Research world-wide on biosensing techniques is motivated by numerous applications in clinical diagnostics. However, the important problem of detecting in parallel a large number of molecular species from the very small samples typical of most collection procedures remains an elusive goal. In fact, the use of conventional biosensing techniques renders the solution to this problem nearly statistically impossible without the use of molecular amplification as provided by a time-consuming intermediate polymerase chain reaction step. This exploratory research plan presents an innovative new approach to solving this problem by merging the science of nanophotonics with traditional waveguide biosensors for the development of a new class of molecular detection array. The major long-term benefit of this research will be to eliminate the molecular amplification step to allow for real-time genetic screenings, for example, which may ultimately open up new avenues in clinical diagnostics. In brief, three new ideas enable these real-time molecular array sensors. First, the immobilization of metallic nanoparticle clusters onto discrete zones of an optical waveguide surface makes the parallel detection of a large number of molecular species feasible. In each zone, capture molecules tethered to the nanoparticles preferentially bind to a particular species (a DNA strand, for example), through an affinity interaction. Second is the key advantage not widely appreciated in the strong localization of light within a small volume about a metallic nanoparticle due to the local plasmon resonance - the dramatic improvement of detection sensitivity to affinity binding via two effects: the enhancement of the signal due to the analyte, and the reduction of noise due to background interference. Third, tailoring of the structure resonances of the nanocluster will allow additional control over the resonance properties such that optimization can be performed based on the method of transduction. These effects will allow the detection of very small numbers of molecules bound within each discrete sensing zone.
| Liu, Yongdong; Blair, Steve (2003) Fluorescence enhancement from an array of subwavelength metal apertures. Opt Lett 28:507-9 |
