably producing all of the pharmaceuticals needed in modern medicine without being limited by the existing four issues of biosynthesis,” Nguyen said.
After creating their proof of concept by synthesizing resveratrol in E. coli, Manifold received a provisional patent and is now filing a full patent. In November, the Virginia iGEM team will present their research and represent the University of Virginia at the international synthetic biology competition called the Giant Jamboree.
“This is a new synthetic biology platform,” Nguyen said. “No company has really done this, and it solves so many problems in pharmaceutical manufacturing and medicine, while introducing future applications in agricultural biotechnology, chemical manufacturing, biofuels and nanotechnology. I can’t wait to see where this technology goes.
In the next iteration of the nanoSTAR entrepreneurial program, the institute hopes to fund 30 to 40 students, instead of nine, and expand to invite historically black colleges and universities in the Mid-Atlantic region to participate.
“The project covers the breadth and depth of nanotechnology here at the University,” Kester said. “At the end of the day, that’s what we want to do… get great ideas, work with professors and turn them into business plans that could be leveraged in companies. “