Xiaoguang Dai, a Materials Science doctoral student at Stevens, has recently made an important new discovery with potentially large-scale impact on gene analysis, medical diagnosis and disease prevention.
Working with his thesis advisor, Professor Matthew Libera, together with fellow graduate student Emre Firlar and collaborators from the Public Health Research Institute (PHRI), New Jersey Medical School, in Newark, N.J., Dai is the first to show how to present molecular beacon probes on a solid substrate, like that used in microarray technology, while preserving the high signal/background ratio needed for a diagnostic device.
Microarray technology has been effectively used for about two decades to detect disruptions or changes in gene expression, which are responsible for many human diseases, including infections by pathogens like MRSA and E. coli. Microarray technology uses DNA probes – typically tethered to solid surfaces – to detect specific sequences of nucleic acids like DNA or RNA. Unlike most DNA probes that require binding to a target nucleic acid strand, which are labeled with a light-emitting fluorophore in a separate step, molecular beacon probes emit light only when they bind to a target molecule with no need for additional steps.
A molecular-beacon-based microarray technology has all sorts of possible detection applications, such as allowing researchers to identify the presence of a specific type of bacteria and decide the best course of treatment. The limitation has thus far been that the molecular beacon probes emit light when they are bound to a solid surface even if they have not become bound to their target DNA or RNA strand.
Dai has now shown how to present molecular beacon probes on a micro hydrogel, which is 95 percent water but still immobilized on a solid surface.
"Xiaoguang has figured out a way to make the beacons think they are in water, where they perform extremely well, while getting them immobilized to specific locations on a solid surface. This is really new," said Libera.
Presenting molecular beacon probes on a solid substrate in this way allows scientists and engineers to combine all of the good aspects of microarray technology with all of the good aspects of molecular beacons.
“This research can have a huge impact on medical diagnostics,” Libera said. “For example, in a hospital setting, speeding up the time required to identify what kind of infection a patient has will allow doctors to know much more quickly what antibiotics to prescribe to that patient. This will overcome two major problems: leaving a disease untreated so a patient gets sicker, or overprescribing antibiotics which can lead to bacteria becoming antibiotic-resistant and the spread of infectious disease.”
Dai’s research draws on almost a decade of work by Stevens researchers supported in part by grants from the Army Research Office to pattern hydrogels onto surfaces through electron-beam lithography, research which has advanced significantly since Stevens received funding from the National Science Foundation for an advanced cryo-scanning electron microscope. Dai realized the potential applications of the lithography methods developed at Stevens to microarrays, so he combined technologies with PHRI, an arm of UMDNJ focused on infectious-disease research. PHRI invented molecular beacon probes in the mid-1990s and has successfully licensed its technology to more than 60 different companies.
“Translation of results to practice is a natural part of the Stevens research experience, and this work is another good example of how strong scientific research at Stevens is able to have an impact on problems important to society. This has been the Stevens tradition since its founding in 1870,” said Provost and University Vice President George Korfiatis.
Dai is supported by a Stevens Innovation & Entrepreneurship Doctoral Fellowship, which funds research with the potential to address scientific problems of broad societal impact through the development of disruptive technology with potential market value. He hopes to patent the intellectual property developed through its research – the research team has already submitted two provisional patent applications – and license the technology to companies interested in this novel approach. The team is working with the Stevens Office of Academic Entrepreneurship, PHRI and UMDNJ to explore licensing opportunities and commercialization pathways.
“Xiaoguang’s work is a perfect example of how basic research can transfer into the development and commercialization of a technology that can address a real-world problem and is exactly what we hope for through the I&E fellowship program,” said Associate Provost for Academic Entrepreneurship Christos Christodoulatos.
Learn more about this research by reading a paper entitled “Surface-patterned microgel-tethered molecular beacons” that was coauthored by the Stevens trio and PHRI Investigator Salvatore Marras and his research student Wei Yang. The paper was selected as the March 2012 cover story of Soft Matter, a leading international research journal focused on the interface between physics, biology, chemical engineering, materials science and chemistry.