The Chemical Measurement and Imaging program (CMI) of the Division of Chemistry supports Professor Robert M. Corn and his group at the University of California-Irvine to develop new instrumentation and methodologies for the label-free detection of biologically relevant molecules at very low concentrations. Specifically, two new optical biosensing techniques are being developed: surface plasmon resonance (SPR) phase imaging and optical diffraction methods from nanowire arrays, nanogaps, and nanostructured interfaces. These two new detection methods use the inherent refractive index of biomolecules as they bind to biosensor surfaces, and require both the implementation of high fidelity surface chemistries for the fabrication of well-characterized bioactive nanostructured surfaces, and the creation of novel optical detection techniques such and SPR-enhanced phase gratings and optical diffraction. These biosensor surfaces will be used in conjunction with microfluidic microarrays to create a multiplexed biosensor format to detect and identify minute quantities of multiple DNAs, RNAs, and proteins at concentrations relevant for many biomedical applications such as discovery of new cancer and cardiac biomarkers.
The development of low cost, easy-to-use biosensors is a key to improving health. The refractive index-based methods being developed by Prof. Corn may offer fast, simple, and relatively inexpensive multiplexed bioassays. The research impacts the education of graduate students and postdoctoral scholars, including members of underrepresented groups, across a variety of related scientific disciplines including biomedical engineering, genomics, and materials science. Undergraduates and high school students who participate in this research are introduced to scientific research as a means to create a better world, and will become aware of how low-cost biosensing can impact community health both locally and globally.
The primary outcome of this NSF project is the development of novel surface chemistries and optical detection methods used in the fabrication biosensors for the simultaneous detection and identification of multiple proteins, DNA and RNA at extremely low concentrations in a single assay from a drop of blood, saliva or urine. Low-cost, easy-to-use multiplexed biosensors are a fundamental technology for both national and international health care. Many organizations (e.g., NSF, World Health Organization, Gates Foundation) have identified low cost biosensing for early disease detection, patient status monitoring, and DNA diagnostics as a key to improving the health of the general population. Protein biomarkers at extremely low concentrations (just thousands of molecules in a single drop) have been used to detect the presence of cancerous tumors and cardiac trauma. This research project developed new surface-sensitive detection methods that utilize the unique optical response of noble metal (e.g., gold, silver) surfaces, denoted as surface plasmon resonance or SPR, to detect the capture of biomarkers. The sensitivity of these biochip assays was greatly enhanced through the use of nanostructured surfaces which incorporated surface arrays of submicroscopic gold nanoparticles, nanowires, nanorings or nanocones. Two types of novel SPR biosensing methods were implemented: first, the phase-sensitive nanoparticle-enhanced SPR imaging of surfaces was used for the multiplexed ultrasensitive detection of biomolecules, and second, surface arrays of nanowire, nanoring, or nanocones were fabricated for use as SPR biosensors with unique optical diffraction and/or absorption properties that change with the binding of biomarkers. These nanostructured surfaces should be easily incorporated into fast, simple, and relatively inexpensive handheld bioassay devices. A second outcome of this research was the creation of nanostructured surfaces with unique optical, chemical and physical properties for biocapture and materials applications. For example, biomimetic plasmonic gold nanocone arrays were used to make highly non-reflective anti-glare surfaces that can be incorporated into various optical devices (e.g. lenses, solar cell panels, LCD displays). These surfaces also have interesting wetting and bactericidal properties. A second example was a collaborative project (with UCI and U Kentucky entomologists) in which we fabricated nanohook array surfaces that can potentially be used for the non-chemical capture of insects such as bedbugs. There is an acute need to deal with rises in the number of new drug resistant bacteria and insect infestations such as bed bugs, and the nanostructured surfaces developed here can possibly provide environmentally friendly biocapture and bactericidal solutions for these problems. Finally, this project also educated graduate, undergraduate and high school students -- not only how to participate in inter-discplinary scientific research and acquire the unique skills required to create these biosensor devices, but also about the need for low cost biosensing for better health care in the local community.
