Professor Quan Cheng of the University of California-Riverside is supported by the Chemical Measurement and Imaging Program in the Division of Chemistry to develop improved surface plasmon resonance (SPR) sensing and imaging techniques for better sensitivity and broader applications. The specific aims of the project are: (1) to develop microwell-confined SPR chips; (2) to develop waveguide-based SPR chips to probe conformational and structural changes stimulated by binding events; and (3) to use the techniques developed in the first two aims to study specific biomolecular interactions. Measurements parallel and perpendicular to the surface with waveguide SPR are expected to yield fundamental information pertinent to conformational and structural changes not obtainable with current SPR technologies.
If successful, the proposed research will lead to important advances in SPR, and better sensitivity with SPR imaging, which will advance high-throughput drug screening and hence impact the pharmaceutical industry and human health. Students involved in the project will receive multidisciplinary training in waveguide physics, chemistry of surface functionalization, and biology of membrane proteins and protein-ligand bindings. The results will be incorporated in advanced bioanalytical chemistry courses.
Surface Plasmon resonance (SPR) is an optical technique that has been broadly employed for the study of molecular interactions including phosphoinositide-protein interaction, glycolipid-cholera toxin interaction, and effect of pore-forming compounds on bilayer lipid membranes. The technique has a significant impact on pharmaceutical industry as it provides a cost-effective label-free approach for screening of drug candidates. However, it is important to point out that current SPR detections have met considerable limitation in assessment of ultralow concentrations and in imaging analysis of complex samples. This has impeded further application of SPR in proteomics and disease diagnostics. We have developed a series of new techniques that improve the performance of SPR. We have addressed the sensitivity issue with the combination of gold nanoparticle (AuNP) and in situ polymer growth, and demonstrated SPR microarray imaging analysis enhanced with the amplification strategy. We have probed the molecular interactions with artificial receptors and lipid bilayer membrane, and shown that a deep cavitand can be incorporated in a membrane bilayer for a variety of studies targeting cell chemistry. An important task in this project is to develop new SPR substrates allowing both quantitative analysis and molecular identification. We have developed a number of new substrates that combine localized surface plasmon resonance (LSPR), mass spectrometric, and Raman spectroscopic detection into one chip, proving an ideal platform that enables orthogonal detection for effective analysis of complex biological samples.
