New Forms of Microscopy Enabled by Nanostructured Surfaces

New Forms of Microscopy Enabled by Nanostructured Surfaces

Prof. Brian T. Cunningham
Donald Biggar Willett Professor of Engineering
Department of Electrical and Computer Engineering
Department of Bioengineering
University of Illinois at Urbana-Champaign

Since the advent of optical microscopy, a flat glass microscope slide has been the standard surface upon which tissues, cells, and biomolecules are attached for observation. Recently, we have utilized the optically resonant properties of nanostructured photonic crystal (PC) surfaces to enable several new microscopy modalities where the nanostructure provides new forms of contrast for a wide variety of compelling applications. By designing PC surfaces with resonances that match the excitation and emission spectra of photon emitters such as fluorophores and quantum dots, PC enhanced fluorescence (PCEF) microscopy reduces the detection limits of any surface-based fluorescence assay. By generating spatial images of the PC resonant reflection intensity, we can selectively and dynamically visualize the cell-extracellular matrix interface during processes that include stem cell differentiation, cancer cell response to drugs, and chemotaxis – including the ability to observe the formation and evolution of cell membrane focal adhesion sites. We call this approach Photonic Resonator Outcoupler Microscopy (PROM), as we observe highly localized outcoupling of light from the PC that occurs due to scattering by dense regions in the cell membrane. By utilizing metallic nanoparticle tags with plasmon resonances that match the PC resonance, we obtain highly efficient coupling of light into nanometer-scale electromagnetic hotspots, that is accompanied by highly localized “quenching” of the PC reflection efficiency, which we are using for digital-resolution detection of miRNA biomarkers for cancer with 100 aM limits of detection, using an approach called Photonic Resonator Absorption Microscopy (PRAM). The seminar will describe the physical principles, nanostructure design/fabrication, instrumentation, and applications for nanostructure-enabled microscopy for disease diagnostics, personalized medicine, and life science research.