Nanotechnology may yield breakthrough advances for many aspects of daily life

By Juan Miguel Pedraza
Nanoparticles will one day perform intricate microsurgery, deliver new drugs precisely on target, and coat surfaces to make them practically wear-proof. Researchers at the University of North Dakota are already making their mark in this cutting-edge science.

“Nanotechnology is a very exciting emerging field,” said Dr. Julia (Xiaojun) Zhao, an assistant professor of chemistry who is conducting nanoscience research in a dedicated lab at UND.  “The whole country realizes that it is something very useful and promising in our daily lives.”

An analytical chemist who received her B.S. in 1985 and her Ph.D. in 1999, both from Jilin University in China, Zhao was a postdoctoral research associate at the University of Florida before she joined the UND faculty in 2004.  Her primary research focus is the development of bionanotechnology — the use of nanotechnology, including nanomaterials, with biomedical and other biotech tools in bioanalysis, such as the detection of bacteria and metal ions (mercury, zinc, and selenium).

“One of the best ways to link biomolecules and nanotechnology is through the generation of bionanomaterials,” said Dr. Mark Hoffmann, a computational and theoretical physical chemist who chairs the Department of Chemistry in UND’s College of Arts and Sciences.

Nanoparticles, he said, have been rapidly developed and show great potential for use as efficient bionanomaterials.

Nanoresearch at UND is keying in on the synthesis of silica-based, surface-functionalized nanoparticles for trace analysis.  The project is funded by the National Science Foundation, with Zhao as principal investigator.  A vital factor in shaping this new science is the surface modification and characterization of nanoparticles.  This includes nanoparticle composition, size, shape, fluorescent intensity,  immobilization of biomolecules onto the nanoparticle surface, and properties of surface biomolecules on the nanoparticles.

“At UND, this is a relatively new line of research, with new faculty, and established faculty who have shifted part of their focus into this area,” said Zhao, a native of the People’s Republic of China who has published extensively in the field of bionanotechnology, including one featured in Nature research highlights, and has several nanotech patents.  “We really are catching up with the national level of research in this area.”

That research focuses on the application of nanoparticles in bioanalysis, including sensitive detection of bacteria using nanoparticle probes, single-strand DNA/RNA sequencing, and cancer cell recognition for early cancer detection.

Instrumental in launching the nanotech enterprise at UND were an EPSCoR (North Dakota Experimental Program to Stimulate Competitive Research) new faculty grant and a BRIN (Biomedical Research Infrastructure Network) grant, notes Dr. Gary Johnson, co-director at UND of this National Science Foundation-funded program.  EPSCoR also helped to link Zhao with Native American students through the NATURE (Nurturing American Tribal Undergraduate Research and Education) program.

“This sponsored project is designed to support collaboration between math, science and engineering faculty from NDSU (North Dakota State University) and UND and North Dakota tribal colleges,” said Johnson, who also is UND’s assistant vice president for research.  

Major programs of this project include a summer camp for tribal college students and faculty, summer camps for high school students at five tribal colleges, and Sunday Academies during the academic year.

Using several analytical tools, including scanning and transmission electron microscopes and a confocal fluorescence microscope in the Imaging Center at the UND School of Medicine and Health Sciences, and a team of researchers that includes a postdoctoral research associate, several graduate, undergraduate, and even a couple of high school students, Zhao is probing deep into the chemical structures that can result in useful nanoparticles.

She and her nanotech research colleagues, including Drs. David Pierce (chemistry), Don Sens (pathology), Min Wu (biochemistry) and Juana Moreno (physics), say this field is leading to a major shift across several technological boundaries, including computing, medicine, engineering, and materials science.

“We are starting with very small structures and building up,” notes Zhao.  “The most promising phenomenon to me is that this is very much an interdisciplinary field: it involves chemists, physicists, biologists, chemical engineers, and computer scientists.

“Our group wants to develop luminescent nanomaterials and applications of the nanomaterials in biomedical and environmental studies,” Zhao said.  A key project for Zhao,  Pierce, and their students, Aize Li, Carrie Amiot, Song Liang, and Paul Selid:  the design and synthesis of novel nanoparticles.  These will be applied in ultra-sensitive bioanalysis and catalysis for electrochemical systems.

“Nanocrystals and fluorescent nanoparticles have shown great potential for use as efficient bionanomaterials,” said Zhao. “We will take advantage of both nanocrystals and nanoparticles to develop new types of luminescent nanomaterials.”

Wu, Zhao, and Ph.D. student Yuhui Jin are investigating the impact of nanomaterials in living organisms.
“We are interested in the toxicity of nanomaterials to living cells at the cellular and molecular levels, such as the effects of nanomaterials on DNA damage and cell proliferation and death,” Zhao explains. “We expect that this study will provide critical information for biotechnological and biomedical applications of nanomaterials.”

With support from the Society of Analytical Chemists of Pittsburgh Starter Award, the UND chemistry nanotech team also is developing nanosensors for monitoring environmental quality.

“We intend to develop various nanosensors for sensitive and simple determination of chemical and biological samples,” said Zhao.

Zhao’s research into the structure and functionality of nanoparticles is one part of a larger interdisciplinary effort.

“This research involves chemistry, physics, biology, chemical engineering, and the computer industry, among others,” she said. “Many areas can be involved, but I believe the most promising is the biomedical field.  We aim to answer some difficult questions using nanotech, for example, single bacterial detection.”

Zhao explains: “Many commercial traditional methods exist which can detect bacteria, but the problem is sensitivity and time; some methods are very fast, from one hour, but many others take one day, and that’s not good for disease detection. Twenty-four hours can mean the difference between epidemic control and noncontrol.  With nanomaterials, we can develop faster and much more sensitive methods of detection.  For example, a nanomaterial such as the kind of fluorescent nanoparticle we (Zhao, Wu, and students Yuhui Jin and Jenna Parisien) are working on here at UND could be targeted to detect a single cell within 30 minutes.”

This would likely be accomplished using a very high luminescence nanoparticle to label a bacterial cell, which would fluoresce in the presence of that nanoparticle, making it much more easily detectable.

“The big challenge is nonspecific binding,” Zhao said.  “You want to go to a very low amount of target — a single cell — and see the antibody-antigen reaction.  But the fear is that we get too many false positives (in the current state of the technology).  The statistical error rate is high.”

 Consequently, her team is trying to sensitize the different types of nanomaterial — the surface coating — so that it is able to reduce nonspecific binding.

“Right now, we are still in the research stage,” said Zhao, who recently garnered a Society of Analytical Chemists $20,000 Starter Award grant that is only given once a year and only to one researcher nationwide.  “We think that it is very promising.”

Zhao’s interest in nanotech emerged from her expertise in analytical and physical chemistry.

“In my master’s and Ph.D. studies in China, I designed and built some analytical instruments and sensors,” she said.  She nailed down her first patent with one of these devices.

“It was a surface plasma resonance sensor that I used for the determination of biomolecules,” she said.

“It had very high sensitivity and was inexpensive, based on chemical binding.  The key component was an optical detector in the visible light range.  No doubt, my analytical chemistry background is key to doing this nanotechnology work.”