Analog SFF, December 2008

by Dell Magazine Authors

  Take it from someone in the industry: “Building complex structures at nanoscale is not something we're going to be able to do,” said R. Stanley Williams, director of quantum science research for Hewlett-Packard Labs, in a plenary address at a nanotechnology conference in Portland, Oregon in 2007.[1]

  [Footnote 1: Much of the background for this article came from that conference, the Micro Nano Breakthrough Conference, held September 10-12. For additional information on this fast-moving field, see Nanotechnology Now, www.nanotech-now.com, a website aimed at nanotechnology investors but containing news releases and other general information. Also available on the web is the 32-page report, Green Nanotechnology: It's Easier than You Think (www.nanotechproject.org/process/assets/files/2701/187greennanopen8.pdf), written by Karen F. Schmidt for the Woodrow Wilson International Center for Scholars. On a more technical level, the semi-annual meetings of the American Chemical Society often feature symposia on nanotechnolgy (green or otherwise) as well as green chemistry (nano- or otherwise).]

  As Lerner concluded, this means the future of nanotechnology—certainly the near future[2]—isn't nanobots. It's the ability to control manufacturing processes to construct super-strong, flawless materials. It's analytical chemistry using molecular probes for super-sensitive analytical tests. It's ever-smaller computer circuits, allowing faster, cheaper processors to drive the computer revolution into the next decade and beyond.

  [Footnote 2: Analog writer Robert A. Frietas, Jr. of the Institute for Molecular Manufacturing still believes in nanobots, although he calls them “nanorobots.” He is working on a multivolume book series entitled Nanomedicine, of which at least two volumes have been published as of the time this article went to press.]

  But there's another aspect of nanotechnology. The conference I attended had “red” and “green” symposia tracks. The “red” one focused on computers, physics, and the types of subjects Lerner talked about. The “green” track was biological and environmental.

  Let's start with the environment.

  * * * *

  Green Revolution, Gray Goo, or Nanolung

  Nanotechnology has the potential of producing products that are both revolutionary and environmentally friendly. It offers the prospect, for example, of creating filters that can clean up toxic-waste sites very quickly, at low cost. The same processes can be used to remove contaminants from water, also at extremely low cost. One company has announced a goal of being able to provide safe drinking water anywhere in the world for $1 per person per year.

  Nanotechnology has also been cited as a way of providing cheap solar power. And it can produce batteries that recharge at a phenomenal rate. The Altairnano company of Reno, Nevada, has developed a battery that can take an SUV 130 miles—then recharge in ten minutes. The battery itself is nothing special—my laptop battery has a higher energy density. What's new is the replacement of graphite electrodes with a nanomaterial that allows super-fast cycling. Historically, one of the limiting factors with electric cars has been limited range. But if you can recharge in the time it takes to get a cup of coffee, that limitation evaporates. “It's not that big an inconvenience,” says company representative Bruce Sabacky.

  Nor do the new batteries appear to show “memory” problems. They appear able to run through thousands—possibly millions—of cycles while retaining at least ninety percent of their capacity. When your car wears out, you might just buy a new chassis and take the old battery with you!

  Automobiles aren't the only use. How about a light rail line that doesn't need wires? Charging stations at each stop would allow the train to top off its batteries while passengers enter and leave.

  * * * *

  Nanotechnology enthusiasts can list dozens of ways to save the planet. But with any new technology, one of the questions science fiction should ask is what might go wrong.

  With nanotechnology, the classic nightmare has been the “gray goo” scenario, in which out-of-control nanobots disassemble everything in sight, including us. It's not a pretty scenario, but neither is it realistic. The real concern about nanotechnology is what we might call nano-toxicity.

  The problem is that nanomaterials are, well, nano-. That allows airborne particles to penetrate more deeply into lungs. Inhaled nanoparticles have even been reported to travel along nasal nerves to the brain, Ken Donaldson, a lung toxicology expert at the University of Edinburgh, U.K., warned in 2004. It's an ability, he said, that they share with some similar-sized viruses. “The importance of nanotechnology to the economy and to our future wellbeing is beyond debate,” Donaldson added, “but its potential adverse impacts need to be studied."

