Ultrasensitive digital detection of nanoparticles: Viral diagnostics and multiplexed protein and nucleic acid assays

摘要

We have developed the Interferometric Reflectance Imaging Sensor (IRIS) for label-free, high throughput, high sensitivity and dynamic detection of molecular binding on a solid surface. Recently, we have demonstrated IRIS with the ability to detect single nanoscale particles. To detect and size nanoparticles, IRIS shines light from visible LED sources on nanoparticles bound to the sensor surface, which consists of a silicon dioxide layer on top of a silicon substrate. Interference of light reflected from the sensor surface is modified by the presence of particles producing a distinct signal that reveals the size of the particle. In our approach the dielectric layered structure acts as an optical antenna optimizing the elastic scattering characteristics of nanoparticles for sensitive detection and analysis. We have successfully detected low-index dielectric particles with r=30 nm, Au and Ag nano particles with r=10nm, and various viruses (H1N1, VSV, Ebola) with accurate size discrimination. Single nanoparticle detection with IRIS led to protein and DNA arrays with attomolar detection sensitivity in serum and unprocessed whole blood.