A Real-Time, Label-Free Diagnostic Platform with Glycan Arrays

DESCRIPTION (provided by applicant): The ultimate goal of the proposed work is to develop a compact, label free, sensitive and real-time platform capable of multiplex detection of biomarkers and pathogens using glycan microarrays. Glycans, which are predominant surface components of immune cells and microorganisms, give rise to high levels of anti-glycan antibodies of all classes that can be used for diagnosis and prognosis. During Phase I of this project, AlphaSniffer will develop glycan microarrays for the detection of two plant lectins, Concanavalin A and jacalin as model analytes to investigate the feasibility of incorporating glycomic tools into its optical platform for multiplex detection. Our long-term vision is to develop a system comprising an instrument and application-specific disposable cartridges that are capable of rapid detection of multiple target pathogens and biomarkers. This system will provide significant advantages over current test methods that take many hours to several days to provide results, and typically only yield information about single pathogens. As an analytical instrument company, AlphaSniffer realized the market's need of a label-free, real-time, robust and sensitive diagnostic platform and is developing the Surface Plasmon Resonance-enhanced Common Path Interferometry platform especially for this purpose. Phase I project will pursue the following objectives: 1. Design and prepare mono- and disaccharide substituted polymeric transducers; 2. Optimize binding density, multi-valency and mitigate nonspecific binding; 3. Implement binding assays for concanavalin A (ConA) and jacalin as model sugar binding proteins; 4. Test the four spot prototype system and generate binding concentration-response curves. The results of this investigation will establish the feasibility of incorporating glycan microarrays into AlphaSniffer's platform and will enable the Phase II research and development to design and develop glycan immobilized transducers for diagnostic and prognostic purposes. Great achievements have been made in understanding the genetic code of disease. However the next great opportunities for influencing public health demand understanding the function of the cellular machinery created by our DNA's instructions. In order to achieve this goal, it is imperative that technologies such as AlphaSniffer's SPR-CPI platform be developed that can analyze the cellular functions of protein and carbohydrates in their natural state, without the use of labels that often change the way these biomolecules behave. The research proposed here seeks to expand the toolbox applied in analysis of cellular carbohydrates and establish processes to further biochemical understanding of their more subtle purposes. The results of this research will be practically applied to protect public health and enhance medical treatment.