had Mirkin of the Department of Chemistry and Institute for Nanotechnology, Northwestern University, Evanston, Illinois, had two remarkable papers published in 2002—one in February and one in August—and both are now in the current Hot Ten, at #6 and #7 respectively. They deal with the identification of DNA at extremely low concentrations, and might one day lead to rapid diagnosis of disease pathogens.

This would clearly have been of benefit at the time his papers were published, when the United States was not only reeling from the events of September 11^th, but was alarmed by a bizarre outbreak of the deadly disease anthrax, whose spores were being distributed via the U.S. mail. Mirkin’s work would have made possible the speedy naming of the disease. Indeed the Northwestern team’s work might one day lead to instruments for analyzing bioterrorist attacks, and they could allow rapid identification of biowarfare agents in battle zones. Both situations would use biodiagnostic kits based on the ground-breaking research of #6 and #7.

These papers built on earlier work in which Mirkin had shown that DNA could attach itself to clusters of gold atoms and thereby cause a color change that would enable it to be detected (see J.J. Storhoff, et al., J. Am. Chem. Soc., 120[9]: 1959-64, 1998; Science Watch March/April 2000, page 7). The drawback was that it required a lot of DNA. The techniques revealed in #6 and #7 reduce the amounts needed to the femtomolar range, which is parts per quadrillion (10¹⁵).

The method in #6 is based on completing an electrical circuit between two electrodes 20 microns apart and mounted on glass, and this is achieved with a line of the unknown DNA strands to which are attached metal clusters. The device works as follows: the gap between two electrodes contains single strands of DNA, which are referred to as capture strands, and these are specially designed to have a sequence of bases that would only recognize the target DNA, which has been tagged at one end with gold nanoparticles. These may not in themselves complete the circuit between the two electrodes, but when they are coated with silver atoms, by adding silver nitrate and hydroquinone, then they do. Bingo! Current flows and this means that the rogue DNA has been identified and the pathogen from which it has come can be nailed. Method #7 uses Raman spectroscopy to detect DNA and RNA, and devices based on this approach can identify up to six strands at a time.

There are several steps to each of the Mirkin processes, but they offer a means of rapid analysis a hundred times quicker than conventional DNA analysis techniques, which rely on the polymerase chain reaction (PCR) to replicate the DNA to a level at which it can be identified. Moreover, the new method can even cope with the mismatching of DNA, something that can bedevil the PCR process. And while Mirkin’s method is still prone to the occasional mismatch, this can be overcome by adding a solution of sodium chloride, which then causes the mismatched strands to float free again.

More recently Mirkin’s group have devised a nanoparticles-based bio bar-code for the ultrasensitive detection of proteins (see J. Nam, et al., Science, 301[5641]: 1884-6, 2003). This relies on magnetic micro particle probes with antibodies that specifically bind a target of interest, and they showed it would identify prostate-specific antigen at an unbelievably low concentration of 30 attomolar (10^-18), and with a little help from a polymerase chain reaction this sensitivity could even be reduced to 3 attomolar. This corresponds to a mere 18 protein molecules in the entire sample!

Such is the interest in Mirkin’s work that some of his systems have already been commercialized and are being evaluated at major U.S. hospitals. They offer advantages in terms of multiplexing, sensitivity, and portability. Says Mirkin: "We have a chance to completely transform molecular diagnostics using some of these advances in nanoscience as a replacement for the conventional systems based upon molecular fluorophores and PCR." Indeed the work being carried out in the Department of Chemistry at Northwestern University may one day help save millions of lives.