Gold nanoparticles designed to detect proteins within cells, using just laser light, could enable simple and highly sensitive monitoring tools for blood clots and other disorders. Researchers in Scotland have shown that the novel particles can accurately detect thrombin, a biomarker for blood clots, in blood samples. They ultimately envision tests in which the gold nanosensors are injected directly into the patient, enabling measurement of protein concentrations by shining laser light through the skin. In the nearer term, the technology will allow scientists to directly examine how proteins, such as those involved in viral infections, interact within a cell.
The sensor consists of a silica core, 120 nanometers in diameter, encapsulated in a thin layer of gold. Mounted on the gold shell are aptamers, short strands of nucleic acids designed to bind to a specific molecular target. When a laser is shone on the aptamer, the molecule absorbs light and reemits it with a characteristic spectrum, called its “Raman signal.” When the aptamer binds with a protein, its conformation changes and subsequently changes the emitted spectrum. The sensor’s gold surface amplifies the signal by increasing changes in the electric field in response to the laser light.
“The gold particle works likes a kind of transducer for the laser,” says Colin Campbell, a chemist at the University of Edinburgh, in Scotland, who led the research. Scientists are able to determine the levels of the target molecule in solution by measuring the spectral changes. Using this technique, they were able to detect sub-femtomolar (10-12) concentrations of thrombin in human serum. The work was published online March 2 in the journal Chemical Communications.
Researchers say the technology could be adapted to detect a number of different proteins, but they are focusing first on thrombin. In the U.K., a country where blood clots cause an estimated 25,000 deaths each year, clinicians assess each patient admitted to the hospital for risk of blood clotting or thrombosis. The current test requires a blood draw and a multistep assay in which a fluorescent antibody binds to the protein. The new technology would provide easy monitoring for high-risk individuals and prevent clot-related deaths, Campbell says. Rather than provide a single measurement of thrombin levels, which can fluctuate, such a test would allow for continuous monitoring and signal when levels of the protein became dangerously high.