By John Giardina (CLAS ’14)
For engineers, it is certainly true that structure and properties are inextricably connected. They are tasked with molding available resources to accomplish tasks and find solutions. That is why spectroscopic techniques are so important to researchers who work at the molecular level; knowledge of the structure helps them predict and understand the properties of materials. Obtaining this structural knowledge is about to become a little bit easier for UConn researchers, thanks to a new grant awarded to three faculty associated with UConn’s Institute of Materials Science (IMS).
Drs. Mu-Ping Nieh of Chemical, Materials & Biomolecular Engineering (CMBE) and the Polymer Program, Douglas Adamson of Chemistry and the Polymer Program, and James Cole of Molecular and Cell Biology, were recently awarded $568,398 by the National Science Foundation that, along with support provided by UConn, will facilitate the purchase of a small angle X-ray scattering (SAXS) instrument.
This new device, to be housed in IMS, will essentially enable researchers to resolve three-dimensional structures of molecules, down to the nanometer scale. It works by detecting how X-rays are scattered as they pass through a material. The X-rays scatter at different angles based on the positions of the atoms in the material. So, from the angle-dependent scattering pattern, a researcher can deduce the approximate structure of the material. In some respects, SAXS is much easier to use than some other methods of determining structure, like X-ray crystallography, because SAXS can be applied to un-oriented samples. In addition to SAXS, the new instrument will be able to perform wide angle X-ray scattering, X-ray reflectometry, and grazing incident SAXS. A score of UConn faculty members from varying scientific disciplines are already planning to utilize the new capabilities in their research, adding a new level of capability to laboratories across UConn.
The addition of SAXS to the UConn research toolbox will greatly increase the ease with which laboratories at UConn can perform their research. Previously, if UConn researchers wanted to use instruments with SAXS capabilities, they were forced to travel to other laboratories, often outside of Connecticut. Dr. Cole, for example, has had to travel as far as Illinois to get access to similar equipment. “Thanks to the new acquisition, we will be able to perform more experiments in a shorter amount of time, without having to apply for access at national laboratories,” he said. [AutoCAD image at right thanks to the University of Copenhagen.]
Enabling Cutting-edge Research
Dr. Nieh, who is the principal investigator on the grant, will use SAXS to help develop self-assembling nanoparticles that could be used to deliver drugs more effectively. “It has been known that size and uniformity of nanoparticles are crucial factors for their functions,” he said. Drugs are often delivered in liposomes and other large vesicles, but, due partially to their size and shape, these assemblies are quickly absorbed by the liver, leading to a short circulation time. Nanometer-sized, single-layered vesicles have a longer body circulation time, and are thus more effective at delivering drugs. These vesicles, however, are often hard to manufacture. So, Dr. Nieh’s research focuses on developing a process to create self-assembling small vesicles. He will use the SAXS instrument to characterize the structure of the nano-vesicles and improve the self-assembling process. “SAXS is one of the most powerful tools which can unambiguously resolve the nano-structures,” he explained. “This enables a faster and better design of these nanoparticles to advance their functions.”
Outside of Engineering, co-PIs Dr. Cole and Dr. Adamson also will utilize the new capabilities provided by SAXS. Dr. Cole will use SAXS to learn more about the structure of the protein known as PKR. This protein is usually activated when it is bound by a segment of double-stranded RNA (dsRNA) found in many viruses. The structural mechanisms that lead to the activation of PKR, however, are not yet clear. It has not proven feasible to crystallize PKR to determine its structure by X-ray crystallography. With SAXS, however, PKR can be analyzed without crystallization. The ultimate goal of Dr. Cole’s research is to discover small molecules that can be used as leads to develop a drug to activate PKR and jump-start the innate immune response.
Dr. Adamson’s research also involves the determination of large molecule structures, but focuses on synthetic polymers rather than biological molecules. His group synthesizes well defined polymers by anionic polymerization and studies their self-assembly. By this method, nanostructured materials with feature sizes of 10 nanometers can be formed, with applications ranging from nanostructured ceramics to polymer-based vesicles. SAXS will provide a convenient and powerful analytical tool to characterize the structure of these materials.
Another project that will utilize SAXS is led by Dr. Anson Ma of CMBE and the Polymer Program. “Our research focuses on understanding how nanoparticles arrange themselves and flow dynamically at junctures that we refer to as ‘fluid-fluid interfaces,” Dr. Ma said. The presence of nanoparticles at these points can alter certain properties. For example, using nanoparticles of specific shapes and chemistry could result in ultra-stable, stimulus responsive, or “smart,” emulsions. These nanoparticles could then be used in tertiary oil recovery and polymer blend processing. SAXS will be used to determine the exact structures and placement of the nanoparticles at the interface, which will let Dr. Ma correlate specific structures with specific properties of the emulsions. Additionally, this type of research could lead to scalable and transformative manufacturing methods for assembling nanoparticles with high precision.
The SAXS instrument is scheduled to be available to UConn faculty by early 2013. Beyond the projects described, many other researchers are preparing to utilize this new tool and dozens more at UConn stand to benefit. The acquisition marks a jump forward in the capability of UConn’s research facilities, allowing for new and important discoveries to be made right here at UConn.