Functionalized Nanoparticles For Clinical Diagnostics

A decade ago, Northwestern University's Chad A. Mirkin and Robert L. Letsinger led a team in devising a nanoparticle-based method for detecting DNA that provided far greater sensitivity than standard fluorometric detection methods at the time. The advance led to the founding of a Northbrook, Ill.-based nanobiotechnology company, Nanosphere, which today makes a line of medical diagnostic systems based on the technology and sold under the Verigene trade name.

The detection process relies on gold nanoparticles functionalized with DNA or RNA oligonucleotides or with antibodies that selectively bind to complementary nucleic acid or protein targets, respectively. By capturing the nanoparticle-tagged targets on a solid support via hybridization reactions, the targets can be detected with high sensitivity as a result of the intensity with which nanoparticles scatter light. For example, compared with the enzyme-linked immunosorbent assay method, a technique commonly used to detect the presence of an antibody or antigen, the nanoparticle method is at least 100 times as sensitive.

According to Mirkin, Nanosphere has received Food & Drug Administration clearance for five of its diagnostic tests. These include tests for early detection of respiratory illnesses and blood coagulation disorders and a test to gauge a patient's ability to metabolize warfarin, an anticoagulant medication. The company is also developing diagnostics for sensitive detection of markers for cancer and heart disease.

Looking back to the mid-1990s, "we started with the idea of functionalizing nanoparticles with DNA to do programmed materials synthesis," Mirkin says. The strategy, he explains, was to organize lattices using particles as atoms and DNA as bonds. "These structures turned out to have extraordinary and unexpected properties that provide major advantages for medical diagnostics," Mirkin adds. "It's a real success story for chemistry."