Robust fluorescent probes allow sensitive detection of small molecules

The invention is an efficient method to synthesize novel silver nanoparticles with bright fluorescence and a giant Raman enhancement effect. These particles, 2 – 20 nm in diameter, exhibit a highly multi-domain structure with grain sizes down to 1 nm or less. The amount of photons emitted from these particles exceeds that from bright fluorescent dye molecules by four orders of magnitude. Unlike typical colloidal silver nanoparticles, where less than 3% of the nanoparticles exhibit optical properties, the present invention is able to produce more than 95% of the nanoparticles with such strong fluorescence. In addition, unlike current state of the art where strong fluorescence and/or Raman enhancement effects are observed for aggregates of nanoparticles, our technology observes the behavior from single nanoparticles.


The ability to image signal transduction, gene expression and other cellular dynamics depends on fluorescent reporters that can probe local chemical information inside a cell. Due to lack of specific reporters, small signaling molecules, metabolites and drugs cannot be adequately imaged in cells. In addition, most of the currently available fluorescent probes exhibit relatively weak emission and photobleach quickly. Therefore, there is a great need in bioimaging development to create bright and robust fluorescent probes that not only can track the location of molecules of interest but also report their local chemical environment. Harvard researchers have addressed this need by developing silver nanoparticles that exhibit enormous Raman enhancement effect, on the order of 1015. The invention enables the Raman spectrum of a single molecule near such a particle to be detected, allowing sensitive detection of small molecules, such as metabolites and signaling molecules. The combination of robust fluorescence, giant Raman enhancement and high optical purity allow these novel nanostructures to be used as powerful probes for chemical imaging inside cells.

U.S. Patent(s) Issued: US8815158B2