  Also, gram for gram, smaller particles tend to be more reactive. Regulators, including the U.S. Environmental Protection Agency, are concerned that this might increase their toxicity when they escape into the environment or are accidentally breathed or ingested from cosmetics, sunscreens, sports equipment, or weather-resistant clothing.

  Many of these materials are made of familiar ingredients, but does that make them safe? Simply put, are carbon nanotubes “graphite?” Or are they something else? Toxicologists are still wrestling with the details, but for most nanomaterials, “something else” appears to be the most likely conclusion. Size, it appears, really does matter.

  But that's only the beginning of the problem, says Eric Tulsky, a nanochemist with Invitrogen Corporation. “The next problem is that there are an infinite number of types of nanotubes."[3 Tube lengths vary. So can their diameters, the ways they fold, their end caps, and the ways they wrap around each other. Should all tubes be lumped together, or do we need to study each type, individually?

  [Footnote 3: Personal communication by e-mail.]

  Nanotubes aren't the only nanomaterials posing such problems. In some cases, the nomenclature doesn't even exist yet for defining potentially important differences in nano-level structure.

  All of this, Tulsky says, presents “a very real barrier” to figuring out how to regulate nanomaterials. The solution, he believes, is to figure out which properties are important and which are irrelevant, thereby reducing the analysis to something at least reasonably manageable.

  But that doesn't mean nanotechnology needs to abandon its “green” leanings. Rather than circling the wagons and going on the defensive, some nanotechnology leaders hope the industry will cooperate with the more responsible environmental groups and face these issues head on.

  "We have the opportunity to design and implement nanotechnology in a responsible way the first time,” says Jim Hutchison of the University of Oregon. “The goal is to get high-performance materials that also pose little harm to the environment and to humans."

  * * * *

  Pulp Nonfiction

  Another “green” aspect of nanotechnology is the ability to make better use of limited materials.

  There is talk, for example, of a cell phone printed on paper. From a science fictional perspective, it adds a new dimension to the hero-on-the-lam trick of making calls only from throwaway phones. Make a call, blow your nose, and destroy the evidence. Not to mention making it a lot easier to lose your phone. Oops, sorry. I think I used it for a shopping list.

  Or maybe the phones of the future are single-use, like packets of Post-Its. Forget recharging. Peel one off and toss it away.

  More seriously, the ability to print phones, batteries, and perhaps even computer screens on paper raises the question of how nanotechnology might change a material that we currently take largely for granted.

  Most paper is made of wood. But so is sawdust. The difference is that the wood in paper was converted to pulp, spread into thin sheets, and allowed to dry. In the drying, the pulp particles bind to each other, keeping them from falling apart the moment you pick up the sheet.

  Pulp itself is formed largely of cellulose, one of the fundamental building blocks of plant cells. That cellulose exists as long, thin nanoscale crystals, sometimes referred to as nanocrystalline cellulose. With a bit of effort, these cr
ystals, which can comprise up to ninety percent of a plant's dry matter, can be liberated from other materials to which they're bound.

  The result is a natural product that's twenty-five to thirty percent as strong as carbon nanotubes.

  "It's stronger than steel and stiffer than aluminum,” says John Simonsen of Oregon State University. “Not bad for an organic polymer that comes from nature."

  So far, isolating the material is expensive—on the order of $100 per gram—but as costs come down, it offers a way to make strong, lightweight plastics, freeing the plastics industry from its dependence on petroleum.

