magine if a doctor could do a simple color-change test that in seconds would diagnose whether a patient had cancer, or a hereditary malfunction, or infection from a microbial pathogen. However, if the test involved using gold, the doctor might wonder if it would be too expensive to become part of his or her medical armory. In fact such tests will soon be possible and cheap to carry out, thanks to the group responsible for paper #5 in the current Hot Ten. (In fact, the cost will be less than 10 cents, because an ounce of gold will provide enough material for thousands of tests.

   The reason is that gold will be in the form of tiny nanospheres, and this is the key to paper #5, which reports an entirely new way of detecting faulty strands of DNA. This is the extraordinary outcome of collaborative work between chemist Chad Mirkin and his team based at Northwestern University, Evanston, Illinois, and their Northwestern colleague Robert Letsinger, a pioneer in solid-phase synthesis and nucleic acid chemistry. They have come up with what promises to be the standard way of diagnosing most life-threatening illnesses.

   The nano-sized gold particles carry short strands of artificial DNA (oligonucleotides) tailored to match known segments of biological DNA that are implicated in, or linked to, disease. The oligonucleotides, made up of 24 bases, are attached to the minute gold particles, which are about 13 nanometers (13 x 10^-9 m) in diameter, via a sulfur atom.

   When such a molecule probe finds its target DNA, the two interact and the result is the formation of a polymeric cluster which affects its plasmon resonance, and there is a dramatic color change from red to blue. Not only that, but the change is reversible and the temperature at which this occurs is quite specific, much more so than with conventional DNA mutation probes, again offering a sensitivity that adds to the certainty of correct identification. This "melting transition" can be monitored at 260 or 700 nm. Paper #5 describes how this one-pot color-change method can identify the target even when it is in the presence of other strands with base imperfections.

   The method is so sensitive that it can detect a mutant strand of DNA which has one wrong base, regardless of where the rogue base is located. Not surprisingly, paper #5 is attracting a lot of attention, being of interest not only to chemists but to medics and especially those working in the area of DNA detection. it points the way to a whole new method of medical diagnosis based on identifying defective genetic material or correct sequences that are associated with a specific disease.

   What makes the method so exciting is that the tests can be carried out without the need for expensive equipment or specialist personnel. More importantly, it eliminates the need to use radioactive nuclides with their associated problems, such as short shelf-lives and the need for careful disposal.

   Mirkin's research first began to attract attention with the paper he and his collaborators published four years ago in Nature (see C.A. Mirkin et al., 382:607-9 , 1996), which opened up the field of using nanoparticles as biomolecular detectors. The potential to diagnose threats from all sources has led to a wide spectrum of funding agencies supporting his work: the National Science Foundation, the National Institutes of Health, the Army Research Office, Office of Naval Research, and the Air Force Office of Scientific Research.