Note to Editors: Downloadable video about Professor David Dandy’s work can be found at http://www.engr.colostate.edu/adr/video/infopage.cfm?id=16.
A Colorado State University chemical and biological engineering professor has proven that miniaturized diagnostic "spot" tests (called microarray assays) used for biomedical disease and drug screening assays could rapidly increase drug discovery, protein characterization and clinical diagnoses of infectious disease if designed correctly. Although not ready for hospital or office use, microarrays represent a novel miniaturized multi-spot diagnostic format that has huge potential for patient diagnosis if found reliable and approved.
Smaller is often better, according to a new scientific study that appears this week in the Proceedings of the National Academy of Sciences by Professor David Dandy, head of the Department of Chemical and Biological Engineering at Colorado State. Dandy co-wrote the paper with David Grainger, a former chemistry professor at Colorado State who now is chair of the Department of Pharmaceutics & Pharmaceutical Chemistry at the University of Utah.
The study was funded by a multi-year, $2.5 million grant from the National Institutes of Health.
"This is in response to the commercial sector’s desire to fit more and more of these assay zones – up to hundreds of thousands of different biological tests – onto a single bioassay platform, about the size of a small napkin right now," Dandy said. "Our research uses corroboration of a theoretical model and experiments to provide definitive proof that the smaller the ‘spot’ available for assay, the faster and stronger the diagnostic response."
Pharmaceutical companies conduct microarray tests, often in thousands of spots per platform, to rapidly screen patient samples for disease markers and drug candidates. Laboratory technicians also use this technology to identify and quantify certain protein levels in blood serum, saliva, and urine that provide useful health and disease information.
"This work is extremely useful from an industrial perspective," said Michael Lochhead, chief scientist at Accelr8 Technology Corp., a Denver-based developer of innovative materials and instrumentation for advanced applications in medical instrumentation, basic research, drug discovery, and bio-detection. "Understanding how reaction rate is related to size in these microspot assays is critical not only for understanding assay results, but for designing new tools as well. The quantitative aspect of the CSU work is particularly relevant."
The critical importance of this work is illustrated by the fact that, to date, a single microarray-based test has been approved by the FDA for clinical use. According to Roche, the manufacturer of this diagnostic microarray, "This test analyzes a patient’s Cytochrome P450 2D6 and 2C19 genotypes from genomic DNA extracted from a blood sample. Test results will allow physicians to consider unique genetic information from patients in selecting medications and doses of medications for a wide variety of common conditions such as cardiac diseases, pain and cancer."
Many other such tests are on the horizon for early detection of disease and identification of patient-specific drug therapies.
Dandy’s research supports the size and density of the spot arrays printed on platforms that might be useful for pharmaceutical and biotechnology companies and laboratory testing. The research shows that the smallest spots effective for assays in current capture formats are 40 microns across, or half the width of a human hair. Additionally, the research indicates that smaller spots do not take as long as larger spots to reach maximum assay signal generation on surfaces. Currently, spot tests in laboratories can take as long as 96 hours to ensure necessary chemical reactions have occurred.
The research is useful particularly in cases where samples such as blood serum or saliva exist in very limited quantities and have low concentrations of infectious agents. Smaller spots do not need as much reagent volume or as much total amount of reagent to produce a signal – an improvement over current formats that had no performance criteria.
"Future research will involve correlation in the increase in assay speed with the size of the assay spot," Dandy said.
Dandy joined Colorado State in 1992 after spending four years as a senior staff member in the Advanced Materials Department at Sandia National Laboratories where he focused on thermal and plasma assisted chemical vapor deposition of thin films. At Colorado State, his work focuses on microfluidics and lab-on-chip platforms for new bioassays, including new biosensors that could speed up diagnoses of plant pathogens or disease markers.