Resonance light scattering particles as ultrasensitive labels for detection of analytes in a wide range of applications

Abstract

We have developed a new detection technology that uses resonance light scattering (RLS) particles as labels for analyte detection in a wide range of formats including immuno and DNA probe type of assays in solution, solid phase, cells, and tissues. When a suspension of nano sized gold or silver particles is illuminated with a fine beam of white light, the scattered light has a clear (not cloudy) color that depends on composition and particle size. This scattered light can be used as the signal for ultrasensitive analyte detection. The advantages of gold particles as detection labels are that (a) their light producing power is equivalent to more than 500,000 fluorescein molecules, (b) they can be detected at concentrations as low as 10(-15) M in suspension by eye and a simple illuminator, (c) they do not photobleach, (d) individual particles can be seen in a simple student microscope with dark field illumination, (e) color of scattered light can be changed by changing particle size or composition for multicolor multiplexing, and (f) they can be conjugated with antibodies, DNA probes, ligands, and protein receptors for specific analyte detection. These advantages allow for ultra-sensitive analyte detection with easiness of use and simple and relatively inexpensive instrumentation. We have shown that our RLS technology can indeed be used for ultra-sensitive detection in a wide range of applications including immuno and DNA probe assays in solution and solid phases, detection of cell surface components and in situ hybridization in cells and tissues. Most of the assay formats described in this article can be adapted for drug fast throughput screening.