  Once we've learned to refine it more cheaply, nanocrystalline cellulose opens the door to stronger, lighter paper—enough that the paper industry has set a goal of making its product forty percent lighter without any loss in strength. That would save billions of dollars in mailing costs alone, says E. Peter Lancaster, formerly a paper chemist for Weyerhaeuser Corporation. But that's just the beginning. Stronger paper could replace other materials. And nanocellulose-based paper might ultimately be cheaper and more environmentally friendly to make. A major input in paper manufacturing is water, which must then be dried out of the finished product. If nanocrystalline-based paper could be designed to repel water, less energy might be needed in drying, not only saving money but reducing the environmental impacts. It's the type of win-win that green nanotechnology advocates most want to achieve.

  Another win-win might come from the elimination of dyes. Pure nanocrystalline cellulose is highly transparent, but it's possible to make it any color you want by slightly altering the chemistry. This could be a major environmental benefit, because dyes tend to be nasty toxicants. Whether the altered cellulose itself might be toxic remains to be seen. But it's certainly worth investigating, especially because color-altered nanocrystals, even if toxic, are probably a lot less likely than dyes to leach into the environment.

  * * * *

  Artificial Bones

  The same biological factors that raise concerns about nanotechnology in some settings make it beneficial in others. The most notable is medicine.

  Let's look again at nanocrystalline cellulose. Even at its current price, it's attractive for implants—basically as a scaffolding on which bone, skin, or other tissues can be regrown. Already, Lancaster says, one company is making artificial, cellulose-based skin for burn patients.

  With a bit of chemical engineering, nanocrystals can be designed as self-assembling lattices that can be molded into any shape you want and which dissolve when the body no longer needs them. The technique, says Simonsen, involves attaching short strands of DNA onto the individual cellulose crystals.

  Most of us think of DNA simply as the coding for our genes. But one of the properties that make it work for that purpose is its tendency to form paired strands, like the double helix of molecular-biology fame. By attaching a single strand to one crystal, and the complimentary strand to another, you can make DNA tags serve like molecular Velcro. Putting the right tags in the right places allows chemists to design the crystals to link like beams and girders, forming any desired lattice, not just in two dimensions, but in three.

  Even more interestingly, Simonsen says, the DNA bonds break at high temperature. This allows blocks of the material to be molded, like thermoplastic. Better yet, you can insert a molecular spacer between the cellulose crystal and the DNA tag, designed so the body degrades it at whatever rate you want. Bingo, you've got a dissolving scaffold for pretty much any type of regenerative medicine you want. With the right spacers, it's even possible to give the lattice the same flexibility as bone, skin, kidneys, etc., allowing damaged tissue to more easily regrow.

  * * * *

  Quantum Imaging

  Cellulose isn't the only nanotechnology material that has medical potential. Quantum dots do, too.

  Quantum dots are tiny semiconductors, comprised of perhaps 100 to 100,000 atoms. Much of the buzz about them focuses on their possible use in quantum computers. Their key feature is that when you shine light on them of the right wavelength, they fluoresce brightly in another—kind of like nanoscale black-light posters. In computers, they can be used to make extremely tiny, rapidly switching gates. (They also show potential for use in high-efficiency solar cells.)

  Biologically, they have the ability to replace tissue-staining dyes. That sounds trivial, but dyes are important because they let you see things that would otherwise be invisible.

  Traditional fluorescent dyes have limitations: basically, if the substances you're trying to tag with them are present at too low a level, you still can't see them. But quantum dots are forty to 100 times brighter—so bright that you can spot them individually, under the right microscopes. Also they don't bleach out after a few minutes’ illumination, allowing them to be used for extended procedures.

  To use them as dyes, all that's necessary is to attach antibodies to their surfaces. Antibodies are like molecular fishhooks: when they find the molecule they're designed to catch (their antigen), they bind to it. If the other end of the antibody is connected to the quantum dot, they've also bound the dot to the antigen.

  It isn't just microscopic analysis that benefits from this. Surgeons can use quantum dots for removing hard-to-find tumors. Christoph Block, of Signalomics GmbH, in Vienna, Austria, reports that this has been used for glioma, a particularly nasty form of brain cancer.

