Activatable Fluorescent Protein/Metal Hybrid Raman Nano-Probes for Biosensing

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Non-technical:This award by the Biomaterials Program in the Division of Materials Research to the University of Southern California is to develop probes that are activatable fluorescent protein/metal hybrids that will be useful in Surface Enhanced Raman Spectroscopy (SERS) for biosensing. Detecting individual pathogenic cells and eliminating them is crucial for early cancer detection and treatments. Raman nanoprobes are among a handful of probes that could provide such high detection sensitivity. Yet, current formulations are molecularly bulky and lacking in specificity and sensitivity, which ultimately limits their efficacy in research and medical settings. This project offers a novel design and implementation of Raman nanoprobes for biosensing, with the goal of achieving highly sensitive but specific detection of cancer cells. Educational and outreach components are an integral part of the project. The proposed activities engage participating researchers and students in highly interdisciplinary research to prepare the next generation of scientists to face the growing demands for interdisciplinary skills at the interface between physics, chemistry and biology. The program also integrates modern technology and interdisciplinary science for young students. Mentoring and cross-disciplinary training of traditionally underrepresented undergraduate and high-school students on emerging nanotechnology methods and on the use of advanced photonic instrumentations will be realized through established programs at the University of Southern California, through partnership with non-profit organizations and through outreach to high-schools in the Greater Los Angeles area. Technical:Plasmonic Raman nanoprobes are highly promising agents for the next generation of biomedical imaging and treatment but current limitations in their design, including large sizes (100 nm) and poor Raman signals, significantly impede their potential for major breakthroughs in molecular imaging and theranostics. This project will investigate the use of split-fluorescent proteins as both molecular glue and Raman reporters for cell-directed assembly of small and activatable surface enhanced Raman scattering (SERS) metal nanoprobes, with the aim of achieving highly sensitive and specific Raman detection of cancer cells. The project offers a novel approach to SERS biosensing and detection and may allow significant advances in the basic understanding of (i) photonic properties emerging at natural chromophore/metal nanoparticle interfaces, (ii) Raman enhancement processes in well-defined nanostructures and (iii) molecular factors affecting the assembly of nanomaterials into controlled nanoclusters in live cells. The studies are expected to contribute knowledge and techniques that will be broadly useful for the directed assembly of nanoparticles into metamaterials and into catalytic/electronic nanostructures to be used in biomedical, prosthetics, therapeutics and fundamental research applications. An integral part of this project is the training and mentoring of underrepresented students in interdisciplinary research in nanotechnology, biomaterials and photonics, through the integration of research findings and instrumentation into classroom teaching, outreach programs to local high-schools, and general public presentations. Significant enhancement of the infrastructure for research and education at the University of Southern California is also provided by the implementation of an optical set-up for single molecule SERS measurements.