“Label-free” optical sensors for biomolecules – devices able to detect and quantitate the presence of specific proteins, nucleic acids, or small molecules in biologically relevant samples without the need for complex workflows or labeling reagents – are growing in importance in basic biological research, pharmaceutical development, and in the clinic. Nanostructured materials have proven highly useful for developing such sensors. Three general classes of optical sensors will be described in this talk. Two of these are based on silicon: one focused on simple, high-multiplex (many targets at one time) detection, and the other focused on ultrasensitive detection. The first technique, termed “Arrayed Imaging Reflectometry”, or AIR, relies on the creation of a near-perfect antireflective coating on the surface of a silicon chip. Binding of analytes (proteins, DNA, etc.) causes a change in the antireflective coating, and light is reflected in proportion to the amount of material captured. In the second sensor type, we are using two-dimensional photonic crystals (2D PhCs) to produce ultra-small, ultrasensitive biosensors. Fabricated on a silicon-on-insulator (SOI) substrate using electron-beam lithography and reactive ion etching, 2D PhC nanocavities provide optical detection based on resonant mode shifts in response to ambient refractive index changes produced by infiltration of target biomaterial in the nanocavity. Use of these PhC devices for detection of virus-like particles in serum, and a “bottom-up”, nano-topographically selective method for their functionalization based on the self-assembly of polymer microgels, will be discussed. Finally, I will also describe sensors employing metal and metal nanoparticle films for detection of nucleic acids.
Benjamin L. Miller is Professor of Dermatology, Biochemistry and Biophysics, Biomedical Engineering, and Optics at the University of Rochester, Rochester, New York, USA. A native of Southwestern Ohio, he completed his undergraduate degree at Miami University (Oxford, Ohio), where he obtained A.B. degrees in Mathematics and German, and a B.S. degree in Chemistry. From there Ben moved to Stanford University, where he carried out his Ph. D. research under the direction of Paul Wender. Following a stint as an NIH postdoctoral fellow in Stuart Schreiber’s laboratories at Harvard University, Ben joined the faculty of the University of Rochester in 1996. He is a recipient of a Research Corporation Research Innovation Award (1998), a Dreyfus Teacher-Scholar Award (2001), the Rochester Business Journal Health Care Achievement Award (2009), and the Future of Health Technology Institute Future of Health Technology Award (2010). He is also the academic lead for the Integrated Photonic Sensors Technical Working Group of AIM Photonics. In addition to his academic duties, Miller is a founder and Scientific Advisory Board Chair of Adarza BioSystems, Inc., a firm developing multiplex label-free biosensors and medical diagnostics.