  Under ordinary light, it's very hard to distinguish the tumor from healthy brain tissue. But if you dose the area with quantum dots designed to bind to surface antigens found on cancer cells, then shine violet light on the dots (the wavelength at which the medical ones are designed to fluoresce), the cancerous areas glow back at you, greatly increasing the chances of finding the entire tumor.

  The same has been done with bladder cancers. “The problem that you don't really see the tumor is pretty frequent,” Block says.

  Encouraged by their successes with bladder cancers and gliomas, surgeons are looking for other ways to use the dots, particularly in minimally invasive surgery, where incisions are small and it's hard to see inside with conventional techniques.

  Quantum dots can also be used for diagnosis. Skin and other tissues are moderately transparent to red light and near infrared, says Tulsky, of Invitrogen Corporation. That's why you can see a red flashlight shining through your hand.

  Quantum dots are equally bright. “An ultra-bright infrared fluor could be imaged in vivo through skin,” Tulsky says.

  A very simple application is for determining which lymph nodes drain a tumor. Since metastasis typically begins with cells moving into the lymphatic system, it's important to determine which nodes serve the tumor site. “Often the surgeon takes out a double-digit [number of] lymph nodes,” Tulsky says. “That [surgery] can be worse for the patient than the removal of the tumor."

  Various techniques are available for doing such mappings, but with quantum dots, all you have to do is inject them into the tumor and watch them move, right through the skin. It's been done in a pig, Tulsky says. “All we need to do this in humans is an FDA-approved nanocrystal."

  That, of course, is the rub. It's one thing to squirt quantum dots into an incision site, where those that bind are going to be cut out with the tumor and the rest will be washed away. It's another thing to let them stay until the body excretes them naturally. Some of the elements that make the dots do their thing, like cadmium, are highly toxic. Though, Tulsky says, “We're working to make them as nontoxic as possible."

  Toxicity isn't as big a problem with basic biological research. In animal experiments, it's possible to paint the outside of stem cells with dots and watch the cells migrate to their target tissues. It's also possible to use quantum dots to track white blood cells. “These are experiments you just couldn't do without the brightness and stability that quantum dots bring to the table,” Tulsky says.

  At a smaller scale, it's possible to tag biochemically interesting molecules with quantum dots and, in tissue culture experiments, watch
how the dots (and therefore the attached molecules) move through living cells.

  Tania Vu is an assistant professor of biomedical engineering at Oregon Health & Science University who's used such techniques to study chemical signaling in neurons. Much of her research centers on figuring out how nerve cells extend filaments, called axons, in response to hormone-like chemicals.

  It is well known that these chemicals bind to receptors on the neuron's cell walls, initiating the cascade of reactions that leads to axon growth. But how exactly does it happen?

  To grow, the cell needs to shift the right proteins to the right locations and keep track of what is going on. And the shipping distances aren't trivial. “We're talking [about] distances that can be as long as 1,000 times the diameter of the cell body,” Vu says.

  Conventional staining allows researchers to take snapshots of what's happening in the cell at any given time. But the act of staining kills the cell. And since it's only a snapshot, it doesn't allow individual molecules’ motions to be tracked.

  "We want to be able to look at protein-protein interactions in live cells, with single-molecule resolution, in a dynamic manner,” Vu says.

  Quantum dots make this possible. What she's learned is that when a receptor is activated by the binding of a hormone, it and the hormone are rapidly drawn into the cell, where they associate with many different types of proteins. (Exactly what proteins are involved at any given stage can be determined by stopping the experiment and extracting the dots to see what they're linked to at the time.)

  The dots then enter the cell's network of microtubules, tiny tunnels that quickly transport them to distant parts of the cell.

  "It's like tracking trucks along the cellular highway,” Tulsky says of similar experiments. “We're tracking single molecules in a cell."

  In Vu's case, the research focused on a potent hormone called nerve growth factor, or NGF. Blockages in the cells’ handling of it are believed to play roles in Alzheimer's, Parkinson's, and Huntington's diseases, and research like hers may help shed light on precisely how these blockages occur.[4]