The faxed pages of BioWorld Today that you hold in your hand are(at least in the U.S.) 8.5 inches wide by 11 inches long. To be morescientific, that's 216 by 279 millimeters.

But for ultimate precision, those dimensions work out at 216 millionnanometers by 279 million. One meter measures one billionnanometers.

As veteran bio-organic chemist and molecular biologist RobertLetsinger explained, "The nanometer, at 10-9 meters in length isthree orders of magnitude smaller than the micrometer [a.k.a. micron]at 10-6."

Letsinger, now an emeritus professor of chemistry at NorthwesternUniversity in Evanston, Ill., is co-senior author of a paper in today'sNature, titled: "A DNA-based method for rationally assemblingnanoparticles into macroscopic materials." It reports an experimentthat lays the groundwork for designing quick, simple clinicaldiagnostic sensors and fabrication of molecule-size electroniccomponents.

Beginning in the early 1960s, Letsinger told BioWorld Today, "Iintroduced the use of solid-phase technology for the high-speedsynthesis of oligonucleotides, which in principle is used today." Hisformer student, Marvin Carruthers, then at the University ofColorado, developed these chemistries, Letsinger continued, "makingit possible to store the reagents, sell them easily and adapt them toautomated machine synthesis."

For the past year at Northwestern, he has teamed up with inorganicmaterials chemist Chad Mirkin "to do some things that neither of uscould have been able to accomplish on our own." Their collaborationmarries Letsinger's mastery of nucleotides with Mirkin's expertise insurface chemistry.

Going For The Gold, Nanowise

Mirkin, also a co-senior author of the article in today's Nature, andleader of the research team, told BioWorld Today: "This is a brandnew area as far as we are concerned, in terms of bringing togetherinorganic particles with DNA. We are using the exquisite recognitionproperties of DNA," he said, "to assemble these particles intoordered, solid materials."

The particles involved are sphericles of elemental gold 13nanometers in diameter. They got that way, Mirkin explained, bymixing a gold salt with a reducing agent, sodium citrate.

The resulting auric nanoparticles swarm far apart in a colloidalsuspension, awaiting their DNA ligands.

"What we had," Letsinger recounted, "were two fragments of double-stranded DNA, each 20 nucleotides long, with 8-nucleotideoverlapping sticky ends. These spontaneously interact with shorteroligos, joined to the particles through a gold-sulfur bond."

This ligation, the co-authors report, causes the bound gold particlesto clump together, an effect made visible by a color change, fromdeep red to purple. Then, as the aggregate precipitates to the bottomof the vessel, the color turns pinkish-grey. Warming reverses thereaction.

"That big optical change can be read out with the naked eye," Mirkinobserved, "which can be quite useful in developing colorimetricdetection sensors for a variety of DNA."

He foresees two types of such sensors, once all the bugs are workedout of the system. "One would be in the lab, where you'd want aquick test to confirm the particular type of DNA you're generating.Say you're generating it hundreds of times a day, or a week," hecontinued, "you have a rapid diagnostic, where you can introduce thatoligo solution into the solution of the colloid _ gold in this case. If itchanges color, you have that DNA; if not, you don't."

The co-authors see this system as potentially useful in point-of-siteclinical diagnostics. "The objective," Letsinger said, "would be to putoligos on the gold that would hybridize specifically with a particularpathogen's DNA or RNA," or, Mirkin added, "Something where youneed a quick answer, like a dipstick-type pregnancy test."

Silicone Valley: Meet Siliclone Highway

Applying this nanotechnology to miniaturized electronic devices,Mirkin observed, "is very far-fetched at this point."

He already is thinking, though, of binding the DNA to a surface _"be it gold or glass or cadmium sulfide semiconductors, for example.What this means," he speculated, "is that you can start thinking aboutgenerating nanoparticle arrays, little microelectrode devices, andpinpoint the position of the little colloids, which would be your littleelectrodes, with the DNA strands that you'd use to assemble yournetworks."

He went on: "Your computer is all based on microfabrication. Thiswould be several orders of magnitude smaller than that _ literally amolecular-scale regime."

Letsinger pictures the possibility, far in the future, "of creatingminiature wires on a surface. It might even be cross-wires, somethingthat had a junction, perhaps a molecular switch in it, maybe even anon-conducting surface _ a nanochip."

He observed: "This is rather a hot field of chemistry right now," andadded, "I'm a little out of my depth here, extending it to practicalapplications, but I think we have to start building."

Mirkin already is "talking with quite a few biotechnology companies"about clinical sensors, "and also thinking about the possibility ofestablishing a private business to develop this technology ourselves.But we haven't reached any firm decisions yet." The university'stechnology transfer office has been filing patent applications "forsome time now," he said.

"This nanotechnology approach is very powerful," Mirkin concluded,"and it really is nice, because it mirrors, or can take advantage of, theentire biotech industry. Those people are developing new types ofmolecules and methods that we can use in constructing ourmaterials."

Another article on the same nanosubject appears in today's Nature. Itreports: "Organization of `nanocrystal molecules,' using DNA." Itssenior author is chemist Peter Schultz at the Howard Hughes MedicalInstitute, University of California at Berkeley.

His group also exploits the properties of DNA oligonucleotides toorganize gold particles, but, Mirkin observed, "their purposes, andwhat they've actually done, are completely different from ours. Ithink we complement each other." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.